Dataset Information

Genetic basis of multidrug resistance in Acinetobacter clinical isolates in Taiwan.

ABSTRACT: Multidrug-resistant (MDR) Acinetobacter spp. have emerged as a threat to public health. We investigated the various genes involved in resistance to fluoroquinolones, aminoglycosides, cephalosporins, and carbapenems in 75 clinical Acinetobacter isolates from a Taiwanese hospital. All isolates were tested for the gyrA mutations, the presence of integrons, bla(AmpC), and carbapenem resistance genes. The Ser83Leu mutation in GyrA accounted for fluoroquinolone resistance. The presence of integrons containing aminoglycoside-modifying enzymes was associated with resistance to gentamicin and tobramycin but not with resistance to amikacin. The presence of an ISAba1 element upstream of bla(AmpC) was correlated with cephalosporin resistance. Although most Acinetobacter baumannii isolates with ISAba1-bla(OXA-51-)(like) were resistant to carbapenems, several isolates remained susceptible to carbapenems. Transformation by the introduction of ISAba1-bla(OXA-23) or ISAba1-bla(OXA-66) into A. baumannii ATCC 15151 (CIP 70.10), resulting in the overexpression of OXA-23 or OXA-66, respectively, suggested the role of the ISAba1 element as a strong promoter. The two transformants showed significantly increased resistance to piperacillin-tazobactam, imipenem, and meropenem. The cefepime resistance conferred by ISAba1-bla(OXA-23) and the impact of ISAba1-bla(OXA-66) on carbapenem resistance in A. baumannii are reported here for the first time. Continuous surveillance of antibiotic resistance genes in MDR Acinetobacter spp. and elucidation of their antibiotic resistance mechanisms are crucial for the development of therapy regimens and for the prevention of further dissemination of these antibiotic resistance genes.

SUBMITTER: Lin YC

PROVIDER: S-EPMC2863617 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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Genetic basis of multidrug resistance in Acinetobacter clinical isolates in Taiwan.

Lin Yu-Chi YC Hsia Ko-Chiang KC Chen Yee-Chun YC Sheng Wang-Huei WH Chang Shan-Chwen SC Liao Mei-Hui MH Li Shu-Ying SY

Antimicrobial agents and chemotherapy 20100301 5

Multidrug-resistant (MDR) Acinetobacter spp. have emerged as a threat to public health. We investigated the various genes involved in resistance to fluoroquinolones, aminoglycosides, cephalosporins, and carbapenems in 75 clinical Acinetobacter isolates from a Taiwanese hospital. All isolates were tested for the gyrA mutations, the presence of integrons, bla(AmpC), and carbapenem resistance genes. The Ser83Leu mutation in GyrA accounted for fluoroquinolone resistance. The presence of integrons co ...[more]

PMID: 20194701

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Project description:In Acinetobacter baumannii (A. baumannii), a wide repertoire of resistance genes is often carried within genomic resistance islands (RIs), particularly in high-risk global clones (GCs). As the first in Egypt, the current study aimed at exploring the diversity and genetic configuration of RIs in the clinical isolates of A. baumannii. For this purpose, draft genomes of 18 isolates were generated by Illumina sequencing. Disk diffusion susceptibility profiling revealed multidrug resistance (MDR) and extensive drug resistance (XDR) phenotypes in 27.7 and 72.2%, respectively. The highest susceptibility was noted for tigecycline (100.0%) followed by colistin (94.4%), for which an MIC50 of 0.25 μg/ml was recorded by the broth microdilution assay. Sequence typing (ST) showed that the majority of the isolates belonged to high-risk global clones (GC1, GC2, and GC9). A novel Oxford sequence type (ST2329) that also formed a novel clonal complex was submitted to the PubMLST database. A novel bla ADC variant (bla ADC-258) was also identified in strain M18 (ST85Pas/1089Oxf). In addition to a wide array of resistance determinants, whole-genome sequencing (WGS) disclosed at least nine configurations of genomic RIs distributed over 16/18 isolates. GC2 isolates accumulated the largest number of RIs (three RIs/isolate) followed by those that belong to GC1 (two RIs/isolate). In addition to Tn6022 (44.4%), the comM gene was interrupted by AbaR4 (5.5%) and three variants of A. baumannii genomic resistance island 1(AbGRI)-type RIs (44.4%), including AbaR4b (16.6%) and two novel configurations of AbGRI1-like RIs (22.2%). Three of which (AbaR4, AbaR4b, and AbGRI1-like-2) carried bla OXA-23 within Tn2006. With less abundance (38.8%), IS26-bound RIs were detected exclusively in GC2 isolates. These included a short version of AbGRI2 (AbGRI2-15) carrying the genes bla TEM-1 and aphA1 and two variants of AbGRI3 RIs carrying up to seven resistance genes [mphE-msrE-armA-sul1-aadA1-catB8-aacA4]. Confined to GC1 (22.2%), sulfonamide resistance was acquired by an ISAba1 bracketed GIsul2 RI. An additional RI (RI-PER-7) was also identified on a plasmid carried by strain M03. Among others, RI-PER-7 carried the resistance genes armA and bla PER-7. Here, we provided a closer view of the diversity and genetic organization of RIs carried by a previously unexplored population of A. baumannii.

Project description:Carbapenem resistant Acinetobacter baumannii is a major global concern, especially in countries of the Middle East and North Africa, where the antibiotic resistance rates are on the rise. The aim of this study was to study the genomic characteristics and antimicrobial susceptibility profile of thirty-six multidrug resistant A. baumannii clinical isolates obtained in hospitals from Alexandria, Egypt. Antibiotic resistance rates were estimated by determination of Minimum Inhibitory Concentrations. Carbapenemase genes, other antibiotic resistance genes and virulence factors were then screened by the use of Whole Genome Sequencing. Isolates were also subjected to Multi Locus Sequence Typing (MLST) using the Pasteur Scheme and to core genome MLST to study their clonal relatedness. In addition, plasmid analysis was performed by the use of a commercial kit and S1- Pulsed Field Gel Electrophoresis, and Hybridization experiments with DIG-labeled DNA probes for bla NDM-1, blaPER-7 and bla GES-like were performed to locate these genes. The majority of isolates were resistant to β-lactams (including carbapenems), fluoroquinolones, aminoglycosides and trimethoprim; and some showed resistance to cefiderocol and minocycline. We identified 8 different bla OXA-51-like variants including bla OXA-51, bla OXA-64, bla OXA-65, bla OXA-66, bla OXA-68, bla OXA-91, bla OXA-94 and bla OXA-336; bla OXA-23, bla NDM-1, bla PER-7, bla GES-like and bla ADC-like and other antibiotic resistance genes, some of these genes were within transposons or class 1 integrons. Multiple virulence factors responsible for adherence, biofilm production, type II and type VI secretion systems, exotoxins, exoenzymes, immune modulation and iron uptake were observed and 34 out of 36 isolates showed motility. Thirty-five out of 36 isolates clustered with International Clones 2, 4, 5, 7, 8 and 9; and 9 STs were identified including ST570, ST2, ST600, ST15, ST113, ST613, ST85, ST158, ST164. Plasmids ranging in size from 1.7 to 70 kb were found; bla NDM-1 and blaPER-7 genes were located in the chromosome and bla GES-like genes were simultaneously located in the chromosome and in a plasmid of 70kb. In conclusion, this study revealed a wide spectrum of antibiotic resistance genes and a variety of lineages among A. baumannii isolated in hospitals from Alexandria, and highlights the importance of investigating the molecular epidemiology to control the spread of multi-drug resistant isolates.

Project description:ObjectiveProteus mirabilis is the one of most important pathogens of catheter-associated urinary tract infections. The emergence of multidrug-resistant (MDR) P. mirabilis severely limits antibiotic treatments, which poses a public health risk. This study aims to investigate the resistance characteristics and virulence potential for a collection of P. mirabilis clinical isolates.Methods and resultsAntibiotic susceptibility testing revealed fourteen MDR strains, which showed high resistance to most β-lactams and trimethoprim/sulfamethoxazole, and a lesser extent to quinolones. All the MDR strains were sensitive to carbapenems (except imipenem), ceftazidime, and amikacin, and most of them were also sensitive to aminoglycosides. The obtained MDR isolates were sequenced using an Illumina HiSeq. The core genome-based phylogenetic tree reveals the high genetic diversity of these MDR P. mirabilis isolates and highlights the possibility of clonal spread of them across China. Mobile genetic elements SXT/R391 ICEs were commonly (10/14) detected in these MDR P. mirabilis strains, whereas the presence of resistance island PmGRI1 and plasmid was sporadic. All ICEs except for ICEPmiChn31006 carried abundant antimicrobial resistance genes (ARGs) in the HS4 region, including the extended-spectrum β-lactamase (ESBL) gene blaCTX-M-65. ICEPmiChn31006 contained the sole ARG blaCMY-2 and was nearly identical to the global epidemic ICEPmiJpn1. The findings highlight the important roles of ICEs in mediating the spread of ARGs in P. mirabilis strains. Additionally, these MDR P. mirabilis strains have great virulence potential as they exhibited significant virulence-related phenotypes including strong crystalline biofilm, hemolysis, urease production, and robust swarming motility, and harbored abundant virulence genes.ConclusionIn conclusion, the prevalence of MDR P. mirabilis with high virulence potential poses an urgent threat to public health. Intensive monitoring is needed to reduce the incidence of infections by MDR P. mirabilis.

Dataset Information

Genetic basis of multidrug resistance in Acinetobacter clinical isolates in Taiwan.

Publications

Genetic basis of multidrug resistance in Acinetobacter clinical isolates in Taiwan.

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