The Nitric Oxide-Responsive Regulator NsrR Controls ResDE-Dependent Gene Expression

Nakano, Michiko; Geng, Hao; Nakano, Shunji; Kobayashi, Kazuo

doi:10.1128/jb.00486-06

Cited by 74 publications

(111 citation statements)

References 40 publications

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“…During the course of this work, Nakano et al identified B. subtilis NsrR as a negative regulator of hmp and nasDEF by using lacZ fusion experiments (24). However, in contradiction to our data, it was suggested that an nsrR mutation does not cause derepression of nasD under aerobic conditions.…”

Section: Resultscontrasting

confidence: 54%

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Mechanisms of Adaptation to Nitrosative Stress inBacillus subtilis

et al. 2007

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Bacteria use a number of mechanisms for coping with the toxic effects exerted by nitric oxide (NO) and its derivatives. Here we show that the flavohemoglobin encoded by the hmp gene has a vital role in an adaptive response to protect the soil bacterium Bacillus subtilis from nitrosative stress. We further show that nitrosative stress induced by the nitrosonium cation donor sodium nitroprusside (SNP) leads to deactivation of the transcriptional repressor NsrR, resulting in derepression of hmp. Nitrosative stress induces the sigma Bcontrolled general stress regulon. However, a sigB null mutant did not show increased sensitivity to SNP, suggesting that the sigma B-dependent stress proteins are involved in a nonspecific protection against stress whereas the Hmp flavohemoglobin plays a central role in detoxification. Mutations in the yjbIH operon, which encodes a truncated hemoglobin (YjbI) and a predicted 34-kDa cytosolic protein of unknown function (YjbH), rendered B. subtilis hypersensitive to SNP, suggesting roles in nitrosative stress management.

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Section: Resultscontrasting

confidence: 54%

“…Nakano et al (24) suggested that it is NO and not nitrite that is sensed by NsrR, and this has also been implied for NsrR in Neisseria gonorrhoeae (28). However, in N. europaea (1,2), it has been suggested that nitrite, not NO, controls the activity of NsrR.…”

Section: Resultsmentioning

confidence: 99%

Mechanisms of Adaptation to Nitrosative Stress inBacillus subtilis

et al. 2007

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“…However, the iron may also be required for full activity of NssR, which is triggered by exposure to NO, GSNO, or related species. The nature of the sensing mechanism has not been elucidated, but in NO-sensing proteins, there are precedents for important roles for iron in Fe-S clusters (5,80,81), a mononuclear non-heme iron center (82), and heme (83)(84)(85). Because NssR is a positive regulator of cgb and the other NssR regulon genes, we suggest that there might exist an iron requirement either for interaction of NO with NssR or for reconstitution of NssR after interaction with NO.…”

Section: Discussionmentioning

confidence: 99%

Oxygen- and NssR-dependent Globin Expression and Enhanced Iron Acquisition in the Response of Campylobacter to Nitrosative Stress

Monk

Pearson

Mulholland

et al. 2008

Journal of Biological Chemistry

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Pathogenic bacteria experience nitrosative stress from NO generated in the host and from nitrosating species such as S-nitrosoglutathione. The food-borne pathogen Campylobacter jejuni responds by activating gene expression from a small regulon under the control of the NO-sensitive regulator, NssR. Here, we describe the full extent of the S-nitrosoglutathione response using transcriptomic and proteomic analysis of batch-and chemostat-cultured C. jejuni. In addition to the NssR regulon, which includes two hemoglobins (Cgb and Ctb), we identify more than 90 other up-regulated genes, notably those encoding heat shock proteins and proteins involved in oxidative stress tolerance and iron metabolism/transport. Up-regulation of a subset of these genes, including cgb, is also elicited by NO-releasing compounds. Mutation of the iron-responsive regulator Fur results in insensitivity of growth to NO, suggesting that derepression of iron-regulated genes and augmentation of iron acquisition is a physiological response to nitrosative damage. We describe the effect of oxygen availability on nitrosative stress tolerance; cells cultured at higher rates of oxygen diffusion have elevated levels of hemoglobins, are more resistant to inhibition by NO of both growth and respiration, and consume NO more rapidly. The oxygen response is mediated by NssR. Thus, in addition to NO detoxification catalyzed by the hemoglobins Cgb and possibly Ctb, C. jejuni mounts an extensive stress response. We suggest that inhibition of respiration by NO may increase availability of oxygen for Cgb synthesis and function.

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“…The regulation of hmp transcription is complex involving several regulators including Fnr [12] and MetR [13]. Recently, it was discovered that the regulator NsrR represses hmp transcription in the absence of NO or nitrite [14,15]. NsrR is proposed to contain a NO-labile [Fe-S] cluster responsible for the NO-sensing capacity [14].…”

mentioning

confidence: 99%

Role of flavohemoglobin in combating nitrosative stress in uropathogenic Escherichia coli – Implications for urinary tract infection

Svensson

Poljakovic

Säve

et al. 2010

Microbial Pathogenesis

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Role of flavohemoglobin in combating nitrosative stress in uropathogenic Escherichia coliimplications for urinary tract infection. During the course of urinary tract infection (UTI) nitric oxide (NO) is generated as part of host response. The aim of this study was to investigate the significance of the NO-detoxifying enzymes flavohemoglobin (Hmp) and flavorubredoxin (Norv) in protection of uropathogenic Escherichia coli (UPEC) against nitrosative stress. Hmp (J96∆hmp) and norV (J96∆norV) knockout mutants of UPEC strain J96 were constructed using a single-gene deletion strategy. Bacterial tolerance and expression of hmp and norV in response to the NO-donor DETA/NO was evaluated in Luria broth and urine from healthy volunteers. Bacterial NO consumption and respiratory inhibition were assessed when exposed to NO. Expression of hmp and norV from E. coli originating from patients with UTI was evaluated using real-time PCR. The colonizing ability of J96 wild-type (wt) compared to an hmp-deficient mutant was assessed using a competition-based mouse UTI model. The viability of J96∆hmp and J96∆norV was significantly reduced compared to the wildtype strain after exposure to DETA/NO. The hmp expression in DETA/NO-exposed cultures was similar in J96wt and J96∆norV, while J96∆hmp showed an increased norV expression compared to J96wt. The NO consumption in J96∆hmp, but not in J96∆norV, was significantly impaired compared to J96wt. An up-regulation of hmp expression was found in E. coli isolated from all UTIpatients while norV expression increased in 50% of the patients. In the mouse UTI model, the hmp-mutant strain was significantly out-competed by the wild-type strain in the bladder and kidney. Hmp and NorV contribute to the protection of UPEC against NOmediated toxicity in vitro. Screening UPEC isolates from UTI patients revealed an increased hmp expression in all patients which confirms that hmp expression occurs in vivo in the infected human urinary tract. The ability to colonize the mouse urinary tract was impaired in the hmp-deficient mutant compared to the wild-type strain. NO-detoxification by Hmp is suggested to be an important characteristic for UPEC in protection against nitrosative stress and may be a virulence-facilitating factor.

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The Nitric Oxide-Responsive Regulator NsrR Controls ResDE-Dependent Gene Expression

Cited by 74 publications

References 40 publications

Mechanisms of Adaptation to Nitrosative Stress inBacillus subtilis

Mechanisms of Adaptation to Nitrosative Stress inBacillus subtilis

Oxygen- and NssR-dependent Globin Expression and Enhanced Iron Acquisition in the Response of Campylobacter to Nitrosative Stress

Role of flavohemoglobin in combating nitrosative stress in uropathogenic Escherichia coli – Implications for urinary tract infection

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