A working model for the type III secretion mechanism in Chlamydia

Ferrell, Joshua C.; Fields, Kenneth A.

doi:10.1016/j.micinf.2015.10.006

Cited by 36 publications

(27 citation statements)

References 75 publications

(150 reference statements)

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“…Sol-mediated suppression of the T3S system has also been reported in enterohemorrhagic Escherichia coli strains (29). The precise details of the T3S process remain unclear in C. trachomatis, but they are developmentally regulated (30)(31)(32), and EBs have the assembled T3S apparatus (33). Our data, indicating that Sol does not prevent EBs from infection, suggest that direct blockage of the T3S apparatus in EBs is unlikely the main mechanism for Sol-induced T3S perturbation.…”

supporting

confidence: 48%

Potency of Solithromycin against Fast- and Slow-Growing Chlamydial Organisms

Gao

Wang

Zeng

et al. 2018

Antimicrob Agents Chemother

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Evidence is provided that solithromycin is a bactericidal against not only fast-growing chlamydial organisms but also those slowed by gamma interferon (IFN-γ) At sublethal concentrations, Sol impedes homotypic fusion of-containing vacuoles and reduces secretion of the type III secretion (T3S) effector IncA. Sol may therefore represent a potential new clinical treatment for infections. Selective perturbation of the T3S system suggests a novel mode of antibacterial action for Sol that warrants further investigation.

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supporting

confidence: 48%

Potency of Solithromycin against Fast- and Slow-Growing Chlamydial Organisms

Gao

Wang

Zeng

et al. 2018

Antimicrob Agents Chemother

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“…Similarly, a loss of function mutation in the gene ctl0233 ( C. trachomatis L2) that codes for CPAF [46] reduced the L2 organism survival in the mouse lower genital tract [47] while mutations in tc0668 and/or tc0237 significantly attenuated the pathogenicity of the C. muridarum organisms [48, 49]. Studies based on the cell culture system have revealed many chromosomal genes that may play significant roles in chlamydial pathogenesis [50–56]. Further animal model evaluations of these gene products in chlamydial pathogenicity may dramatically expand the list of chlamydial virulence factors.…”

Section: The Plasmid Contributes To Chlamydial Pathogenicitymentioning

confidence: 99%

Chlamydial Plasmid-Dependent Pathogenicity

Zhong

2017

Trends in Microbiology

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Most Chlamydia species carry a 7.5kb plasmid encoding 8 open reading frames conventionally called plasmid glycoproteins 1–8 or pGP1–8. Although the plasmid is not critical for chlamydial growth in vitro, its role in chlamydial pathogenesis is clearly demonstrated in the genital tracts of mice infected with Chlamydia muridarum, a model for investigating the human pathogen Chlamydia trachomatis. Plasmid-free C. trachomatis is also attenuated in both the mouse genital tract and nonhuman primate ocular tissue. Deficiency in pGP3 alone, which is regulated by pGP4, largely reproduced the in vivo but not in vitro phenotypes of the plasmid-free organisms, suggesting that pGP3 is a key in vivo virulence factor. The positive and negative regulations of some chromosomal genes by pGP4 and pGP5 respectively may allow the plasmid to promote chlamydial adaptation to varied animal tissue environments. The focus of this review is to summarize the progress on the pathogenic functions of the plasmid-encoded open reading frames, which may motivate further investigation of the molecular mechanisms of chlamydial pathogenicity and development of medical utility of the chlamydial plasmid system.

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“…Furthermore, we found that 2-amino-phenoxazine-3-one (phenoxazine derivate, Phx-3: a small hydrophobic molecule) induced the destruction of C. pneumoniae in inclusion bodies in immortal epithelial HEp-2 cells, resulting in bacterial growth inhibition [34]. Interestingly, since chlamydial maturation in inclusion bodies is required for manipulation of infected host cells through several effector molecules secreted by type III machinery [35], the dysfunction of type III secretion machinery by the binding of small hydrophobic molecules impaired chlamydia growth in host cells [36]. Although more studies are needed to clarify the mechanisms by which capsaicin causes bacterial morphological changes, it may be that the interaction of small hydrophobic molecules with unknown receptors on the bacterial cell wall is responsible for the dysfunction in bacterial maturation.…”

Section: Discussionmentioning

confidence: 99%

Impact of capsaicin, an active component of chili pepper, on pathogenic chlamydial growth ( Chlamydia trachomatis and Chlamydia pneumoniae ) in immortal human epithelial HeLa cells

Yamakawa

Matsuo

Okubo

et al. 2018

Journal of Infection and Chemotherapy

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Chlamydia trachomatis is the leading cause of sexually transmitted infections worldwide. Capsaicin, a component of chili pepper, which can stimulate actin remodeling via capsaicin receptor TRPV1 (transient receptor potential vanilloid 1) and anti-inflammatory effects via PPARγ (peroxisome proliferator-activated receptor-γ) and LXRα (liver X receptor α), is a potential candidate to control chlamydial growth in host cells. We examined whether capsaicin could inhibit C. trachomatis growth in immortal human epithelial HeLa cells. Inclusion forming unit and quantitative PCR assays showed that capsaicin significantly inhibited bacterial growth in cells in a dose-dependent manner, even in the presence of cycloheximide, a eukaryotic protein synthesis inhibitor. Confocal microscopic and transmission electron microscopic observations revealed an obvious decrease in bacterial numbers to inclusions bodies formed in the cells. Although capsaicin can stimulate the apoptosis of cells, no increase in cleaved PARP (poly (ADP-ribose) polymerase), an apoptotic indicator, was observed at a working concentration. All of the drugs tested (capsazepine, a TRPV1 antagonist; 5CPPSS-50, an LXRα inhibitor; and T0070907, a PPARγ inhibitor) had no effect on chlamydial inhibition in the presence of capsaicin. In addition, we also confirmed that capsaicin inhibited Chlamydia pneumoniae growth, indicating a phenomena not specific to C. trachomatis. Thus, we conclude that capsaicin can block chlamydial growth without the requirement of host cell protein synthesis, but by another, yet to be defined, mechanism.

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A working model for the type III secretion mechanism in Chlamydia

Cited by 36 publications

References 75 publications

Potency of Solithromycin against Fast- and Slow-Growing Chlamydial Organisms

Potency of Solithromycin against Fast- and Slow-Growing Chlamydial Organisms

Chlamydial Plasmid-Dependent Pathogenicity

Impact of capsaicin, an active component of chili pepper, on pathogenic chlamydial growth ( Chlamydia trachomatis and Chlamydia pneumoniae ) in immortal human epithelial HeLa cells

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