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1. Stochastic Chlamydia Dynamics and Optimal Spread

   https://doi.org/10.1007/s11538-020-00846-4  

   Enciso, German; Sütterlin, Christine; Tan, Ming; Wan, Frederic Y. (April 2021, Bulletin of Mathematical Biology)

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2. Shift work influences the outcomes of Chlamydia infection and pathogenesis

   https://doi.org/10.1038/s41598-020-72409-5  

   Lundy, Stephanie R.; Richardson, Shakyra; Ramsey, Anne; Ellerson, Debra; Fengxia, Yan; Onyeabor, Sunny; Kirlin, Ward; Thompson, Winston; Black, Carolyn M.; DeBruyne, Jason P.; et al (December 2020, Scientific Reports)

   null (Ed.)

   Abstract Shift work, performed by approximately 21 million Americans, is irregular or unusual work schedule hours occurring after 6:00 pm. Shift work has been shown to disrupt circadian rhythms and is associated with several adverse health outcomes and chronic diseases such as cancer, gastrointestinal and psychiatric diseases and disorders. It is unclear if shift work influences the complications associated with certain infectious agents, such as pelvic inflammatory disease, ectopic pregnancy and tubal factor infertility resulting from genital chlamydial infection. We used an Environmental circadian disruption (ECD) model mimicking circadian disruption occurring during shift work, where mice had a 6-h advance in the normal light/dark cycle (LD) every week for a month. Control group mice were housed under normal 12/12 LD cycle. Our hypothesis was that compared to controls, mice that had their circadian rhythms disrupted in this ECD model will have a higher Chlamydia load, more pathology and decreased fertility rate following Chlamydia infection. Results showed that, compared to controls, mice that had their circadian rhythms disrupted (ECD) had higher Chlamydia loads, more tissue alterations or lesions, and lower fertility rate associated with chlamydial infection. Also, infected ECD mice elicited higher proinflammatory cytokines compared to mice under normal 12/12 LD cycle. These results imply that there might be an association between shift work and the increased likelihood of developing more severe disease from Chlamydia infection. 

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3. Division without Binary Fission: Cell Division in the FtsZ-Less Chlamydia

   https://doi.org/10.1128/JB.00252-20  

   Ouellette, Scot P.; Lee, Junghoon; Cox, John V. (August 2020, Journal of Bacteriology)

   Margolin, William (Ed.)

   ABSTRACT Chlamydia is an obligate intracellular bacterial pathogen that has significantly reduced its genome size in adapting to its intracellular niche. Among the genes that Chlamydia has eliminated is ftsZ , encoding the central organizer of cell division that directs cell wall synthesis in the division septum. These Gram-negative pathogens have cell envelopes that lack peptidoglycan (PG), yet they use PG for cell division purposes. Recent research into chlamydial PG synthesis, components of the chlamydial divisome, and the mechanism of chlamydial division have significantly advanced our understanding of these processes in a unique and important pathogen. For example, it has been definitively confirmed that chlamydiae synthesize a canonical PG structure during cell division. Various studies have suggested and provided evidence that Chlamydia uses MreB to substitute for FtsZ in organizing and coordinating the divisome during division, components of which have been identified and characterized. Finally, as opposed to using an FtsZ-dependent binary fission process, Chlamydia employs an MreB-dependent polarized budding process to divide. A brief historical context for these key advances is presented along with a discussion of the current state of knowledge of chlamydial cell division. 

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4. Inhibition of tRNA Synthetases Induces Persistence in Chlamydia

   https://doi.org/10.1128/IAI.00943-19  

   Hatch, Nathan D.; Ouellette, Scot P.; Roy, Craig R. (March 2020, Infection and Immunity)

   ABSTRACT Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections, and Chlamydia pneumoniae causes community-acquired respiratory infections. In vivo , the host immune system will release gamma interferon (IFN-γ) to combat infection. IFN-γ activates human cells to produce the tryptophan (Trp)-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO). Consequently, there is a reduction in cytosolic Trp in IFN-γ-activated host cells. In evolving to obligate intracellular dependence, Chlamydia has significantly reduced its genome size and content, as it relies on the host cell for various nutrients. Importantly, C. trachomatis and C. pneumoniae are Trp auxotrophs and are starved for this essential nutrient when the human host cell is exposed to IFN-γ. To survive this, chlamydiae enter an alternative developmental state referred to as persistence. Chlamydial persistence is characterized by a halt in the division cycle, aberrant morphology, and, in the case of IFN-γ-induced persistence, Trp codon-dependent changes in transcription. We hypothesize that these changes in transcription are dependent on the particular amino acid starvation state. To investigate the chlamydial response mechanisms acting when other amino acids become limiting, we tested the efficacy of prokaryote-specific tRNA synthetase inhibitors, indolmycin and AN3365, to mimic starvation of Trp and leucine, respectively. We show that these drugs block chlamydial growth and induce changes in morphology and transcription consistent with persistence. Importantly, growth inhibition was reversed when the compounds were removed from the medium. With these data, we find that indolmycin and AN3365 are valid tools that can be used to mimic the persistent state independently of IFN-γ. 

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5. Penicillin-binding proteins regulate multiple steps in the polarized cell division process of Chlamydia

   https://doi.org/10.1038/s41598-020-69397-x  

   Cox, John V.; Abdelrahman, Yasser Mohamed; Ouellette, Scot P. (December 2020, Scientific Reports)

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