Dataset Information

A tailored phosphoaspartate probe unravels CprR as a response regulator in Pseudomonas aeruginosa interkingdom signaling

ABSTRACT: Pseudomonas aeruginosa is a difficult-to-treat Gram-negative bacterial pathogen causing life-threatening infections. Adaptive resistance (AR) to cationic peptide antibiotics such as polymyxin B impairs the therapeutic success. This self-protection is mediated by two component systems consisting of a membrane-bound histidine kinase and an intracellular response regulator (RR). As phosphorylation of the key RR aspartate residue is transient during signaling and hydrolytically unstable, the study of these systems is challenging. Therefore, we applied a tailored reverse polarity chemical proteomic strategy to capture this transient modification and read-out RR phosphorylation in complex proteomes using a nucleophilic probe. Analysis of Bacillus subtilis and P. aeruginosa proteomes revealed the detection of multiple phosphoaspartate sites, which closely resembled the conserved RR sequence motif. With this validated strategy we dissected the signaling of dynorphin A, a human peptide stress hormone, which is sensed by P. aeruginosa to prepare AR. Intriguingly, our methodology combined with parallel reaction monitoring identified CprR as an unprecedented RR in dynorphin A interkingdom signaling.

ORGANISM(S): Pseudomonas Aeruginosa Pao1

SUBMITTER: Patrick Allihn

PROVIDER: PXD022470 | panorama | Thu Aug 19 00:00:00 BST 2021

REPOSITORIES: PanoramaPublic

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A tailored phosphoaspartate probe unravels CprR as a response regulator in <i>Pseudomonas aeruginosa</i> interkingdom signaling.

Allihn Patrick W A PWA Hackl Mathias W MW Ludwig Christina C Hacker Stephan M SM Sieber Stephan A SA

Chemical science 20210208 13

<i>Pseudomonas aeruginosa</i> is a difficult-to-treat Gram-negative bacterial pathogen causing life-threatening infections. Adaptive resistance (AR) to cationic peptide antibiotics such as polymyxin B impairs the therapeutic success. This self-protection is mediated by two component systems (TCSs) consisting of a membrane-bound histidine kinase and an intracellular response regulator (RR). As phosphorylation of the key RR aspartate residue is transient during signaling and hydrolytically unstabl ...[more]

PMID: 34168754

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Dataset Information

A tailored phosphoaspartate probe unravels CprR as a response regulator in Pseudomonas aeruginosa interkingdom signaling

Publications

A tailored phosphoaspartate probe unravels CprR as a response regulator in <i>Pseudomonas aeruginosa</i> interkingdom signaling.

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