Staphylococcus haemolyticus
Encyclopedia
Staphylococcus haemolyticus is a member of the coagulase-negative
Coagulase
Coagulase is a protein produced by several microorganisms that enables the conversion of fibrinogen to fibrin. In the laboratory, it is used to distinguish between different types of Staphylococcus isolates. Coagulase negativity excludes S. aureus. That is to say, S...

 staphylococci (CoNS). It is part of the skin flora
Skin flora
The skin flora are the microorganisms which reside on the skin. Most research has been upon those that reside upon the 2 square metres of human skin. Many of them are bacteria of which there are around 1000 species upon human skin from 19 phyla. The total number of bacteria on an average human has...

 of humans, and its largest populations are usually found at the axillae, perineum
Perineum
In human anatomy, the perineum is a region of the body including the perineal body and surrounding structures...

, and inguinal
Inguinal
In human anatomy, the inguinal region refers to either the groin or the lower lateral regions of the abdomen. It may also refer to:* Conjoint tendon, previously known as the inguinal aponeurotic falx, a structure formed from the transversus abdominis insertion into the pecten pubis* Granuloma...

 areas. S. haemolyticus also colonizes prosimians, monkeys, and domestic animals. It is a well-known opportunistic pathogen, and is the second most frequently isolated CoNS (S. epidermidis is the first). Infections can be localized or systemic, and are often associated with the insertion of medical devices. The highly antibiotic resistant phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...

 and ability to form biofilms make S. haemolyticus a difficult pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...

 to treat.

Biology and biochemistry

S. haemolyticus is non-motile, non-sporulating, facultatively anaerobic
Facultative anaerobic organism
A facultative anaerobic organism is an organism, usually a bacterium, that makes ATP by aerobic respiration if oxygen is present but is also capable of switching to fermentation...

, and Gram-stain positive. Cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

 are typically coccus-shaped
Coccus
Coccus can be used to describe any bacterium that has a spherical shape. It is one of the three distinct types of bacteria shapes, the other two being bacillus and spirillum cells...

 and range from 0.8-1.3 μm in diameter. It lives on a wide variety of substrates, including (but not limited to): glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

, glycerol
Glycerol
Glycerol is a simple polyol compound. It is a colorless, odorless, viscous liquid that is widely used in pharmaceutical formulations. Glycerol has three hydroxyl groups that are responsible for its solubility in water and its hygroscopic nature. The glycerol backbone is central to all lipids...

, maltose
Maltose
Maltose , or malt sugar, is a disaccharide formed from two units of glucose joined with an αbond, formed from a condensation reaction. The isomer "isomaltose" has two glucose molecules linked through an α bond. Maltose is the second member of an important biochemical series of glucose chains....

, sucrose
Sucrose
Sucrose is the organic compound commonly known as table sugar and sometimes called saccharose. A white, odorless, crystalline powder with a sweet taste, it is best known for its role in human nutrition. The molecule is a disaccharide composed of glucose and fructose with the molecular formula...

, and trehalose
Trehalose
Trehalose, also known as mycose or tremalose, is a natural alpha-linked disaccharide formed by an α,α-1,1-glucoside bond between two α-glucose units. In 1832, H.A.L. Wiggers discovered trehalose in an ergot of rye, and in 1859 Marcellin Berthelot isolated it from trehala manna, a substance made...

. It also tests positive for acetonin production, arginine
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...

, dihydrolase, benzidine
Benzidine
Benzidine, the trivial name for 4,4'-diaminobiphenyl, is the solid organic compound with the formula 2. This aromatic amine is a component of a test for cyanide and also in the production of dyes...

, catalase
Catalase
Catalase is a common enzyme found in nearly all living organisms that are exposed to oxygen, where it catalyzes the decomposition of hydrogen peroxide to water and oxygen...

, hemolysis
Hemolysis
Hemolysis —from the Greek meaning "blood" and meaning a "loosing", "setting free" or "releasing"—is the rupturing of erythrocytes and the release of their contents into surrounding fluid...

, and lipase
Lipase
A lipase is an enzyme that catalyzes the formation or cleavage of fats . Lipases are a subclass of the esterases.Lipases perform essential roles in the digestion, transport and processing of dietary lipids in most, if not all, living organisms...

; it tests negative for coagulase
Coagulase
Coagulase is a protein produced by several microorganisms that enables the conversion of fibrinogen to fibrin. In the laboratory, it is used to distinguish between different types of Staphylococcus isolates. Coagulase negativity excludes S. aureus. That is to say, S...

, DNase, ornithine decarboxylase
Ornithine decarboxylase
The enzyme ornithine decarboxylase catalyzes the decarboxylation of ornithine to form putrescine. This reaction is the committed step in polyamine synthesis. In humans, this protein has 461 amino acids and forms a homodimer....

, phosphatase
Phosphatase
A phosphatase is an enzyme that removes a phosphate group from its substrate by hydrolysing phosphoric acid monoesters into a phosphate ion and a molecule with a free hydroxyl group . This action is directly opposite to that of phosphorylases and kinases, which attach phosphate groups to their...

, urease
Urease
Urease is an enzyme that catalyzes the hydrolysis of urea into carbon dioxide and ammonia. The reaction occurs as follows:In 1926, James Sumner showed that urease is a protein. Urease is found in bacteria, yeast, and several higher plants. The structure of urease was first solved by P.A...

, and oxidase
Oxidase
An oxidase is any enzyme that catalyzes an oxidation-reduction reaction involving molecular oxygen as the electron acceptor. In these reactions, oxygen is reduced to water or hydrogen peroxide ....

.

Growth conditions

Optimal growth occurs between 30-40°C in the presence of oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

 and 10% NaCl. However, some strains can grow at temperatures that range between 18-45°C. Growth at 15°C or 15% NaCl is poor or absent.

Genome structure

The S. haemolyticus strain JCSC1435 genome contains a 2,685,015 bp
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...

 chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...

 and three plasmids of 2,300 bp
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...

, 2,366 bp
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...

, and 8,180 bp
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...

. The chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...

 is comparable in size to those of S. aureus
S. aureus
S. aureus may refer to:* Scleropages aureus, a proposed species of the Asian arowana, a fish species native to Southeast Asia* Senecio aureus, the golden ragwort, a perennial flowering plant species native to eastern North America...

 and S. epidermidis and contains a similar G+C content. In addition, a large proportion of the ORFs
Open reading frame
In molecular genetics, an open reading frame is a DNA sequence that does not contain a stop codon in a given reading frame.Normally, inserts which interrupt the reading frame of a subsequent region after the start codon cause frameshift mutation of the sequence and dislocate the sequences for stop...

 are conserved across all three species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...

. On average, orthologous ORFs
Open reading frame
In molecular genetics, an open reading frame is a DNA sequence that does not contain a stop codon in a given reading frame.Normally, inserts which interrupt the reading frame of a subsequent region after the start codon cause frameshift mutation of the sequence and dislocate the sequences for stop...

 are 78% identical. However, S. haemolyticus does have unique chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...

 regions distributed near oriC (the origin of chromosomal DNA replication
Origin of replication
The origin of replication is a particular sequence in a genome at which replication is initiated. This can either be DNA replication in living organisms such as prokaryotes and eukaryotes, or RNA replication in RNA viruses, such as double-stranded RNA viruses...

), and these regions are collectively referred to as the “oriC environ”.

As noted, there are also S. haemolyticus ORFs
Open reading frame
In molecular genetics, an open reading frame is a DNA sequence that does not contain a stop codon in a given reading frame.Normally, inserts which interrupt the reading frame of a subsequent region after the start codon cause frameshift mutation of the sequence and dislocate the sequences for stop...

 that differ from S. aureus
S. aureus
S. aureus may refer to:* Scleropages aureus, a proposed species of the Asian arowana, a fish species native to Southeast Asia* Senecio aureus, the golden ragwort, a perennial flowering plant species native to eastern North America...

 and S. epidermidis. Some of these ORFs
Open reading frame
In molecular genetics, an open reading frame is a DNA sequence that does not contain a stop codon in a given reading frame.Normally, inserts which interrupt the reading frame of a subsequent region after the start codon cause frameshift mutation of the sequence and dislocate the sequences for stop...

 encode gene products with known biological features, such as the regulation of RNA synthesis, the transport of ribose
Ribose
Ribose is an organic compound with the formula C5H10O5; specifically, a monosaccharide with linear form H––4–H, which has all the hydroxyl groups on the same side in the Fischer projection....

 and ribitol
Ribitol
Ribitol or adonitol is a crystalline pentose alcohol formed by the reduction of ribose. It occurs naturally in the plant Adonis vernalis, as well as in the cell walls of Gram positive bacteria . It also contributes to the chemical structure of riboflavin.-External links:**...

, and the essential components of nucleic acid
Nucleic acid
Nucleic acids are biological molecules essential for life, and include DNA and RNA . Together with proteins, nucleic acids make up the most important macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information...

 and cell wall
Cell wall
The cell wall is the tough, usually flexible but sometimes fairly rigid layer that surrounds some types of cells. It is located outside the cell membrane and provides these cells with structural support and protection, and also acts as a filtering mechanism. A major function of the cell wall is to...

 teichoic acid
Teichoic acid
Teichoic acids are bacterial polysaccharides of glycerol phosphate or ribitol phosphate linked via phosphodiester bonds.-Location and structure:...

 biosynthesis. Other unique ORFs
Open reading frame
In molecular genetics, an open reading frame is a DNA sequence that does not contain a stop codon in a given reading frame.Normally, inserts which interrupt the reading frame of a subsequent region after the start codon cause frameshift mutation of the sequence and dislocate the sequences for stop...

 likely encode products involved with bacterial pathogenesis
Pathogenesis
The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...

 and at least three of these ORFs
Open reading frame
In molecular genetics, an open reading frame is a DNA sequence that does not contain a stop codon in a given reading frame.Normally, inserts which interrupt the reading frame of a subsequent region after the start codon cause frameshift mutation of the sequence and dislocate the sequences for stop...

 show homology
Homology
Homology may refer to:* Homology , analogy between human beliefs, practices or artifacts owing to genetic or historical connections* Homology , any characteristic of biological organisms that is derived from a common ancestor....

 to staphylococcal hemolysins.

The S. haemolyticus genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....

 also contains many insertion sequences (IS
Insertion sequence
An insertion sequence is a short DNA sequence that acts as a simple transposable element...

s). These IS elements may promote frequent genomic rearrangements which accelerate the diversification of the species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...

. Theoretically, these adaptations might help S. haemolyticus overcome the adverse effects of chemical exposure (i.e. the use of antibiotics). The table below contains a list of genes that are known to be associated with S. haemolyticus antibiotic resistance.
Class Antimicrobial Agent MIC
Minimum inhibitory concentration
In microbiology, minimum inhibitory concentration is the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation. Minimum inhibitory concentrations are important in diagnostic laboratories to confirm resistance of microorganisms...

 (mg/L)
ORF
Open reading frame
In molecular genetics, an open reading frame is a DNA sequence that does not contain a stop codon in a given reading frame.Normally, inserts which interrupt the reading frame of a subsequent region after the start codon cause frameshift mutation of the sequence and dislocate the sequences for stop...

 ID
Gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

 Name
Product Location
Penicillins  Oxacillin
Oxacillin
Oxacillin sodium is a narrow spectrum beta-lactam antibiotic of the penicillin class.It was developed by Beecham.-Uses:...

 
>512 SH0091 mecA Penicillin-binding protein 2'
Penicillin binding proteins
Penicillin-binding proteins are a group of proteins that are characterized by their affinity for and binding of penicillin. They are a normal constituent of many bacteria; the name just reflects the way by which the protein was discovered...

 
ΨSCCmec(h1435)
Ampicillin
Ampicillin
Ampicillin is a beta-lactam antibiotic that has been used extensively to treat bacterial infections since 1961. Until the introduction of ampicillin by the British company Beecham, penicillin therapies had only been effective against Gram-positive organisms such as staphylococci and streptococci...

 
64 SH1764 blaZ β-Lactamase  Tn552
methicillin
Methicillin
Meticillin or methicillin is a narrow-spectrum beta-lactam antibiotic of the penicillin class. It should not be confused with the antibiotic metacycline.-History:Methicillin was developed by Beecham in 1959...

 
mecA Penicillin-binding protein 2'
Penicillin binding proteins
Penicillin-binding proteins are a group of proteins that are characterized by their affinity for and binding of penicillin. They are a normal constituent of many bacteria; the name just reflects the way by which the protein was discovered...

 
ΨSCCmec(h1435)
Cephalosporins  Ceftizoxime
Ceftizoxime
Ceftizoxime is a parenteral third-generation cephalosporin.Unlike other 3rd generation cephalosporins , in ceftizoxime the whole C-3 side chain has been removed to prevent deactivation by hydrolytic enzymes ....

 
>512 SH0091 mecA Penicillin-binding protein 2'
Penicillin binding proteins
Penicillin-binding proteins are a group of proteins that are characterized by their affinity for and binding of penicillin. They are a normal constituent of many bacteria; the name just reflects the way by which the protein was discovered...

 
ΨSCCmec(h1435)
Macrolides  Erythromycin
Erythromycin
Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma and...

 
>512 pSHaeB1 ermC rRNA adenine N-6-methyltransferase Plasmid
Plasmid
In microbiology and genetics, a plasmid is a DNA molecule that is separate from, and can replicate independently of, the chromosomal DNA. They are double-stranded and, in many cases, circular...

 pSHaeB
SH2305 msrSA ATP-dependent efflux system πSh1
SH2306 mphBM Macrolide 2'-phosphotransferase πSh1
Quinolones  Ofloxacin
Ofloxacin
Ofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class considered to be a second-generation fluoroquinolone. The original brand, Floxin, has been discontinued by the manufacturer in the United States on 18 June 2009, though generic equivalents continue to be...

 
8 SH0006 gyrA DNA gyrase
DNA gyrase
DNA gyrase, often referred to simply as gyrase, is an enzyme that relieves strain while double-stranded DNA is being unwound by helicase. This causes negative supercoiling of the DNA...

 (topoisomerase II) subunit A (point mutation
Point mutation
A point mutation, or single base substitution, is a type of mutation that causes the replacement of a single base nucleotide with another nucleotide of the genetic material, DNA or RNA. Often the term point mutation also includes insertions or deletions of a single base pair...

 C7313T)
SH1553 parC (grlA) Topoisomerase IV
Topoisomerase IV
Topoisomerase IV is one of two type-II topoisomerases in bacteria, the other being DNA gyrase. Like gyrase, topoisomerase IV is able to pass one double-strand of DNA through another double-strand of DNA, thereby changing the linking number of DNA by two in each enzymatic...

 subunit A (point mutation
Point mutation
A point mutation, or single base substitution, is a type of mutation that causes the replacement of a single base nucleotide with another nucleotide of the genetic material, DNA or RNA. Often the term point mutation also includes insertions or deletions of a single base pair...

 G1598138A)
Tetracyclines  Tetracycline  2
Minocycline
Minocycline
Minocycline is a broad-spectrum tetracycline antibiotic, and has a broader spectrum than the other members of the group. It is a bacteriostatic antibiotic, classified as a long-acting type...

 
0.5
Aminoglycosides  Kanamycin
Kanamycin
Kanamycin sulfate is an aminoglycoside antibiotic, available in oral, intravenous, and intramuscular forms, and used to treat a wide variety of infections. Kanamycin is isolated from Streptomyces kanamyceticus.-Mechanism:...

 
>512 SH1611 aacA-aphD Bifunctional aminoglycoside N-acetyltransferase and aminoglycoside phosphotransferase Tn4001
Tobramycin  16 SH1611 aacA-aphD Bifunctional Tn4001
Gentamicin
Gentamicin
Gentamicin is an aminoglycoside antibiotic, used to treat many types of bacterial infections, particularly those caused by Gram-negative organisms. However, gentamicin is not used for Neisseria gonorrhoeae, Neisseria meningitidis or Legionella pneumophila...

 
64 SH1611 aacA-aphD Bifunctional Tn4001
Glycopeptides  Vancomycin
Vancomycin
Vancomycin INN is a glycopeptide antibiotic used in the prophylaxis and treatment of infections caused by Gram-positive bacteria. It has traditionally been reserved as a drug of "last resort", used only after treatment with other antibiotics had failed, although the emergence of...

 
4
Teicoplanin
Teicoplanin
Teicoplanin is an antibiotic used in the prophylaxis and treatment of serious infections caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and Enterococcus faecalis. It is a glycopeptide antibiotic extracted from Actinoplanes teichomyceticus, with a similar...

 
64
Fosfomycin
Fosfomycin
Fosfomycin is a broad-spectrum antibiotic produced by certain Streptomyces species.-Uses:...

 
Fosfomycin
Fosfomycin
Fosfomycin is a broad-spectrum antibiotic produced by certain Streptomyces species.-Uses:...

 
>512 pSHaeA1 fosB Glutathione transferase  Plasmid
Plasmid
In microbiology and genetics, a plasmid is a DNA molecule that is separate from, and can replicate independently of, the chromosomal DNA. They are double-stranded and, in many cases, circular...

 pSHaeA

Cell wall

Like other Gram-positive
Gram-positive
Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. This is in contrast to Gram-negative bacteria, which cannot retain the crystal violet stain, instead taking up the counterstain and appearing red or pink...

 microbes, S. haemolyticus has a thick, rather homogenous, cell wall
Cell wall
The cell wall is the tough, usually flexible but sometimes fairly rigid layer that surrounds some types of cells. It is located outside the cell membrane and provides these cells with structural support and protection, and also acts as a filtering mechanism. A major function of the cell wall is to...

 (~60-80 nm) composed of peptidoglycan
Peptidoglycan
Peptidoglycan, also known as murein, is a polymer consisting of sugars and amino acids that forms a mesh-like layer outside the plasma membrane of bacteria , forming the cell wall. The sugar component consists of alternating residues of β- linked N-acetylglucosamine and N-acetylmuramic acid...

, teichoic acid
Teichoic acid
Teichoic acids are bacterial polysaccharides of glycerol phosphate or ribitol phosphate linked via phosphodiester bonds.-Location and structure:...

, and protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

. Peptidoglycan
Peptidoglycan
Peptidoglycan, also known as murein, is a polymer consisting of sugars and amino acids that forms a mesh-like layer outside the plasma membrane of bacteria , forming the cell wall. The sugar component consists of alternating residues of β- linked N-acetylglucosamine and N-acetylmuramic acid...

 of group A3 (with L-lysine as the diamino acid
Diamino acid
In chemistry, a diamino acid, also called a diamino carboxylic acid, is a molecule containing at least one carboxyl and two amine functional groups. Diamino acids belong to the class of amino acids.- Biochemical function :...

 in position 3 of the peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...

 subunit and a glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...

-rich interpeptide bridge) is a characteristic feature of this microbe, and the two predominant cross bridges are COOH-Gly-Gly-Ser-Gly-Gly-NH2 and COOH-Ala-Gly-Ser-Gly-Gly-NH2. Alterations of these cross bridges are implicated in glycopeptide
Glycopeptide
Glycopeptides are peptides that contain carbohydrate moieties covalently attached to the side chains of the amino acid residues that constitute the peptide. Over the past few decades it has been recognised that glycans on cell surface and those bound to proteins play a critical role in biology...

 resistance. S. haemolyticus teichoic acids are water-soluble polymers with repeating phosphodiester groups covalently linked to peptidoglycan
Peptidoglycan
Peptidoglycan, also known as murein, is a polymer consisting of sugars and amino acids that forms a mesh-like layer outside the plasma membrane of bacteria , forming the cell wall. The sugar component consists of alternating residues of β- linked N-acetylglucosamine and N-acetylmuramic acid...

. Peptidoglycan
Peptidoglycan
Peptidoglycan, also known as murein, is a polymer consisting of sugars and amino acids that forms a mesh-like layer outside the plasma membrane of bacteria , forming the cell wall. The sugar component consists of alternating residues of β- linked N-acetylglucosamine and N-acetylmuramic acid...

 type L-Lys-Gly 3.5-4.0, L-Ser0.9-1.5 Teichoic acid
Teichoic acid
Teichoic acids are bacterial polysaccharides of glycerol phosphate or ribitol phosphate linked via phosphodiester bonds.-Location and structure:...

 contains both glycerol
Glycerol
Glycerol is a simple polyol compound. It is a colorless, odorless, viscous liquid that is widely used in pharmaceutical formulations. Glycerol has three hydroxyl groups that are responsible for its solubility in water and its hygroscopic nature. The glycerol backbone is central to all lipids...

 and N-acetylglucosamine
N-Acetylglucosamine
N-Acetylglucosamine is a monosaccharide derivative of glucose. It is an amide between glucosamine and acetic acid...

. The major cell wall fatty acids are CBr-15, CBr-17, C18, and C20.

Capsule

Certain strains of S. haemolyticus are capable of producing a capsular polysaccharide
Polysaccharide encapsulated bacteria
Polysaccharide encapsulated bacteria, frequently referred to simply as encapsulated bacteria and less precisely called encapsulated organisms, are a group of bacteria that have an outer covering, a bacterial capsule, made of polysaccharide....

 (CP). S. haemolyticus strain JCSC1435 contains a capsule operon
Operon
In genetics, an operon is a functioning unit of genomic DNA containing a cluster of genes under the control of a single regulatory signal or promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo trans-splicing to create...

 located within the “oriC environ”. This operon contains 13 ORFs
Open reading frame
In molecular genetics, an open reading frame is a DNA sequence that does not contain a stop codon in a given reading frame.Normally, inserts which interrupt the reading frame of a subsequent region after the start codon cause frameshift mutation of the sequence and dislocate the sequences for stop...

 in a 14,652 bp
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...

 region and is referred to as the capsh locus
Locus (genetics)
In the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map...

. The first seven genes
Gênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...

 of capsh (capAsh through capGsh) are homologous to the S. aureus
S. aureus
S. aureus may refer to:* Scleropages aureus, a proposed species of the Asian arowana, a fish species native to Southeast Asia* Senecio aureus, the golden ragwort, a perennial flowering plant species native to eastern North America...

 cap5 or cap8 locus
Locus (genetics)
In the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map...

. However, capH through capM are unique to S. haemolyticus, and this region encodes enzymes for a unique trideoxy sugar residue that is N-acylated by aspartic acid
Aspartic acid
Aspartic acid is an α-amino acid with the chemical formula HOOCCHCH2COOH. The carboxylate anion, salt, or ester of aspartic acid is known as aspartate. The L-isomer of aspartate is one of the 20 proteinogenic amino acids, i.e., the building blocks of proteins...

.

CP production is influenced by culture medium and growth phase
Bacterial growth
250px|right|thumb|Growth is shown as L = log where numbers is the number of colony forming units per ml, versus T Bacterial growth is the division of one bacterium into two daughter cells in a process called binary fission. Providing no mutational event occurs the resulting daughter cells are...

. Cultivation in TSB
Tryptic Soy Broth
Tryptic Soy Broth is used as a culture broth to grow aerobic bacteria.It is frequently used in commercial diagnostics in conjunction with Thio which promotes growth of anaerobes....

, TSB
Tryptic Soy Broth
Tryptic Soy Broth is used as a culture broth to grow aerobic bacteria.It is frequently used in commercial diagnostics in conjunction with Thio which promotes growth of anaerobes....

 with 1% glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

, brain heart infusion broth
Brain heart infusion broth
Brain heart infusion broth is a highly nutritious general-purpose growth medium for fastidious microorganisms, such as streptococci, pneumococci and meningococci. It is made by the recuperation of nutrients from boiled cattle hearts and brains. Soluble factors are released into the broth during...

, or Columbia broth with 2% NaCl favors the production of CP; cultivation on Columbia salt agar plates is suboptimal. Only trace amounts of CP are generated before the end of exponential phase, and the maximal rate of CP production does not occur until early stationary phase.

CP is considered a virulence factor
Virulence factor
Virulence factors are molecules expressed and secreted by pathogens that enable them to achieve the following:* colonization of a niche in the host...

 because it provides resistance against complement
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...

-mediated PMN phagocytosis.

Biofilm formation

The ability to adhere to medical devices and subsequently form biofilms is a major virulence factor
Virulence factor
Virulence factors are molecules expressed and secreted by pathogens that enable them to achieve the following:* colonization of a niche in the host...

 associated with S. haemolyticus. Biofilm
Biofilm
A biofilm is an aggregate of microorganisms in which cells adhere to each other on a surface. These adherent cells are frequently embedded within a self-produced matrix of extracellular polymeric substance...

 formation increases antibiotic resistance
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...

 and often leads to persistent infections. S. haemolyticus biofilms are not polysaccharide intercellular adhesin (PIA) dependent, and the lack of the ica operon
Operon
In genetics, an operon is a functioning unit of genomic DNA containing a cluster of genes under the control of a single regulatory signal or promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo trans-splicing to create...

 (the gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

 cluster that encodes the production of PIA) can be used to distinguish S. haemolyticus isolates from other CoNS species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...

.

Biofilm
Biofilm
A biofilm is an aggregate of microorganisms in which cells adhere to each other on a surface. These adherent cells are frequently embedded within a self-produced matrix of extracellular polymeric substance...

 formation is influenced by a variety of factors including carbohydrates, proteins, and extracellular DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

. Detachment assays with NaIO4, proteinase K
Proteinase K
Proteinase K is a broad-spectrum serine protease. The enzyme was discovered in 1974 in extracts of the fungus Engyodontium album . Proteinase K is able to digest native keratin , hence, the name "Proteinase K"...

, or DNase result in 38%, 98%, and 100% detachment, respectively. The high level of detachment associated with DNase treatment has led several authors to suggest a cell-to-surface and/or cell-to-cell adhesion
Cell adhesion
Cellular adhesion is the binding of a cell to a surface, extracellular matrix or another cell using cell adhesion molecules such as selectins, integrins, and cadherins. Correct cellular adhesion is essential in maintaining multicellular structure...

 function for extracellular DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

. Biofilm
Biofilm
A biofilm is an aggregate of microorganisms in which cells adhere to each other on a surface. These adherent cells are frequently embedded within a self-produced matrix of extracellular polymeric substance...

 formation also appears to be influenced by the presence of glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

 and NaCl. Biofilm
Biofilm
A biofilm is an aggregate of microorganisms in which cells adhere to each other on a surface. These adherent cells are frequently embedded within a self-produced matrix of extracellular polymeric substance...

 formation is enhanced when cultivated in TSB
Tryptic Soy Broth
Tryptic Soy Broth is used as a culture broth to grow aerobic bacteria.It is frequently used in commercial diagnostics in conjunction with Thio which promotes growth of anaerobes....

 with 1% glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

 and decreased when cultivated in TSB
Tryptic Soy Broth
Tryptic Soy Broth is used as a culture broth to grow aerobic bacteria.It is frequently used in commercial diagnostics in conjunction with Thio which promotes growth of anaerobes....

 with 3% NaCl. The production of a capsular polysaccharide
Polysaccharide encapsulated bacteria
Polysaccharide encapsulated bacteria, frequently referred to simply as encapsulated bacteria and less precisely called encapsulated organisms, are a group of bacteria that have an outer covering, a bacterial capsule, made of polysaccharide....

 decreases biofilm formation.

Subinhibitory concentrations (sub-MIC
Minimum inhibitory concentration
In microbiology, minimum inhibitory concentration is the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation. Minimum inhibitory concentrations are important in diagnostic laboratories to confirm resistance of microorganisms...

) of the antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

 dicloxacillin
Dicloxacillin
Dicloxacillin is a narrow-spectrum beta-lactam antibiotic of the penicillin class. It is used to treat infections caused by susceptible Gram-positive bacteria. It is active against beta-lactamase-producing organisms such as Staphylococcus aureus, which would otherwise be resistant to most...

 also affect the growth of S. haemolyticus biofilms. Biofilms formed in the presence of subinhibitory concentrations of dicloxacillin
Dicloxacillin
Dicloxacillin is a narrow-spectrum beta-lactam antibiotic of the penicillin class. It is used to treat infections caused by susceptible Gram-positive bacteria. It is active against beta-lactamase-producing organisms such as Staphylococcus aureus, which would otherwise be resistant to most...

 contain less biomass
Biomass (ecology)
Biomass, in ecology, is the mass of living biological organisms in a given area or ecosystem at a given time. Biomass can refer to species biomass, which is the mass of one or more species, or to community biomass, which is the mass of all species in the community. It can include microorganisms,...

 and have an altered composition. They are thinner, cover less surface area
Surface area
Surface area is the measure of how much exposed area a solid object has, expressed in square units. Mathematical description of the surface area is considerably more involved than the definition of arc length of a curve. For polyhedra the surface area is the sum of the areas of its faces...

, and are less hydrophobic, but they also have an increased level of resistance to dicloxacillin
Dicloxacillin
Dicloxacillin is a narrow-spectrum beta-lactam antibiotic of the penicillin class. It is used to treat infections caused by susceptible Gram-positive bacteria. It is active against beta-lactamase-producing organisms such as Staphylococcus aureus, which would otherwise be resistant to most...

.

Toxins

Some S. haemolyticus strains
Strain (biology)
In biology, a strain is a low-level taxonomic rank used in three related ways.-Microbiology and virology:A strain is a genetic variant or subtype of a micro-organism . For example, a "flu strain" is a certain biological form of the influenza or "flu" virus...

 produce enterotoxins (SE) and/or hemolysins. In a study of 64 S. haemolyticus strains
Strain (biology)
In biology, a strain is a low-level taxonomic rank used in three related ways.-Microbiology and virology:A strain is a genetic variant or subtype of a micro-organism . For example, a "flu strain" is a certain biological form of the influenza or "flu" virus...

, production of SEA, SEB, SEC, and/or SEE was noted (only SED was absent). In addition, 31.3% of the strains
Strain (biology)
In biology, a strain is a low-level taxonomic rank used in three related ways.-Microbiology and virology:A strain is a genetic variant or subtype of a micro-organism . For example, a "flu strain" is a certain biological form of the influenza or "flu" virus...

 were found to produce at least one type of enterotoxin
Enterotoxin
An enterotoxin is a protein toxin released by a microorganism in the intestine. Enterotoxins are chromosomally encoded exotoxins that are produced and secreted from several bacterial organisms. They are often heat-stable, and are of low molecular weight and water-soluble...

.

Identification

S. haemolyticus can be identified on the species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...

 level using a variety of manual and automated methods. The most frequently employed are as follows: the reference method (based on growth tests), API ID 32 Staph (bioMe´rieux), Staph-Zym (Rosco), UZA (a rapid 4-h method), and PCR
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....

 and electrophoretic analysis of the 16S rRNA, hsp60
HSP60
Heat shock proteins are generally responsible for preventing damage to proteins in response to high levels of heat. Heat shock proteins are classified into six major families based on their molecular mass: small HSPs, HSP40, HSP60, HSP70, HSP90, and HSP110...

, or sodA gene sequence. Preference towards a particular method usually depends on convenience, economics, and required specificity (some species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...

 have identical 16S rRNA).
Name of Method Tests Performed Interpretation of Results
Reference 16 conventional growth tests including: colony pigment, DNase, alkaline phosphatase, ornithine decarboxylase, urease, acetoin production, novobiocin resistance, polymyxin resistance, and acid production from D-trehalose, D-mannitol, D-mannose, D-turanose, D-xylose, D-cellobiose, maltose, and sucrose Results are compared to the literature on Staphylococcal species
API ID 32 Staph (bioMe´rieux) A bacterial suspension is added to a set of wells containing dried substrates for 26 colorimetric tests. After 24 hours of incubation at 37°, and the addition of a few other reagents, the results are determined by an automated computer using APILAB ID 32 software
Staph-Zym (Rosco) A bacterial suspension is added to minitubes for 10 metabolic or enzymatic tests The results are determined by color changes, after 24 hours of incubation, and tests for polymyxin and novobiocin susceptibility
UZA (a rapid 4-h method) This method is a two step process. Step one consists of three tests measured after four hours incubation at 37°: acid production from D-trehalose, urease, and alkaline phosphatase. Step two includes four possible tests, which are administered as needed after 24 hours of incubation at 37°. They are as follows: ornithine decarboxylase, novobiocin susceptibility, fosfomycin susceptibility, and anaerobic growth Results are compared to the literature on Staphylococcal species
PCR and Electrophoresis Uses gene specific degenerate primers to amplify pieces of DNA. These fragments are resolved using electrophoresis, and then purified for DNA sequencing Results are determined by a sequence analysis

Clinical importance

S. haemolyticus is the second-most clinically isolated CoNS (S. epidermidis is the first) and it is considered an important nosocomial pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...

. Human infections include: native valve endocarditis
Endocarditis
Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves . Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or even on intracardiac devices...

, septicemia, peritonitis
Peritonitis
Peritonitis is an inflammation of the peritoneum, the serous membrane that lines part of the abdominal cavity and viscera. Peritonitis may be localised or generalised, and may result from infection or from a non-infectious process.-Abdominal pain and tenderness:The main manifestations of...

, and urinary tract
Urinary tract infection
A urinary tract infection is a bacterial infection that affects any part of the urinary tract. Symptoms include frequent feeling and/or need to urinate, pain during urination, and cloudy urine. The main causal agent is Escherichia coli...

, wound, bone, and joint infection. Infrequent soft-tissue infections usually occur in immunocompromised patients. Like other CoNS, S. haemolyticus is often associated with the insertion of foreign bodies, such as prosthetic valves, cerebrospinal fluid shunts, orthopedic prostheses, and intravascular, urinary, and dialysis catheters. S. haemolyticus is multi-drug resistant and able to form biofilms, which makes infections especially difficult to treat.

Vascular catheter-associated infections

S. haemolyticus can colonize central venous catheters and cause serious medical complications. Colonization occurs when S. haemolyticus migrates from the skin, along the external surface of the device, or from the hub, due to manipulation by health care workers. In either scenario, there is a high probability that the microbe will form a biofilm
Biofilm
A biofilm is an aggregate of microorganisms in which cells adhere to each other on a surface. These adherent cells are frequently embedded within a self-produced matrix of extracellular polymeric substance...

. These infections can remain localized or become systemic (i.e. bacteremia
Bacteremia
Bacteremia is the presence of bacteria in the blood. The blood is normally a sterile environment, so the detection of bacteria in the blood is always abnormal....

). The severity of infection varies depending on the type of catheter
Catheter
In medicine, a catheter is a tube that can be inserted into a body cavity, duct, or vessel. Catheters thereby allow drainage, administration of fluids or gases, or access by surgical instruments. The process of inserting a catheter is catheterization...

, frequency of manipulation, and virulence factors of the S. haemolyticus strain. Removal of the catheter
Catheter
In medicine, a catheter is a tube that can be inserted into a body cavity, duct, or vessel. Catheters thereby allow drainage, administration of fluids or gases, or access by surgical instruments. The process of inserting a catheter is catheterization...

 is usually considered to be the best treatment, but this is not always possible. Alternatively, Vancomycin
Vancomycin
Vancomycin INN is a glycopeptide antibiotic used in the prophylaxis and treatment of infections caused by Gram-positive bacteria. It has traditionally been reserved as a drug of "last resort", used only after treatment with other antibiotics had failed, although the emergence of...

 or Teicoplanin
Teicoplanin
Teicoplanin is an antibiotic used in the prophylaxis and treatment of serious infections caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and Enterococcus faecalis. It is a glycopeptide antibiotic extracted from Actinoplanes teichomyceticus, with a similar...

 may be administered. Recent evidence suggests that glycopeptides can be supplemented with β-lactams to work synergistically.

Antibiotic resistance

S. haemolyticus has the highest level of antibiotic resistance
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...

 among the CoNS. Various strains
Strain (biology)
In biology, a strain is a low-level taxonomic rank used in three related ways.-Microbiology and virology:A strain is a genetic variant or subtype of a micro-organism . For example, a "flu strain" is a certain biological form of the influenza or "flu" virus...

 are resistant to one or more of the following antibiotics: penicillins, cephalosporins, macrolides, quinolones, tetracyclines, aminoglycosides, glycopeptides, and fosfomycin
Fosfomycin
Fosfomycin is a broad-spectrum antibiotic produced by certain Streptomyces species.-Uses:...

 (see table in Genome Structure), and multidrug resistance
Multidrug resistance
Multiple drug resistance or Multidrug resistance is a condition enabling a disease-causing organism to resist distinct drugs or chemicals of a wide variety of structure and function targeted at eradicating the organism...

 is common. As indicated above, even glycopeptide
Glycopeptide
Glycopeptides are peptides that contain carbohydrate moieties covalently attached to the side chains of the amino acid residues that constitute the peptide. Over the past few decades it has been recognised that glycans on cell surface and those bound to proteins play a critical role in biology...

 (Vancomycin
Vancomycin
Vancomycin INN is a glycopeptide antibiotic used in the prophylaxis and treatment of infections caused by Gram-positive bacteria. It has traditionally been reserved as a drug of "last resort", used only after treatment with other antibiotics had failed, although the emergence of...

 and Teicoplanin
Teicoplanin
Teicoplanin is an antibiotic used in the prophylaxis and treatment of serious infections caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and Enterococcus faecalis. It is a glycopeptide antibiotic extracted from Actinoplanes teichomyceticus, with a similar...

) resistant strains
Strain (biology)
In biology, a strain is a low-level taxonomic rank used in three related ways.-Microbiology and virology:A strain is a genetic variant or subtype of a micro-organism . For example, a "flu strain" is a certain biological form of the influenza or "flu" virus...

have begun to emerge.
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