PerR controls Mn‐dependent resistance to oxidative stress inNeisseria gonorrhoeae

Abstract

SummaryIn previous studies it has been established that resistance to superoxide by Neisseria gonorrhoeae is dependent on the accumulation of Mn(II) ions involving the ABC transporter, MntABC. A mutant strain lacking the periplasmic binding protein component (MntC) of this transport system is hypersensitive to killing by superoxide anion. In this study the mntC mutant was found to be more sensitive to H 2 O 2 killing than the wild-type. Analysis of regulation of MntC expression revealed that it was de-repressed under low Mn(II) conditions. The N. gonorrhoeae mntABC locus lacks the mntR repressor typically found associated with this locus in other organisms. A search for a candidate regulator of mntABC expression revealed a homologue of PerR, a Mn-dependent peroxide-responsive regulator found in Gram-positive organisms. A perR mutant expressed more MntC protein than wild-type, and expression was independent of Mn(II), consistent with a role for PerR as a repressor of mntABC expression. The PerR regulon of N. gonorrhoeae was defined by microarray analysis and includes ribosomal proteins, TonB-dependent receptors and an alcohol dehydrogenase. Both the mntC and perR mutants had reduced intracellular survival in a human cervical epithelial cell model.

The Zinc-Responsive Regulon of Neisseria meningitidis Comprises 17 Genes under Control of a Zur Element

“…Extenuated biofilm formation has previously also been seen upon deletion of znuA in gonococci (30) and nmb0587 (znuB) in E. coli (19). A gonococcal znuA (mntC) mutant in vitro also was more sensitive to hydrogen peroxide than the wild-type strain and showed reduced invasion to primary human cervical epithelial cells (64). Furthermore, znuA contributes to the in vivo pathogenicity of Salmonella enterica (3).…”

A manganese transporter, BB0219 (BmtA), is required for virulence by the Lyme disease spirochete, Borrelia burgdorferi

“…First, in comparison with WT, the Bb bmtA mutant was sensitive to t-butyl hydroperoxide, suggesting that BmtA (and thus Mn) is probably involved in the detoxification of ROS. Akin to the situation for other bacterial pathogens (17,31,32), the most obvious role for BmtA and Mn likely is in the Bb oxidative stress response. For example, in the process of tick feeding or during the process of mammalian host dissemination, BmtA and Mn may be required by Bb to counter superoxide contained in mammalian blood (36,37).…”

“…but does accumulate Mn (Mn accumulation was severely impaired in the bmtA mutant), (ii) Mn is believed to be involved in the oxidative stress response of a number of pathogens (17,31,32), and (iii) Bb SodA (BB0153) has been predicted to be Mn-dependent (22, 33), we explored whether the inactivation of bmtA adversely impacted Bb's ability to detoxify intracellular superoxide. When WT 297 was exposed to 5 mM or 10 mM t-butyl hydroperoxide, Ϸ100% or 93%, respectively, of the cells survived (Fig.…”

dpr and sod in Streptococcus mutans Are Involved in Coexistence with S. sanguinis, and PerR Is Associated with Resistance to H 2 O 2

“…Thus, we suggest that PerR regulates dpr and sod directly. As described above, PerR is considered to regulate many genes, mainly factors responsible for oxidative stress resistance and metal transporters (10,39,40). ABC-type metal ion transporters are responsible for efflux or incorporation of metal ions, Fe and Mn, which are associated with oxidative stress responses because PerR and other Fur-like proteins bind metal ions for activation (10,26).…”