Interactions of Neisseria gonorrhoeae with human neutrophils

Rest, Richard F.; Shafer, William M.

doi:10.1128/cmr.2.suppl.s83

Cited by 40 publications

(34 citation statements)

References 120 publications

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“…Earlier studies have suggested that receptor binding is determined by the variable portions of Opa proteins, in particular, the HV-1 and the HV-2 regions (10,47). Opa protein variants with deletions in extracellular loops and chimeric Opa proteins have underscored the critical role of both HV regions (48).…”

Section: Discussionmentioning

confidence: 99%

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Innate Recognition by Neutrophil Granulocytes Differs between Neisseria gonorrhoeae Strains Causing Local or Disseminating Infections

et al. 2013

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Members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family serve as cellular receptors for Neisseria gonorrhoeae. More specifically, neisserial colony opacity (Opa CEA ) proteins bind to epithelial CEACAMs (CEACAM1, CEA, CEACAM6) to promote bacterial colonization of the mucosa. In contrast, recognition by CEACAM3, expressed by human granulocytes, results in uptake and destruction of Opa CEA -expressing bacteria. Therefore, CEACAM3-mediated uptake might limit the spread of gonococci. However, some strains can cause disseminating gonococcal infections (DGIs), and it is currently unknown how these strains escape detection by granulocyte CEACAM3. Therefore, the opa gene loci from N. gonorrhoeae strain VP1, which was derived from a patient with disseminated gonococcal disease, were cloned and constitutively expressed in Escherichia coli. Similar to Opa proteins of the nondisseminating strain MS11, the majority of Opa proteins from strain VP1 bound epithelial CEACAMs and promoted CEACAM-initiated responses by epithelial cells. In sharp contrast to the Opa proteins of strain MS11, the Opa proteins of strain VP1 failed to interact with the human granulocyte receptor CEACAM3. Accordingly, bacteria expressing VP1 Opa proteins were not taken up by primary human granulocytes and did not trigger a strong oxidative burst. Analysis of Opa variants from four additional clinical DGI isolates again demonstrated a lack of CEACAM3 binding. In summary, our results reveal that particular N. gonorrhoeae strains express an Opa protein repertoire allowing engagement of epithelial CEACAMs for successful mucosal colonization, while avoiding recognition and elimination via CEACAM3-mediated phagocytosis. A failure of CEACAM3-mediated innate immune detection might be linked to the ability of gonococci to cause disseminated infections.

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Section: Discussionmentioning

confidence: 99%

“…Granulocytes are massively recruited to the sites of infection and are able to recognize and eliminate gonococci in an opsonin-independent manner (10). A key host factor mediating rapid phagocytosis and destruction of gonococci is carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3), a granulocyte membrane glycoprotein (11,12).…”

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confidence: 99%

Innate Recognition by Neutrophil Granulocytes Differs between Neisseria gonorrhoeae Strains Causing Local or Disseminating Infections

et al. 2013

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“…These ROS can damage proteins, lipids, carbohydrates, and DNA (53). The ability of N. gonorrhoeae to survive oxidative damage is illustrated by its ability to survive among neutrophils (31,42,45). During infection, N. gonorrhoeae is also likely to encounter H 2 O 2 produced by commensal lactobacilli, which inhibit the growth of N. gonorrhoeae in vitro (61,49).…”

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confidence: 99%

“…The hallmark of symptomatic gonococcal infection is a massive influx of activated neutrophils into the urethra, resulting in a purulent discharge consisting of neutrophils and N. gonorrhoeae (42,31). Neutrophils kill bacteria through the combined action of antimicrobial proteins and reactive oxygen species (ROS) (37), perpetrating a potent bactericidal oxidative burst that generates substantial amounts of superoxide anion, hydroxyl radical, and hydrogen peroxide (H 2 O 2 ).…”

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Neisseria gonorrhoeae DNA Recombination and Repair Enzymes Protect against Oxidative Damage Caused by Hydrogen Peroxide

Stohl

Seifert

2006

J Bacteriol

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The strict human pathogen Neisseria gonorrhoeae is exposed to oxidative damage during infection. N. gonorrhoeae has many defenses that have been demonstrated to counteract oxidative damage. However, recN is the only DNA repair and recombination gene upregulated in response to hydrogen peroxide (H 2 O 2 ) by microarray analysis and subsequently shown to be important for oxidative damage protection. We therefore tested the importance of RecA and DNA recombination and repair enzymes in conferring resistance to H 2 O 2 damage. recA mutants, as well as RecBCD (recB, recC, and recD) and RecF-like pathway mutants (recJ, recO, and recQ), all showed decreased resistance to H 2 O 2 . Holliday junction processing mutants (ruvA, ruvC, and recG) showed decreased resistance to H 2 O 2 resistance as well. Finally, we show that RecA protein levels did not increase as a result of H 2 O 2 treatment. We propose that RecA, recombinational DNA repair, and branch migration are all important for H 2 O 2 resistance in N. gonorrhoeae but that constitutive levels of these enzymes are sufficient for providing protection against oxidative damage by H 2 O 2 .

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“…Both the gonococcus and meningococcus undergo pilin antigenic variation (15,36), while the commensal Neisseria strains do not carry the silent pilin copies required for this diversity-generating system (43). Additionally, both gonococci and meningococci elicit an innate response consisting mainly of neutrophils (38), which can elaborate antimicrobial responses that can damage DNA, but these oxidative responses are ineffective in killing Neisseria (8,44). It is not known whether the commensal neisseriae elicit an inflammatory response, but the prevailing assumption is that they are not perceived by the innate immune system as being foreign and therefore do not elicit inflammation.…”

Section: Downloaded Frommentioning

confidence: 99%

Genomic Content ofNeisseriaSpecies

Tobiason

Seifert

2010

J Bacteriol

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The physical properties of most bacterial genomes are largely unexplored. We have previously demonstrated that the strict human pathogen Neisseria gonorrhoeae is polyploid, carrying an average of three chromosome copies per cell and only maintaining one pair of replication forks per chromosome (D. M. Tobiason and H. S. Seifert, PLos Biol. 4:1069-1078, 2006). We are following up this initial report to test several predictions of the polyploidy model of gonococcal chromosome organization. We demonstrate that the N. gonorrhoeae chromosomes exist solely as monomers and not covalently linked dimers, and in agreement with the monomer status, we show that distinct nucleoid regions can be detected by electron microscopy. Two different approaches to isolate heterozygous N. gonorrhoeae resulted in the formation of merodiploids, showing that even with more than one chromosome copy, these bacteria are genetically haploid. We show that the closely related bacterium Neisseria meningitidis is also polyploid, while the commensal organism Neisseria lactamica maintains chromosomes in single copy. We conclude that the pathogenic Neisseria strains are homozygous diploids.

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Interactions of Neisseria gonorrhoeae with human neutrophils

Cited by 40 publications

References 120 publications

Innate Recognition by Neutrophil Granulocytes Differs between Neisseria gonorrhoeae Strains Causing Local or Disseminating Infections

Innate Recognition by Neutrophil Granulocytes Differs between Neisseria gonorrhoeae Strains Causing Local or Disseminating Infections

Neisseria gonorrhoeae DNA Recombination and Repair Enzymes Protect against Oxidative Damage Caused by Hydrogen Peroxide

Genomic Content ofNeisseriaSpecies

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