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Neisseria gonorrhoeae metalloprotease NGO1686 is required for full piliation, and piliation is required for resistance to H2O2- and neutrophil-mediated killing.

Stohl EA, Dale EM, Criss AK, Seifert HS - MBio (2013)

Bottom Line: The M23B family zinc metallopeptidase NGO1686 is required for gonococci to survive oxidative killing by H2O2- and PMN-mediated killing through unknown mechanisms, but the only known target of NGO1686 is peptidoglycan.Successful infectious agents need to overcome host defense systems to establish infection.We also show that to express the pilus, an enzyme needs to partially degrade the cell wall of the bacterium.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

ABSTRACT

Unlabelled: The sexually transmitted infection gonorrhea is caused exclusively by the human-specific pathogen Neisseria gonorrhoeae. Type IV pili are an essential virulence factor uniformly expressed on clinical gonococcal isolates and are required for several aspects of gonococcal pathogenesis, including adherence to host tissues, autoagglutination, twitching motility, and the uptake of DNA during transformation. Symptomatic gonococcal infection is characterized by the influx of neutrophils or polymorphonuclear leukocytes (PMNs) to the site of infection. PMNs are a key component of gonococcal pathogenesis, mediating the innate immune response through the use of oxidative and nonoxidative killing mechanisms. The M23B family zinc metallopeptidase NGO1686 is required for gonococci to survive oxidative killing by H2O2- and PMN-mediated killing through unknown mechanisms, but the only known target of NGO1686 is peptidoglycan. We report that the effect of NGO1686 on survival after exposure to H2O2 and PMNs is mediated through its role in elaborating pili and that nonpiliated mutants of N. gonorrhoeae are less resistant to killing by H2O2, LL-37, and PMNs than the corresponding piliated strains. These findings add to the various virulence-associated functions attributable to gonococcal pili and may explain the selection basis for piliation in clinical isolates of N. gonorrhoeae.

Importance: Successful infectious agents need to overcome host defense systems to establish infection. We show that the Neisseria pilus, a major virulence factor of this organism, which causes gonorrhea, helps protect the bacterium from two major killing mechanisms used by the host to combat infections. We also show that to express the pilus, an enzyme needs to partially degrade the cell wall of the bacterium.

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Resistance of pilQ mutant strains to H2O2 and PMN-mediated killing. (A) Dose-response curve of H2O2 resistance after 15 min of treatment of the pilQ mutant strain. *, P < 0.02. (B) Resistance of the pilQ mutant strain to PMN-mediated killing. *, P < 0.0005 (Student’s two-tailed t test).
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fig5: Resistance of pilQ mutant strains to H2O2 and PMN-mediated killing. (A) Dose-response curve of H2O2 resistance after 15 min of treatment of the pilQ mutant strain. *, P < 0.02. (B) Resistance of the pilQ mutant strain to PMN-mediated killing. *, P < 0.0005 (Student’s two-tailed t test).

Mentions: To confirm a role for piliation in gonococcal resistance to H2O2 and PMN-mediated killing, we examined the effect of a pilQ mutation on resistance to H2O2 and PMN-mediated killing. PilQ encodes the pore through which the pilus is extruded, and a pilQ mutant has been shown to not elaborate pili (35). The pilQ mutant showed decreased resistance to both H2O2 and PMN killing (Fig. 5). A pilC mutant, which is also P−, was also less resistant to H2O2 than the parent strain (data not shown). Thus far, all the gonococcal mutants which decrease or abolish piliation that we have tested also confer decreased resistance to H2O2 (data not shown).


Neisseria gonorrhoeae metalloprotease NGO1686 is required for full piliation, and piliation is required for resistance to H2O2- and neutrophil-mediated killing.

Stohl EA, Dale EM, Criss AK, Seifert HS - MBio (2013)

Resistance of pilQ mutant strains to H2O2 and PMN-mediated killing. (A) Dose-response curve of H2O2 resistance after 15 min of treatment of the pilQ mutant strain. *, P < 0.02. (B) Resistance of the pilQ mutant strain to PMN-mediated killing. *, P < 0.0005 (Student’s two-tailed t test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3735123&req=5

fig5: Resistance of pilQ mutant strains to H2O2 and PMN-mediated killing. (A) Dose-response curve of H2O2 resistance after 15 min of treatment of the pilQ mutant strain. *, P < 0.02. (B) Resistance of the pilQ mutant strain to PMN-mediated killing. *, P < 0.0005 (Student’s two-tailed t test).
Mentions: To confirm a role for piliation in gonococcal resistance to H2O2 and PMN-mediated killing, we examined the effect of a pilQ mutation on resistance to H2O2 and PMN-mediated killing. PilQ encodes the pore through which the pilus is extruded, and a pilQ mutant has been shown to not elaborate pili (35). The pilQ mutant showed decreased resistance to both H2O2 and PMN killing (Fig. 5). A pilC mutant, which is also P−, was also less resistant to H2O2 than the parent strain (data not shown). Thus far, all the gonococcal mutants which decrease or abolish piliation that we have tested also confer decreased resistance to H2O2 (data not shown).

Bottom Line: The M23B family zinc metallopeptidase NGO1686 is required for gonococci to survive oxidative killing by H2O2- and PMN-mediated killing through unknown mechanisms, but the only known target of NGO1686 is peptidoglycan.Successful infectious agents need to overcome host defense systems to establish infection.We also show that to express the pilus, an enzyme needs to partially degrade the cell wall of the bacterium.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

ABSTRACT

Unlabelled: The sexually transmitted infection gonorrhea is caused exclusively by the human-specific pathogen Neisseria gonorrhoeae. Type IV pili are an essential virulence factor uniformly expressed on clinical gonococcal isolates and are required for several aspects of gonococcal pathogenesis, including adherence to host tissues, autoagglutination, twitching motility, and the uptake of DNA during transformation. Symptomatic gonococcal infection is characterized by the influx of neutrophils or polymorphonuclear leukocytes (PMNs) to the site of infection. PMNs are a key component of gonococcal pathogenesis, mediating the innate immune response through the use of oxidative and nonoxidative killing mechanisms. The M23B family zinc metallopeptidase NGO1686 is required for gonococci to survive oxidative killing by H2O2- and PMN-mediated killing through unknown mechanisms, but the only known target of NGO1686 is peptidoglycan. We report that the effect of NGO1686 on survival after exposure to H2O2 and PMNs is mediated through its role in elaborating pili and that nonpiliated mutants of N. gonorrhoeae are less resistant to killing by H2O2, LL-37, and PMNs than the corresponding piliated strains. These findings add to the various virulence-associated functions attributable to gonococcal pili and may explain the selection basis for piliation in clinical isolates of N. gonorrhoeae.

Importance: Successful infectious agents need to overcome host defense systems to establish infection. We show that the Neisseria pilus, a major virulence factor of this organism, which causes gonorrhea, helps protect the bacterium from two major killing mechanisms used by the host to combat infections. We also show that to express the pilus, an enzyme needs to partially degrade the cell wall of the bacterium.

Show MeSH
Related in: MedlinePlus