Rhodococcus equi
Encyclopedia
Rhodococcus equi is a Gram-positive
coccobacillus
bacterium. The organism is commonly found in dry and dusty soil and can be important for diseases of domesticated animals (horses and goats). The frequency of infection can reach near 60 percent. R. equi is an important pathogen causing pneumonia
in foals. Since 2008, it is known that R. equi can infect wild boar as well as domestic pig
s. In addition, R. equi can infect humans. At risk groups are immunocompromised people, such as HIV-AIDS-patients or transplant
recipients. Rhodococcus infection in these groups of patients resemble clinical and pathological signs of pulmonary tuberculosis
. It is facultative intracellular.
Taxonomically, R. equi has been categorized as Corynebacterium equi, Bacillus hoagii, Corynebacterium purulentus, Mycobacterium equi, Mycobacterium restrictum, Nocardia restricta and Proactinomyces restrictus.
, which fuses with the lysosome
to become a phagolysosome
. The internal environment of the phagolysosome contains nuclease
s and protease
s, which are activated by the low pH of the compartment. The macrophage produces bacteriocidal compounds (e.g., oxygen radicals) following the respiratory burst
. However, like its close relative Mycobacterium tuberculosis
, R. equi prevents the fusion of the phagosome with the lysosome and acidification of the phagosome. Additionally, the respiratory burst is inhibited. This allows R. equi to multiply within the phagosome where it is shielded from the immune system by the very cell that was supposed to kill it . After about 48 hours, the macrophage is killed by necrosis
, not apoptosis
. Necrosis is pro-inflammatory attracting additional phagocytic cells to the site of infection, eventually resulting in massive tissue damage.
. This plasmid has been shown to be essential for infection of foals, and presumably plays a similar role for infection
of other hosts, although this has not been established yet. Strains that lack the virulence plasmid are unable to proliferate in macrophages. This virulence plasmid has been characterised in detail from equine (horse) and porcine (pig) strains, although only the former has been functionally characterised . These circular plasmids consist of a conserved backbone that is responsible for replication and bacterial conjugation
of the plasmid. This portion of the plasmid is highly conserved and found in non-pathogenic Rhodococci plasmids. In addition to the conserved region, the virulence plasmids contain a highly variable region that has undergone substantial genetic rearrangements, including inversion
and deletions. This region has a different GC-content
from the rest of the plasmid, and is flanked by genes associated with mobile genetic elements
. It is therefore assumed to be derived from a different bacterial species than the backbone of the plasmid via lateral gene transfer.
that contains genes that are essential for virulence.
A hallmark of the pathogenicity island
(PAI) is that many genes within it do not have homologues
in other species. The most notable of these are the virulence associated protein (vap) genes. All foals infected with R. equi produce high levels of antibodies
specific for vapA, the first vap gene to be characterised. Deletion of vapA renders the resulting strain avirulent . In addition to vapA, the pathogenicity island encodes a further five full length vap homologues, one truncated vap gene and two pseudo vap genes
. The porcine pathogenicity island contains five full length vap genes, including the vapA homologue, vapB. In addition to these unique genes, the pathogencity island contains genes that have a known function, in particular two regulatory genes encoding the LysR-type regulator VirR and the response regulator Orf8. These two proteins have been shown to control expression of a number of pathogenicity island genes including vapA. Other genes have homology to transport proteins and enzymes. However, the functionality of these genes has not yet been established, nor how the proteins encoded within pathogenicity island subvert the macrophage.
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...
coccobacillus
Coccobacillus
A coccobacillus is a type of rod-shaped bacteria. The word coccobacillus reflects an intermediate shape between coccus and bacillus . Coccobacilli rods are so short and wide that they resemble cocci. Haemophilus influenzae and Chlamydia trachomatis are coccobacilli...
bacterium. The organism is commonly found in dry and dusty soil and can be important for diseases of domesticated animals (horses and goats). The frequency of infection can reach near 60 percent. R. equi is an important pathogen causing pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
in foals. Since 2008, it is known that R. equi can infect wild boar as well as domestic pig
Domestic pig
The domestic pig is a domesticated animal that traces its ancestry to the wild boar, and is considered a subspecies of the wild boar or a distinct species in its own right. It is likely the wild boar was domesticated as early as 13,000 BC in the Tigris River basin...
s. In addition, R. equi can infect humans. At risk groups are immunocompromised people, such as HIV-AIDS-patients or transplant
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
recipients. Rhodococcus infection in these groups of patients resemble clinical and pathological signs of pulmonary tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
. It is facultative intracellular.
Taxonomically, R. equi has been categorized as Corynebacterium equi, Bacillus hoagii, Corynebacterium purulentus, Mycobacterium equi, Mycobacterium restrictum, Nocardia restricta and Proactinomyces restrictus.
Hosts
- PigPigA pig is any of the animals in the genus Sus, within the Suidae family of even-toed ungulates. Pigs include the domestic pig, its ancestor the wild boar, and several other wild relatives...
s (wild and domestic) - GoatGoatThe domestic goat is a subspecies of goat domesticated from the wild goat of southwest Asia and Eastern Europe. The goat is a member of the Bovidae family and is closely related to the sheep as both are in the goat-antelope subfamily Caprinae. There are over three hundred distinct breeds of...
s - HorseHorseThe horse is one of two extant subspecies of Equus ferus, or the wild horse. It is a single-hooved mammal belonging to the taxonomic family Equidae. The horse has evolved over the past 45 to 55 million years from a small multi-toed creature into the large, single-toed animal of today...
s - Sheep
- Cattle
- HumanHumanHumans are the only living species in the Homo genus...
s
Virulence
The most common route of infection in horses is likely via inhalation of contaminated dust particles. Inhaled virulent strains of R. equi are phagocytosed by alveolar macrophages. During normal phagocytosis, bacteria are enclosed by the phagosomePhagosome
In cell biology, a phagosome is a vacuole formed around a particle absorbed by phagocytosis. The vacuole is formed by the fusion of the cell membrane around the particle. A phagosome is a cellular compartment in which pathogenic microorganisms can be killed and digested...
, which fuses with the lysosome
Lysosome
thumb|350px|Schematic of typical animal cell, showing subcellular components. [[Organelle]]s: [[nucleoli]] [[cell nucleus|nucleus]] [[ribosomes]] [[vesicle |vesicle]] rough [[endoplasmic reticulum]]...
to become a phagolysosome
Phagolysosome
A phagolysosome is the membrane-enclosed organelle which forms when a phagosome fuses with a lysosome. After fusion, the food particles or pathogens contained within the phagosome are usually digested by the enzymes contained within the lysosome. Phagolysosome formation follows phagocytosis...
. The internal environment of the phagolysosome contains nuclease
Nuclease
A nuclease is an enzyme capable of cleaving the phosphodiester bonds between the nucleotide subunits of nucleic acids. Older publications may use terms such as "polynucleotidase" or "nucleodepolymerase"....
s and protease
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....
s, which are activated by the low pH of the compartment. The macrophage produces bacteriocidal compounds (e.g., oxygen radicals) following the respiratory burst
Respiratory burst
Respiratory burst is the rapid release of reactive oxygen species from different types of cells....
. However, like its close relative Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...
, R. equi prevents the fusion of the phagosome with the lysosome and acidification of the phagosome. Additionally, the respiratory burst is inhibited. This allows R. equi to multiply within the phagosome where it is shielded from the immune system by the very cell that was supposed to kill it . After about 48 hours, the macrophage is killed by necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
, not apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
. Necrosis is pro-inflammatory attracting additional phagocytic cells to the site of infection, eventually resulting in massive tissue damage.
Virulence plasmid
All strains isolated from foals and the majority of human, cattle and pig isolates contain a large plasmidPlasmid
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...
. This plasmid has been shown to be essential for infection of foals, and presumably plays a similar role for infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
of other hosts, although this has not been established yet. Strains that lack the virulence plasmid are unable to proliferate in macrophages. This virulence plasmid has been characterised in detail from equine (horse) and porcine (pig) strains, although only the former has been functionally characterised . These circular plasmids consist of a conserved backbone that is responsible for replication and bacterial conjugation
Bacterial conjugation
Bacterial conjugation is the transfer of genetic material between bacterial cells by direct cell-to-cell contact or by a bridge-like connection between two cells...
of the plasmid. This portion of the plasmid is highly conserved and found in non-pathogenic Rhodococci plasmids. In addition to the conserved region, the virulence plasmids contain a highly variable region that has undergone substantial genetic rearrangements, including inversion
Chromosomal inversion
An inversion is a chromosome rearrangement in which a segment of a chromosome is reversed end to end. An inversion occurs when a single chromosome undergoes breakage and rearrangement within itself. Inversions are of two types: paracentric and pericentric.Paracentric inversions do not include the...
and deletions. This region has a different GC-content
GC-content
In molecular biology and genetics, GC-content is the percentage of nitrogenous bases on a DNA molecule that are either guanine or cytosine . This may refer to a specific fragment of DNA or RNA, or that of the whole genome...
from the rest of the plasmid, and is flanked by genes associated with mobile genetic elements
Mobile genetic elements
Mobile genetic elements are a type of DNA that can move around within the genome. They include:*Transposons **Retrotransposons**DNA transposons**Insertion sequences*Plasmids...
. It is therefore assumed to be derived from a different bacterial species than the backbone of the plasmid via lateral gene transfer.
Pathogenicity island
The variable region of the virulence plasmid contain genes that are highly expressed following phagocytosis of R. equi by macrophages . It is believed that this variable region is a pathogenicity islandPathogenicity island
Pathogenicity islands are a distinct class of genomic islands acquired by microorganisms through horizontal gene transfer. They are incorporated in the genome of pathogenic organisms but are usually absent from those non-pathogenic organisms of the same or closely related species...
that contains genes that are essential for virulence.
A hallmark of the pathogenicity island
Pathogenicity island
Pathogenicity islands are a distinct class of genomic islands acquired by microorganisms through horizontal gene transfer. They are incorporated in the genome of pathogenic organisms but are usually absent from those non-pathogenic organisms of the same or closely related species...
(PAI) is that many genes within it do not have homologues
Homology (biology)
Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...
in other species. The most notable of these are the virulence associated protein (vap) genes. All foals infected with R. equi produce high levels of antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
specific for vapA, the first vap gene to be characterised. Deletion of vapA renders the resulting strain avirulent . In addition to vapA, the pathogenicity island encodes a further five full length vap homologues, one truncated vap gene and two pseudo vap genes
Pseudogene
Pseudogenes are dysfunctional relatives of known genes that have lost their protein-coding ability or are otherwise no longer expressed in the cell...
. The porcine pathogenicity island contains five full length vap genes, including the vapA homologue, vapB. In addition to these unique genes, the pathogencity island contains genes that have a known function, in particular two regulatory genes encoding the LysR-type regulator VirR and the response regulator Orf8. These two proteins have been shown to control expression of a number of pathogenicity island genes including vapA. Other genes have homology to transport proteins and enzymes. However, the functionality of these genes has not yet been established, nor how the proteins encoded within pathogenicity island subvert the macrophage.
Literature
- Monika Venner und Erich Klug: Die Rhodococcus-equi-Pneumonie beim Fohlen: Diagnose, Therapie, Prophylaxe In: Pferde spiegel Nummer 4, 2005. Seiten 155-158 PDF
- J. Ashour and M. K. Hondalus: Phenotypic mutants of the intracellular actinomycete Rhodococcus equi created by in vivo Himar1 transposon mutagenesis. In: Journal of Bacteriology. Volume 185, Nummer 8, April 2003. Seiten 2644-2652.
- A. Triskatis: Semiquantitative Bestimmung von Antikörpern gegen Rhodococcus equi in Serum und Klolostrum bei Stuten und Fohlen mittels ELISA und der Vergleich mit Befunden der Lungenuntersuchung PDF
- Letek M et al.: Evolution of the Rhodococcus equi vap Pathogenicity Island Seen through Comparison of Host-Associated vapA and vapB Virulence Plasmids. In: Journal of Bacteriology. Volume 190, Number 17, September 2008. 5797–5805.
- G. Muscatello, D. P. Leadon, M. Klay, A. Ocampo-Sosa, D. A. Lewis, U. Fogarty, T. Buckley, J. R. Gilkerson, W. G. Meijer, and J. A. Vázquez-Boland. (2007) Rhodococcus equi infection in foals: the science of 'rattles'. Equine Vet.J. 39:470-478.