Chlamydophila abortus

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A Microbial Biorealm page on the genus Chlamydophila abortus

Classification

Higher order taxa

Kingdom: Bacteria Phylum: Chlamydiae Class: Chlamydiae(class) Order: Chlamydiales Family: Chlamydiaceae Genus: Chlamydophila Species: Chlamydiae

Species

Genus species:Chlamydophila abortus Description and significance This Gram-negative bacterium is an obligate intracellular pathogen of eukaryotic cells. Chlamydophila abortus is found in cows, goats, sheep, and pigs where it causes abortion during the later period of pregnancy by colonizing in the placenta. This bacterium is enzootic where its infection is specific to animals; or it can be zoonotic where an animal disease spreads and infects a human. The enzootic abortion in sheep is called ovine enzootic abortion (OEA). This pathogen when zoonotic will cause abortion or serious health problems in women, by invading the placenta and causing infection and irritation. It is important to know the genome sequence due to its pathogenic affects on humans. The infection of C.abortus also kills many livestock and causes economic burden to agricultural industries worldwide.(1 and 2) The first report of C. abortus was in 1936 in Scotland by J.R. Grieg who described an unexpected abortion in a sheep. Grieg believed the abortion was due to a dietary deficiency; years later in 1950 Stamp and his associates discovered the abortion was due to an infection caused by an organism. This organism was later named C. abortus and sequence S26/3 was isolated years later in 1979 in Scotland.(2) C. abortus is derived from the group Chlamydiales, which is divided into four families including Chlamydiaceae, Simkaniaceae, Parachlamydiaceae, and Waddliaceae. The Chlamydiaceae family is divided into two genera including Chlamydophila or Chlamydia. Chlamydia includes those microbes that are responsible for STDS. Chlamydophila abortus once went by Chlamydophila psittaci, and is responsible for feeble newborn bovine animals or abortions. (11) Genome structure This bacterium contains 1,144,377 base pairs within its genome, with guanine-cytosine pairing taking up 39.9% of the base pairs. C. abortus contains 961 genes which are all arranged in a circular manner. 842 of the 961 genes are conserved with Chlamydophila caviae and Chlamydophila pneumoniae. Through experimental evidence it was shown that 746 of the 961 coding sequences have identified functional assignments, while 215 have no found function. 110 of the 215 non-functional sequences were found to be similar in other proteins of Chlamydiaceae. Of the whole genome there is a coding density of 88.2%. The genome shows there are 18 Pmp genes (polymorphic membrane proteins), 38 tRNAs, and 1 rRNA. (6) The genome sequence shows TMH families of proteins; TMH (Transmembrane Helical Proteins) that along with Pmp proteins make the microorganism diverse in host tropism and disease causation. The genome contains single copies of 23S, 16S, and 5S rRNA genes which is different from Chlamydia. There is no evidence of any phage genes in C. abortus, although genes for phage have been found in other Chlamydophila. Through its genome sequence scientists observed the pathogen has many different proteins along it membrane that account for its variable contents. (6,2) Cell structure and metabolism This bacterium has two membranes and no flagella. Through genomic sequencing it was discovered that C. abortus and C. caviae have genes that encode ABC type membrane transport systems. It contains four specific proteins on its outer membrane, coded by the genes POMP (putative outer membrane proteins) 90A/B, and 91A/B. These genes are believed to be glycosylated which may be the reason for their heterogeneity. It was discovered that there are 11 coding sequences in the C. abortus genome that code for N-terminal transmembrane domains with alpha helical coiled-coil domains of different lengths. These membrane proteins are composed of leucine, glutamate, and serine. These special proteins are called transmembrane head proteins (TMH), and are unique to Chlamydophila abortus.(6) Since C. abortus is a pathogen, this organism depends on its host for its proper nutrients and energy. A study was done to compare the C. caviae genome and C. abortus; C. abortus was found to lack any toxin genes and genes involved in tryptophan metabolism and nucleotide salvaging while C. caviae displayed the genes for all these traits. It is shown that without tryptophan metabolism in chlamydiae, the microbes are not allowed to grow and multiply. An interesting trait of C. abortus is that it lacks a tryptophan biosynthetic operon and does not metabolize tryptophan, yet it has the ability to grow and colonize the placenta. This trait is still not well understood, but believed that C. abortus is able to get enough tryptophan from the mother who is passing food to her fetus.(2,6) Ecology C. abortus lives and infects the placenta of pregnant livestock such as sheep, cows, and pigs. It has also been found in humans. Bacteria have been found in milk of cattle and also in bulls. If released to the environment through vaginal emission the bacteria is still animate and can be easily spread to infect other organisms. Pathology The class Chlamydiaceae has a very interesting developmental characteristic where they undergo a biphasic process of being infectious but metabolically inactive known as the elementary body, and then switching to a noninfectious but metabolically active cell called the reticulate body. Chlamydophila abortus causes infection by the elementary body binding to a host cell and becoming metabolically active, it then multiplies within the cells inclusion bodies. The inclusion bodies evade lysosomes and avoid the endocytic pathway and intercept the exocytic pathway. They become secretory vacuoles to the host. The reticulate body is changed back to elementary bodies, then the inclusion bodies are lysed off or exocytosis occurs, completing the infection.(6) The metabolically active form can be spread through ingestion, aerosols, or physical contact with the infected organism. The bacterium is easily contracted if one infected animal excretes uterine fluid in the environment and another animal comes into contact with it. In humans the symptoms are severe pain in the abdomen area, along with inflammation, influenza-like symptoms, and respiratory problems. If women contract the pathogen during the first trimester of pregnancy then spontaneous abortion is likely to occur. If the infection occurs later, than stillbirths or preterm labor is most likely to occur.(4) Chlamydophila abortus may cause infertility in bovine animals. C. abortus was used to infect bovine oviduct cells. After infection, inclusion bodies and vacuoles formed in the cells; the cells appeared to be damaged and the microvilli were congregated and stuck together, this causes infertility within the animals. (9) Application to Biotechnology This organism is not known to produce any useful compounds or enzymes. C. abortus is mostly known to infect its host and cause health problems. Due to its problematic and pathogenic nature there have been many studies to try to prevent or fight off this pathogen. There is an experimental vaccine against this pathogen that includes the inactivated C. abortus and C. pecorum elementary bodies. This experimental vaccine was injected in cattle and seemed to prevent bovine mastitis and increase the antibody level against Chlamydophila. (3) Because of C. abortus’ pathogenic nature there are many scientists trying to find ways to fight the infections. An interesting characteristic of C. abortus is its immune response in mice. A study was done on mice and how their T cells respond to infection of C. abortus. Mice were depleted of CD8+ and CD4+ through monoclonal antibody injections and infected with C. abortus. The results of this experiment show that the mice depleted of the CD8+ T cells had all died. This shows that CD8+ may be needed to stop infection of C. abortus. However using CD8+ as a vaccine would not be good because the absence of CD8+ caused Chlamydial burden on the liver, more apoptotic cells in the hepatic inflammatory foci, and also halted IFN-gamma production by the spleen cells. (6) The CD4+ depleted mice had a lower morbidity than all the other samples; this may show that CD4+ has a play into the activation of C. abortus. Studies like these are helping fight against the infection of C. abortus and one day there may be a cure to the pathogen. (8) Current Research December 2006 - C. abortus has become a major problem all around the world infecting livestock, and causing them to abort their babies. A study done in 2006, looked at the abortion rate of a group of sheep and goats in Hungary. The study took place over a seven and a half year period. They found that 63% of all the abortions were due to Chlamydophila abortus. As this study shows, C. abortus is very common and it has become more important to study to try to prevent the death of so many livestock.(5) February 2007 - Recent research was done on cows who often suffer from bovine mastitis which is characterized by the inflammation of the bovine mammary gland. The presence of C. abortus and the lack of antibodies where associated with the presence of bovine mastitis. A vaccine against Chlamydophila reduced milk somatic cell numbers and reduced the presence of bovine mastitis, as well as increased the amount of antibodies. The vaccine lasted 14 weeks then C. abortus became present again in the milk produced by the cow. The presence of C. abortus increased after the vaccination. This study shows the presence of C. abortus causes bovine mastitis. This first attempt with the vaccine can lead to many more experiments and studies of the disease, and soon a solution will be found to rid C. abortus from milk ensuring the safety of the dairy cows and the humans that drink the milk.(3) In April 2007 a study was done on endangered Hawaiian monk seals. Samples were collected from these monk seals from 1997 to 2001. The samples were tested for bacteria and parasites that are known to cause morbidity or mortality in other marine animals; the seals were also tested for antibodies against viruses. Antibodies for phocine herpesvirus-1, Leptospira bratislava, L. hardjo, L. icterohaemorrhagiae, L. Pomona, and Brucella spp. were found in the samples along with antibodies for Clamydophila abortus. The amount of antibody for C. abortus increased as the monk seal aged. The constant observation of these bacteria, pathogens, and antibodies are important to the survival of this species of seals. (10) June 2007- A study was done to tests the effects of polymorphonuclear neutrophils (PMN) and NK cells on Chlamydophila abortus. The main prevention method to stop the spread of Chlamydophila abortus is to vaccinate the flock of livestock. Successful vaccinations induce Th-1 immune responses, which are done by production of IFN gamma, and also the activation of CD8+ T cells is required. This study used live attenuated 1B vaccine and two inactive experimental vaccines that were adjuvated with aluminum hydroxide or QS-21 in polymorphonuclear neutrophil and NK depleted mice. RB6-8C5 was used in the polymorphonuclear neutrophil depleted mice because it recognizes GR-1+ receptors and is used as a monoclonal antibody. The NK depleted mice test used anti-asialo GM1 polyclonal antibody. The elimination of polymorphonuclear neutrophils caused all the non-vaccinated mice to die and there was a 60% mortality in the aluminum hydroxide vaccinated mice. Both groups of the aluminum hydroxide and QS-21 mice had an increase in bacterial burden in their liver. The depletion of NK cells caused mortality only in the non-vaccinated groups but the mice still underwent liver burden from the bacterial increase. The results show that the function on polymorphonuclear neutrophils depends on the adjuvant used, but it looks as if PMN is needed for the livelihood of the mouse; and that the role of NK cells is more dominant in live vaccines than in inactive vaccines. (12) References 1) Chlamydophila abortus. We Trust Sanger Institute. http://www.sanger.ac.uk/Projects/C_abortus/ 2) HAMAP: Chlamydophila abortus complete proteome. http://expasy.org/sprot/hamap/CHLAB.html 3) Biesenkamp-Uhe, C., Li, Y., Hehnen, HR., Sachse, K., Kaltenboeck, B., "Therapeutic Chlamydophila abortua and C. pecorum vaccination transiently reduces bovine mastitis associated with Chlamydophila infection". Infect Immun. 2007 Feb. 4) Entrican, G., BSc PhD, Buxton, D., BVM&S PhD, Longbottom, D., "Chlamydial infection in sheep: immune control versus fetal pathology". The Royal Society of Medicine 2001. June. 94(6): 273-277. 5) Szeredi, L., Janosi, S., Tenk, M., Tekes, L., Bozso, M., Deim, Z., Molnar, T. "Epidemiological and pathological study on the causes of abortion in sheep and goats in Hungary". Acta Vet Hung. 2006. Dec. 54(4): 503-15. 6) Thompson, N.,Yeats, C., Bell, K., Holden, M.,Bentley, S.,Livingstone, M., Cerdeno-Tarraga, A., Harris, B., Doggett, J., Ormund, D., Mungall, K., Clarke, K., Feltwell, T., Hance, Z., Sanders, M., Quail, M., Price, C., Barrell, B., Parkhill, J., Longbottom, D. "The Chlamydophila abortus sequence reveals an array of variable proteins that contribute to interspecies variation." Published online April 18, 2005. 7) Vretou1, E., Giannikopoulou1, P., Psarrou1, E. "Polymorphic outer-membrane proteins of Chlamydophila abortus are glycosylated". Microbiology. 2001. 8) Martinez, C., Buendia, A., Sanchez, j., Ortega, N., Caro, M., Gallego, M., Navarro, J., Cuallo, F., Salinas, J. "Relative importance of CD4+ and CD8+ T cells in resolution of Chlamydophila abortus primary infection in mice." Journal of comparative pathology. 2006. 9) Appino S, Pregel P, Manuali E, Vincenti L, Rota A, Carnieletto P, Tiberi C, Bollo E. "Infection of Bovine Oviduct cell cultures with Chlamydophila abortus." Animal Reproductive Science. 2007. Apr. 98(3-4):350-6. 10) Aguirre, A., Keefe, T., Reif, J., Kashinsky, L., Yochem, P., Saliki, J., Stott, J., Goldstein, T., Dubey. J., Braun. R., Antonelis, G. "Infectious disease monitoring of the endangered hawaiian monk seal." Journal of wildlife diseases. 2007. Apr. 43(2):229-41. 11) [1] 12) Ortega, N., Caro, M., Buendia, A., Gallego, M., Del Rio, L., Martinez, C., Nicolas, L., Cuello, F., Salinas, J. “Role of polymorphonuclear neutrophils (PMNs) and NK cells in the protection conferred by different vaccines against Clamydophila abortus infection.” Research in veterinary science. 2007. June. 82(3):314-322. Edited by Kylee Lim, student of Rachel Larsen and Kit Pogliano