Mucosal infection with Neisseria gonorrhoeae. Bacterial adaptation and mucosal defenses.

Cohen, Myron S.; Sparling, P. Frederick

doi:10.1172/jci115770

Cited by 42 publications

(23 citation statements)

References 69 publications

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“…Gonococcal infection of the female genital tract can induce inflammatory cytokines (27) although typically a large percentage of infected females are asymptomatic (34). This can be a serious medical issue as prolonged gonococcal infection can cause more dangerous complications such as pelvic inflammatory disease (PID), a common cause of infertility and ectopic pregnancy (12,22). We previously demonstrated through in vivo studies that gonococcal genes involved in iron homeostasis are upregulated during infection in men and women.…”

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confidence: 99%

Fur-Mediated Activation of Gene Transcription in the Human Pathogen Neisseria gonorrhoeae

Genco

2012

J Bacteriol

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It is well established that the ferric uptake regulatory protein (Fur) functions as a transcriptional repressor in diverse microorganisms. Recent studies demonstrated that Fur also functions as a transcriptional activator. In this study we defined Fur-mediated activation of gene transcription in the sexually transmitted disease pathogen Neisseria gonorrhoeae. Analysis of 37 genes which were previously determined to be iron induced and which contained putative Fur boxes revealed that only 30 of these genes exhibited reduced transcription in a gonococcal fur mutant strain. Fur-mediated activation was established by examining binding of Fur to the putative promoter regions of 16 Fur-activated genes with variable binding affinities observed. Only ϳ50% of the newly identified Fur-regulated genes bound Fur in vitro, suggesting that additional regulatory circuits exist which may function through a Fur-mediated indirect mechanism. The gonococcal Fur-activated genes displayed variable transcription patterns in a fur mutant strain, which correlated with the position of the Fur box in each (promoter) region. These results suggest that Fur-mediated direct transcriptional activation is fulfilled by multiple mechanisms involving either competing with a repressor or recruiting RNA polymerase. Collectively, our studies have established that gonococcal Fur functions as an activator of gene transcription through both direct and indirect mechanisms.

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confidence: 99%

Fur-Mediated Activation of Gene Transcription in the Human Pathogen Neisseria gonorrhoeae

Genco

2012

J Bacteriol

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“…The sexually transmitted disease pathogen Neisseria gonorrhoeae is typically seen as a pathogen of mucosal surfaces, predominantly associated with symptomatic urethritis in males and an often asymptomatic endocervicitis in women. For women, this can progress to pelvic inflammatory disease and salpingitis, potentially resulting in ectopic pregnancy and sterility (15,22). Iron is sequestered on the urogenital mucosal surface by lactoferrin and transferrin (1), while during menses hemoglobin is released into the environment (36).…”

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confidence: 99%

Identification of the Iron-Responsive Genes of Neisseria gonorrhoeae by Microarray Analysis in Defined Medium

et al. 2005

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To ensure survival, most bacteria must acquire iron, a resource that is sequestered by mammalian hosts. Pathogenic bacteria have therefore evolved intricate systems to sense iron limitation and regulate gene expression appropriately. We used a pan-Neisseria microarray to examine genes regulated in Neisseria gonorrhoeae in response to iron availability in defined medium. Overall, 203 genes varied in expression, 109 up-regulated and 94 down-regulated by iron deprivation. In iron-replete medium, genes essential to rapid bacterial growth were preferentially expressed, while iron transport functions, and predominantly genes of unknown function, were expressed in low-iron medium. Of those TonB-dependent proteins encoded in the FA1090 genome with unknown ligand specificity, expression of three was not controlled by iron availability, suggesting that these receptors may not be high-affinity transporters for iron-containing ligands. Approximately 30% of the operons regulated by iron appeared to be directly under control of Fur. Our data suggest a regulatory cascade where Fur indirectly controls gene expression by affecting the transcription of three secondary regulators. Our data also suggest that a second MerR-like regulator may be directly responding to iron availability and controlling transcription independent of the Fur protein. Comparison of our data with those recently published for Neisseria meningitidis revealed that only a small portion of genes were found to be similarly regulated in these closely related pathogens, while a large number of genes derepressed during iron starvation were unique to each organism.

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“…Furthermore, we show that the secreted form of the PilB protein is involved in survival in the presence of oxidative damage. P athogenic bacteria that contact the human host at the mucosal surface are subjected to host responses including localized membrane defenses such as the production of mucus, lysozyme, secretory antibodies, lactoferrin, reactive oxygen species (ROS), and reactive nitrogen intermediates (1,2). The obligate human pathogen, Neisseria gonorrhoeae, is the causative agent of the disease gonorrhea.…”

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The outer membrane localization of the Neisseria gonorrhoeae MsrA/B is involved in survival against reactive oxygen species

Skaar

Tobiason

Quick

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

123

146

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The PilB protein of Neisseria gonorrhoeae has been reported to be involved in the regulation of pilin gene transcription, but it also possesses significant homology to the peptide methionine sulfoxide reductase family of enzymes, specifically MsrA and MsrB from Escherichia coli. MsrA and MsrB in E. coli are able to reduce methionine sulfoxide residues in proteins to methionines. In addition, the gonococcal PilB protein encodes for both MsrA and MsrB activity associated with the repair of oxidative damage to proteins. In this work, we demonstrate that the PilB protein of Neisseria gonorrhoeae is not involved in pilus expression. Additionally, we show that wild-type N. gonorrhoeae produces two forms of this polypeptide, one of which contains a signal sequence and is secreted from the bacterial cytoplasm to the outer membrane; the other lacks a signal sequence and is cytoplasmic. Furthermore, we show that the secreted form of the PilB protein is involved in survival in the presence of oxidative damage.

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Mucosal infection with Neisseria gonorrhoeae. Bacterial adaptation and mucosal defenses.

Cited by 42 publications

References 69 publications

Fur-Mediated Activation of Gene Transcription in the Human Pathogen Neisseria gonorrhoeae

Fur-Mediated Activation of Gene Transcription in the Human Pathogen Neisseria gonorrhoeae

Identification of the Iron-Responsive Genes of Neisseria gonorrhoeae by Microarray Analysis in Defined Medium

The outer membrane localization of the Neisseria gonorrhoeae MsrA/B is involved in survival against reactive oxygen species

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