Infection and Disease Epidemiology

Schachter, Julius

doi:10.1128/9781555818203.ch6

Cited by 190 publications

(79 citation statements)

References 92 publications

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“…For instance, distinct serovariants of Chlamydia trachomatis cause a gamut of diseases, including blinding trachoma (serovars A-C), urogenital tract infections leading to urethritis, cervicitis, and proctitis (serovars D-K), and systemic lymphogranuloma venereum (LGV) disease (serovars L1 -L3) (Schachter 1999). In genital tract infections, C. trachomatis primarily replicates within the epithelium of the urethra of men and endocervix of women causing inflammation, edema, and mucosal discharge.…”

mentioning

confidence: 99%

Chlamydial Intracellular Survival Strategies

Bastidas

Elwell

Engel

et al. 2013

Cold Spring Harbor Perspectives in Medicine

202

197

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Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen and the causative agent of blinding trachoma. Although Chlamydia is protected from humoral immune responses by residing within remodeled intracellular vacuoles, it still must contend with multilayered intracellular innate immune defenses deployed by its host while scavenging for nutrients. Here we provide an overview of Chlamydia biology and highlight recent findings detailing how this vacuole-bound pathogen manipulates host -cellular functions to invade host cells and maintain a replicative niche.

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mentioning

confidence: 99%

Chlamydial Intracellular Survival Strategies

Bastidas

Elwell

Engel

et al. 2013

Cold Spring Harbor Perspectives in Medicine

202

197

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“…In humans, Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen (2). C. trachomatis is known for its ability to efficiently ascend from the lower genital tract to the upper genital tract, where chlamydial replication can have many devastating consequences, including infertility and pelvic inflammatory disease in women.…”

mentioning

confidence: 99%

“…C. trachomatis is known for its ability to efficiently ascend from the lower genital tract to the upper genital tract, where chlamydial replication can have many devastating consequences, including infertility and pelvic inflammatory disease in women. In addition, some C. trachomatis serovars cause eye infection, which is still a major cause of blindness in underdeveloped countries (2).…”

mentioning

confidence: 99%

Chlamydia trachomatis protein GrgA activates transcription by contacting the nonconserved region of σ ⁶⁶

Bao¹,

Nickels

Fan³

2012

Proc. Natl. Acad. Sci. U.S.A.

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The bacterial RNA polymerase holoenzyme consists of a catalytic core enzyme in complex with a σ factor that is required for promoter-specific transcription initiation. Primary, or housekeeping, σ factors are responsible for most of the gene expression that occurs during the exponential phase of growth. Primary σ factors share four regions of conserved sequence, regions 1-4, which have been further subdivided. Many primary σ factors also contain a nonconserved region (NCR) located between subregions 1.2 and 2.1, which can vary widely in length. Interactions between the NCR of the primary σ factor of Escherichia coli, σ 70 , and the β′ subunit of the E. coli core enzyme have been shown to influence gene expression, suggesting that the NCR of primary σ factors represents a potential target for transcription regulation. Here, we report the identification and characterization of a previously undocumented Chlamydia trachomatis transcription factor, designated GrgA (general regulator of genes A). We demonstrate in vitro that GrgA is a DNA-binding protein that can stimulate transcription from a range of σ 66 -dependent promoters. We further show that GrgA activates transcription by contacting the NCR of the primary σ factor of C. trachomatis, σ 66 . Our findings suggest GrgA serves as an important regulator of σ 66 -dependent transcription in C. trachomatis. Furthermore, because GrgA is present only in chlamydiae, our findings highlight how nonconserved regions of the bacterial RNA polymerase can be targets of regulatory factors that are unique to particular organisms.

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“…Both VEGF and MMP-9 playa critical role in the initiation and progression of vascular pathologies (25). MMPs have been implicated in the pathogenesis of chlamydial infections because they are considered classic matrix-remodeling enzymes, and the long-term sequelae of these infections are primarily the result of scar tissue formation (26). We also demonstrated that when HUVEC were preincubated with inhibitors of VEGF, C. pneumoniae-induced MMP expression and gelatinolytic activity were significantly reduced, supporting the involvement of these pathways in MMP induction.…”

Section: Discussionmentioning

confidence: 99%

Induction of VEGF and MMP-9 Expression by Toll-like Receptor 2/4 in Human Endothelial Cells Infected withChlamydia Pneumoniae

Paolillo

Iovene

Carratelli

et al. 2012

Int J Immunopathol Pharmacol

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Matrix metalloproteinases (MMP) are a family of host-derived enzymes involved in the turnover of extracellular matrix (ECM) molecules, and, in particular, it is demonstrated that the 92 KDa gelatinase MMP-9 is often expressed in atherosclerotic plaques by macrophages and smooth muscle cells. Recent evidence supports a role of Toll-like receptor (TLR) signaling in the development of atherosclerosis lesions. In this study, we analyzed the TLR2/TLR4 expression in HUVEC infected with C. pneumoniae and correlated it to the production of VEGF and MMP-9. The results obtained showed an increased VEGF and MMP-9 production correlated with a time-dependent increase in cellular proliferation in HUVEC infected with C. pneumoniae at a multiplicity of infection (MOl) of 2 IFU/cell. HUVEC preincubated with VEGF antibody did not release MMP-9, as detected by zymography assessment and ELISA assay. In addition, we demonstrated that TLR2/TLR4 are expressed in HUVEC infected with viable microorganisms (25% and 17%, respectively), while UV-inactivated microorganisms induced a lesser expression (20% and 11%, respectively) compared to control cells and HUVEC exposed to heatkilled bacteria showed a percentage of TLR-expressing cells similar to the control cells. In addition, the cells preincubated for 60 min with TLR2/TLR4 neutralizing antibodies showed a decrease in C. pneumoniae-induced VEGF and MMP-9 production.

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Infection and Disease Epidemiology

Cited by 190 publications

References 92 publications

Chlamydial Intracellular Survival Strategies

Chlamydial Intracellular Survival Strategies

Chlamydia trachomatis protein GrgA activates transcription by contacting the nonconserved region of σ ⁶⁶

Induction of VEGF and MMP-9 Expression by Toll-like Receptor 2/4 in Human Endothelial Cells Infected withChlamydia Pneumoniae

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Infection and Disease Epidemiology

Cited by 190 publications

References 92 publications

Chlamydial Intracellular Survival Strategies

Chlamydial Intracellular Survival Strategies

Chlamydia trachomatis protein GrgA activates transcription by contacting the nonconserved region of σ 66

Induction of VEGF and MMP-9 Expression by Toll-like Receptor 2/4 in Human Endothelial Cells Infected withChlamydia Pneumoniae

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Chlamydia trachomatis protein GrgA activates transcription by contacting the nonconserved region of σ ⁶⁶