{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:55:56Z","timestamp":1790776556393,"version":"4.1.0"},"reference-count":62,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01175220"],"award-info":[{"award-number":["R01175220"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Members of the Family\n                      <jats:italic toggle=\"yes\">Chlamydiaceae<\/jats:italic>\n                      are obligate intracellular bacteria displaying a range of host and tissue tropisms. Genetic tractability, first established for\n                      <jats:italic toggle=\"yes\">Chlamydia trachomatis<\/jats:italic>\n                      LGV serovar L2, is now being expanded to additional\n                      <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                      species. This capability facilitates the comparative assessment of chlamydial virulence factors during infection. All\n                      <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                      spp. express a type III secretion system, and the translocated membrane-associated protein A (TmeA) represents a pivotal effector exhibiting species-specific divergence.\n                      <jats:italic toggle=\"yes\">Chlamydia muridarum<\/jats:italic>\n                      is a murine-specific species that has been leveraged in a host-appropriate small-animal model of disease. We utilized FRAEM mutagenesis to delete the putative\n                      <jats:italic toggle=\"yes\">tmeA<\/jats:italic>\n                      ortholog\n                      <jats:italic toggle=\"yes\">tc0066<\/jats:italic>\n                      in\n                      <jats:italic toggle=\"yes\">C. muridarum<\/jats:italic>\n                      to enable pathogenesis studies. Work confirms that, similar to TmeA, TC0066 is capable of interacting with host AHNAK and N-WASP. The interaction with N-WASP was important for\n                      <jats:italic toggle=\"yes\">C. muridarum<\/jats:italic>\n                      invasion and for subsequent intracellular development in tissue culture. During murine infections of the female genital tract, the absence of\n                      <jats:italic toggle=\"yes\">tc0066<\/jats:italic>\n                      did not impact infection parameters, including bacterial shedding or gross pathology. These results indicate that TC0066 and\n                      <jats:italic toggle=\"yes\">C. trachomatis<\/jats:italic>\n                      TmeA exhibit conserved functions, but these activities do not translate to detectable, overt changes to\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      genital-tract pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                      spp. are prevalent pathogens capable of infecting a wide range of hosts and tissues, yet the molecular determinants mediating differences in tropism remain incompletely defined.\n                      <jats:italic toggle=\"yes\">Chlamydia trachomatis<\/jats:italic>\n                      employs a type III secreted effector protein, TmeA, to manipulate Arp2\/3-dependent actin polymerization in order to create and maintain a protected intracellular niche. The\n                      <jats:italic toggle=\"yes\">tmeA<\/jats:italic>\n                      -encoding locus shows evidence of divergence among chlamydial species. We demonstrate herein that\n                      <jats:italic toggle=\"yes\">C. muridarum<\/jats:italic>\n                      TC0066 represents a functionally conserved TmeA homolog and leverage this similarity to probe the contribution of this effector to chlamydial pathogenesis. Results from murine infection studies using mutant\n                      <jats:italic toggle=\"yes\">C. muridarum<\/jats:italic>\n                      strains contrast with those from\n                      <jats:italic toggle=\"yes\">C. trachomatis<\/jats:italic>\n                      , emphasizing the need for care when interpreting outcomes of human chlamydial infection in the murine model.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.02359-26","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:02:21Z","timestamp":1790773341000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["<i>Chlamydia muridarum<\/i>\n                    TC0066 is required for invasion and intracellular development in tissue culture but dispensable in the murine infection 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