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Quorum sensing inhibition of hordenine analogs on Pseudomonas aeruginosa and Serratia marcescens.

ABSTRACT: Quorum sensing (QS) plays an essential role in virulence factor production, biofilm formation, and antimicrobial resistance. As a potent QS inhibitor, hordenine can inhibit both QS and biofilm formation in Pseudomonas aeruginosa and Serratia marcescens. In this work, we tested the QS inhibitory potential of 27 hordenine analogs against QS and biofilm formation in P. aeruginosa and S. marcescens. Among the tested analogs, seven (12, 28, 27, 26, 2, 23, and 7) exhibited strong QS inhibitory activity against P. aeruginosa, five of which (12, 28, 27, 26, and 2) showed better inhibitory activity than hordenine. In addition, seven analogs (28, 12, 23, 7, 26, 2, and 27) exhibited better biofilm inhibition against P. aeruginosa than hordenine. Four analogs (7, 28, 2, and 12) showed QS inhibitory activity against S. marcescens, two of which (7 and 28) demonstrated better inhibitory activity than hordenine. Furthermore, analog 7 showed similar biofilm inhibition against S. marcescens as hordenine. Structure-activity relationship (SAR) analysis indicated that the inhibitory activities of the analogs were related to four factors, i.e., carbon chain length, presence or absence of an α,β-C[bond, double bond]C bond, amino group with/without lipophilic group, such as methyl group, and hydroxyl group in benzene ring.

SUBMITTER: Liu Y

PROVIDER: S-EPMC8573111 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Quorum sensing inhibition of hordenine analogs on Pseudomonas aeruginosa and Serratia marcescens.

Liu Yue Y Li Jun-Jian JJ Li Hong-Yuan HY Deng Shi-Ming SM Jia Ai-Qun AQ

Synthetic and systems biotechnology 20211101 4

Quorum sensing (QS) plays an essential role in virulence factor production, biofilm formation, and antimicrobial resistance. As a potent QS inhibitor, hordenine can inhibit both QS and biofilm formation in Pseudomonas aeruginosa and Serratia marcescens. In this work, we tested the QS inhibitory potential of 27 hordenine analogs against QS and biofilm formation in P. aeruginosa and S. marcescens. Among the tested analogs, seven (12, 28, 27, 26, 2, 23, and 7) exhibited ...[more]

PMID: 34786511

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Project description:With the rising development of bacterial resistance the search for new medical treatments beyond conventional antimicrobials has become a key aim of public health research. Possible innovative strategies include the inhibition of bacterial virulence. However, consideration must be given to the evolutionary and environmental consequences of such new interventions. Virulence and cooperative social behaviour of the bacterium Pseudomonas aeruginosa rely on the quorum-sensing (QS) controlled production of extracellular products (public goods). Hence QS is an attractive target for anti-virulence interventions. During colonization, non-cooperating (and hence less virulent) P. aeruginosa QS-mutants, benefiting from public goods provided by wild type isolates, naturally increase in frequency providing a relative protection from invasive infection. We hypothesized that inhibition of QS-mediated gene expression removes this growth advantage and selection of less virulent QS-mutants, and maintains the predominance of more virulent QS-wild type bacteria. We addressed this possibility in a placebo-controlled trial investigating the anti-QS properties of azithromycin, a macrolide antibiotic devoid of bactericidal activity on P. aeruginosa, but interfering with QS, in intubated patients colonized by P. aeruginosa. In the absence of azithromycin, non-cooperating (and hence less virulent) lasR (QS)-mutants increased in frequency over time. Azithromycin significantly reduced QS-gene expression measured directly in tracheal aspirates. Concomitantly the advantage of lasR-mutants was lost and virulent wild-type isolates predominated during azithromycin treatment. We confirmed these results in vitro with fitness and invasion experiments. Azithromycin reduced growth rate of the wild-type, but not of the lasR-mutant. Furthermore, the lasR-mutant efficiently invaded wild-type populations in the absence, but not in the presence of azithromycin. These in vivo and in vitro results demonstrate that anti-virulence interventions based on QS-blockade diminish natural selection towards reduced virulence and therefore may increase the prevalence of more virulent genotypes in the Hospital environment. More generally, the impact of intervention on the evolution of virulence of pathogenic bacteria should be assessed.

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Quorum sensing inhibition of hordenine analogs on Pseudomonas aeruginosa and Serratia marcescens.

Publications

Quorum sensing inhibition of hordenine analogs on <i>Pseudomonas aeruginosa</i> and <i>Serratia marcescens</i>.

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