Dataset Information

Synergistic Activity of Fluoroquinolones Combining with Artesunate Against Multidrug-Resistant Escherichia coli.

ABSTRACT: Multidrug resistance (MDR) is an increasing public health concern worldwide. Artesunate (ART) has been reported to be significantly effective in enhancing the effectiveness of various ?-lactam antibiotics against MDR Escherichia coli via inhibiting the efflux pump genes. Apart from ?-lactam antibiotics, there is no report regarding the potential synergistic effects of ART combining with fluoroquinolones (FQs). In this study, we investigated whether ART can enhance the antibacterial effects of FQs in vitro. The antibacterial activity of ART and antibiotics against 13 animal-derived E. coli clinical isolates was assessed for screening MDR strains. Then the synergistic activity of FQs with ART against MDR E. coli isolates was evaluated. Daunorubicin (DNR) accumulation within E. coli and messenger RNA (mRNA) expressions of acrA, acrB, tolC, and qnr genes were investigated. The results showed that ART did not show significant antimicrobial activity. However, a dramatically synergistic activity of ART combining with FQs was obsessed with (?FIC)?=?0.12-0.33. ART increased the DNR accumulation and reduced acrAB-tolC mRNA expression, but enhanced the mRNA expression of qnrS and qnrB within MDR E. coli isolates. These findings suggest that ART can potentiate FQs activity which may be associated with drug accumulation by inhibiting the expression of acrAB-tolC.

SUBMITTER: Wei S

PROVIDER: S-EPMC6978754 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Synergistic Activity of Fluoroquinolones Combining with Artesunate Against Multidrug-Resistant <i>Escherichia coli</i>.

Wei SiMin S Yang YueFei Y Tian Wei W Liu MingJiang M Yin ShaoJie S Li JinGui J

Microbial drug resistance (Larchmont, N.Y.) 20191122 1

Multidrug resistance (MDR) is an increasing public health concern worldwide. Artesunate (ART) has been reported to be significantly effective in enhancing the effectiveness of various β-lactam antibiotics against MDR <i>Escherichia coli</i> via inhibiting the efflux pump genes. Apart from β-lactam antibiotics, there is no report regarding the potential synergistic effects of ART combining with fluoroquinolones (FQs). In this study, we investigated whether ART can enhance the antibacterial effect ...[more]

PMID: 31738637

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Project description:Urinary tract infections (UTIs) are among the most common bacterial infections in humans. Uropathogenic Escherichia coli (UPEC), which are the most frequent agents causing community as well as hospital-acquired UTIs, have become highly drug-resistant, thus making the treatment of these infections challenging. Recently, the use of bacteriophages (or 'phages') against multidrug-resistant (MDR) and extensively drug-resistant (XDR) microorganisms has garnered significant global attention. Bacterial biofilms play a vital role in the pathogenesis of UTIs caused by UPEC. Phages have the potential to disrupt bacterial biofilms using lytic enzymes such as EPS depolymerases and endolysins. We isolated a lytic phage (590B) from community sewage in Chandigarh, which was active against multiple MDR and XDR biofilm-forming UPEC strains. During whole-genome sequencing, the 44.3 kb long genome of phage 590B encoded 75 ORFs, of which 40 were functionally annotated based on homology with similar phage proteins in the database. Comparative analysis of associated phage genomes indicated that phage 590B evolved independently and had a distinct taxonomic position within the genus Kagunavirus in the subfamily Guernseyvirinae of Siphoviridae. The phage disrupted biofilm mass effectively when applied to 24 h old biofilms formed on the Foley silicon catheter and coverslip biofilm models. To study the effect of intact biofilm architecture on phage predation, the biofilms were disrupted. The phage reduced the viable cells by 0.6-1.0 order of magnitude after 24 h of incubation. Regrowth and intact bacterial cells were observed in the phage-treated planktonic culture and biofilms, respectively, which indicated the emergence of phage-resistant bacterial variants. The phage genome encoded an endolysin which might have a role in the disruption and inhibition of bacterial biofilms. Moreover, the genome lacked genes encoding toxins, virulence factors, antibiotic resistance, or lysogeny. Therefore, lytic phage 590B may be a good alternative to antibiotics and can be included in phage cocktails for the treatment of UTIs caused by biofilm-forming MDR and XDR UPEC strains.

Dataset Information

Synergistic Activity of Fluoroquinolones Combining with Artesunate Against Multidrug-Resistant Escherichia coli.

Publications

Synergistic Activity of Fluoroquinolones Combining with Artesunate Against Multidrug-Resistant <i>Escherichia coli</i>.

Similar Datasets

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