An, S.-q. | Search bioRxiv

bioRxiv2018

Diffusible Signal Factor signaling regulates multiple functions in the opportunistic pathogen Stenotrophomonas maltophilia

Stenotrophomonas maltophilia is a Gram-negative bacterium commonly isolated from nosocomial infections. Analysis of the genome of the clinical Stenotrophomonas maltophilia isolate K279a indicates that it encodes a diffusible signal factor (DSF)-dependent cell-cell signaling mechanism that is highly similar to the system previously described in phytopathogens from the genera Xanthomonas and Xylella. Here we demonstrate that in S. maltophilia strain K279a, DSF signaling regulates factors contributing to virulence, biofilm formation and motility of this important opportunistic pathogen.

microbiology↗

bioRxiv2018

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

The opportunistic pathogen Pseudomonas aeruginosa can participate in inter-species communication through signaling by cis-2-unsaturated fatty acids of the diffusible signal factor (DSF) family. Sensing these signals involves the histidine kinase PA1396 and leads to altered biofilm formation and increased tolerance to various antibiotics. Here, we show that the membrane-associated sensory input domain of PA1396 has five trans-membrane 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 for novel adjuvants to improve the efficacy of existing antibiotics.

microbiology↗