Dataset Information

Efflux pump inhibitor combined with ofloxacin decreases MRSA biofilm formation by regulating the gene expression of NorA and quorum sensing.

ABSTRACT: Carbonyl cyanide p-nitrophenylhydrazone (2e) displayed a lone or synergistic efficacy against MRSA (RSC Adv., 2020, 10, 17854). In this work, the synergistic mechanism of 2e with ofloxacin was studied. MRSA2858 had potential for biofilm formation, and the value of MBEC of 2e alone was 0.78-1.56 μM, while that of 2e + ofloxacin was 0.39-0.78 μM. 2e combined with ofloxacin showed a synergistic anti-biofilm effect against MRSA. Efflux pump inhibitor 2e can better bind to NorA protein. After MRSA2858 was treated with 2e of 1/2MIC (0.78 μM) and ofloxacin of 1/8MIC (0.097 μM), the transcript levels of efflux genes (norA) and quorum-sensing (QS) regulatory genes (agrA, sarA, icaA, hla) were substantially down-regulated, and alpha-hemolysin (Hla) was inhibited by 99.15%. 2e combined with ofloxacin was more effective than 2e alone in reducing bacterial load in vivo. All in all, efflux pump inhibitor 2e enhanced the bactericidal activities of antibiotics through regulating the gene expression of NorA and QS system.

SUBMITTER: Lu X

PROVIDER: S-EPMC9850365 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Efflux pump inhibitor combined with ofloxacin decreases MRSA biofilm formation by regulating the gene expression of NorA and quorum sensing.

Lu Xueer X Wang Guifeng G Xie Yunfeng Y Tang Wenjian W Liu Biyong B Zhang Jing J

RSC advances 20230119 4

Carbonyl cyanide <i>p</i>-nitrophenylhydrazone (2e) displayed a lone or synergistic efficacy against MRSA (<i>RSC Adv.</i>, 2020, 10, 17854). In this work, the synergistic mechanism of 2e with ofloxacin was studied. MRSA2858 had potential for biofilm formation, and the value of MBEC of 2e alone was 0.78-1.56 μM, while that of 2e + ofloxacin was 0.39-0.78 μM. 2e combined with ofloxacin showed a synergistic anti-biofilm effect against MRSA. Efflux pump inhibitor 2e can better bind to NorA protein. ...[more]

PMID: 36741169

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Project description:Quorum sensing (QS) can regulate diverse critical phenotypic responses in Pseudomonas. aeruginosa (P. aeruginosa), enabling bacterial adaptation to external environmental fluctuations and optimizing population advantages. While there is emerging evidence of QS's involvement in influencing phage infections, our current understanding remains limited, necessitating further investigation. In this study, we isolated and characterized a novel phage designated as BUCT640 that infected P. aeruginosa PAO1. This phage belonged to class Caudoviricetes, genus Bruynoghevirus, with a podovirus morphology, and its adsorption was dependent on Psl polysaccharides, a repeating pentamer used to support biofilm structure. Leveraging phage BUCT640 as a model, we analyzed the role of both rhl QS and las QS in bacteria-phage interactions. Based on its distinctive plaque formation performances on different QS-related mutants, we investigated the variations of phage sensitivity to these strains and ultimately elucidated the mechanism underlying how QS inhibited phage infection to PAO1. Specifically, we unveiled that the las QS could inhibit phage adsorption, which is related to the thickness change caused by biofilm differentiation. Our findings suggest that the inhibition of QS may enhance phage infectivity, potentially facilitating advanced phage therapy combined with QS interference.ImportancePhage therapy is a powerful solution to combat drug-resistant pathogenic bacterial infections and has earned remarkable success in clinical treatment. However, recent insights underscore the potential impact of bacterial QS on phage infection dynamics. Here, we reported a unique phenomenon wherein QS, particularly in the las QS pathway, showed distinctive plaque formation behaviors by enlarging halos around plaques in mutant strains. In addition to this, we first elucidated the correlation between biofilm formation and phage infection. Notably, the las QS could inhibit phage adsorption, an effect closely related to biofilm thickness. Such research could be the evidence to steer bacterial QS toward favorable therapeutical outcomes. Therefore, our work can extend the comprehension of the interactions between bacteria and phages influenced by QS, thereby providing new perspectives on leveraging QS interference to enhance the efficacy of phage therapy for clinical applications.

Dataset Information

Efflux pump inhibitor combined with ofloxacin decreases MRSA biofilm formation by regulating the gene expression of NorA and quorum sensing.

Publications

Efflux pump inhibitor combined with ofloxacin decreases MRSA biofilm formation by regulating the gene expression of NorA and quorum sensing.

Similar Datasets

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