Cinacalcet exhibits rapid bactericidal and efficient anti-biofilm activities against multidrug-resistant Gram-positive pathogens

Infections caused by Gram-positive bacteria pose a serious threat to global public health. Drug resistance, dormant persister cells, and biofilm formation are the key challenges affecting the efficacy of antibiotics against Gram-positive bacterial infections. In this study, cinacalcet exhibited good...

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Veröffentlicht in:iScience 2023-04, Vol.26 (4), p.106378-106378, Article 106378
Hauptverfasser: Xiong, Yanpeng, Liu, Shanghong, Zheng, Jinxin, Chen, Jinlian, Wen, Zewen, Deng, Xiangbin, Bai, Bing, Li, Duoyun, Yu, Zhijian, Han, Shiqing, Liu, Xiaoju, Li, Peiyu
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Sprache:eng
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Zusammenfassung:Infections caused by Gram-positive bacteria pose a serious threat to global public health. Drug resistance, dormant persister cells, and biofilm formation are the key challenges affecting the efficacy of antibiotics against Gram-positive bacterial infections. In this study, cinacalcet exhibited good inhibitory activity against multidrug-resistant Gram-positive bacteria, with minimum inhibitory concentrations (MICs) ranging from 3.13 μg/mL to 25 μg/mL. Cinacalcet displayed more rapid and stronger bactericidal activity against planktonic and persister cells of Staphylococcus aureus and Enterococcus faecalis compared with the antibiotics vancomycin or ampicillin, as well as potent inhibition and eradication of mature biofilms of methicillin-resistant S. aureus (MRSA) and linezolid-resistant E. faecalis (LRE). In addition, the robust antibacterial activity was demonstrated in vivo by a pneumonia infection model and a biofilm formation and deep-seated infection model. Collectively, these findings indicate that cinacalcet may be a promising new candidate antibiotic to combat infections caused by multidrug-resistant Gram-positive pathogens. [Display omitted] •Cinacalcet exhibits rapid bactericidal activity against Gram-positive bacteria•Inhibition and eradication of cinacalcet against biofilm of Gram-positive pathogens•Cinacalcet inhibits the expression of virulence- and biofilm-related genes•A superior anti-infective efficacy of cinacalcet in vivo Drugs; Microbiology; Bacteriology; Microbiofilms
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2023.106378