3 years ago

CpxR-dependent thermoregulation of Serratia marcescens PrtA metalloprotease expression and its contribution to bacterial biofilm formation.

María Victoria Molino, Martina Lazzaro, Roberto E Bruna, Javier F Mariscotti, Eleonora García Véscovi
PrtA is the major secreted metalloprotease of Serratia marcescens. Previous reports implicate PrtA in the pathogenic capacity of this bacteria. PrtA is also clinically used as a potent analgesic and anti-inflammatory drug and its catalytic properties attract industrial interest. Comparatively, there is scarce knowledge about the mechanisms that physiologically govern PrtA expression in Serratia In this work, we demonstrate that PrtA production is de-repressed when the bacterial growth temperature decreases from 37°C to 30°C. We show that this thermoregulation occurs at the transcriptional level. We determine that upstream prtA, there is a conserved motif that is directly recognized by the CpxR transcriptional regulator. This feature is found along Serratia strains irrespective of their isolation source, suggesting an evolutionary conservation of CpxR-dependent regulation of PrtA expression. We found that, in S. marcescens, the CpxAR system is more active at 37°C compared to 30°C. In good agreement with these results, in a cpxR mutant background, prtA is de-repressed at 37°C, while over-expression of the NlpE lipoprotein, a well-known CpxAR inducing condition, inhibits PrtA expression, suggesting that the levels of the activated form of CpxR are increased at 37°C compared to 30°C. In addition, we establish that PrtA is involved in the ability of S. marcescens to develop biofilm. In accordance, CpxR influences the biofilm phenotype only when bacteria are grown at 37°C. In sum, our findings shed light over regulatory mechanisms that finely-tune PrtA expression and reveal a novel role for PrtA in S. marcescens lifestyle.Importance We demonstrate that S. marcescens metalloprotease PrtA expression is transcriptionally thermoregulated. While strongly activated below 30°C, its expression is down-regulated at 37°C. We found that, in S. marcescens, the CpxAR signal transduction system, which responds to envelope stress and bacterial surface adhesion, is activated at 37°C and able to down-regulate PrtA expression by CpxR direct interaction with a binding motif located upstream the prtA gene. Moreover, we reveal that PrtA expression favors S. marcescens ability to develop biofilm, irrespective of the bacterial growth temperature. In this context, thermoregulation along with a highly conserved CpxR-dependent modulation mechanism give clues about PrtA relevance as a factor implicated in S. marcescens persistence on abiotic surfaces and in the bacterial host colonization capacity.

Publisher URL: http://doi.org/10.1128/JB.00006-18

DOI: 10.1128/JB.00006-18

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