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Dynorphin-sensing two-component systems ParRS and CprRS in Pseudomonas aeruginosa pathogenesis

ABSTRACT: The widespread presence of antibiotic-resistant bacteria in the environment has been recognized as an important emerging environmental contaminant. Hospital wards, as a special public indoor environment, are of great concern for the risks associated with this emerging environmental contaminant. Pseudomonas aeruginosa, a common nosocomial bacterium, is a contamination risk in the hospital environment due to its drug resistance and transmission of virulence factors. Notably, the antimicrobial peptide-sensing two-component system (TCS) ParRS and CprRS have been implicated in dynorphin-induced signaling, but the underlying Manuscript2 mechanism has remained elusive. In this study, we performed proteomic analysis to systematically investigate the contributions of ParRS and CprRS to P. aeruginosa pathogenesis and dynorphin-induced resistance to polymyxins. Additionally, we characterized the significance of the extracellular sensor domains of ParS and CprS in dynorphin perception. Furthermore, through structural biology, we identified additional TCS sensors with similar extracellular domain conformations, which also directly interacted with dynorphin in vitro. This suggests convergent evolution in different bacterial TCSs for host-derived synthetic peptide signal transmitting. Our findings establish a link between CAMPs resistance associated TCSs and virulence regulation of common nosocomial bacteria. This further illustrates the danger of this emerging contaminant for the environment and humans.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Pseudomonas Aeruginosa

TISSUE(S): Cell Culture

SUBMITTER: hanzhong feng

LAB HEAD: Yomngxing He

PROVIDER: PXD043746 | Pride | 2024-07-04

REPOSITORIES: Pride

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Project description:Enterococci are normal inhabitants of the gastrointestinal tracts of humans and animals and thanks to their capability to tolerate different environmental conditions and their high rates of gene transfer, they are able to colonize various ecological niches, as food matrices. Enterococcus faecalis bacteria are defined as “border line” microorganisms. From one side they are used as food starters, bio-control agents and probiotics to improve human or animal health. From the other side, in the last 2 two decades enterococci have emerged as important nosocomial pathogens, because bearing high-level of resistance to antibiotics and several putative virulence factors. In this study the proteomic (LC-MS/MS) and the phenotypic characterization (enzymatic methods) of three strains of E. faecalis with different origin were performed in order to investigate the differences and/or similarities occurring between pathogenic and health promoting bacteria. The E. faecalis D27 isolated as cheese contaminant, E. faecalis Symbioflor 1 a probiotic strain and E. faecalis UW3114 a clinical isolate involved in urinary tract infection were the objects of the study. The comparison of cytosolic protein expression profiles of the three strains, highlighted statistically significant changes in the abundance of proteins mainly involved in specific metabolic pathways, nutrient transport, stress response and cell wall modulation. Moreover, especially in the food contaminant and the clinical isolate, several proteins with potential pathogenic implications were found. The analysis of the extracellular proteome provided interesting results concerning proteins involved in bacterial communication, such as pheromones and conjugative elements and also proteins able to interact with human components. The phenotypic assays evaluating i) biofilm formation ii) hemolytic activity on blood agar plates iii) protease activity, allowed typing of bacteria in relation to well-known pathogenic traits. The obtained results confirmed the pathogenic profile associated to the clinical isolate as compared to the food contaminant and to the probiotic and allowed to elucidate the risks associated with the poor characterized foodborne E. faecalis D27.

			Action	DRS
	PA14.faa	Other
	PA14_result.csv	Csv
	WT_1.raw	Raw
	WT_2.raw	Raw
	WT_3.raw	Raw

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Dynorphin-sensing two-component systems ParRS and CprRS in Pseudomonas aeruginosa pathogenesis

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