To test the hypothesis that Hmp overexpression , and not that of other NsrR-regulated gene products ( such as ytfE , hcp -- hcr , tehA , tehB and ygbA ) is responsible for hypersensitivity to peroxynitrite , we determined the effect of peroxynitrite on a double mutant ( hmp and nsrR ) .
NsrR regulates expression of not only hmp .
A novel NsrR-regulated gene designated STM1808 has been identified , along with hmp , hcp-hcr , yeaR-yoaG , ygbA and ytfE .
Collectively , these findings demonstrate that NsrR-regulated genes in addition to hmp are important for NO · detoxification , nitrosative-stress resistance and Salmonella virulence .
In addition , double mutant strains lacking both hmp and other NsrR-regulated genes were constructed to determine the contribution to nitrosative-stress resistance in the absence of NO · detoxification by Hmp .
These data confirm previous findings with regard to hmp , and additionally demonstrate that the NsrR-regulated ytfE and STM1808 genes contribute to Salmonella virulence .
The NsrR-regulated hmp gene encodes a flavohemoglobin that is capable of detoxifying NO · under both aerobic and anaerobic conditions and is required for S. Typhimurium virulence ( Bang et al. , 2006 ; Crawford and Goldberg , 1998 ; Stevanin et al. , 2002 ) .
We have identified a novel NsrR-regulated gene designated STM1808 , and demonstrated a role for specific NsrR-regulated genes in promoting growth during nitrosative-stress in-vitro ( hmp , STM1808 , ygbA and hcp ) and during systemic infection of mice in-vivo ( hmp , STM1808 , ytfE ) .
In S. Typhimurium the principal regulator of hmp expression during nitrosative-stress is the transcriptional repressor NsrR .
NsrR-dependent expression of hmp was significantly greater at DEA/NO concentrations as low as 1 μM in comparison to genes regulated by Sox .
NsrR-dependent expression of hmp was significantly greater at DEA/NO concentrations as low as 1 μM in comparison to genes regulated by Fu .
NsrR-dependent expression of hmp was significantly greater at DEA/NO concentrations as low as 1 μM in comparison to genes regulated by Nor .
Microarray analysis of the S. Typhimurium NsrR regulon In previous studies , NsrR was identified as the major regulator of hmp transcription in S. Typhimurium .