Chlamydia use proteolysis to evade host defences
Multiple species of Chlamydia exist, which have a diverse range of tissue tropisms and are involved in various diseases. Chlamydia trachomatis and Chlamydia pneumoniae are human pathogens causing ocular and urogenital tract infections, and respiratory infection, respectively. Despite profound differences in host range, different species of Chlamydia display a remarkable similarity in their genome sequences and possess a conserved intracellular growth cycle with distinct biphasic stages. The infectious particle (also called elementary body or EB) can invade non-phagocytic epithelial cells via induced phagocytosis. The EB-laden cytoplasmic vacuole (also called inclusion) migrates to the peri-Golgi region as the EB starts to differentiate into a noninfectious but metabolically active reticulate body (RB) that can undergo rapid replication. The progeny RBs eventually differentiate back to EBs for spreading to other cells. The entire intracellular growth cycle occurs within the initial inclusion that expands to occupy a large proportion of the host cytoplasmic space as the parasites replicate. It takes several days for most human chlamydiae to complete a productive infection cycle in cell culture. However, infection in humans can become persistent, during which the RBs, instead of undergoing rapid replication and differentiating into infectious EBs, are limited in numbers and each becomes the so-called aberrant or persistent body with enlarged size and multiple nucleoids. The aberrant body-laden inclusions can persist in the infected hosts for long periods of time. Intracellular survival and growth are considered major contributors to chlamydial pathogenesis. Some infected women, if untreated, can develop inflammatory pathologies, including pelvic inflammatory diseases, ectopic pregnancy and infertility.
Killing me softly: chlamydial use of proteolysis for evading host defenses. Trends Microbiol. Sep 16 2009
Chlamydial infections in humans cause severe health problems, including blinding trachoma and sexually transmitted diseases. Although the involved pathogenic mechanisms remain unclear, the ability to replicate and maintain long-term residence in the infected cells seems to significantly contribute to chlamydial pathogenicity. These obligate intracellular parasites maintain a delicate balance between exploiting and protecting their host: they occupy intracellular space and acquire nutrients from the infected cells, but at the same time they have to maintain the integrity of the host cells for the completion of their intracellular growth. For this purpose, chlamydiae hijack certain signaling pathways that prevent the host cells from undergoing apoptosis induced by intracellular stress and protect the infected cells from recognition and attack by host defenses. Interestingly, one of the strategies that chlamydiae use for these purposes is the induction of limited proteolysis of host proteins, which is the main focus of this article.
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Tags: Biology, Chlamydia, Health, Immunology, Medicine, Microbiology, Parasitology
