scholarly journals Functional Characterization of AbaQ, a Novel Efflux Pump Mediating Quinolone Resistance inAcinetobacter baumannii

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
María Pérez-Varela ◽  
Jordi Corral ◽  
Jesús Aranda ◽  
Jordi Barbé
Keyword(s):  
Acinetobacter Baumannii ◽  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Functional Characterization ◽  
Multidrug Resistant ◽  
Quinolone Resistance ◽  
Nosocomial Pathogen ◽  
Content Type ◽  
Mfs Transporter

ABSTRACTAcinetobacter baumanniihas emerged as an important multidrug-resistant nosocomial pathogen. In previous work, we identified a putative MFS transporter, AU097_RS17040, involved in the pathogenicity ofA. baumannii(M. Pérez-Varela, J. Corral, J. A. Vallejo, S. Rumbo-Feal, G. Bou, J. Aranda, and J. Barbé, Infect Immun 85:e00327-17, 2017,https://doi.org/10.1128/IAI.00327-17). In this study, we analyzed the susceptibility to diverse antimicrobial agents ofA. baumanniicells defective in this transporter, referred to as AbaQ. Our results showed that AbaQ is mainly involved in the extrusion of quinolone-type drugs inA. baumannii.

scholarly journals Distribution and Molecular Characterization of Acinetobacter baumannii International Clone II Lineage in Japan

2017 ◽  
Vol 62 (2) ◽  
Author(s):  
Mari Matsui ◽  
Masato Suzuki ◽  
Masahiro Suzuki ◽  
Jun Yatsuyanagi ◽  
Masanori Watahiki ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Fluoroquinolone Resistance ◽  
Content Type ◽  
Low Prevalence ◽  
Prevalent Species ◽  
Sequence Types ◽  
Insight Into

ABSTRACTMultidrug-resistant (MDR)Acinetobacterspp. have been globally disseminated in association with the successful clonal lineageAcinetobacter baumanniiinternational clone II (IC II). Because the prevalence of MDRAcinetobacterspp. in Japan remains very low, we characterized allAcinetobacterspp. (n= 866) from 76 hospitals between October 2012 and March 2013 to describe the entire molecular epidemiology ofAcinetobacterspp. The most prevalent species wasA. baumannii(n= 645; 74.5%), withA. baumanniiIC II (n= 245) accounting for 28.3% of the total. Meropenem-resistant isolates accounted for 2.0% (n= 17) and carried ISAba1-blaOXA-23-like(n= 10),blaIMP(n= 4), or ISAba1-blaOXA-51-like(n= 3). Multilocus sequence typing of 110 representativeA. baumanniiisolates revealed the considerable prevalence of domestic sequence types (STs).A. baumanniiIC II isolates were divided into the domestic sequence type 469 (ST469) (n= 18) and the globally disseminated STs ST208 (n= 14) and ST219 (n= 4). ST469 isolates were susceptible to more antimicrobial agents, while ST208 and ST219 overproduced the intrinsic AmpC β-lactamase.A. baumanniiIC II and someA. baumanniinon-IC II STs (e.g., ST149 and ST246) were associated with fluoroquinolone resistance. This study revealed that carbapenem-susceptibleA. baumanniiIC II was moderately disseminated in Japan. The low prevalence of acquired carbapenemase genes and presence of domestic STs could contribute to the low prevalence of MDRA. baumannii. A similar epidemiology might have appeared before the global dissemination of MDR epidemic lineages. In addition, fluoroquinolone resistance associated withA. baumanniiIC II may provide insight into the significance ofA. baumanniiepidemic clones.

Resistance to nitrofurantoin is an indicator of extensive drug-resistant (XDR) Enterobacteriaceae

2021 ◽  
Vol 70 (4) ◽  
Author(s):  
Balaram Khamari ◽  
Prakash Kumar ◽  
Bulagonda Eswarappa Pradeep
Keyword(s):  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Treatment Options ◽  
Strong Association ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Content Type ◽  
Link Type

Introduction. Nitrofurantoin is one of the preferred antibiotics in the treatment of uropathogenic multidrug-resistant (MDR) infections. However, resistance to nitrofurantoin in extensively drug-resistant (XDR) bacteria has severely limited the treatment options. Gap statement. Information related to co-resistance or collateral sensitivity (CS) with reference to nitrofurantoin resistant bacteria is limited. Aim. To study the potential of nitrofurantoin resistance as an indicator of the XDR phenotype in Enterobacteriaceae . Methods. One hundred (45 nitrofurantoin-resistant, 21 intermediately resistant and 34 nitrofurantoin-susceptible) Enterobacteriaceae were analysed in this study. Antibiotic susceptibility testing (AST) against nitrofurantoin and 17 other antimicrobial agents across eight different classes was performed by using the Vitek 2.0 system. The isolates were screened for the prevalence of acquired antimicrobial resistance (AMR) and efflux pump genes by PCR. Results. In total, 51 % of nitrofurantoin-resistant and 28 % of intermediately nitrofurantoin resistant isolates exhibited XDR characteristics, while only 3 % of nitrofurantoin-sensitive isolates were XDR (P=0.0001). Significant co-resistance was observed between nitrofurantoin and other tested antibiotics (β-lactam, cephalosporin, carbapenem, aminoglycoside and tetracycline). Further, the prevalence of AMR and efflux pump genes was higher in the nitrofurantoin-resistant strains compared to the susceptible isolates. A strong association was observed between nitrofurantoin resistance and the presence of bla PER-1, bla NDM-1, bla OXA-48, ant(2) and oqxA-oqxB genes. Tigecycline (84 %) and colistin (95 %) were the only antibiotics to which the majority of the isolates were susceptible. Conclusion. Nitrofurantoin resistance could be an indicator of the XDR phenotype among Enterobacteriaceae , harbouring multiple AMR and efflux pump genes. Tigecycline and colistin are the only antibiotics that could be used in the treatment of such XDR infections. A deeper understanding of the co-resistance mechanisms in XDR pathogens and prescription of AST-based appropriate combination therapy may help mitigate this problem.

scholarly journals Characterization of RelA in Acinetobacter baumannii

2020 ◽  
Vol 202 (12) ◽  
Author(s):  
María Pérez-Varela ◽  
Aimee R. P. Tierney ◽  
Ju-Sim Kim ◽  
Andrés Vázquez-Torres ◽  
Philip Rather
Keyword(s):  
Acinetobacter Baumannii ◽  
Galleria Mellonella ◽  
Multidrug Resistant ◽  
Cell Physiology ◽  
Content Type ◽  
Content Model ◽  
Transposon Insertion ◽  
Downstream Effectors

ABSTRACT In response to nutrient depletion, the RelA and SpoT proteins generate the signaling molecule (p)ppGpp, which then controls a number of downstream effectors to modulate cell physiology. In Acinetobacter baumannii strain AB5075, a relA ortholog (ABUW_3302) was identified by a transposon insertion that conferred an unusual colony phenotype. An in-frame deletion in relA (ΔrelA) failed to produce detectable levels of ppGpp when amino acid starvation was induced with serine hydroxamate. The ΔrelA mutant was blocked from switching from the virulent opaque colony variant (VIR-O) to the avirulent translucent colony variant (AV-T), but the rate of AV-T to VIR-O switching was unchanged. In addition, the ΔrelA mutation resulted in a pronounced hypermotile phenotype on 0.35% agar plates. This hypermotility was dependent on the activation of a LysR regulator ABUW_1132, which was required for expression of AbaR, a LuxR family quorum-sensing regulator. In the ΔrelA mutant, ABUW_1132 was also required for the increased expression of an operon composed of the ABUW_3766-ABUW_3773 genes required for production of the surfactant-like lipopeptide acinetin 505. Additional phenotypes identified in the ΔrelA mutant included (i) cell elongation at high density, (ii) reduced formation of persister cells tolerant to colistin and rifampin, and (iii) decreased virulence in a Galleria mellonella model. IMPORTANCE Acinetobacter baumannii is a pathogen of worldwide importance. Due to the increasing prevalence of antibiotic resistance, these infections are becoming increasingly difficult to treat. New therapies are required to combat multidrug-resistant isolates. The role of RelA in A. baumannii is largely unknown. This study demonstrates that like in other bacteria, RelA controls a variety of functions, including virulence. Strategies to inhibit the activity of RelA and the resulting production of ppGpp could inhibit virulence and may represent a new therapeutic approach.

scholarly journals Homeostasis of Glutathione Is Associated with Polyamine-Mediated β-Lactam Susceptibility in Acinetobacter baumannii ATCC 19606

2013 ◽  
Vol 57 (11) ◽  
pp. 5457-5461 ◽  
Author(s):  
Dong H. Kwon ◽  
Saboor Hekmaty ◽  
Gomattie Seecoomar
Keyword(s):  
Acinetobacter Baumannii ◽  
Redox State ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Transport Systems ◽  
Toxic Substances ◽  
Cellular Redox ◽  
Content Type ◽  
Intracellular Glutathione ◽  
Cellular Redox State

ABSTRACTGlutathione is a tripeptide (l-γ-glutamyl–l-cysteinyl–glycine) thiol compound existing in many bacteria and maintains a proper cellular redox state, thus protecting cells against toxic substances such as reactive oxygen species. Polyamines (spermine and spermidine) are low-molecular-weight aliphatic polycations ubiquitously presenting in all living cells and modulate many cellular functions. We previously reported that exogenous polyamines significantly enhanced β-lactam susceptibility of β-lactam-associated multidrug-resistantAcinetobacter baumannii. In this study, three genes differentially associated with the polyamine effects on β-lactam susceptibility were identified by transposon mutagenesis ofA. baumanniiATCC 19606. All three genes encoded components of membrane transport systems. Inactivation of one of the genes encoding a putative glutathione transport ATP-binding protein increased the accumulation of intracellular glutathione (∼150 to ∼200%) and significantly decreased the polyamine effects on β-lactam susceptibility inA. baumanniiATCC 19606. When the cells were grown with polyamines, the levels of intracellular glutathione inA. baumanniiATCC 19606 significantly decreased from ∼0.5 to ∼0.2 nmol, while the levels of extracellular glutathione were correspondingly increased. However, the levels of total glutathione (intra- plus extracellular) were unchanged when the cells were grown with or without polyamines. Overall, these results suggest that exogenous polyamines induce glutathione export, resulting in decreased levels of intracellular glutathione, which may produce an improper cellular redox state that is associated with the polyamine-mediated β-lactam susceptibility ofA. baumannii. This finding may provide a clue for development of new antimicrobial agents and/or novel strategies to treat multidrug-resistantA. baumannii.

Characterization of Quinolone Resistance in Salmonella enterica from Farm Animals in China

2017 ◽  
Vol 80 (10) ◽  
pp. 1742-1748 ◽  
Author(s):  
Ting-Ting Cao ◽  
Guo-Hui Deng ◽  
Liang-Xing Fang ◽  
Run-Shi Yang ◽  
Jian Sun ◽  
...  
Keyword(s):  
Resistance Gene ◽  
Salmonella Enterica ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Quinolone Resistance ◽  
Farm Animals ◽  
Gyra Gene ◽  
Republic Of China ◽  
Resistance Plasmids

ABSTRACT This study was focused on the prevalence and antimicrobial susceptibilities of Salmonella directly isolated at animal clinics in Guangdong, People's Republic of China. The isolation rates from chickens, ducks, and pigs were 11.3% (11 of 97 samples), 15.4% (53 of 344 samples), and 3.0% (13 of 434 samples), respectively. Among the 77 Salmonella enterica isolates, the most predominant serovar was Typhimurium (81.8%, 63 isolates), followed by serovars Meleagridis (2.6%, 2 isolates) and Abaetetuba (1.3%, 1 isolate). Salmonella isolates were resistant to ciprofloxacin (16.9% of isolates) and nalidixic acid (66.2% of isolates), and 68 isolates (88.3%) were multidrug resistant, displaying resistance to three or more classes of antimicrobial agents. Eighteen isolates (23.4%) had at least one plasmid-mediated quinolone resistance gene, which was identified using PCR and DNA sequencing. The most prevalent plasmid-mediated quinolone resistance gene was aac(6′)-Ib-cr, found in 14 isolates (18.2%), followed by oqxAB (9.1%) and qnrS (7.8%). Alterations in the gyrA gene were detected in 24 (57.1%) of 42 strains with a ciprofloxacin MIC of ≥0.25 μg/mL; the same level of susceptibility was found for enrofloxacin. Six types of mutations were found in the quinolone resistance determining regions of gyrA, and the predominant one (S83Y) was found singly in 15 (62.5%) of 24 isolates. We also found 22 different pulsed-field gel electrophoresis types among the Salmonella isolates. The Salmonella serovars and MICs of ciprofloxacin were similar within clusters, although individual differences were noted. This finding suggests that resistance plasmids were horizontally transmitted but also clonally spread.

scholarly journals Whole-Genome Sequences of Two Multidrug-Resistant Acinetobacter baumannii Strains Isolated from Patients with Urinary Tract Infection in Ghana

2019 ◽  
Vol 8 (31) ◽  
Author(s):  
Nicholas Agyepong ◽  
Usha Govinden ◽  
Alex Owusu-Ofori ◽  
Mushal Allam ◽  
Arshad Ismail ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Urinary Tract Infection ◽  
Acinetobacter Baumannii ◽  
Multidrug Resistant ◽  
Multiple Resistance ◽  
Whole Genome ◽  
Nosocomial Pathogen ◽  
Genome Sequences ◽  
Content Type ◽  
Multiple Resistance Genes

Multidrug-resistant Acinetobacter baumannii is a major nosocomial pathogen. We describe the whole-genome sequences of two multidrug-resistant Acinetobacter baumannii strains isolated from hospitalized patients in the intensive care unit at Komfo Anokye Teaching Hospital in Ghana. The isolates carry multiple resistance genes, including those for β-lactams, sulfonamides, aminoglycosides, and tetracycline.

Characterization of Nalidixic Acid–Resistant and Fluoroquinolone-Reduced Susceptible Salmonella Typhimurium in Swine

2011 ◽  
Vol 74 (4) ◽  
pp. 610-615 ◽  
Author(s):  
K. E. LEE ◽  
J. H. JUNG ◽  
B. Y. JUNG ◽  
Y. H. PARK ◽  
Y. H. LEE
Keyword(s):  
Salmonella Typhimurium ◽  
Nalidixic Acid ◽  
Antimicrobial Agents ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Multidrug Resistant ◽  
Quinolone Resistance ◽  
Specific Primers ◽  
Serovar Typhimurium ◽  
Clonal Spread

From 2001 to 2008, a total of 27 isolates of Salmonella enterica serovar Typhimurium were obtained from 930 swine. All 27 isolates were resistant to streptomycin and tetracycline. Seventeen isolates were multidrug resistant to more than three antimicrobial agents. Seven of these multidrug-resistant isolates were pentaresistant to ampicillin, chloramphenicol, streptomycin, tetracycline, and nalidixic acid. Among 27 isolates, 14 isolates (51.8%) were nalidixic acid resistant (MIC, ≥128 μg/ml) and had reduced susceptibility to various quinolones (MIC, 0.125 to 2 μg/ml). When quinolone resistance–determining regions in the gyrA and gyrB genes of these isolates were sequenced, 13 isolates had Asp87→Tyr mutations and 1 isolate had Asp87→Gly mutation in the quinolone resistance–determining region of gyrA, whereas no mutation was found in gyrB. Genes for qnrA, qnrB, and qnrS were not detected by PCR with specific primers. Pulsed-field gel electrophoresis of genomic DNA digested with XbaI showed two patterns suggesting a clonal spread of Salmonella Typhimurium in swine in Korea.

scholarly journals First Identification and Characterization of an AdeABC-Like Efflux Pump inAcinetobacterGenomospecies 13TU

2011 ◽  
Vol 55 (3) ◽  
pp. 1285-1286 ◽  
Author(s):  
Ignasi Roca ◽  
Paula Espinal ◽  
Sara Martí ◽  
Jordi Vila
Keyword(s):  
Multidrug Resistance ◽  
Acinetobacter Baumannii ◽  
Clinical Isolate ◽  
Nosocomial Infections ◽  
Efflux Pump ◽  
Hospital Setting ◽  
Multidrug Resistant ◽  
Identification Techniques ◽  
Identification And Characterization

ABSTRACTNon-Acinetobacter baumanniispp. are emerging among clinicalAcinetobacterisolates causing nosocomial infections, and some (such as genomospecies 13TU) appear to be multidrug resistant. The prevalence of non-Acinetobacter baumanniispp. in the hospital setting is likely understated due to poor identification techniques. We report the first identification of an AdeABC-type efflux pump in anAcinetobactergenomospecies 13TU clinical isolate, its contribution to multidrug resistance, and the coexistence of three Ade-type efflux pumps in this strain.

scholarly journals Globally Expanding Carbapenemase Finally Appears in Spain: Nosocomial Outbreak of Acinetobacter baumannii Producing Plasmid-Encoded OXA-23 in Barcelona, Spain

2013 ◽  
Vol 57 (10) ◽  
pp. 5155-5157 ◽  
Author(s):  
Noraida Mosqueda ◽  
Paula Espinal ◽  
Clara Cosgaya ◽  
Sergio Viota ◽  
Virginia Plasensia ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Molecular Characterization ◽  
Multidrug Resistant ◽  
Sequence Type ◽  
Clinical Isolates ◽  
Nosocomial Outbreak ◽  
Content Type ◽  
Hospital Outbreak

ABSTRACTResistance ofAcinetobacter baumanniiclinical isolates to carbapenems is on the rise worldwide mainly in association with the production of OXA-23. Until recently, however, OXA-23 was absent in Spain. In this work, we report the molecular characterization of a hospital outbreak of OXA-23-producingA. baumanniiin Barcelona caused by a multidrug-resistant (MDR) clone belonging to international clone IC-II/sequence type ST85 between October 2010 and May 2011.blaOXA-23was carried in a plasmid of 90 kb and located within the composite transposon Tn2006.

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