Mutational analysis of quinolone resistance in the plasmid-encoded pentapeptide repeat proteins QnrA, QnrB and QnrS.
نویسندگان
چکیده
OBJECTIVES Pentapeptide repeat proteins (PRPs) QnrA, QnrB and QnrS confer reduced susceptibility to quinolones. This study presents an in vitro analysis of the genetic evolution of quinolone resistance mediated by changes in the coding sequences and promoter regions of qnrA1, qnrS1 and qnrB1 genes. METHODS A random mutagenesis technique was used to predict the evolutionary potential of these PRPs against nalidixic acid and fluoroquinolones. After comparing the amino acid sequences of these and other PRPs protecting bacteria from quinolone activity, several conserved positions were found. The role of these residues in their effect against quinolones was evaluated by site-directed mutagenesis. RESULTS Three different phenotypes (similar resistance, higher resistance or lower resistance to quinolones) were obtained in the random mutagenesis assays when compared with wild-type phenotypes. Only one mutant increased quinolone resistance: QnrS1 containing D185Y substitution (4-fold for ciprofloxacin). Using site-directed mutagenesis, residues G56, C72, C92, G96, F114, C115, S116, A117 and L159, according to the sequence of QnrA1, were analysed and despite the wide amino acid variability of the PRPs, most conserved residues analysed were critical to QnrA1, QnrB1 and QnrS1. CONCLUSIONS Amino acid sequences of PRPs QnrA1, QnrB1 and QnrS1 could be already optimized for quinolone resistance. One or several changes appear to be insufficient to obtain variants producing fluoroquinolone clinical resistance (MIC > 1 mg/L). Critical residues for quinolone resistance in PRPs were described. Interestingly, different effects were observed for QnrA1, QnrB1 and QnrS1 with the same substitution in several positions.
منابع مشابه
The Emergence of Qnr-resistance Among Klebsiella pneumoniae spp in Zahedan
Objective: Although quinolone resistance results mostly from chromosomal mutations in Klebsiella pneumoniae, it may also be mediated by plasmid – encoded qnr determinants. Plasmid-mediated quinolone resistance (PMQR) was increasingly identified in Enterobacteriaceae family worldwide. The aim of this study was to investigate the prevalence of qnr genes in clinical isolates of Klebsiella pn...
متن کاملPrevalence of Plasmid-Mediated Quinolones Resistance among Klebsiella pneumoniae Strains Isolated from Hospitals in Borujerd, Iran
ABSTRACT Background and Objective: Klebsiella pneumoniae is one of the most common causes of bacterial infections. Presence of plasmid-mediated quinolone resistance genes causes low level of resistance in K. pneumoniae. This study investigated the prevalence of resistance to quinolones and fluoroquinolones, and the frequency of qnrA, qnrB and qnrS genes amo...
متن کاملفراوانی ژنهای پلاسمیدی qnrA، qnrB و qnrS و تعیین حساسیت آنتی بیوتیکی در ایزولههای اشرشیاکلی مقاوم به کینولون و فلوروکینولون جدا شده از نمونههای بالینی کرمان
Background: Plasmid-mediated quinolone resistance, which complicates treatment, has been increasingly identified in Escherichia coli isolates worldwide. The purpose of this study was to investigate the frequency of plasmid-mediated qnrA, qnrB, and qnrS genes among quinolones resistant E.coli isolated from Kerman hospitals, Iran. Methods: In the current study, 80 E. coli isolates...
متن کاملInvestigation of plasmid-mediated quinolone resistance among isolates obtained in a Turkish intensive care unit.
The aim of this study was to search for three plasmid-encoded, quinolone-resistant determinants: qnrA, qnrB, and qnrS. Thus, 460 Gram-negative strains belonging to 11 different genera (clinical, 347; non-clinical, i.e., from a rectal swab, 113), of which 40% were ciprofloxacin-resistant, were recovered from patients in an intensive care unit at the Istanbul Medical Faculty, Turkey, in the years...
متن کاملPlasmid-mediated quinolone resistance determinants in urinary isolates of Escherichia coli and Klebsiella pneumoniae in a large Singapore hospital.
INTRODUCTION At the time of the study, 3 plasmid-borne qnr determinants (qnrA, qnrB and qnrS) and 1 plasmid-borne aminoglycoside-modifying enzyme determinant that confers quinolone resistance (aac(6')-Ib-cr) had been described in the literature. MATERIALS AND METHODS We studied the prevalence of the 3 qnr determinants in a total of 117 nalidixic acid-resistant urinary isolates of Klebsiella p...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of antimicrobial chemotherapy
دوره 63 6 شماره
صفحات -
تاریخ انتشار 2009