scholarly journals Fluoroquinolone resistance conferred by gyrA, parC mutations, and AbaQ efflux pump among Acinetobacter baumannii clinical isolates causing ventilator-associated pneumonia

2019 ◽  
pp. 1-5 ◽  
Author(s):  
Nancy M. Attia ◽  
Amira ElBaradei
Keyword(s):  
Acinetobacter Baumannii ◽  
Efflux Pump ◽  
Quinolone Resistance ◽  
Fluoroquinolone Resistance ◽  
Ventilator Associated Pneumonia ◽  
Drug Resistant ◽  
The Novel ◽  
New Mutation ◽  
Extensively Drug Resistant ◽  
High Level

Acinetobacter baumannii has emerged as an important nosocomial pathogen due to its ability to survive in hospital settings and its antimicrobial resistance. It is one of the key pathogens in ventilator-associated pneumonia (VAP). The aim of this study was to characterize the mechanisms of quinolone resistance among A. baumannii isolates causing VAP and to investigate the presence of the novel abaQ gene among them. Quinolone-resistant A. baumannii isolates causing VAP were collected over a period of 4 months. Mutations within gyrA and parC were analyzed and the presence of qnrA, qnrB, qnrS, and abaQ was investigated genotypically. Twenty-one A. baumannii isolates were collected, most of them (76.2%) were extensively drug-resistant (XDR) and only one isolate (4.8%) was pandrug-resistant (PDR). All isolates showed high level of resistance to ciprofloxacin, while qnrA, qnrB and qnrS were absent among our isolates. This is the first report of A. baumannii isolates co-harboring Ser81Leu in gyrA and Ser84Leu in parC together with the novel abaQ gene. Interestingly, a new mutation in gyrA quinolone resistance-determining region Arg89Cys was detected among two of our isolates. The emergence of XDR and PDR isolates among A. baumannii causing VAP is an alarming threat.

scholarly journals In Vitro Activity of the Novel Pleuromutilin Lefamulin (BC-3781) and Effect of Efflux Pump Inactivation on Multidrug-Resistant and Extensively Drug-Resistant Neisseria gonorrhoeae

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Susanne Jacobsson ◽  
Susanne Paukner ◽  
Daniel Golparian ◽  
Jörgen S. Jensen ◽  
Magnus Unemo
Keyword(s):  
Efflux Pump ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Drug Resistant ◽  
The Novel ◽  
Extensively Drug Resistant ◽  
Optimal Dosing ◽  
And Performance ◽  
Reference Strains

ABSTRACT We evaluated the activity of the novel semisynthetic pleuromutilin lefamulin, inhibiting protein synthesis and growth, and the effect of efflux pump inactivation on clinical gonococcal isolates and reference strains (n = 251), including numerous multidrug-resistant and extensively drug-resistant isolates. Lefamulin showed potent activity against all gonococcal isolates, and no significant cross-resistance to other antimicrobials was identified. Further studies of lefamulin are warranted, including in vitro selection and mechanisms of resistance, pharmacokinetics/pharmacodynamics, optimal dosing, and performance in randomized controlled trials.

Whole genome analysis of extensively drug-resistant Acinetobacter bau-mannii clinical isolates in Thailand

2020 ◽  
Vol 20 ◽  
Author(s):  
Peechanika Chopjitt ◽  
Anusak Kerdsin ◽  
Dan Takeuchi ◽  
Rujirat Hatrongjit ◽  
Parichart Boueroy ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Acinetobacter Baumannii ◽  
Genome Sequencing ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Whole Genome ◽  
Drug Resistant ◽  
Resistant Genes ◽  
Extensively Drug Resistant ◽  
Antibiotic Efflux

Background:: Acinetobacter baumannii is recognized as a majority opportunistic nosocomial pathogen and caus-ing hospital-acquired infection worldwide. The increasing prevalence of extensively drug-resistant Acinetobacter baumannii (XDRAB) has become a rising concern in healthcare facilities and has impeded public health due to limitation of therapeutic options and are associated with high morbidity and mortality as well as longer hospitalization. Whole-genome sequencing of highly multidrug resistant A. baumannii will increase understanding of resistant mechanisms, the emergence of novel re-sistance, genetic relationships among the isolates, source tracking, and treatment decisions in selected patients. Objective:: This study revealed the genomic analysis to explore blaOXA-23 harboring XDRAB isolates in Thailand. Methods:: Whole-genome sequencing of the two XDRAB isolates was carried out on a HiSeq2000 Illumina platform and susceptibility on antimicrobials was conducted. Results:: Both isolates revealed sequence types of international, clone II-carrying, multiple antimicrobial-resistant genes—ST195 and ST451. They were resistant to antimicrobial agents in all drug classes tested for Acinetobacter spp. They carried 18 antimicrobial-resistant genes comprising of 4 -lactamase genes (blaOXA-23, blaOXA-66, blaTEM-1D, blaADC-25), 4 aminogly-coside-resistant genes (armA, aph(3')-Ia, aph(3'')-Ib, aph(6)-Id), 3 macrolide-resistant genes (amvA, mphE, msrE), 1 sulfon-amide-resistant gene (sul-2), 2 tetracycline-resistant genes (tetB, tetR), 1 resistant-nodulation-cell division (RND) antibiotic efflux pump gene cluster, 2 major facilitator superfamily (MFS) antibiotic efflux pump genes (abaF, abaQ), and 1 small multidrug-resistant (SMR) antibiotic efflux pump gene (abeS). Mutation of gyrA (S81L) occurred in both isolates. Conclusions:: Whole-genome sequencing revealed both blaOXA-23 harboring XDRAB isolates were clustered under interna-tional clone II with difference STs and carrying multiple antimicrobial-resistant genes conferred their resistance to antimi-crobial agents. Inactivation of antimicrobials and target modification by enzymes, and pumping antibiotics by efflux pump are mainly resistance mechanism of the XDRAB in this study.

scholarly journals The molecular basis of extensively drug-resistant Salmonella Typhi isolates from pediatric septicemia patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257744
Author(s):  
Chanmi Kim ◽  
Iqra Latif ◽  
Durga P. Neupane ◽  
Gi Young Lee ◽  
Ryan S. Kwon ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Typhoid Fever ◽  
Molecular Basis ◽  
Efflux Pump ◽  
Detection Methods ◽  
Fluoroquinolone Resistance ◽  
Medium Size ◽  
Drug Resistant ◽  
Pump System ◽  
Extensively Drug Resistant

Sepsis is a syndromic response to infections and is becoming an emerging threat to the public health sector, particularly in developing countries. Salmonella Typhi (S. Typhi), the cause of typhoid fever, is one primary cause of pediatric sepsis in typhoid endemic areas. Extensively drug-resistant (XDR) S. Typhi is more common among pediatric patients, which is responsible for over 90% of the reported XDR typhoid cases, but the majority of antibiotic resistance studies available have been carried out using S. Typhi isolates from adult patients. Here, we characterized antibiotic-resistance profiles of XDR S. Typhi isolates from a medium size cohort of pediatric typhoid patients (n = 45, 68.89% male and 31.11% female) and determined antibiotic-resistance-related gene signatures associated with common treatment options to typhoid fever patients of 18 XDR S. Typhi representing all 45 isolates. Their ages were 1–13 years old: toddlers aging 1–2 years old (n = 9, 20%), pre-schoolers aging 3–5 years old (n = 17, 37.78%), school-age children aging 6–12 years old (n = 17, 37.78%), and adolescents aging 13–18 years old (n = 2, 4.44%). Through analyzing blaTEM1, dhfR7, sul1, and catA1genes for multidrug-resistance, qnrS, gyrA, gyrB, parC, and parE for fluoroquinolone-resistance, blaCTX-M-15 for XDR, and macAB and acrAB efflux pump system-associated genes, we showed the phenotype of the XDR S. Typhi isolates matches with their genotypes featured by the acquisitions of the genes blaTEM1, dhfR7, sul1, catA1, qnrS, and blaCTX-M-15 and a point mutation on gyrA. This study informs the molecular basis of antibiotic-resistance among recent S. Typhi isolates from pediatric septicemia patients, therefore providing insights into the development of molecular detection methods and treatment strategies for XDR S. Typhi.

Molecular Characterization of Fluoroquinolone Resistance Mechanisms of Campylobacter Isolates from Duck Meats

2017 ◽  
Vol 80 (12) ◽  
pp. 2056-2059
Author(s):  
Min Kang ◽  
Bai Wei ◽  
Sung-Woon Choi ◽  
Se-Yeoun Cha ◽  
Hyung-Kwan Jang
Keyword(s):  
Nalidixic Acid ◽  
Efflux Pump ◽  
Resistance Mechanisms ◽  
Quinolone Resistance ◽  
Fluoroquinolone Resistance ◽  
Gyra Gene ◽  
Meat Samples ◽  
High Level ◽  
Level Resistance

ABSTRACT The purpose of this study was to identify the molecular basis of quinolone resistance of Campylobacter isolates recovered from duck meats. Sixty-one isolates from duck meat samples were studied using sequence analysis of the gyrA gene, and PCR assays were used to identify the presence of the CmeABC efflux pump and its restored sensitivity in the presence of efflux-pump inhibitors. High-level resistance to nalidixic acid and ciprofloxacin was attributed to amino acid substitutions Thr-86-Ile in some isolates. The PCR assay confirmed the presence of the cmeB gene in 29 (47.5%) of the 61 Campylobacter isolates. Phenylalanine arginine β-naphthylamide reduced the MICs of ciprofloxacin and nalidixic acid in 16 (55.2%) and 26 (89.7%) isolates, respectively. The Thr-86-Ile substitution in the gyrA was the primary contributor to the high-level quinolone resistance in Campylobacter isolates from duck meats.

Molecular Characterization of Tigecycline Non-Susceptibility among Extensively Drug-Resistant Acinetobacter baumannii Isolates of Clinical Origin

Chemotherapy ◽  
2021 ◽  
pp. 1-7
Author(s):  
Mehri Haeili ◽  
Ali Abdollahi ◽  
Amin Ahmadi ◽  
Amin Khoshbayan
Keyword(s):  
Acinetobacter Baumannii ◽  
Molecular Mechanisms ◽  
Efflux Pump ◽  
Genetic Alterations ◽  
Disk Diffusion ◽  
Diffusion Method ◽  
Transcriptional Level ◽  
Drug Resistant ◽  
Disk Diffusion Method ◽  
Extensively Drug Resistant

<b><i>Introduction:</i></b> Tigecycline (TGC) is one of the last-resort therapeutic agents for treating infections caused by extensively drug resistant <i>Acinetobacter baumannii</i> isolates. Although resistance to TGC is not common, non-susceptible <i>A. baumannii</i> (NSAB) isolates have been described. In the current study, we aimed to assess the molecular mechanisms mediating TGC non-susceptibility in 5 clinical isolates of <i>A. baumannii</i> with reduced susceptibility to TGC. <b><i>Methods:</i></b> Susceptibility of isolates to TGC as well as various classes of antibiotics was evaluated by broth dilution and disk diffusion methods, respectively. The presence of <i>tetX</i> and <i>tetX1</i> genes was investigated by PCR. The nucleotide sequences of <i>adeR</i> and <i>adeS</i> genes were assessed by PCR amplicon sequencing. To evaluate the association between reduced susceptibility to TGC and upregulation of AdeABC efflux pump, transcriptional level of <i>adeB</i> gene was quantified by RT-qPCR analysis. <b><i>Results:</i></b> All 5 TGC-NSAB isolates had a TGC MIC of ≥4 mg/L and were resistant to all antimicrobials tested by disk diffusion method except for minocycline and doxycycline for which a susceptibility rate of 40% and 20% was observed, respectively. The <i>tetX/X1</i> genes were not detected in any isolates. All TGC non-susceptible isolates harbored genetic alterations in the <i>adeRS</i> operon, including AdeS G186V, N268H, and D60N and AdeR A136V and V120I substitutions among, which G186V and D60N were predicted by PROVEAN tool analysis as inactivating alterations. Reduced TGC susceptibility was associated with upregulation of AdeABC efflux pump in all TGC non-susceptible isolates. <b><i>Conclusion:</i></b> It can be concluded from our results that reduced susceptibility to TGC in the studied isolates was mainly mediated by genetic alterations in the AdeRS system, which resulted in overexpression of AdeABC efflux pump. Emergence of TGC non-susceptibility among isolates that had not been previously exposed to TGC is an issue of great concern.

scholarly journals Epidemiology and Genetic Diversity of Colistin Nonsusceptible Nosocomial Acinetobacter baumannii Strains from Russia for 2013-2014

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Eugene A. Sheck ◽  
Mikhail V. Edelstein ◽  
Marina V. Sukhorukova ◽  
Natali V. Ivanchik ◽  
Elena Yu. Skleenova ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Nosocomial Infections ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Epidemiological Features ◽  
High Level ◽  
Therapeutic Possibilities

A high level of resistance to carbapenems in Acinetobacter baumannii strains severely limits therapeutic possibilities. Colistin is the last resort drug against such strains, although the cases of resistance to this drug have become more frequent. This article presents the epidemiological features and genetic diversity of colistin nonsusceptible A. baumannii strains collected as part of a national multicenter epidemiological study of the antibiotic resistance of pathogens of nosocomial infections (MARATHON), which was conducted in 2013-2014 in Russia. A total of 527 A. baumannii isolates were collected, 10 (1.9%) of which were nonsusceptible to colistin. The majority of nonsusceptible A. baumannii isolates to colistin showed resistance to carbapenems and had the genes of the acquired OXA-40-like carbapenemases (n=6). In one case, a combination of OXA-23-like + OXA-40-like (n=1) genes was identified. One strain had the multidrug-resistant (MDR) phenotype, 6 isolates had extensively drug-resistant (XDR) phenotype, and 3 isolates had pandrug-resistant (PDR) phenotype. Among the colistin nonsusceptible A. baumannii isolates, 6 individual genotypes were identified, most of which belonged to successful international clones (CC92OXF/CC2PAS, n=4; CC944OXF/ST78PAS, n=4; CC109OXF/CC1PAS, n=1).

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