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Quorum Sensing Inhibitors: Curbing Pathogenic Infections through Inhibition of Bacterial Communication.

ABSTRACT: Currently, most of the developed and developing countries are facing the problem of infectious diseases. The genius way of an exaggerated application of antibiotics led the infectious agents to respond by bringing a regime of persisters to resist antibiotics attacks prolonging their survival. Persisters have the dexterity to communicate among themself using signal molecules via the process of Quorum Sensing (QS), which regulates virulence gene expression and biofilms formation, making them more vulnerable to antibiotic attack. Our review aims at the different approaches applied in the ordeal to solve the riddle for QS inhibitors. QS inhibitors, their origin, structures and key interactions for QS inhibitory activity have been summarized. Solicitation of a potent QS inhibitor molecule would be beneficial, giving new life to the simplest antibiotics in adjuvant therapy.

SUBMITTER: Singh S

PROVIDER: S-EPMC8457738 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Quorum Sensing Inhibitors: Curbing Pathogenic Infections through Inhibition of Bacterial Communication.

Singh Shaminder S Bhatia Sonam S

Iranian journal of pharmaceutical research : IJPR 20210101 2

Currently, most of the developed and developing countries are facing the problem of infectious diseases. The genius way of an exaggerated application of antibiotics led the infectious agents to respond by bringing a regime of persisters to resist antibiotics attacks prolonging their survival. Persisters have the dexterity to communicate among themself using signal molecules via the process of Quorum Sensing (QS), which regulates virulence gene expression and biofilms formation, making them more ...[more]

PMID: 34567177

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Project description:Avian pathogenic Escherichia coli (APEC) associated with colibacillosis results in high morbidity and mortality, and severe economic losses to the poultry industry. APEC is a zoonotic pathogen and can infect humans through contaminated poultry products. Vaccination and antibiotic treatment are currently used to control APEC infections; however, the limited effect of vaccines and the emergence of antibiotic-resistant strains have necessitated the development of novel therapeutics. Here, we evaluated seven quorum sensing inhibitors (QSI) identified in our previous study, in APEC-infected chickens. QSIs were administered orally (~92 to 120 μg/bird) and chickens were challenged subcutaneously with APEC. Among them, QSI-5 conferred the best protection (100% reduction in mortality, 82% to 93% reduction in lesions [airsacculitis, perihepatitis, lung congestion, pericarditis] severity, and 5.2 to 6.1 logs reduction in APEC load). QSI-5 was further tested in chickens raised on built-up floor litter using an optimized dose (1 mg/L) in drinking water. QSI-5 reduced the mortality (88.4%), lesion severity (72.2%), and APEC load (2.8 logs) in chickens, which was better than the reduction observed with currently used antibiotic sulfadimethoxine (SDM; mortality 35.9%; lesion severity up to 36.9%; and APEC load up to 2.4 logs). QSI-5 was detected in chicken's blood after 0.5 h with no residues in muscle, liver, and kidney. QSI-5 increased the body weight gain with no effect on the feed conversion ratio and cecal microbiota of the chickens. Metabolomic studies revealed reduced levels of 5'-methylthioadenosine in QSI-5-treated chicken serum. In conclusion, QSI-5 displayed promising effects in chickens and thus, represents a novel anti-APEC therapeutic. IMPORTANCE Avian pathogenic Escherichia coli (APEC), a subgroup of ExPEC, is a zoonotic pathogen with public health importance. Quorum sensing is a mechanism that regulates virulence, biofilm formation, and pathogenesis in bacteria. Here, we identified a novel quorum sensing autoinducer-2 inhibitor, QSI-5, which showed higher anti-APEC efficacy in chickens compared to the currently used antibiotic, sulfadimethoxine at a much lower dose (up to 4,500 times). QSI-5 is readily absorbed with no residues in the tissues. QSI-5 also increased the chicken's body weight gain and did not impact the cecal microbiota composition. Overall, QSI-5 represents a promising lead compound for developing novel anti-virulence therapies with significant implications for treating APEC infections in chickens as well as other ExPEC associated infections in humans. Further identification of its target(s) and understanding the mechanism of action of QSI-5 in APEC will add to the future novel drug development efforts that can overcome the antimicrobial resistance problem.

Dataset Information

Quorum Sensing Inhibitors: Curbing Pathogenic Infections through Inhibition of Bacterial Communication.

Publications

Quorum Sensing Inhibitors: Curbing Pathogenic Infections through Inhibition of Bacterial Communication.

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