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bioRxiv · 10.1101/2024.09.27.615489

Regulatory effects on virulence and phage susceptibility revealed by sdiA mutation in Klebsiella pneumoniae

Silva-Bea, S.·Maseda, P.·Otero, A.·Romero, M.
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Abstract

The World Health Organization has identified multi-drug resistant (MDR) Klebsiella pneumoniae strains as the highest priority in 2024. SdiA, a LuxR-like quorum sensing (QS) receptor that responds to N-acyl-homoserine lactones (AHLs), exerts a substantial regulatory influence on the virulence of numerous Gram-negative bacteria. The function of this receptor in the virulence of K. pneumoniae remains uncertain. Nevertheless, further investigation into the significance of this receptor is needed, as it represents an intriguing avenue with the potential to contribute to the development of novel antimicrobial strategies. The objective of the present study was to elucidate the function of SdiA in K. pneumoniae biofilm formation and virulence. To this end, a genetic knockout of sdiA was conducted, and virulence-related phenotypic studies were performed following AHL provision. The results demonstrate that SdiA deficiency increases susceptibility to phage infection and human serum resistance, and promotes biofilm maturation and cell filamentation. No effect on virulence was observed in vivo in the Galleria mellonella infection model. The addition of N-hexanoyl-L-homoserine lactone (C6-HSL) promoted SdiA-dependent biofilm maturation but also enhanced serum resistance and reduced virulence against G. mellonella in the absence of SdiA. The results of this study demonstrate that C6-HSL and SdiA exert a dual influence on virulence phenotypes, operating both independently and hierarchically. These findings provide new insights into the virulence of K. pneumoniae and its regulation by SdiA. ImportanceThis study represents a significant contribution to our understanding of the complex regulatory mechanisms that govern the virulence of multi-drug resistant Klebsiella pneumoniae through quorum sensing (QS). The study offers insights into the function of SdiA, a QS receptor, in the regulation of biofilm formation, susceptibility to phage infection, serum resistance, and cell filamentation in this bacterium. Furthermore, the findings of this study demonstrate that exogenous N-acyl-homoserine lactone (AHL) signalling influences the aforementioned virulence phenotypes in both a SdiA-dependent and independent manner, as well as in a hierarchical manner.

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Silva-Bea, S., Maseda, P., Otero, A., Romero, M.. 2024-09-27. Regulatory effects on virulence and phage susceptibility revealed by sdiA mutation in Klebsiella pneumoniae. https://doi.org/10.1101/2024.09.27.615489

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