Fighting Acinetobacter baumannii infections with the acylase PvdQ

Acinetobacter baumannii is an opportunistic Gram-negative bacterial pathogen that poses a threat for frail patients worldwide. The high ability to withstand environmental stresses as well as its resistance towards a broad range of antibiotics make A. baumannii an effective hard-to-eradicate pathogen. One of the key mechanisms mediating tolerance against antibiotic treatment is the formation of biofilms, a process that is controlled by a multitude of different regulatory mechanisms. A key factor with major impact on biofilm formation is cell-to-cell communication by quorum-sensing, which in A. baumannii is mediated by acyl homoserine lactone signaling molecules. Here we show that the Ntn-Hydrolase PvdQ from Pseudomonas aeruginosa can reduce biofilm formation by the A. baumannii ATCC 17978 type strain and several clinical isolates on abiotic surfaces. Further, our study shows that a combination treatment of PvdQ-mediated quorum-quenching with the antibiotic gentamicin has a synergistic effect on the clearance of A. baumannii biofilms and possible biofilm dispersal. Moreover, we demonstrate in a Galleria mellonella larval infection model that PvdQ administration significantly prolongs survival of the larvae. Altogether, we conclude that the acylase-mediated irreversible cleavage of quorum-sensing signaling molecules as exemplified with PvdQ can set a profound limit to the progression of A. baumannii infections.(c) 2022 The Author(s). Published by Elsevier Masson SAS on behalf of Institut Pasteur. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

Acinetobacter baumannii is an opportunistic Gram-negative bacterial pathogen that poses a threat to frail patients worldwide. It has high tolerance to environmental stresses and broad-spectrum antibiotic resistance, making it difficult to eradicate. The formation of biofilms, regulated by multiple mechanisms including quorum-sensing, plays a key role in antibiotic tolerance. This study demonstrates that PvdQ from Pseudomonas aeruginosa can reduce biofilm formation by A. baumannii and enhance the effect of gentamicin treatment. Additionally, PvdQ administration prolongs the survival of Galleria mellonella larvae. The findings suggest that acylase-mediated cleavage of quorum-sensing signaling molecules can limit the progression of A. baumannii infections.