Robustness of nitric oxide detoxification to nitrogen starvation in Escherichia coli requires RelA

Wan, Xuanqing; Brynildsen, Mark P.

doi:10.1016/j.freeradbiomed.2021.10.005

Cited by 7 publications

(2 citation statements)

References 75 publications

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“…•NO is a broad-spectrum antimicrobial, and a sizeable number of bacteria rely on •NO detoxification systems to impart their virulence [8,10,11,50]. As such, increased understanding of bacterial •NO defense networks could identify novel therapeutic targets for the treatment of bacterial infections [8,9,18,39,40,[51][52][53][54]. Recently, the global transcriptional regulator, DksA, has been revealed to play an important role in both S. Typhimurium •NO defenses and virulence, as well as •NO detoxification in E. coli [15,16,18].…”

Section: Discussionmentioning

confidence: 99%

Gre factors protect against phenotypic diversification and cheating inEscherichia colipopulations under toxic metabolite stress

Sivaloganathan

Wan

Brynildsen

2023

Preprint

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Nitric oxide (NO) is one of the toxic metabolites that bacteria can be exposed to within phagosomes. Gre factors, which are also known as transcript cleavage factors or transcription elongation factors, relieve back-tracked transcription elongation complexes by cleaving nascent RNAs, which allows transcription to resume after stalling. Here we discovered that loss of both Gre factors in E. coli, GreA and GreB, significantly compromised NO detoxification through a phenotypic diversification of the population. Under normal culturing conditions, both wild-type and ΔgreAΔgreB synthesized protein uniformly. However, treatment with NO led to bimodal protein expression in ΔgreAΔgreB, whereas wild-type remained unimodal. Interestingly, exposure to another toxic metabolite of phagosomes, hydrogen peroxide (H2O2), produced similar results. We found that the diversification in ΔgreAΔgreB cultures required E. coli RNAP, occurred at the level of transcription, and could produce cheating where transcriptionally-deficient cells benefit from the detoxification activities of the transcriptionally-proficient subpopulation. Collectively, these results indicate that Gre factors bolster bacterial defenses by preventing phenotypic diversification and cheating in environments with fast-diffusing toxic metabolites.

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Section: Discussionmentioning

confidence: 99%

Gre factors protect against phenotypic diversification and cheating inEscherichia colipopulations under toxic metabolite stress

Sivaloganathan

Wan

Brynildsen

2023

Preprint

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“…In E. coli , DksA and ppGpp contribute to regulation of the hmp gene encoding the flavohemoglobin, Hmp, which is responsible for detoxifying nitric oxide (11, 58, 59). In P. denitrificans , we find that deletion of dksA2 or relA leads to modestly increased hmp promoter activity and dramatically reduced ability to form biofilm.…”

Section: Discussionmentioning

confidence: 99%

DksA, ppGpp and RegAB regulate nitrate respiration inParacoccus denitrificans

Ray

Spiro

2023

Preprint

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The Paracoccus denitrificans genome encodes three members of the DksA/TraR family of transcription factors, two of which appear to be bona fide DksA proteins (hence designated DksA1Pd and DksA2Pd). There is a single relA/spoT gene in the genome encoding a predicted bifunctional ppGpp synthetase and hydrolase (designated RSH, for RelASpoT Homolog). Both DksA1Pd and DksA2Pd can rescue the amino acid auxotrophy of an Escherichia coli dksA mutant. Deletion of either dksA1 or relA/spoT eliminates the upregulation of expression of the periplasmic nitrate reductase (NAP) that is seen when cultures are grown on a reduced substrate such as butyrate. Thus, we conclude that DksA1Pd and ppGpp activate nap transcription in response to growth on a reduced substrate and that these proteins therefore help to maintain redox homeostasis by activating a mechanism for the disposal of excess reductant. We also show that the redox-sensing RegAB two-component pair acts as a negative regulator of nap expression under anaerobic growth conditions. Under the same conditions, RegAB acts as a positive regulator of expression of the membrane-associated nitrate reductase Nar and thus mediates reciprocal regulation of the two nitrate reductases that have distinct physiological roles. The dksA1 and relA genes are conditionally synthetically lethal; the double mutant has a null phenotype for growth on butyrate and other reduced substrates while growing normally on succinate and citrate. The flavohemoglobin gene hmp is modestly upregulated in dksA2 and relA mutants, which are also defective for biofilm formation (possibly because of enhanced scavenging of nitric oxide).

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Amino acids can deplete ATP and impair nitric oxide detoxification by Escherichia coli

Wan

Chou

Brynildsen

2023

Free Radical Biology and Medicine

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Robustness of nitric oxide detoxification to nitrogen starvation in Escherichia coli requires RelA

Cited by 7 publications

References 75 publications

Gre factors protect against phenotypic diversification and cheating inEscherichia colipopulations under toxic metabolite stress

Gre factors protect against phenotypic diversification and cheating inEscherichia colipopulations under toxic metabolite stress

DksA, ppGpp and RegAB regulate nitrate respiration inParacoccus denitrificans

Amino acids can deplete ATP and impair nitric oxide detoxification by Escherichia coli

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