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Modulation of antibiotic sensitivity and biofilm formation in Pseudomonas aeruginosa by interspecies signal analogues. | LitMetric

Modulation of antibiotic sensitivity and biofilm formation in Pseudomonas aeruginosa by interspecies signal analogues.

Nat Commun

State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Life Science and Technology, Guangxi University, 100 Daxue Road, Nanning, 530004, China.

Published: May 2019

AI Article Synopsis

  • Pseudomonas aeruginosa, a harmful pathogen, communicates with other species using specific fatty acids called diffusible signal factors (DSFs), affecting biofilm creation and antibiotic resistance.
  • The research focuses on the histidine kinase PA1396, which detects DSFs, having a structure with five transmembrane helices critical for sensing these signals.
  • Synthetic DSF analogues can either block DSF's effects or act as inverse agonists, offering potential new drug compounds to enhance current antibiotics' effectiveness against infections.

Article Abstract

Pseudomonas aeruginosa, a significant opportunistic pathogen, can participate in inter-species communication through signaling by cis-2-unsaturated fatty acids of the diffusible signal factor (DSF) family. Sensing these signals leads to altered biofilm formation and increased tolerance to various antibiotics, and requires the histidine kinase PA1396. Here, we show that the membrane-associated sensory input domain of PA1396 has five transmembrane helices, two of which are required for DSF sensing. DSF binding is associated with enhanced auto-phosphorylation of PA1396 incorporated into liposomes. Further, we examined the ability of synthetic DSF analogues to modulate or inhibit PA1396 activity. Several of these analogues block the ability of DSF to trigger auto-phosphorylation and gene expression, whereas others act as inverse agonists reducing biofilm formation and antibiotic tolerance, both in vitro and in murine infection models. These analogues may thus represent lead compounds to develop novel adjuvants improving the efficacy of existing antibiotics.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536496PMC
http://dx.doi.org/10.1038/s41467-019-10271-4DOI Listing

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