Archaeocin
Encyclopedia
Archaeocin is the name given to a new type of potentially useful 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...

 that is derived from the Archaea
Archaea
The Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon...

 group of organisms. Eight archaeocins have been partially or fully characterized, but hundreds of archaeocins are believed to exist, especially within the haloarchaea
Haloarchaea
Haloarchaea are microrganisms and members of the halophile community, in that they require high salt concentrations to grow. They are a distinct evolutionary branch of the Archaea, and are generally considered extremophiles, although not all members of this group can be considered as such.-Living...

. Production of these archaeal proteinaceous antimicrobial
Antimicrobial
An anti-microbial is a substance that kills or inhibits the growth of microorganisms such as bacteria, fungi, or protozoans. Antimicrobial drugs either kill microbes or prevent the growth of microbes...

s is a nearly universal feature of the rod-shaped haloarchaea.

The prevalence of archaeocins from other members of this domain is unknown simply because no one has looked for them. The discovery of new archaeocins hinges on recovery and cultivation of archaeal organisms from the environment. For example, samples from a novel hypersaline field site, Wilson Hot Springs in the Fish Springs National Wildlife Refuge in eastern Utah
Utah
Utah is a state in the Western United States. It was the 45th state to join the Union, on January 4, 1896. Approximately 80% of Utah's 2,763,885 people live along the Wasatch Front, centering on Salt Lake City. This leaves vast expanses of the state nearly uninhabited, making the population the...

, recovered 350 halophilic organisms; preliminary analysis of 75 isolates showed that 48 were archaeal and 27 were bacterial.

Halocins

Halocins are classified as either 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...

 (≤ 10 kDa
Atomic mass unit
The unified atomic mass unit or dalton is a unit that is used for indicating mass on an atomic or molecular scale. It is defined as one twelfth of the rest mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of...

; 'microhalocins') or 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...

 (> 10 kDa) antibiotics produced by members of the archaeal family Halobacteriaceae
Halobacteriaceae
In taxonomy, the Halobacteriaceae are a family of the Halobacteriales in the domain Archaea.- Overview :Halobacteriaceae are found in water saturated or nearly saturated with salt. They are also called halophiles, though this name is also used for other organisms which live in somewhat less...

. To date, all of the known halocin genes are encoded on megaplasmids (> 100 kbp
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 possess typical haloarcheal TATA and BRE promoter regions. Halocin transcripts are leaderless and the translated preproteins or preproproteins are most likely exported using the twin arginine translocation (Tat) pathway, as the Tat signal motif (two adjacent arginine residues) is present within the amino terminus
N-terminal end
The N-terminus refers to the start of a protein or polypeptide terminated by an amino acid with a free amine group . The convention for writing peptide sequences is to put the N-terminus on the left and write the sequence from N- to C-terminus...

. Halocin genes are almost universally expressed at the transition between exponential and stationary phases of growth; the only exception is halocin H1, which is induced during exponential phase. In contrast, the larger halocin proteins are heat-labile and typically obligately halophilic as they lose their activity (or activity is reduced) when desalted.

Microhalocins, peptide halocins

Currently, five peptide halocins have been partially or completely characterized at the protein and/or genetic levels: HalS8, HalR1, HalC8, HalH7, and HalU1. These antimicrobial peptides
Antimicrobial peptides
Antimicrobial peptides are an evolutionarily conserved component of the innate immune response and are found among all classes of life. Fundamental differences exist between prokaryotic and eukaryotic cells that may represent targets for antimicrobial peptides...

 range from ~3 to 7.4 kDa in molecular mass
Molecular mass
The molecular mass of a substance is the mass of one molecule of that substance, in unified atomic mass unit u...

, consisting of 36 to 76 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 residues. Two of the microhalocins (HalS8 and HalC8) are produced by proteolytic cleavage from a larger preproprotein by an unknown mechanism. Microhalocins are hydrophobic peptides that remain active even if desalted and/or stored at 4°C and are fairly insensitive to heat and organic solvents. The first microhalocin to be characterized was HalS8, produced by the uncharacterized haloarchaeon S8a isolated from the Great Salt Lake, UT, USA.

Protein halocins

Two can be classified as protein halocins: HalH1 and HalH4; the molecular masses of the remaining halocins have yet to be elucidated. Halocin H1 is produced by Hfx. mediterranei M2a (formerly strain Xia3), isolated from a solar saltern near Alicante, Spain
Alicante (province)
Alicante or Alacant is a province of eastern Spain, in the southern part of the Valencian Community. It is bordered by the provinces of Murcia on the southwest, Albacete on the west, Valencia on the north, and the Mediterranean Sea on the east...

. It is a 31 kDa protein that is heat-labile, loses activity when desalted, and exhibits a broad range of inhibition within the haloarchaea. Halocin H1 has yet to be characterized at the protein and genetic levels. In contrast, HalH4, produced by Hfx. mediterranei R4 (ATCC 33500), also isolated from a solar saltern near Alicante, Spain was the first halocin discovered. The molecular mass of the mature HalH4 protein is 34.9 kDa (359 amino acids), processed from a preprotein of 39.6 kDa; the mechanism for processing is unknown. Halocin H4 is an archaeolytic halocin and adsorbs to sensitive Hbt. salinarum cells where it may be disrupting membrane permeability.

Sulfolobicins

The archaeocins produced by Sulfolobus
Sulfolobus
Sulfolobus is a genus of microorganism in the family Sulfolobaceae. It belongs to the archea domain.Sulfolobus species grow in volcanic springs with optimal growth occurring at pH 2-3 and temperatures of 75-80 °C, making them acidophiles and thermophiles respectively...

are entirely different from halocins, since their activity is predominantly associated with the cells and not the supernatant. To date, the spectrum of sulfolobicin activity appears to be restricted to other members of the Sulfolobales: the sulfolobicin inhibited S. solfataricus P1, S. shibatae B12, and six nonproducing strains of S. islandicus. Activity appears to be archaeocidal but not archaeolytic.
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