The Composition and Metabolic Phenotype of Neisseria gonorrhoeae Biofilms

Abstract

Neisseria gonorrhoeae has been shown to form biofilms during cervical infection. Thus, biofilm formation may play an important role in the infection of women. The ability of N. gonorrhoeae to form membrane blebs is crucial to biofilm formation. Blebs contain DNA and outer membrane structures, which have been shown to be major constituents of the biofilm matrix. The organism expresses a DNA thermonuclease that is involved in remodeling of the biofilm matrix. Comparison of the transcriptional profiles of gonococcal biofilms and planktonic runoff indicate that genes involved in anaerobic metabolism and oxidative stress tolerance are more highly expressed in biofilm. The expression of aniA , ccp , and norB , which encode nitrite reductase, cytochrome c peroxidase, and nitric oxide reductase respectively, is required for mature biofilm formation over glass and human cervical cells. In addition, anaerobic respiration occurs in the substratum of gonococcal biofilms and disruption of the norB gene required for anaerobic respiration, results in a severe biofilm attenuation phenotype. It has been demonstrated that accumulation of nitric oxide (NO) contributes to the phenotype of a norB mutant and can retard biofilm formation. However, NO can also enhance biofilm formation, and this is largely dependent on the concentration and donation rate or steady-state kinetics of NO. The majority of the genes involved in gonococcal oxidative stress tolerance are also required for normal biofilm formation, as mutations in the following genes result in attenuated biofilm formation over cervical cells and/or glass: oxyR , gor , prx , mntABC , trxB , and estD . Overall, biofilm formation appears to be an adaptation for coping with the environmental stresses present in the female genitourinary tract. Therefore, this review will discuss the studies, which describe the composition and metabolic phenotype of gonococcal biofilms.

Characterization of an ntrX Mutant of Neisseria gonorrhoeae Reveals a Response Regulator That Controls Expression of Respiratory Enzymes in Oxidase-Positive Proteobacteria

“…2A). It is known that gonococcal growth in a biofilm requires both nitrite reductase and nitric oxide reductase (52,53), and both of these enzymes, as well as cytochrome cbb 3 , showed decreased expression in the Ng-ntrX strain. This result suggests that NtrX and the genes regulated by NtrX play an important role in gonococcal survival in the oxygen-depleted substrata of gonococcal biofilms.…”

“…The NarPQ TCS and the repressor NsrR are also involved in the control of aniA expression as part of the partial (AniA-NorB) denitrification pathway in N. gonorrhoeae (67). NorB, AniA, and Ccp, all of which are controlled by NtrX, are all essential for biofilm formation in N. gonorrhoeae (53). In the NtrYX-containing pathogen Ehrlichia chaffeensis, inhibitors of histidine kinase activity also reduced the ability of these bacteria to evade the cellular clearance that normally occurs through their delivery to the lysosomes (57).…”

Identification of Genes Involved in Neisseria meningitidis Colonization

“…In a screen of a subset of ϳ1,600 mutants representative of this mutant library, we have identified five mutants. Except estD and narP that are known to be involved directly (estD) or indirectly (narP) in biofilm formation (25)(26)(27), the three other genes have never been linked to biofilm formation. Since meningococcus is restricted to human host, no animal model is available for studying the meningococcal colonization process.…”

Antimicrobial Resistance in Neisseria gonorrhoeae in the 21st Century: Past, Evolution, and Future

“…Gonococci, like other bacteria (291), have the ability to form biofilms under laboratory conditions, and this community lifestyle also likely exists during infection (292,293). Bacteria growing in biofilms are often more resistant to antimicrobials than their planktonic counterparts, and this property should be considered in evaluating the possible efficacy of newly developed an-timicrobials to treat gonorrhea.…”