Fluorescence-Reported Allelic Exchange Mutagenesis Reveals a Role for \u3cem\u3eChlamydia trachomatis\u3c/em\u3e TmeA in Invasion That Is Independent of Host AHNAK

Development of approaches to genetically manipulate Chlamydia is fostering important advances in understanding pathogenesis. Fluorescence-reported allelic exchange mutagenesis (FRAEM) now enables the complete deletion of specific genes in C. trachomatis L2. We have leveraged this technology to delete the coding sequences for a known type III effector. The evidence provided here indicates that CT694/CTL0063 is a virulence protein involved in chlamydial invasion. Based on our findings, we designate the gene product corresponding to ct694-ctl0063 translocated membrane-associated effector A (TmeA). Deletion of tmeA did not impact development of intracellular chlamydiae. However, the absence of TmeA manifested as a decrease in infectivity in both tissue culture and murine infection models. The in vitro defect was reflected by impaired invasion of host cells. TmeA binds human AHNAK, and we demonstrate here that AHNAK is transiently recruited by invading chlamydiae. TmeA, however, is not required for endogenous AHNAK recruitment. TmeA also impairs AHNAK-dependent actin bundling activity. This TmeA-mediated effect likely does not explain impaired invasion displayed by the tmeA strain of Chlamydia, since AHNAK-deficient cells revealed no invasion phenotype. Overall, our data indicate the efficacy of FRAEM and reveal a role of TmeA during chlamydial invasion that manifests independently of effects on AHNAK

Family Ties and Child Placement

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73323/1/j.1545-5300.1978.00289.x.pd

Love\u27s been good to me

https://digitalcommons.library.umaine.edu/mmb-vp-copyright/6399/thumbnail.jp

Jean (Main Theme)

No cover arthttps://scholarsjunction.msstate.edu/cht-sheet-music/10146/thumbnail.jp

Swastika, Volume 70, 1976

New Mexico State University yearbook for 1976

Assessing a Potential Role of Host Pannexin 1 during <i>Chlamydia trachomatis</i> Infection

<div><p>Pannexin 1 (Panx1) is a plasma membrane channel glycoprotein that plays a role in innate immune response through association with the inflammasome complex. Probenecid, a classic pharmacological agent for gout, has also been used historically in combination therapy with antibiotics to prevent cellular drug efflux and has been reported to inhibit Panx1. As the inflammasome has been implicated in the progression of <i>Chlamydia</i> infections, and with chlamydial infections at record levels in the US, we therefore investigated whether probenecid would have a direct effect on <i>Chlamydia trachomatis</i> development through inhibition of Panx1. We found chlamydial development to be inhibited in a dose-dependent, yet reversible manner in the presence of probenecid. Drug treatment induced an aberrant chlamydial morphology consistent with persistent bodies. Although Panx1 was shown to localize to the chlamydial inclusion, no difference was seen in chlamydial development during infection of cells derived from wild-type and Panx1 knockout mice. Therefore, probenecid may inhibit <i>C. trachomatis</i> growth by an as yet unresolved mechanism.</p></div