| RRC ID |
79392
|
| Author |
Getz LJ, Brown JM, Sobot L, Chow A, Mahendrarajah J, Thomas NA.
|
| Title |
Attenuation of a DNA cruciform by a conserved regulator directs T3SS1 mediated virulence in Vibrio parahaemolyticus.
|
| Journal |
Nucleic Acids Res
|
| Abstract |
Pathogenic Vibrio species account for 3-5 million annual life-threatening human infections. Virulence is driven by bacterial hemolysin and toxin gene expression often positively regulated by the winged helix-turn-helix (wHTH) HlyU transcriptional regulator family and silenced by histone-like nucleoid structural protein (H-NS). In the case of Vibrio parahaemolyticus, HlyU is required for virulence gene expression associated with type 3 Secretion System-1 (T3SS1) although its mechanism of action is not understood. Here, we provide evidence for DNA cruciform attenuation mediated by HlyU binding to support concomitant virulence gene expression. Genetic and biochemical experiments revealed that upon HlyU mediated DNA cruciform attenuation, an intergenic cryptic promoter became accessible allowing for exsA mRNA expression and initiation of an ExsA autoactivation feedback loop at a separate ExsA-dependent promoter. Using a heterologous E. coli expression system, we reconstituted the dual promoter elements which revealed that HlyU binding and DNA cruciform attenuation were strictly required to initiate the ExsA autoactivation loop. The data indicate that HlyU acts to attenuate a transcriptional repressive DNA cruciform to support T3SS1 virulence gene expression and reveals a non-canonical extricating gene regulation mechanism in pathogenic Vibrio species.
|
| Volume |
51(12)
|
| Pages |
6156-6171
|
| Published |
2023-7-7
|
| DOI |
10.1093/nar/gkad370
|
| PII |
7157527
|
| PMID |
37158250
|
| PMC |
PMC10325908
|
| MeSH |
Bacterial Proteins / metabolism
DNA, Cruciform / metabolism
Escherichia coli / genetics
Gene Expression Regulation, Bacterial
Humans
Type III Secretion Systems / genetics
Vibrio parahaemolyticus* / genetics
Vibrio parahaemolyticus* / metabolism
Virulence / genetics
|
| IF |
11.502
|
| Resource |
| Pathogenic bacteria |
JNBP_30766 |
