Fluoroquinolone Resistance: Mechanisms, Restrictive Dosing, and Anti-Mutant Screening Strategies for New Compounds

2011 ◽  
pp. 485-514 ◽  
Author(s):  
Karl Drlica ◽  
Xilin Zhao ◽  
Muhammad Malik ◽  
Tal Salz ◽  
Robert Kerns
Keyword(s):  
Resistance Mechanisms ◽  
Fluoroquinolone Resistance ◽  
Mutant Screening ◽  
Screening Strategies ◽  
New Compounds

First characterization of fluoroquinolone resistance mechanisms in CTX-M-producing Escherichia coli from Mongolia

2016 ◽  
Vol 38 ◽  
pp. 79-81 ◽  
Author(s):  
Cheng-Yen Kao ◽  
Uuganbayar Udval ◽  
Hsiu-Mei Wu ◽  
Enkhbaatar Bolormaa ◽  
Jing-Jou Yan ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Resistance Mechanisms ◽  
Fluoroquinolone Resistance

scholarly journals Overexpression of Efflux Pumps, Mutations in the Pumps’ Regulators, Chromosomal Mutations, and AAC(6′)-Ib-cr Are Associated With Fluoroquinolone Resistance in Diverse Sequence Types of Neonatal Septicaemic Acinetobacter baumannii: A 7-Year Single Center Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Subhasree Roy ◽  
Somdatta Chatterjee ◽  
Amrita Bhattacharjee ◽  
Pinaki Chattopadhyay ◽  
Bijan Saha ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Efflux Pump ◽  
Critical Role ◽  
Holistic Approach ◽  
Efflux Pumps ◽  
Resistance Mechanisms ◽  
Fluoroquinolone Resistance ◽  
Active Efflux ◽  
Chromosomal Mutations ◽  
Sequence Types

This study investigates susceptibility toward three fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin), multiple fluoroquinolone-resistance mechanisms, and epidemiological relationship of neonatal septicaemic Acinetobacter baumannii. Previous studies on fluoroquinolone resistance in A. baumannii focused primarily on ciprofloxacin susceptibility and assessed a particular mechanism of resistance; a more holistic approach was taken here. Epidemiological relationship was evaluated by Multi Locus Sequence Typing. Minimum Inhibitory Concentrations of fluoroquinolones was determined with and without efflux pump inhibitors. Overexpression of efflux pumps, resistance-nodulation-cell-division (RND)-type, and multidrug and toxic compound extrusion (MATE)-type efflux pumps were evaluated by reverse transcriptase-qPCR. Mutations within regulatory proteins (AdeRS, AdeN, and AdeL) of RND-pumps were examined. Chromosomal mutations, presence of qnr and aac(6′)-Ib-cr were investigated. A. baumannii were highly diverse as 24 sequence-types with seven novel STs (ST-1440/ST-1441/ST-1481/ST-1482/ST-1483/ST-1484/ST-1486) were identified among 47 A. baumannii. High resistance to ciprofloxacin (96%), levofloxacin (92%), and particularly moxifloxacin (90%) was observed, with multiple mechanisms being active. Resistance to 4th generation fluoroquinolone (moxifloxacin) in neonatal isolates is worrisome. Mutations within GyrA (S83L) and ParC (S80L) were detected in more than 90% of fluoroquinolone-resistant A. baumannii (FQRAB) spread across 10 different clonal complexes (CC1/CC2/CC10/CC25/CC32/CC126/CC149/CC216/CC218/CC513). Efflux-based FQ resistance was found in 65% of FQRAB with ≥2 different active pumps in 38% of strains. Overexpression of adeB was highest (2.2−34-folds) followed by adeJ, adeG, and abeM. Amino acid changes in the regulators (AdeRS/AdeN/AdeL) either as single or multiple substitutions substantiated the overexpression of the pumps. Diverse mutations within AdeRS were detected among different CCs whereas mutations within AdeN linked to CC10 and CC32. Chromosomal mutations and active efflux pumps were detected simultaneously among 64% of FQRAB. Presence of aac(6′)-Ib-cr was also high (74% of FQRAB) but qnrS were absent. As most FQRABs had chromosomal mutations, this was considered predominant, however, isolates where pumps were also active had higher MIC values, establishing the critical role of the efflux pumps. The high variability of FQ susceptibility among FQRAB, possessing the same set of mutations in gyrA, parC, and efflux pump regulators, was also noted. This reveals the complexity of interpreting the interplay of multiple resistance mechanisms in A. baumannii.

scholarly journals Contribution of Different Mechanisms to Ciprofloxacin Resistance in Salmonella spp.

2021 ◽  
Vol 12 ◽  
Author(s):  
Man-Xia Chang ◽  
Jin-Fei Zhang ◽  
Yin-Huan Sun ◽  
Rong-Sheng Li ◽  
Xiao-Ling Lin ◽  
...  
Keyword(s):  
Resistance Mechanisms ◽  
Quinolone Resistance ◽  
Gene Location ◽  
Fluoroquinolone Resistance ◽  
Salmonella Spp ◽  
Resistance Development ◽  
Bacterial Fitness ◽  
Ciprofloxacin Resistance ◽  
Gyra Mutation ◽  
Chromosomal Mutations

Development of fluoroquinolone resistance can involve several mechanisms that include chromosomal mutations in genes (gyrAB and parCE) encoding the target bacterial topoisomerase enzymes, increased expression of the AcrAB-TolC efflux system, and acquisition of transmissible quinolone-resistance genes. In this study, 176 Salmonella isolates from animals with a broad range of ciprofloxacin MICs were collected to analyze the contribution of these different mechanisms to different phenotypes. All isolates were classified according to their ciprofloxacin susceptibility pattern into five groups as follows: highly resistant (HR), resistant (R), intermediate (I), reduced susceptibility (RS), and susceptible (S). We found that the ParC T57S substitution was common in strains exhibiting lowest MICs of ciprofloxacin while increased MICs depended on the type of GyrA mutation. The ParC T57S substitution appeared to incur little cost to bacterial fitness on its own. The presence of PMQR genes represented an route for resistance development in the absence of target-site mutations. Switching of the plasmid-mediated quinolone resistance (PMQR) gene location from a plasmid to the chromosome was observed and resulted in decreased ciprofloxacin susceptibility; this also correlated with increased fitness and a stable resistance phenotype. The overexpression of AcrAB-TolC played an important role in isolates with small decreases in susceptibility and expression was upregulated by MarA more often than by RamA. This study increases our understanding of the relative importance of several resistance mechanisms in the development of fluoroquinolone resistance in Salmonella from the food chain.

scholarly journals Genomic Sequences of Uropathogenic Escherichia coli Strains with Various Fluoroquinolone Resistance Profiles

2020 ◽  
Vol 9 (38) ◽  
Author(s):  
Kayo Okumura ◽  
Masako Kaido ◽  
Eiki Yamasaki ◽  
Yasumasa Akai ◽  
Hisao Kurazono ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Resistance Mechanisms ◽  
Uropathogenic Escherichia Coli ◽  
Fluoroquinolone Resistance ◽  
Whole Genome ◽  
Drug Resistant ◽  
Valuable Resource ◽  
Sequencing Data ◽  
Content Type ◽  
Tract Infections

ABSTRACT The emergence of drug-resistant uropathogenic Escherichia coli (UPEC) has hampered antibiotic therapy for urinary tract infections. To elucidate the resistance mechanisms of UPEC, we performed whole-genome sequencing of eight UPEC strains with different fluoroquinolone resistance levels. Here, we report our sequencing data, providing a valuable resource for understanding such mechanisms.

scholarly journals Molecular Characterization of Fluoroquinolone Resistance Mechanisms in Isolates from the Delafloxacin Acute Bacterial Skin and Skin Structure Infections Clinical Trials

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S131-S131
Author(s):  
Rodrigo E Mendes ◽  
Dee Shortridge ◽  
Sandra P McCurdy ◽  
Sue K Cammarata ◽  
Michael D Huband ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Molecular Characterization ◽  
Resistance Mechanisms ◽  
Fluoroquinolone Resistance ◽  
Skin Structure

Evaluation of Fluoroquinolone Resistance Mechanisms inPseudomonas aeruginosaMultidrug Resistance Clinical Isolates

2012 ◽  
Vol 18 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Maria Rosalia Pasca ◽  
Claudia Dalla Valle ◽  
Ana Luisa De Jesus Lopes Ribeiro ◽  
Silvia Buroni ◽  
Maria Cristiana Papaleo ◽  
...  
Keyword(s):  
Resistance Mechanisms ◽  
Clinical Isolates ◽  
Fluoroquinolone Resistance

Fluoroquinolone resistance mechanisms in multidrug-resistant Escherichia coli isolated from extraintestinal infections in dogs

2010 ◽  
Vol 146 (1-2) ◽  
pp. 161-166 ◽  
Author(s):  
Justine S. Gibson ◽  
Rowland N. Cobbold ◽  
Myat T. Kyaw-Tanner ◽  
Peter Heisig ◽  
Darren J. Trott
Keyword(s):  
Escherichia Coli ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Fluoroquinolone Resistance

scholarly journals Fluoroquinolone Resistance in Haemophilus influenzae Is Associated with Hypermutability

2007 ◽  
Vol 51 (4) ◽  
pp. 1566-1569 ◽  
Author(s):  
María Pérez-Vázquez ◽  
Federico Román ◽  
Silvia García-Cobos ◽  
José Campos
Keyword(s):  
Haemophilus Influenzae ◽  
Resistance Mechanisms ◽  
Fluoroquinolone Resistance ◽  
Control Group ◽  
Step Process ◽  
Porin Protein ◽  
Susceptible Control

ABSTRACT Forty-three percent (12/28) of ciprofloxacin (CIP)-nonsusceptible respiratory isolates of Haemophilus influenzae were hypermutable, compared with 8.5% (3/35) in the CIP-susceptible control group (P = 0.002). CIP-nonsusceptible mutants were obtained with hypermutable strains only; these mutants developed three resistance mechanisms in a step-by-step process: target modifications, loss of a porin protein, and increased efflux.

scholarly journals The Prevalence of Fluoroquinolone Resistance Mechanisms in ColonizingEscherichia coliIsolates Recovered from Hospitalized Patients

2010 ◽  
Vol 51 (3) ◽  
pp. 280-285 ◽  
Author(s):  
Ebbing Lautenbach ◽  
Joshua P. Metlay ◽  
Xiangqun Mao ◽  
Xiaoyan Han ◽  
Neil O. Fishman ◽  
...  
Keyword(s):  
Resistance Mechanisms ◽  
Hospitalized Patients ◽  
Fluoroquinolone Resistance
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