<i>Neisseria gonorrhoeae</i>
            Catalase Is Not Required for Experimental Genital Tract Infection despite the Induction of a Localized Neutrophil Response

Soler-García, Ángel A.; Jerse, Ann E.

doi:10.1128/iai.01513-06

Cited by 30 publications

(38 citation statements)

References 51 publications

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“…Also consistent with human infection, mice develop an unremarkable and transient antibody response to N. gonorrhoeae and are susceptible to reinfection with the same strain (56). Additionally, the in vivo phenotype of several defined gonococcal mutants when tested in mice was the phenotype predicted from studies with human neutrophils and antimicrobial peptides (55,(63)(64)(65). The recovery of Opa variants during infection of female mice is also similar to the selection dynamics that is predicted from analysis of human cervical isolates.…”

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confidence: 48%

Opacity Proteins Increase Neisseria gonorrhoeae Fitness in the Female Genital Tract Due to a Factor under Ovarian Control

2010

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The neisserial opacity (Opa) proteins are a family of antigenically distinct outer membrane proteins that undergo phase-variable expression. Opa ؉ variants of Neisseria gonorrhoeae strain FA1090 are selected in a cyclical pattern from the lower genital tract of estradiol-treated mice. Here we show that cyclical recovery of Opa ؉ gonococci does not occur in ovariectomized mice; therefore, the reproductive cycle plays a role in the selection kinetics in vivo. As predicted by the selection pattern shown by wild-type gonococci, we demonstrated that a constitutive Opa-expressing strain was more fit than an Opa-deficient mutant in the early and late phases of infection. We found no evidence that Opa-mediated colonization selects for Opa ؉ variants during murine infection based on adherence assays with cultured murine epithelial cells. We also tested the hypothesis that complement selects for Opa protein expression during infection. Although some Opa ؉ variants of a serum-sensitive derivative of strain FA1090 were more resistant to the bactericidal activity of normal human serum, selection for Opa expression was not abrogated in C3-depleted mice. Finally, as previously reported, Opa ؉ gonococci were more sensitive to serine proteases. Thus, proteases or protease inhibitors may contribute to the observed in vivo selection pattern. We concluded that Opa proteins promote persistence of N. gonorrhoeae in the female genital tract and that opa gene phase variation allows gonococci to evade or capitalize upon unidentified host factors of the mammalian reproductive cycle. This work revealed an intimate interaction between pathogen and host and provides evidence that hormonally related factors shape bacterial adaptation.

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confidence: 48%

Opacity Proteins Increase Neisseria gonorrhoeae Fitness in the Female Genital Tract Due to a Factor under Ovarian Control

2010

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“…Thus, in several cases, inactivation of genes encoding ROS-eliminating enzymes failed to cause a significant defect in bacterial virulence. For instance, inactivation of catalase-encoding genes had little if any effect on pathogenicity-associated traits of Salmonella Typhimurium (5), Yersinia pestis (15), Francisella tularensis (21), Staphylococcus aureus (9), and Neisseria gonorrhoeae (34). In the present study, we addressed the question of the involvement of cytoplasmic H 2 O 2 -degrading enzymes in Salmonella virulence.…”

Section: Discussionmentioning

confidence: 99%

Redundant Hydrogen Peroxide Scavengers Contribute to Salmonella Virulence and Oxidative Stress Resistance

et al. 2009

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Salmonella enterica serovar Typhimurium is an intracellular pathogen that can survive and replicate within macrophages. One of the host defense mechanisms that Salmonella encounters during infection is the production of reactive oxygen species by the phagocyte NADPH oxidase. Among them, hydrogen peroxide (H 2 O 2 ) can diffuse across bacterial membranes and damage biomolecules. Genome analysis allowed us to identify five genes encoding H 2 O 2 degrading enzymes: three catalases (KatE, KatG, and KatN) and two alkyl hydroperoxide reductases (AhpC and TsaA). Inactivation of the five cognate structural genes yielded the HpxF ؊ mutant, which exhibited a high sensitivity to exogenous H 2 O 2 and a severe survival defect within macrophages. When the phagocyte NADPH oxidase was inhibited, its proliferation index increased 3.7-fold. Moreover, the overexpression of katG or tsaA in the HpxF ؊ background was sufficient to confer a proliferation index similar to that of the wild type in macrophages and a resistance to millimolar H 2 O 2 in rich medium. The HpxF ؊ mutant also showed an attenuated virulence in a mouse model. These data indicate that Salmonella catalases and alkyl hydroperoxide reductases are required to degrade H 2 O 2 and contribute to the virulence. This enzymatic redundancy highlights the evolutionary strategies developed by bacterial pathogens to survive within hostile environments.

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“…N. gonorrhoeae also cannot use murine lactoferrin or transferrin as sources of iron (14,43), and the gonococcal immunoglobulin A1 (IgA1) protease cannot cleave mouse IgA (40). Despite these host restrictions, studying gonococcal pathogenesis in the murine model has yielded considerable insight into the host response to infection (25,31,58,76) and the role of certain gonococcal virulence factors in evasion of host defenses (34,75,81,84,85). The mouse model has also allowed the demonstration of hormonal (13,32,73), as well as the effect of certain antibiotic resistance mutations on microbial fitness (82).…”

Section: Discussionmentioning

confidence: 99%

“…18 to 20% of mice (32). Infected mice have an inflammatory response that is characterized by PMN influx and the induction of tumor necrosis factor alpha (TNF-␣), IL-6, macrophage inflammatory protein 2 (MIP-2), and KC (32,58,75). Similarly to human infection, mice elicit an unremarkable humoral response and are susceptible to repeat infection with the same strain (76).…”

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Chlamydial Infection Increases Gonococcal Colonization in a Novel Murine Coinfection Model

et al. 2011

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Genital tract infections caused by Neisseria gonorrhoeae and Chlamydia trachomatis serovars D to K occur at high incidence in many areas of the world. Despite high rates of coinfection with these pathogens, investigations of host-parasite interactions have focused on each pathogen individually. We describe here a coinfection model in which female BALB/c mice were first infected with the mouse Chlamydia species C. muridarum and then inoculated with N. gonorrhoeae following treatment with water-soluble 17␤-estradiol to promote long-term gonococcal infection. Viable gonococci and chlamydiae were recovered for an average of 8 to 10 days, and diplococci and chlamydial inclusions were observed in lower genital tract tissue by immunohistochemical staining. Estradiol treatment reduced proinflammatory cytokine and chemokine levels in chlamydia-infected mice; however, coinfected mice had a higher percentage of vaginal neutrophils compared to mice infected with either pathogen alone. We detected no difference in pathogen-specific antibody levels due to coinfection. Interestingly, significantly more gonococci were recovered from coinfected mice compared to mice infected with N. gonorrhoeae alone. We found no evidence that C. muridarum increases gonococcal adherence to, or invasion of, immortalized murine epithelial cells. However, increased vaginal concentrations of inflammatory mediators macrophage inflammatory protein 2 and tumor necrosis factor alpha were detected in C. muridarum-infected mice prior to inoculation with N. gonorrhoeae concurrently with the downregulation of cathelicidin-related antimicrobial peptide and secretory leukocyte peptidase inhibitor genes. We conclude that female mice can be successfully infected with both C. muridarum and N. gonorrhoeae and that chlamydia-induced alterations in host innate responses may enhance gonococcal infection.Chlamydia and gonorrhea are the two most common notifiable infectious diseases in the United States, with over 1 million cases of chlamydia and 350,000 cases of gonorrhea reported to the Centers for Disease Control in 2008 (9). Actual rates of infection are much higher due to high rates of asymptomatic infection (50). As many as 50 to 70% of individuals with gonorrhea also have a chlamydial infection (20,50,55), and empirical treatment for chlamydia upon detection of N. gonorrhoeae is recommended (10,27). Neisseria gonorrhoeae and Chlamydia trachomatis are both Gram-negative, humanspecific pathogens. In symptomatic infections, both organisms elicit a proinflammatory response characterized by the influx of polymorphonuclear leukocytes (PMNs). Clinically, gonorrhea is typically more pyogenic. Postinfection complications can occur with either pathogen and complications are generally more common and more severe in women. Infections that ascend to the upper genital tract in women lead to pelvic inflammatory disease (PID), the complications of which include chronic pelvic pain, ectopic pregnancy, and infertility (28, 78).The incidence (50, 55), transmission (45,46,48), and...

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Neisseria gonorrhoeae Catalase Is Not Required for Experimental Genital Tract Infection despite the Induction of a Localized Neutrophil Response

Cited by 30 publications

References 51 publications

Opacity Proteins Increase Neisseria gonorrhoeae Fitness in the Female Genital Tract Due to a Factor under Ovarian Control

Opacity Proteins Increase Neisseria gonorrhoeae Fitness in the Female Genital Tract Due to a Factor under Ovarian Control

Redundant Hydrogen Peroxide Scavengers Contribute to Salmonella Virulence and Oxidative Stress Resistance

Chlamydial Infection Increases Gonococcal Colonization in a Novel Murine Coinfection Model

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