scholarly journals The Chromosome-Encoded Hypothetical Protein TC0668 Is an Upper Genital Tract Pathogenicity Factor of Chlamydia muridarum

2015 ◽  
Vol 84 (2) ◽  
pp. 467-479 ◽  
Author(s):  
Turner Allen Conrad ◽  
Siqi Gong ◽  
Zhangsheng Yang ◽  
Patrick Matulich ◽  
Jonathon Keck ◽  
...  

We previously associated a missense mutation of thetc0668gene of serialin vitro-passagedChlamydia muridarum, a murine model of human urogenitalC. trachomatis, with severely attenuated disease development in the upper genital tract of female mice. Since these mutants also contained a TC0237 Q117E missense mutation that enhances theirin vitroinfectivity, an effort was made here to isolate and characterize atc0668single mutant to determine its individual contribution to urogenital pathogenicity. Detailed genetic analysis ofC. muridarumpassages revealed a truncated variant with a G216* nonsense mutation of the 408-amino-acid TC0668 protein that does not produce a detectable product. Intracellular growth and infectivity ofC. muridarum in vitroremain unaffected in the absence of TC0668. Intravaginal inoculation of the TC0668 null mutant into C3H/HeJ mice results in a typical course of lower genital tract infection but, unlike a pathogenic isogenic control, is unable to elicit significant chronic inflammation of the oviduct and fails to induce hydrosalpinx. Thus, TC0668 is demonstrated as an important chromosome-encoded urogenital pathogenicity factor ofC. muridarumand the first with these characteristics to be discovered for aChlamydiapathogen.

2014 ◽  
Vol 82 (7) ◽  
pp. 2688-2696 ◽  
Author(s):  
Hongbo Zhang ◽  
Zhou Zhou ◽  
Jianlin Chen ◽  
Ganqiu Wu ◽  
Zhangsheng Yang ◽  
...  

ABSTRACTLower genital tract infection withChlamydia trachomatisandC. muridarumcan induce long-lasting hydrosalpinx in the upper genital tract of women and female mice, respectively. However, A/J mice were highly resistant to induction of long-lasting hydrosalpinx byC. muridarum. We further compared host inflammatory responses and chlamydial infection courses between the hydrosalpinx-resistant A/J mice and CBA/J mice known to be susceptible to hydrosalpinx induction. Both mouse strains developed robust pyosalpinx during the acute phase followed by hydrosalpinx during the chronic phase. However, the hydrosalpinges disappeared in A/J mice by day 60 after infection, suggesting that some early hydrosalpinges are reversible. Although the overall inflammatory responses were indistinguishable between CBA/J and A/J mice, we found significantly more neutrophils in oviduct lumen of A/J mice on days 7 and 10, which correlated with a rapid but transient oviduct invasion byC. muridarumwith a peak infection on day 7. In contrast, CBA/J mice developed a delayed and extensive oviduct infection. These comparisons have revealed an important role of the interactions of oviduct infection with inflammatory responses in chlamydial induction of long-lasting hydrosalpinx, suggesting that a rapid but transient invasion of oviduct by chlamydial organisms can prevent the development of the long-lasting hydrosalpinges.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang Gao ◽  
Pengpeng Qu ◽  
Yang Zhou ◽  
Wei Ding

Abstract Background The purpose of this study was to assess the risk factors associated with the development of tubo-ovarian abscesses in women with ovarian endometriosis cysts. Methods This retrospective single-center study included 176 women: 44 with tubo-ovarian abscesses associated with ovarian endometriosis and 132 age-matched (1:3) patients with ovarian endometriosis but without tubo-ovarian abscesses. Diagnoses were made via surgical exploration and pathological examination. The potential risk factors of tubo-ovarian abscesses associated with ovarian endometriosis were evaluated using univariate analysis. The results (p ≤ 0.05) of these parameters were analyzed using a multivariate model. Results Five factors were included in the multivariate conditional logistic regression model, including in vitro fertilization, presence of an intrauterine device, lower genital tract infection, spontaneous rupture of ovarian endometriosis cysts, and diabetes mellitus. The presence of a lower genital tract infection (odds ratio 5.462, 95% CI 1.772–16.839) and spontaneous rupture of ovarian endometriosis cysts (odds ratio 2.572, 95% CI 1.071–6.174) were found to be statistically significant risk factors for tubo-ovarian abscesses associated with ovarian endometriosis. Conclusions Among the factors investigated, genital tract infections and spontaneous rupture of ovarian endometriosis cysts were found to be involved in the occurrence of tubo-ovarian abscesses associated with ovarian endometriosis. Our findings indicate that tubo-ovarian abscesses associated with ovarian endometriosis may not be linked to in vitro fertilization as previously thought.


2019 ◽  
Vol 87 (5) ◽  
Author(s):  
Tianyuan Zhang ◽  
Zhi Huo ◽  
Jingyue Ma ◽  
Cheng He ◽  
Guangming Zhong

ABSTRACTAlthoughChlamydia trachomatisis a human genital tract pathogen, chlamydial organisms have frequently been detected in both vaginal and rectal swab samples of animals and humans. The plasmid-encoded pGP3, a genital tract virulence factor, is essential forChlamydia muridarumto colonize the mouse gastrointestinal tract. However, intracolon inoculation to bypass the gastric barrier rescued the colonization ability of a pGP3-deficientC. muridarummutant, suggesting that pGP3 is required forC. muridarumto reach but not to colonize the large intestine. The pGP3-deficient mutant was rapidly cleared in the stomach and was 100-fold more susceptible to gastric killing. In mice genetically deficient in gastrin, a key regulator for gastric acid production, or pharmacologically treated with a proton pump inhibitor, the ability of pGP3-deficientC. muridarumto colonize the gastrointestinal tract was rescued. The pGP3-dependent resistance was further recapitulatedin vitrowith treatments with HCl, pepsin, or sarkosyl. In the genital tract, deficiency in pGP3 significantly reducedC. muridarumsurvival in the mouse vagina and increasedC. muridarumsusceptibility to vaginal killing by ∼8 times. The pGP3-deficientC. muridarumwas more susceptible to lactic acid killing, and the pGP3 deficiency also significantly increasedC. trachomatissusceptibility to lactic acid. The above-described observations together suggest thatChlamydiamay have acquired the plasmid-encoded pGP3 to overcome the gastric barrier during its adaptation to the gastrointestinal tract and the pGP3-dependent resistance may enable chlamydial evasion of the female lower genital tract barrier during sexual transmission.


2020 ◽  
Author(s):  
Yang Gao ◽  
Pengpeng Qu ◽  
Yang Zhou ◽  
Wei Ding

Abstract Background: The purpose of this study was to assess the risk factors associated with the development of tubo-ovarian abscesses in women with ovarian endometriosis cysts. Methods: This retrospective single-center study included 176 women: 44 with tubo-ovarian abscesses associated with ovarian endometriosis and 132 age-matched (1:3) patients with ovarian endometriosis but without tubo-ovarian abscesses. Diagnoses were made via surgical exploration and pathological examination. The potential risk factors of tubo-ovarian abscesses associated with ovarian endometriosis were evaluated using univariate analysis. The results (p ≤ 0.05) of these parameters were analyzed using a multivariate model.Results: Five factors were included in the multivariate conditional logistic regression model, including in vitro fertilization, presence of an intrauterine device, lower genital tract infection, spontaneous rupture of ovarian endometriosis cysts, and diabetes mellitus. The presence of a lower genital tract infection (odds ratio 5.462, 95% confidence interval, 1.772–16.839) and spontaneous rupture of ovarian endometriosis cysts (odds ratio 2.572, 95% confidence interval, 1.071–6.174) were found to be statistically significant risk factors for tubo-ovarian abscesses associated with ovarian endometriosis.Conclusions: Of the factors investigated, the occurrence of tubo-ovarian abscesses associated with ovarian endometriosis was found to be associated with genital tract infections and spontaneous rupture of ovarian endometriosis cysts. Our findings indicate that tubo-ovarian abscesses associated with ovarian endometriosis may not be linked to in vitro fertilization as previously thought.


2020 ◽  
Vol 19 (1) ◽  
pp. 37-41
Author(s):  
S. M. Yasnikovska ◽  
A. V. Hoshovska

The article presents the results of a study of the vaginal microbiota in women with miscarriage in early term of gestation. It has been established that pregnant women with lower genital tract infections are at high risk for perinatal and postpartum complications. In most of them (76.0 %) there was a lack of Preconception Prevention with the study of the vaginal biotope. In pregnant women at risk of miscarriage on the background of lower genital tract infection, microbial and viral associations are more common than monoinfection. Taking into account the negative effects of lower genital tract infection on the further course of pregnancy and childbirth and the condition of newborns, at the stage of Preconception Prevention should be studied vaginal microbiota. During pregnancy, it is necessary to conduct a thorough examination of women with timely identification of risk factors for miscarriage, which include associated infections, and their adequate correction.


mBio ◽  
2013 ◽  
Vol 4 (6) ◽  
Author(s):  
Marcia M. Hobbs ◽  
James E. Anderson ◽  
Jacqueline T. Balthazar ◽  
Justin L. Kandler ◽  
Russell W. Carlson ◽  
...  

ABSTRACT Phosphoethanolamine (PEA) on Neisseria gonorrhoeae lipid A influences gonococcal inflammatory signaling and susceptibility to innate host defenses in in vitro models. Here, we evaluated the role of PEA-decorated gonococcal lipid A in competitive infections in female mice and in male volunteers. We inoculated mice and men with mixtures of wild-type N. gonorrhoeae and an isogenic mutant that lacks the PEA transferase, LptA. LptA production conferred a marked survival advantage for wild-type gonococci in the murine female genital tract and in the human male urethra. Our studies translate results from test tube to animal model and into the human host and demonstrate the utility of the mouse model for studies of virulence factors of the human-specific pathogen N. gonorrhoeae that interact with non-host-restricted elements of innate immunity. These results validate the use of gonococcal LptA as a potential target for development of novel immunoprophylactic strategies or antimicrobial treatments. IMPORTANCE Gonorrhea is one of the most common bacterial sexually transmitted infections, and increasing antibiotic resistance threatens the use of currently available antimicrobial therapies. In this work, encompassing in vitro studies and in vivo studies of animal and human models of experimental genital tract infection, we document the importance of lipid A’s structure, mediated by a single bacterial enzyme, LptA, in enhancing the fitness of Neisseria gonorrhoeae. The results of these studies suggest that novel agents targeting LptA may offer urgently needed prevention or treatment strategies for gonorrhea.


2004 ◽  
Vol 190 (4) ◽  
pp. 1004-1008 ◽  
Author(s):  
Daniel V Landers ◽  
Harold C Wiesenfeld ◽  
R Phillip Heine ◽  
Marijane A Krohn ◽  
Sharon L Hillier

2016 ◽  
Vol 84 (9) ◽  
pp. 2697-2702 ◽  
Author(s):  
Zhangsheng Yang ◽  
Lingli Tang ◽  
Lili Shao ◽  
Yuyang Zhang ◽  
Tianyuan Zhang ◽  
...  

Despite the extensivein vitrocharacterization of CPAF (chlamydialprotease/proteasome-likeactivityfactor), its role in chlamydial infection and pathogenesis remains unclear. We now report that aChlamydia trachomatisstrain deficient in expression of CPAF (L2-17) is no longer able to establish a successful infection in the mouse lower genital tract following an intravaginal inoculation. The L2-17 organisms were cleared from the mouse lower genital tract within a few days, while a CPAF-sufficientC. trachomatisstrain (L2-5) survived in the lower genital tract for more than 3 weeks. However, both the L2-17 and L2-5 organisms maintained robust infection courses that lasted up to 4 weeks when they were directly delivered into the mouse upper genital tract. The CPAF-dependent chlamydial survival in the lower genital tract was confirmed in multiple strains of mice. Thus, we have demonstrated a critical role of CPAF in promotingC. trachomatissurvival in the mouse lower genital tracts. It will be interesting to further investigate the mechanisms of the CPAF-dependent chlamydial pathogenicity.


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