Abstract
Colistin is being considered as “the last ditch” treatment in many infections caused by Gram-negative stains. However, colistin is becoming increasingly invalid in treating patients who are infected with colistin-resistant Escherichia coli (E. coli) and Klebsiella Pneumoniae (K. pneumoniae). To cope with the continuous emergence of colistin resistance, the development of new drugs and therapies is highly imminent. Herein, in this work, we surprisingly found that the combination of quercetin with colistin could efficiently and synergistically eradicate the colistin-resistant E. coli and K. pneumoniae, as confirmed by the synergy checkboard and time-kill assay. Mechanismly, the treatment of quercetin combined with colistin could significantly downregulate the expression of mcr-1 and mgrB that are responsible for colistin-resistance, synergistically enhancing the bacterial cell membrane damage efficacy of colistin. The colistin/quercetin combination was notably efficient in eradicating the colistin-resistant E. coli and K. pneumoniae both in vitro and in vivo. Therefore, our results may provide an efficient alternative pathway against colistin-resistant E. coli and K. pneumoniae infections.
Highlights
Antibiotics undertake a significant duty in terms of decreasing the morbidity and mortality associated with bacteria-induced infections
Quercetin was purchased from MedChem Express (MCE) Co., Ltd. (New Jersey, United States), and all antibiotics used in this study, including colistin, aztreonam, ceftazidime, cefepime, imipenem, ciprofloxacin, levofloxacin, gentamicin, tobramycin, and amikacin were purchased from Wenzhou Kangtai Biological Technology Co., Ltd. (Zhejiang, China)
1 E. coli strain, DC90, and 1 K. pneumoniae strain, FK 1913, were found extremely resistant to colistin treatment (MIC ≥64 μg/ml). These results suggest the colistin resistance of those clinically isolated E. coli and K. pneumoniae strains
Summary
Antibiotics undertake a significant duty in terms of decreasing the morbidity and mortality associated with bacteria-induced infections. The development of novel antibiotics is considerably slow and challenging, which increased the therapeutic difficulty for infections caused by drug-resistant bacterial infections (Cordoba et al, 2015). To address this issue, new antibacterial materials and the combination of non-antibacterial and antibiotics have been regarded as a new treatment strategy in overcoming the drug resistance of bacteria (Li et al, 2020; Su et al, 2020). As a cationic antimicrobial peptide, colistin exploits the antibacterial effect through interplaying with the lipid A section of lipopolysaccharide (LPS) and destroys the Gram-negative bacteria outer membrane afterward (Phan et al, 2017; Shen et al, 2018; Tran et al, 2018). Despite colistin remaining high-efficient in antimicrobial activity, the massive use of colistin as a clinical therapeutic
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