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

2007 ◽  
Vol 75 (5) ◽  
pp. 2225-2233 ◽  
Author(s):  
Ángel A. Soler-García ◽  
Ann E. Jerse
Keyword(s):  
Tract Infection ◽  
Neisseria Gonorrhoeae ◽  
Genital Tract ◽  
Female Genital Tract ◽  
Antioxidant Defenses ◽  
Wild Type ◽  
Genital Tract Infection ◽  
Estradiol Treatment ◽  
Significant Difference

ABSTRACT Neisseria gonorrhoeae produces several antioxidant defenses, including high levels of catalase, which may facilitate the persistence during an inflammatory response via neutralization of H2O2 produced by phagocytes. In vivo testing of the role of catalase in gonococcal survival is critical since several physiological factors impact interactions between N. gonorrhoeae and polymorphonuclear leukocytes (PMNs). Here we assessed the importance of gonococcal catalase in a surrogate model of female genital tract infection. Female BALB/c mice were treated with 17-β estradiol to promote susceptibility to N. gonorrhoeae and inoculated intravaginally with wild-type gonococci or a catalase (kat) deletion mutant. A localized PMN influx occurred in an average of 43 and 81% of mice infected with wild-type or kat mutant gonococci, respectively, and PMNs associated with numerous wild-type or catalase-deficient bacteria were observed in vaginal smears. The combined results of six experiments showed a significant difference in the number of days wild-type bacteria were recovered compared to the catalase-deficient gonococci. However, there was much variability between experiments, and we found no correlation between PMN influx, colonization load, and clearance of wild-type or kat mutant bacteria. Estradiol treatment did not impair bacterial uptake, the luminol-dependent chemiluminescence response, or the killing capacity of isolated murine PMNs against N. gonorrhoeae or Staphylococcus aureus. Our data suggest N. gonorrhoeae is not significantly challenged by H2O2 produced by PMNs in the murine lower genital tract; alternatively, redundant defense mechanisms may protect the gonococcus from reactive oxygen species during infection.

scholarly journals Lipid A’s Structure Mediates Neisseria gonorrhoeae Fitness during Experimental Infection of Mice and Men

mBio ◽  
2013 ◽  
Vol 4 (6) ◽  
Author(s):  
Marcia M. Hobbs ◽  
James E. Anderson ◽  
Jacqueline T. Balthazar ◽  
Justin L. Kandler ◽  
Russell W. Carlson ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Genital Tract ◽  
Lipid A ◽  
Female Genital Tract ◽  
Treatment Strategies ◽  
Wild Type ◽  
Genital Tract Infection ◽  
Content Type

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.

scholarly journals α-2,3-Sialyltransferase Enhances Neisseria gonorrhoeae Survival during Experimental Murine Genital Tract Infection

2006 ◽  
Vol 74 (7) ◽  
pp. 4094-4103 ◽  
Author(s):  
Hong Wu ◽  
Ann E. Jerse
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Genital Tract ◽  
In Vitro Assays ◽  
In Vivo Model ◽  
Wild Type ◽  
Genital Tract Infection ◽  
Direct Demonstration ◽  
Increased Sensitivity

ABSTRACT The addition of host-derived sialic acid to Neisseria gonorrhoeae lipooligosaccharide is hypothesized to be an important mechanism by which gonococci evade host innate defenses. This hypothesis is based primarily on in vitro assays of complement-mediated and phagocytic killing. Here we report that a nonpolar α-2,3-sialyltransferase (lst) mutant of N. gonorrhoeae was significantly attenuated in its capacity to colonize the lower genital tract of 17-β estradiol-treated female BALB/c mice during competitive infection with the wild-type strain. Genetic complementation of the lst mutation restored recovery of the mutant to wild-type levels. Studies with B10.D2-HCoH2dH2-T18c/OSN (C5-deficient) mice showed that attenuation of the lst mutant was not due to increased sensitivity to complement-mediated bacteriolysis, a result that is consistent with recently reported host restrictions in the complement cascade. However, Lst-deficient gonococci were killed more rapidly than sialylated wild-type gonococci following intraperitoneal injection into normal mice, which is consistent with sialylation conferring protection against killing by polymorphonuclear leukocytes (PMNs). As reported for human PMNs, sialylated gonococci were more resistant to killing by murine PMNs, and sialylation led to reduced association with and induction of a weaker respiratory burst in PMNs from estradiol-treated mice. In summary, these studies suggest sialylation confers a survival advantage to N. gonorrhoeae in mice by increasing resistance to PMN killing. This report is the first direct demonstration that α-2,3-sialyltransferase contributes to N. gonorrhoeae pathogenesis in an in vivo model. This study also validates the use of experimental murine infection to study certain aspects of gonococcal pathogenesis.

scholarly journals TheChlamydia trachomatisPlasmid and CT135 Virulence Factors Are Not Essential for Genital Tract Infection or Pathology in Female Pig-Tailed Macaques

2018 ◽  
Vol 86 (5) ◽  
Author(s):  
Dorothy L. Patton ◽  
Yvonne C. Sweeney ◽  
Audrey E. Baldessari ◽  
Linda Cles ◽  
Laszlo Kari ◽  
...  
Keyword(s):  
Tract Infection ◽  
Virulence Factors ◽  
Genital Tract ◽  
Inflammatory Responses ◽  
Interleukin 1 ◽  
Female Genital Tract ◽  
Wild Type ◽  
Genital Tract Infection ◽  
Content Type ◽  
Cytokine Analysis

ABSTRACTTheChlamydia trachomatisplasmid and inclusion membrane protein CT135 are virulence factors in the pathogenesis of murine female genital tract infection. To determine if these virulence factors play a similar role in female nonhuman primates, we infected pig-tailed macaques with the sameC. trachomatisstrains shown to be important in the murine model. Wild-typeC. trachomatisand its isogenic mutant strain deficient in both plasmid and CT135 were used to infect macaques. Macaques were given primary and repeated cervicovaginal challenges with the wild-type and mutant strains. The infection rate, infection duration, and antibody response were similar among macaques infected with both strains. Unexpectedly, colposcopy, laparoscopy, and histologic analysis revealed no substantial genital tract pathology following either primary or repeated cervicovaginal challenges. Cytokine analysis of cervicovaginal secretions from both challenged groups revealed low concentrations of interleukin 1β (IL-1β) and elevated levels of the interleukin 1 receptor agonist (IL-1RA). We propose that an imbalance of IL-1β and IL-1RA in macaques is the reason for the mild inflammatory responses observed in infected urogenital tissues. Thus, understanding the pathobiology of chlamydial infection requires a better understanding of host epigenetic and chlamydial genetic factors. Our findings also have implications for understanding the high frequency of asymptomatic infections in humans.

scholarly journals Lactate Acquisition Promotes Successful Colonization of the Murine Genital Tract by Neisseria gonorrhoeae

2006 ◽  
Vol 75 (3) ◽  
pp. 1318-1324 ◽  
Author(s):  
Rachel M. Exley ◽  
Hong Wu ◽  
Jonathan Shaw ◽  
Muriel C. Schneider ◽  
Harry Smith ◽  
...  
Keyword(s):  
Carbon Source ◽  
Tract Infection ◽  
Neisseria Gonorrhoeae ◽  
Genital Tract ◽  
Defined Medium ◽  
Growth Defect ◽  
Wild Type ◽  
Genital Tract Infection ◽  
Lactate Utilization

ABSTRACT Previous studies on Neisseria gonorrhoeae have demonstrated that metabolism of lactate in the presence of glucose increases the growth rate of the bacterium and enhances its resistance to complement-mediated killing. Although these findings in vitro suggest that the acquisition of lactate promotes gonococcal colonization, the significance of this carbon source to the survival of the gonococcus in vivo remains unknown. To investigate the importance of lactate utilization during Neisseria gonorrhoeae genital tract infection, we identified the gene lctP, which encodes the gonococcal lactate permease. A mutant that lacks a functional copy of lctP was unable to take up exogenous lactate and did not grow in defined medium with lactate as the sole carbon source, in contrast to the wild-type and complemented strains; the mutant strain exhibited no growth defect in defined medium containing glucose. In defined medium containing physiological concentrations of lactate and glucose, the lctP mutant demonstrated reduced early growth and increased sensitivity to complement-mediated killing compared with the wild-type strain; the enhanced susceptibility to complement was associated with a reduction in lipopolysaccharide sialylation of the lctP mutant. The importance of lactate utilization during colonization was evaluated in the murine model of lower genital tract infection. The lctP mutant was significantly attenuated in its ability to colonize and survive in the genital tract, while the complemented mutant exhibited no defect for colonization. Lactate is a micronutrient in the genital tract that contributes to the survival of the gonococcus.

scholarly journals Efficacy of an Immune Modulator in ExperimentalChlamydia trachomatisInfection of the Female Genital Tract

2006 ◽  
Vol 2006 ◽  
pp. 1-6
Author(s):  
Joseph M. Lyons ◽  
James I. Ito ◽  
Servaas A. Morré
Keyword(s):  
Tract Infection ◽  
Murine Model ◽  
Genital Tract ◽  
Female Genital Tract ◽  
Response Modifier ◽  
Genital Tract Infection ◽  
Prophylactic Dose ◽  
Duration Of Infection ◽  
Immune Response Modifier ◽  
Female Genital

Objective.The aim of this study was to determine if vaginal application of the immune response modifier imiquimod (Aldara cream, 3M Pharmaceuticals, St Paul, Minn) would alter the course and/or outcome of female genital tract infection with a human isolate ofChlamydia trachomatisin a murine model.Methods.Groups of CF-1 mice were treated with Aldara on three different schedules: (1) ongoing beginning 5 days prior to and continuing through day 5 of infection; (2) a single prophylactic dose 2 hours prior to infection; and (3) therapeutic from day 4 to day 14 of infection. Mice were infected vaginally with a serovar D strain ofC trachomatis, and monitored by culture to determine the level of shedding and duration of infection.Results.We observed a significant reduction in both duration of infection and the level of shedding during the acute phase in mice treated on an ongoing basis commencing 5 days prior to infection. There was no effect with respect to the other regimens.Conclusion.These results demonstrate that ongoing Aldara treatment has efficacy and may enhance local innate immunity which reduces the duration of subsequent infection with human isolates ofC trachomatisin a murine model of female genital tract infection.

scholarly journals Growth of Neisseria gonorrhoeae in the Female Mouse Genital Tract Does Not Require the Gonococcal Transferrin or Hemoglobin Receptors and May Be Enhanced by Commensal Lactobacilli

2002 ◽  
Vol 70 (5) ◽  
pp. 2549-2558 ◽  
Author(s):  
Ann E. Jerse ◽  
Emily T. Crow ◽  
Amy N. Bordner ◽  
Ishrat Rahman ◽  
Cynthia Nau Cornelissen ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Genital Tract ◽  
Female Genital Tract ◽  
Iron Chelator ◽  
Iron Store ◽  
Human Transferrin ◽  
Mucosal Surfaces ◽  
Phase Variants

ABSTRACT Neisseria gonorrhoeae is capable of utilizing a variety of iron sources in vitro, including human transferrin, human lactoferrin, hemoglobin, hemoglobin-haptoglobin complexes, heme, and heterologous siderophores. Transferrin has been implicated as a critical iron store for N. gonorrhoeae in the human male urethra. The demonstration that gonococci can infect the lower genital tracts of estradiol-treated BALB/c mice in the absence of human transferrin, however, suggests that other usable iron sources are present in the murine genital tract. Here we demonstrate that gonococcal transferrin and hemoglobin receptor mutants are not attenuated in mice, thereby ruling out transferrin and hemoglobin as essential for murine infection. An increased frequency of phase variants with the hemoglobin receptor “on” (Hg+) occurred in ca. 50% of infected mice; this increase was temporally associated with an influx of neutrophils and detectable levels of hemoglobin in the vagina, suggesting that the presence of hemoglobin in inflammatory exudates selects for Hg+ phase variants during infection. We also demonstrate that commensal lactobacilli support the growth of N. gonorrhoeae in vitro unless an iron chelator is added to the medium. We hypothesize that commensal lactobacilli may enhance growth of gonococci in vivo by promoting the solubilization of iron on mucosal surfaces through the production of metabolic intermediates. Finally, transferrin-binding lipoprotein (TbpB) was detected on gonococci in vaginal smears, suggesting that although gonococci replicate within the genital tracts of mice, they may be sufficiently iron-stressed to express iron-repressible proteins. In summary, these studies support the potential role of nontransferrin, nonhemoglobin iron sources during gonococcal infection of the female genital tract.

Anaerobes in ejaculates of subfertile men

1995 ◽  
Vol 1 (5) ◽  
pp. 462-478 ◽  
Author(s):  
Waltraud Eggert-Kruse ◽  
Gerhard Rohr ◽  
Wolfram Ströck ◽  
Susanne Pohl ◽  
Beate Schwalbach ◽  
...  
Keyword(s):  
Tract Infection ◽  
Genital Tract ◽  
Anaerobic Bacteria ◽  
Cervical Mucus ◽  
Anaerobic Growth ◽  
Pathogenic Species ◽  
Genital Tract Infection ◽  
Micro Organisms

Abstract The clinical significance of micro-organisms in semen samples of asymptomatic subfertile patients is a matter of constant debate. Usually little attention is paid to anaerobic bacteria as they are sensitive to transportation and culturing, and differentiation is difficult, costly and time-consuming. In the present study, special screening was carried out for anaerobes in ejaculates in addition to the routine microbial cultures of genital secretions of both partners. In addition to standard semen analysis and evaluation of sperm ability to penetrate cervical mucus (CM) in vivo (postcoital testing) and in vitro using a standardized test system, semen samples from 126 randomly chosen males of couples with a median duration of infertility of 4 years were examined for colonization with anaerobic bacteria. All couples were without clinical signs or symptoms of genital tract infection. The special care taken for anaerobic growth in semen samples gave a high rate of positive cultures and showed that nearly all ejaculates (99%) were colonized with anaerobic micro-organisms, and potentially pathogenic species were found in 71% of men. This rate was more than four times higher than that obtained with routine cultures and standard transportation (16%). Anaerobic bacterial growth of ≥106 colony forming units (CFU)/ml was seen in 42% (total range 103-108 CFU/ml). In addition, aerobic growth was found in 96%(≥106 CFU/ml in 21%), potentially pathogenic species in 61% of semen specimens. There were no marked differences in the prevalence of anaerobic micro-organisms in patients with reduced or normal sperm count, motility or morphology. Nor was there any significant difference in anaerobic colonization between samples with impaired or good ability to penetrate CM of female partners (in vivo or in vitro), or the CM of fertile donors in the in-vitro sperm-cervical mucus penetration test (SCMPT) in this asymptomatic group of patients. There was no clear association between microbial colonization and subsequent fertility in vivo within an observation period of 6 months. The results of this study suggest that anaerobic bacteria are often not detected when routine methods for microbial evaluation are used. This should be considered during assisted reproduction and in patients with symptoms of genital tract infection and should lead to further studies in infertile patients where subclinical infection or inflammation is indicated by specific markers in semen samples.

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