Abstract
Resistance of various pathogens toward quinolones has emerged as a serious threat to combat infections. Analysis of plethora of genes and resistance mechanisms associated with quinolone resistance reveals chromosome-borne and transferable determinants. qnr genes have been found to be responsible for transferable quinolone resistance. In the present work, a new allele qnrVC5 earlier reported in Vibrio fluvialis from this laboratory was characterized in detail for its sequence, genetic context and propensity to decrease the susceptibility for quinolones. The study has revealed persistence of qnrVC5 in clinical isolates of V. fluvialis from Kolkata region through the years 2002–2006. qnrVC5 existed in the form of a gene cassette with the open reading frame being flanked by an upstream promoter and a downstream V. cholerae repeat region suggestive of its superintegron origin. Sequence analysis of different qnrVC alleles showed that qnrVC5 was closely related to qnrVC2 and qnrVC4 and these alleles were associated with V. cholerae repeats. In contrast, qnrVC1, qnrVC3, and qnrVC6 belonging to another group were associated with V. parahaemolyticus repeats. The gene manifested its activity in native V. fluvialis host as well as in Escherichia coli transformants harboring it by elevating the MIC toward various quinolones by twofold to eightfold. In combination with other quinolone resistance factors such as topoisomerase mutations and aac(6’)-Ib-cr gene, qnrVC5 gene product contributed toward higher quinolone resistance displayed by V. fluvialis isolates. Silencing of the gene using antisense peptide nucleic acid sensitized the V. fluvialis parent isolates toward ciprofloxacin. Recombinant QnrVC5 vividly demonstrated its role in conferring quinolone resistance. qnrVC5 gene, its synergistic effect and global dissemination should be perceived as a menace for quinolone-based therapies.
Highlights
Vibrio fluvialis is known to cause severe cholera-like diarrhea in humans and has been perceived as an emerging pathogen (Bhattacharjee et al, 2010; Ramamurthy et al, 2014)
Clinical isolates of V. fluvialis BD146, L13828, L10734, L9978, and L15318 were obtained from patients suffering from acute cholera-like diarrhea admitted to The Infectious Diseases Hospital, Kolkata during 2002–2006
The same gene was found in plasmid preparations from two V. fluvialis isolates L10734
Summary
Vibrio fluvialis is known to cause severe cholera-like diarrhea in humans and has been perceived as an emerging pathogen (Bhattacharjee et al, 2010; Ramamurthy et al, 2014). Diarrheal illnesses caused by this kind of bacteria are generally treated using quinolone class of antibiotics. Increase in the reports of emergence of multi drug resistant (MDR) V. fluvialis, showing considerable resistance to quinolones has been a public health concern (Srinivasan et al, 2006; Singh et al, 2012; Ramamurthy et al, 2014). The synergistic action of these mechanisms helps the pathogen to achieve higherlevel of resistance toward quinolones (Baranwal et al, 2002; Srinivasan et al, 2006; Rushdy et al, 2013; Zhu et al, 2013)
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