Characterization of phenotypical changes of P. aeruginosa according to the action of murein endopeptidases MepM

Abstract

Pseudomonas aeruginosa is a Gram-negative rod-shaped bacterium found ubiquitously. This pathogen has multiple intrinsic resistance mechanisms and a high prevalence of MDR strains, making Pa. a concern in healthcare centres. On the quest of discovering novel antimicrobial methods against MDR P. aeruginosa infections, previous research findings have thrown light on enzymes involved in the turnover of the bacterial cell wall such as murein endopeptidases (MepM). MepMs seem to contribute to ß-lactam resistance of the MDR P. aeruginosa strain ID40. The aim of the presented study is to investigate whether and which of the MepMs affect the abundance of the efflux pump MexEF-OprN and virulence phenotypes such as biofilm production, pyocyanin and elastase secretion as well as affecting virulence in a Galleria mellonella infection model. The findings of the current study reveal that MepMs indeed influence the abundance of the MexEF-OprN efflux pump found in the cell envelope. MepM1, MepM2 and MepM3 seem to act in concert to modulate the abundance of MexEF-OprN, which as recently proposed might be another contributor of ß-lactam resistance in P. aeruginosa strain ID40, together with the expression level of ampC. We furthermore report that the ability of biofilm formation as a virulent factor is subject to the activity of MepM1, MepM2 and MepM3 via a yet unknown mechanism. The involvement of efflux pumps in the formation of biofilm can be assumed. In contrast to various studies indicating an interaction between increased MexEF-OprN abundance and the secretion of virulence factors such as elastase or pyocyanin, our current study could not validate such a correlation. To conclude, this work has confirmed previous findings in this area and furthermore spotlighted murein endopeptidases (MepM) as avid contributors to P. aeruginosa’s ß-lactam resistance and virulence. Thereby suggesting a promising potential upon targeting of MepMs with antimicrobial agents to enable a novel way of controlling MDR P. aeruginosa strains.