{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T02:25:45Z","timestamp":1784600745912,"version":"3.55.0"},"reference-count":72,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["2R15AI109566"],"award-info":[{"award-number":["2R15AI109566"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2024,12,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Partner switching mechanisms (PSMs) are signal transduction systems comprised of a sensor phosphatase (RsbU), an anti-sigma factor (RsbW, kinase), an anti-anti-sigma factor (RsbV, the RsbW substrate), and a target sigma factor.\n              <jats:italic>Chlamydia<\/jats:italic>\n              spp. are obligate intracellular bacterial pathogens of animals that undergo a developmental cycle transitioning between the infectious elementary body (EB) and replicative reticulate body (RB) within a host cell-derived vacuole (inclusion). Secondary differentiation events (RB to EB) are transcriptionally regulated, in part, by the housekeeping sigma factor (\u03c3\n              <jats:sup>66<\/jats:sup>\n              ) and two late-gene sigma factors (\u03c3\n              <jats:sup>54<\/jats:sup>\n              and \u03c3\n              <jats:sup>28<\/jats:sup>\n              ). Prior research supports that the PSM in\n              <jats:italic>Chlamydia trachomatis<\/jats:italic>\n              regulates availability of \u03c3\n              <jats:sup>66<\/jats:sup>\n              . Pan-genome analysis revealed that PSM components are conserved across the phylum Chlamydiota, with\n              <jats:italic>Chlamydia<\/jats:italic>\n              spp. possessing an atypical arrangement of two anti-anti-sigma factors, RsbV1 and RsbV2. Bioinformatic analyses support RsbV2 as the homolog to the pan-genome-conserved RsbV with RsbV1 as an outlier. This, combined with\n              <jats:italic>in vitro<\/jats:italic>\n              data, indicates that RsbV1 and RsbV2 are structurally and biochemically distinct. Reduced levels or overexpression of RsbV1\/RsbV2 did not significantly impact\n              <jats:italic>C. trachomatis<\/jats:italic>\n              growth or development. In contrast, overexpression of a non-phosphorylatable RsbV2 S55A mutant, but not overexpression of an RsbV1 S56A mutant, resulted in a 3 log reduction in infectious EB production without reduction in genomic DNA (total bacteria) or inclusion size, suggesting a block in secondary differentiation. The block was corroborated by reduced production of \u03c3\n              <jats:sup>54\/28<\/jats:sup>\n              -regulated late proteins and via transmission electron microscopy.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                <jats:italic>Chlamydia trachomatis<\/jats:italic>\n                is the leading cause of reportable bacterial sexually transmitted infections (STIs) and causes the eye infection trachoma, a neglected tropical disease. Broad-spectrum antibiotics used for treatment can lead to microbiome dysbiosis and increased antibiotic resistance development in other bacteria, and treatment failure for chlamydial STIs is a recognized clinical problem. Here, we show that disruption of a partner switching mechanism (PSM) significantly reduces infectious progeny production via blockage of reticulate body to elementary body differentiation. We also reveal a novel PSM expansion largely restricted to the species infecting animals, suggesting a role in pathogen evolution. Collectively, our results highlight the chlamydial PSM as a key regulator of development that could be a potential target for novel therapeutics.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.01846-24","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T13:02:14Z","timestamp":1730206934000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Distinct impacts of each anti-anti-sigma factor ortholog of the chlamydial Rsb partner switching mechanism on development in\n            <i>Chlamydia trachomatis<\/i>"],"prefix":"10.1128","volume":"12","author":[{"given":"Shiomi","family":"Junker","sequence":"first","affiliation":[{"name":"Molecular Biology, Microbiology and Biochemistry Graduate Program, Southern Illinois University Carbondale","place":["Carbondale, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vandana","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, College of Medicine, University of Nebraska Medical Center","place":["Omaha, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9501-221X","authenticated-orcid":false,"given":"Aamal G. 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