Defenses against Oxidative Stress inNeisseria gonorrhoeae: a System Tailored for a Challenging Environment

Abstract

SUMMARY Neisseria gonorrhoeae is a host-adapted pathogen that colonizes primarily the human genitourinary tract. This bacterium encounters reactive oxygen and reactive nitrogen species as a consequence of localized inflammatory responses in the urethra of males and endocervix of females and also of the activity of commensal lactobacilli in the vaginal flora. This review describes recent advances in the understanding of defense systems against oxidative stress in N. gonorrhoeae and shows that while some of its defenses have similarities to the paradigm established with Escherichia coli, there are also some key differences. These differences include the presence of a defense system against superoxide based on manganese ions and a glutathione-dependent system for defense against nitric oxide which is under the control of a novel MerR-like transcriptional regulator. An understanding of the defenses against oxidative stress in N. gonorrhoeae and their regulation may provide new insights into the ways in which this bacterium survives challenges from polymorphonuclear leukocytes and urogenital epithelial cells.

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

“…Detoxifying enzymes such as catalase may protect bacteria by directly neutralizing ROS produced by normal respiration, exposure to metal ions, phagocytes, epithelial cells, and H 2 O 2 -producing commensal flora as recently reviewed by Seib et al (40). Here we showed that catalase was not required for infection of the lower genital tract of female mice, at least not when doses equal to or 10-fold lower than the 80% infective dose were used.…”

“…gonorrhoeae is equipped with a battery of antioxidant factors that may neutralize ROS produced by phagocytes during infection (40). The increased sensitivity of genetically defined kat mutants to H 2 O 2 or chemical inducers of oxidative stress (25,43,48) and the fact that this enzyme is produced at relatively high levels among bacteria (1,20) suggests that catalase protects N. gonorrhoeae against the phagocytic respiratory burst.…”

“…In addition, sialylation of lipooligosaccharide (LOS), which in N. gonorrhoeae requires exogenous substrate provided artificially or by the host, should also be considered in the design of such studies since LOS sialylation clearly influences gonococcal interactions with phagocytes (18,37,52). Environmental stimuli may also influence the expression of catalase and other antioxidant factors (40), which may or may not be present in certain assay media.…”

Neisseria gonorrhoeae RecQ Helicase HRDC Domains Are Essential for Efficient Binding and Unwinding of the pilE Guanine Quartet Structure Required for Pilin Antigenic Variation

“…The pathogenic Neisseria strains exist only in humans, and therefore the Neisseria repair capabilities are predicted to be specialized for damage that might occur within the host. For example, the pathogenic Neisseria strains possess a diverse range of mechanisms for coping with the reactive oxygen species (ROS) that are encountered during aerobic respiration and interactions with phagocytic cells (39,40), in addition to evasion of the human immune response by high-frequency recombination at pilE (15). D. radiodurans is an extremophile that can survive massive levels of DNA-damaging radiation.…”

Widespread Distribution in Pathogenic Bacteria of Di-Iron Proteins That Repair Oxidative and Nitrosative Damage to Iron-Sulfur Centers

“…Similarly, the repressor activity of NsrR, which from sequence analysis is assumed to contain an [2Fe-2S] iron-sulfur center, is inactivated on exposure to nitric oxide (2,10,41). There is overlap between the biological responses to oxidative stress caused by exposure to hydrogen peroxide and to nitrosative stress (4,18,48,59,60). This overlap in-cludes various iron-sulfur-containing enzymes and the transcription factors that regulate their synthesis, which is a reflection of the fact that iron-sulfur centers are damaged by both reactive oxygen and nitrogen species.…”