A Strain-Specific Catalase Mutation and Mutation of the Metal-Binding Transporter Gene
            <i>mntC</i>
            Attenuate
            <i>Neisseria gonorrhoeae</i>
            In Vivo but Not by Increasing Susceptibility to Oxidative Killing by Phagocytes

Wu, Haorui; Soler-García, Ángel A.; Jerse, Ann E.

doi:10.1128/iai.00825-08

Cited by 38 publications

(49 citation statements)

References 60 publications

(71 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PEA decoration of lipid A confers a survival advantage to N. gonorrhoeae during competitive genital tract infection. The host innate response to N. gonorrhoeae infection in female BALB/c mice is well characterized (8,11,27,28), and this model has been used to study other mechanisms by which N. gonorrhoeae evades innate effectors, including CAMPs, during infection (23,(29)(30)(31). When tested by competitive infection with the wild-type strain, the FA19 lptA mutant was attenuated in vivo, similar to our recent results with an lptA mutant of strain FA1090 (17).…”

Section: Resultssupporting

confidence: 74%

“…The increased fitness of the C=lptA mutant relative to the wild-type strain may be due to higher expression of the lptA gene in the C=lptA mutant. In this strain, the complementing lptA gene is under the control of the lac promoter (14), and increased expression of isopropyl-␤-Dthiogalactopyranoside (IPTG)-inducible genes has been demonstrated previously during murine infection (17,31). These results suggest that the PEA moiety on wild-type lipid A is beneficial to N. gonorrhoeae during infection and provides a fitness advantage over the fitness of gonococci devoid of PEA-decorated lipid A.…”

Section: Resultsmentioning

confidence: 66%

See 1 more Smart Citation

Phosphoethanolamine Decoration of Neisseria gonorrhoeae Lipid A Plays a Dual Immunostimulatory and Protective Role during Experimental Genital Tract Infection

et al. 2014

Self Cite

View full text Add to dashboard Cite

eThe induction of an intense inflammatory response by Neisseria gonorrhoeae and the persistence of this pathogen in the presence of innate effectors is a fascinating aspect of gonorrhea. Phosphoethanolamine (PEA) decoration of lipid A increases gonococcal resistance to complement-mediated bacteriolysis and cationic antimicrobial peptides (CAMPs), and recently we reported that wild-type N. gonorrhoeae strain FA1090 has a survival advantage relative to a PEA transferase A (lptA) mutant in the human urethral-challenge and murine lower genital tract infection models. Here we tested the immunostimulatory role of this lipid A modification. Purified lipooligosaccharide (LOS) containing lipid A devoid of the PEA modification and an lptA mutant of strain FA19 induced significantly lower levels of NF-B in human embryonic kidney Toll-like receptor 4 (TLR4) cells and murine embryonic fibroblasts than wild-type LOS of the parent strain. Moreover, vaginal proinflammatory cytokines and chemokines were not elevated in female mice infected with the isogenic lptA mutant, in contrast to mice infected with the wild-type and complemented lptA mutant bacteria. We also demonstrated that lptA mutant bacteria were more susceptible to human and murine cathelicidins due to increased binding by these peptides and that the differential induction of NF-B by wild-type and unmodified lipid A was more pronounced in the presence of CAMPs. This work demonstrates that PEA decoration of lipid A plays both protective and immunostimulatory roles and that host-derived CAMPs may further reduce the capacity of PEA-deficient lipid A to interact with TLR4 during infection.

show abstract

Section: Resultssupporting

confidence: 74%

Section: Resultsmentioning

confidence: 66%

Phosphoethanolamine Decoration of Neisseria gonorrhoeae Lipid A Plays a Dual Immunostimulatory and Protective Role during Experimental Genital Tract Infection

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…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.…”

supporting

confidence: 48%

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

2010

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…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%

Chlamydial Infection Increases Gonococcal Colonization in a Novel Murine Coinfection Model

et al. 2011

Self Cite

View full text Add to dashboard Cite

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...

show abstract

A Strain-Specific Catalase Mutation and Mutation of the Metal-Binding Transporter Gene mntC Attenuate Neisseria gonorrhoeae In Vivo but Not by Increasing Susceptibility to Oxidative Killing by Phagocytes

Cited by 38 publications

References 60 publications

Phosphoethanolamine Decoration of Neisseria gonorrhoeae Lipid A Plays a Dual Immunostimulatory and Protective Role during Experimental Genital Tract Infection

Phosphoethanolamine Decoration of Neisseria gonorrhoeae Lipid A Plays a Dual Immunostimulatory and Protective Role during Experimental Genital Tract Infection

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

Chlamydial Infection Increases Gonococcal Colonization in a Novel Murine Coinfection Model

Contact Info

Product

Resources

About