Trachoma: Past, present and future

Mohammadpour, Mehrdad; Abrishami, Mojtaba; Masoumi, Ahmad; Hashemi, Hassan

doi:10.1016/j.joco.2016.08.011

Cited by 41 publications

(31 citation statements)

References 32 publications

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“…C hlamydia trachomatis is an obligate intracellular bacterial pathogen of humans that causes blinding trachoma and sexually transmitted disease, both of which afflict hundreds of millions of people globally (1,2). C. trachomatis isolates are classified into 2 biovars-lymphogranuloma venereum (LGV) and trachoma-which are distinguished biologically by their host cell infection tropism.…”

Section: Abstract Chlamydia Trachomatis Plasmid Proteomics Virulenmentioning

confidence: 99%

Plasmid Negative Regulation of CPAF Expression Is Pgp4 Independent and Restricted to InvasiveChlamydia trachomatisBiovars

Patton

Chen

Yang

et al. 2018

mBio

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Chlamydia trachomatis is an obligate intracellular bacterial pathogen that causes blinding trachoma and sexually transmitted disease. C. trachomatis isolates are classified into 2 biovars-lymphogranuloma venereum (LGV) and trachomawhich are distinguished biologically by their natural host cell infection tropism.LGV biovars infect macrophages and are invasive, whereas trachoma biovars infect oculourogenital epithelial cells and are noninvasive. The C. trachomatis plasmid is an important virulence factor in the pathogenesis of these infections. Central to its pathogenic role is the transcriptional regulatory function of the plasmid protein Pgp4, which regulates the expression of plasmid and chromosomal virulence genes. As many gene regulatory functions are post-transcriptional, we employed a comparative proteomic study of cells infected with plasmid-cured C. trachomatis serovars A and D (trachoma biovar), a L2 serovar (LGV biovar), and the L2 serovar transformed with a plasmid containing a nonsense mutation in pgp4 to more completely elucidate the effects of the plasmid on chlamydial infection biology. Our results show that the Pgp4-dependent elevations in the levels of Pgp3 and a conserved core set of chromosomally encoded proteins are remarkably similar for serovars within both C. trachomatis biovars. Conversely, we found a plasmid-dependent, Pgp4-independent, negative regulation in the expression of the chlamydial protease-like activity factor (CPAF) for the L2 serovar but not the A and D serovars. The molecular mechanism of plasmiddependent negative regulation of CPAF expression in the LGV serovar is not understood but is likely important to understanding its macrophage infection tropism and invasive infection nature. IMPORTANCEThe Chlamydia trachomatis plasmid is an important virulence factor in the pathogenesis of chlamydial infection. It is known that plasmid protein 4 (Pgp4) functions in the transcriptional regulation of the plasmid virulence protein 3 (Pgp3) and multiple chromosomal loci of unknown function. Since many gene regulatory functions can be post-transcriptional, we undertook a comparative proteomic analysis to better understand the plasmid's role in chlamydial and host protein expression. We report that Pgp4 is a potent and specific master positive regulator of a common core of plasmid and chromosomal virulence genes shared by multiple C. trachomatis serovars. Notably, we show that the plasmid is a negative regulator of the expression of the chlamydial virulence factor CPAF. The plasmid regulation of CPAF is independent of Pgp4 and restricted to a C. trachomatis macrophage-tropic strain. These findings are important because they define a previously unknown role for the plasmid in the pathophysiology of invasive chlamydial infection.

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Section: Abstract Chlamydia Trachomatis Plasmid Proteomics Virulenmentioning

confidence: 99%

Plasmid Negative Regulation of CPAF Expression Is Pgp4 Independent and Restricted to InvasiveChlamydia trachomatisBiovars

Patton

Chen

Yang

et al. 2018

mBio

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“…Men with gonorrhea typically exhibit symptomatic urethritis, while women are more likely to be asymptomatic with silent damage to their reproductive tract . The obligate intracellular bacterium Ct is one of the most prevalent human pathogens and is associated with both genital tract and ocular pathologies . Ct has the highest incidence of infection among all reportable infectious diseases in the US, with almost two million new cases reported every year .…”

Section: Introductionmentioning

confidence: 99%

“…5 The obligate intracellular bacterium Ct is one of the most prevalent human pathogens and is associated with both genital tract and ocular pathologies. 6,7 Ct has the highest incidence of infection among all reportable infectious diseases in the US, with almost two million new cases reported every year. 8,9 While both sexes can be infected with Ct, young women are disproportionately at risk for severe and chronic reproductive pathologies.…”

Section: Introductionmentioning

confidence: 99%

Structures of glyceraldehyde 3‐phosphate dehydrogenase in Neisseria gonorrhoeae and Chlamydia trachomatis

et al. 2020

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Neisseria gonorrhoeae (Ng) and Chlamydia trachomatis (Ct) are the most commonly reported sexually transmitted bacteria worldwide and usually present as co‐infections. Increasing resistance of Ng to currently recommended dual therapy of azithromycin and ceftriaxone presents therapeutic challenges for syndromic management of Ng‐Ct co‐infections. Development of a safe, effective, and inexpensive dual therapy for Ng‐Ct co‐infections is an effective strategy for the global control and prevention of these two most prevalent bacterial sexually transmitted infections. Glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) is a validated drug target with two approved drugs for indications other than antibacterials. Nonetheless, any new drugs targeting GAPDH in Ng and Ct must be specific inhibitors of bacterial GAPDH that do not inhibit human GAPDH, and structural information of Ng and Ct GAPDH will aid in finding such selective inhibitors. Here, we report the X‐ray crystal structures of Ng and Ct GAPDH. Analysis of the structures demonstrates significant differences in amino acid residues in the active sites of human GAPDH from those of the two bacterial enzymes suggesting design of compounds to selectively inhibit Ng and Ct is possible. We also describe an efficient in vitro assay of recombinant GAPDH enzyme activity amenable to high‐throughput drug screening to aid in identifying inhibitory compounds and begin to address selectivity.

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“…Trachoma, an eye disease caused by Chlamydia trachomatis (serotypes A, B, Ba, and C), continues to be the leading infectious cause of blindness in the world [ 1 , 2 ]. The clinical presentation of trachoma is characterized by follicular and papillary hyperplasia in the conjunctiva, forming grayish-yellow follicles; the development of scars on the eyelid conjunctiva; trichiasis (inverted lashes touching the eyeball); and corneal opacity (which includes formation of pannus, epithelial vascularization, and infiltration), responsible for the blindness stage of trachoma [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Prevalence of trachoma in school children in the Marajó Archipelago, Brazilian Amazon, and the impact of the introduction of educational and preventive measures on the disease over eight years

et al. 2018

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Trachoma is the leading infectious cause of blindness in the world and is associated with precarious living conditions in developing countries. The aim of the present study was to evaluate the prevalence of trachoma in three municipalities of the Marajó Archipelago, located in the state of Pará, Brazil. In 2008, 2,054 schoolchildren from the public primary school system of the urban area of the region and their communicants were clinically examined; in 2016, 1,502 schoolchildren were examined. The positive cases seen during the clinical evaluation were confirmed by direct immunofluorescence (DIF) laboratory tests. The presence of antibodies against the genus Chlamydia was evaluated by indirect immunofluorescence (IIF), and the serotypes were determined by microimmunofluorescence (MIF). In 2008, the prevalence of trachoma among schoolchildren was 3.4% (69 cases) and it was more frequent in children between six and nine years of age and in females; among the communicants, a prevalence of 16.5% was observed. In 2016, three cases of trachoma were diagnosed (prevalence of 0.2%), found only in the municipality of Soure. The results of the present study showed that in 2008, trachoma had a low prevalence (3.4%) among schoolchildren in the urban area of Marajó Archipelago; eight years after the first evaluation and the introduction of control and prevention measures (SAFE strategy), there was a drastic reduction in the number of cases (0.2%), demonstrating the need for constant monitoring and effective measures for the elimination of trachoma.

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Trachoma: Past, present and future

Cited by 41 publications

References 32 publications

Plasmid Negative Regulation of CPAF Expression Is Pgp4 Independent and Restricted to InvasiveChlamydia trachomatisBiovars

Plasmid Negative Regulation of CPAF Expression Is Pgp4 Independent and Restricted to InvasiveChlamydia trachomatisBiovars

Structures of glyceraldehyde 3‐phosphate dehydrogenase in Neisseria gonorrhoeae and Chlamydia trachomatis

Prevalence of trachoma in school children in the Marajó Archipelago, Brazilian Amazon, and the impact of the introduction of educational and preventive measures on the disease over eight years

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