Molecular Epidemiology of Emerging
                    bla
                     OXA-23-Like
                    - and
                    bla
                     OXA-24-Like
                    -Carrying
                    Acinetobacter baumannii
                    in Taiwan

ABSTRACT The rate of recovery of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates has increased significantly in recent decades in Taiwan. This study investigated the molecular epidemiology of CRAB with a focus on the mechanisms of resistance and spread in isolates with bla OXA-23-like or bla OXA-24-like . All 555 CRAB isolates in our multicenter collection, which were recovered from 2002 to 2010, were tested for the presence of class A, B, and D carbapenemase genes. All isolates with bla OXA-23-like or bla OXA-24-like were subjected to pulsed-field gel electrophoresis, and 82 isolates (60 isolates with bla OXA-23-like and 22 isolates with bla OXA-24-like ) were selected for multilocus sequence typing to determine the sequence type (ST) and clonal group (CG) and for detection of additional β-lactamase and aminoglycoside resistance genes. The flanking regions of carbapenem and aminoglycoside resistance genes were identified by PCR mapping and sequencing. The localization of bla OXA was determined by S1 nuclease and I-CeuI assays. The numbers of CRAB isolates carrying bla OXA-23-like or bla OXA-24-like , especially those carrying bla OXA-23-like , increased significantly from 2008 onward. The bla OXA-23-like gene was carried by antibiotic resistance genomic island 1 (AbGRI1)-type structures located on plasmids and/or the chromosome in isolates of different STs (CG92 and novel CG786), whereas bla OXA-24-like was carried on plasmids in CRAB isolates of limited STs (CG92). No class A or B carbapenemase genes were identified. Multiple aminoglycoside resistance genes coexisted in CRAB. Tn 6180 -borne armA was found in 74 (90.2%) CRAB isolates, and 58 (70.7%) isolates had Tn 6179 upstream, constituting AbGRI3. bla TEM was present in 38 (46.3%) of the CRAB isolates tested, with 35 (92.1%) isolates containing bla TEM in AbGRI2-type structures, and 61% of ampC genes had IS Aba1 upstream. We conclude that the dissemination and spread of a few dominant lineages of CRAB containing various resistance island structures occurred in Taiwan.

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Molecular Epidemiology of Emerging Carbapenem Resistance inAcinetobacter nosocomialisandAcinetobacter pittiiin Taiwan, 2010 to 2014

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02007-18 ◽

2019 ◽

Vol 63 (4) ◽

Cited By ~ 6

Author(s):

Feng-Jui Chen ◽

Wei-Cheng Huang ◽

Yu-Chieh Liao ◽

Hui-Ying Wang ◽

Jui-Fen Lai ◽

...

Keyword(s):

Molecular Epidemiology ◽

Species Identification ◽

Carbapenem Resistance ◽

Close Monitoring ◽

Aminoglycoside Resistance ◽

Content Type ◽

Carbapenem Resistant ◽

Acinetobacter Pittii ◽

Aminoglycoside Resistance Genes ◽

Genetic Structures

ABSTRACTThis study investigated the molecular epidemiology of carbapenem-resistantAcinetobacter nosocomialisandAcinetobacter pittii(ANAP). Clinical isolates ofAcinetobacterspp. collected by the biennial nationwide Taiwan Surveillance of Antimicrobial Resistance program from 2010 to 2014 were subjected to species identification, antimicrobial susceptibility testing, and PCR for detection of carbapenemase genes. Whole-genome sequencing or PCR mapping was performed to study the genetic surroundings of the carbapenemase genes. Among 1,041Acinetobacterisolates, the proportion of ANAP increased from 11% in 2010 to 22% in 2014. The rate of carbapenem resistance in these isolates increased from 7.5% (3/40) to 22% (14/64), with a concomitant increase in their resistance to other antibiotics. TheblaOXA-72andblaOXA-58genes were highly prevalent in carbapenem-resistant ANAP. Various genetic structures were found upstream ofblaOXA-58in different plasmids. Among the plasmids found to containblaOXA-72flanked by XerC/XerD, pAB-NCGM253-like was identified in 8 of 10 isolates. Conjugations of plasmids carryingblaOXA-72orblaOXA-58toA. baumanniiwere successful. In addition, three isolates with chromosome-locatedblaOXA-23embedded in AbGRI1-type structure with disruption of genes other thancomMwere detected. Two highly similar plasmids carrying class I integron containingblaIMP-1and aminoglycoside resistance genes were also found. The universal presence ofblaOXA-272/213-likeonA. pittiichromosomes and their lack of contribution to carbapenem resistance indicate its potential to be a marker for species identification. The increase of ANAP, along with their diverse mechanisms of carbapenem resistance, may herald their further spread and warrants close monitoring.

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Novel Aminoglycoside Resistance Transposons and Transposon-Derived Circular Forms Detected in Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02143-15 ◽

2016 ◽

Vol 60 (3) ◽

pp. 1801-1818 ◽

Cited By ~ 29

Author(s):

Nabil Karah ◽

Chinmay Kumar Dwibedi ◽

Karin Sjöström ◽

Petra Edquist ◽

Anders Johansson ◽

...

Keyword(s):

Antibiotic Resistance ◽

Acinetobacter Baumannii ◽

Resistance Genes ◽

Point Mutations ◽

Antibiotic Resistance Genes ◽

Opportunistic Pathogen ◽

Clinical Isolates ◽

Aminoglycoside Resistance ◽

Content Type ◽

Carbapenem Resistant

Acinetobacter baumanniihas emerged as an important opportunistic pathogen equipped with a growing number of antibiotic resistance genes. Our study investigated the molecular epidemiology and antibiotic resistance features of 28 consecutive carbapenem-resistant clinical isolates ofA. baumanniicollected throughout Sweden in 2012 and 2013. The isolates mainly belonged to clonal complexes (CCs) with an extensive international distribution, such as CC2 (n= 16) and CC25 (n= 7). Resistance to carbapenems was related toblaOXA-23(20 isolates),blaOXA-24/40-like(6 isolates),blaOXA-467(1 isolate), and ISAba1-blaOXA-69(1 isolate). Ceftazidime resistance was associated withblaPER-7in the CC25 isolates. Two classical point mutations were responsible for resistance to quinolones in all the isolates. Isolates with high levels of resistance to aminoglycosides carried the 16S rRNA methylasearmAgene. The isolates also carried a variety of genes encoding aminoglycoside-modifying enzymes. Several novel structures involved in aminoglycoside resistance were identified, including Tn6279, ΔTn6279, Ab-ST3-aadB, and different assemblies of Tn6020and TnaphA6. Importantly, a number of circular forms related to the IS26or ISAba125composite transposons were detected. The frequent occurrence of these circular forms in the populations of several isolates indicates a potential role of these circular forms in the dissemination of antibiotic resistance genes.

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Accumulation of Antibiotic Resistance Genes in Carbapenem-Resistant Acinetobacter baumannii Isolates Belonging to Lineage 2, Global Clone 1, from Outbreaks in 2012–2013 at a Tehran Burns Hospital

mSphere ◽

10.1128/msphere.00164-20 ◽

2020 ◽

Vol 5 (2) ◽

Cited By ~ 2

Author(s):

Masoumeh Douraghi ◽

Johanna J. Kenyon ◽

Parisa Aris ◽

Mahla Asadian ◽

Sedighe Ghourchian ◽

...

Keyword(s):

Middle East ◽

Acinetobacter Baumannii ◽

Resistance Genes ◽

Carbapenem Resistance ◽

Antibiotic Resistant ◽

Content Type ◽

Carbapenem Resistant ◽

East Region ◽

Lineage 2 ◽

Middle East Region

ABSTRACT The worldwide distribution of carbapenem-resistant Acinetobacter baumannii (CRAB) has become a global concern, particularly in countries where antibiotic prescription is not tightly regulated. However, knowledge of the genomic aspects of CRAB from many parts of the world is still limited. Here, 50 carbapenem-resistant A. baumannii isolates recovered at a single hospital in Tehran, Iran, during several outbreaks in 2012 and 2013 were found to be resistant to multiple antibiotics. They were examined using PCR mapping and multilocus sequence typing (MLST). All Iranian strains belonged to sequence type 328 in the Institut Pasteur MLST scheme (ST328IP), a single-locus variant of ST81IP, and all Iranian strains contained two carbapenem resistance genes, oxa23 and oxa24. The oxa23 gene is in the transposon Tn2006 in AbaR4, which interrupts the chromosomal comM gene. Phylogenetic analysis using whole-genome sequence (WGS) data for 9 isolates showed that they belonged to the same clade, designated the ST81/ST328 clade, within lineage 2 of global clone 1 (GC1). However, there were two groups that included either KL13 or KL18 at the K locus (KL) for capsular polysaccharide synthesis and either a tet39 or an aadB resistance gene, respectively. The genetic context of the resistance genes was determined, and the oxa24 (OXA-72 variant) and tet39 (tetracycline resistance) genes were each in a pdif module in different plasmids. The aadB gene cassette (which encodes gentamicin, kanamycin, and tobramycin resistance) was harbored by pRAY*, and the aphA6 gene (which encodes amikacin resistance) and sul2 gene (which encodes sulfamethoxazole resistance) were each harbored by a different plasmid. The sequences obtained here will underpin future studies of GC1 CRAB strains from the Middle East region. IMPORTANCE Carbapenem-resistant Acinetobacter baumannii strains are among the most critical antibiotic-resistant bacteria causing hospital-acquired infections and treatment failures. The global spread of two clones has been responsible for the bulk of the resistance, in particular, carbapenem resistance. However, there is a substantial gap in our knowledge of which clones and which specific lineages within each clone are circulating in many parts of the world, including Africa and the Middle East region. This is the first genomic analysis of carbapenem-resistant A. baumannii strains from Iran. All the isolates, from a single hospital, belonged to lineage 2 of global clone 1 (GC1) but fell into two groups distinguished by genes in the locus for capsule biosynthesis. The analysis suggests a potential origin of multiply antibiotic-resistant lineage 2 in the Middle East region and highlights the ongoing evolution of carbapenem-resistant GC1 A. baumannii strains. It will enhance future studies on the local and global GC1 population structure.

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The Molecular Epidemiology of Resistance to Antibiotics among Klebsiella pneumoniae Isolates in Azerbaijan, Iran

Journal of Tropical Medicine ◽

10.1155/2021/9195184 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Mehdi Kashefieh ◽

Hassan Hosainzadegan ◽

Shabnam Baghbanijavid ◽

Reza Ghotaslou

Keyword(s):

Drug Resistance ◽

Klebsiella Pneumoniae ◽

Molecular Epidemiology ◽

Resistance Genes ◽

Susceptibility Testing ◽

Multidrug Resistant ◽

Aminoglycoside Resistance ◽

State Hospitals ◽

Aminoglycoside Resistance Genes ◽

Hospital Acquired

Introduction. Klebsiella pneumoniae (K. pneumoniae) is one of the leading causes of hospital-acquired and community-acquired infections in the world. This study was conducted to investigate the molecular epidemiology of drug resistance in clinical isolates of K. pneumoniae in Azerbaijan, Iran. Materials and Methods. A total of 100 nonduplicated isolates were obtained from the different wards of Azerbaijan state hospitals, Iran, from 2019 to 2020. Antibiotic susceptibility testing was done. The DNA was extracted, and the PCR for evaluation of the resistance genes was carried out. Results. The highest antibiotic resistance was shown to ampicillin (96%), and the highest susceptibility was shown to tigecycline (9%), and 85% of isolates were multidrug resistant. The most frequent ESBL gene in the tested isolates was blaSHV-1 in 58%, followed by blaCTXM-15 (55%) and blaSHV-11(42%). The qepA, oqxB, and oqxA genes were found to be 95%, 87.5%, and 70%, respectively. We detected tetB in 42%, tetA in 32%, tetD in 21%, and tetC in 16%. Seventy isolates were resistant to co-trimoxazole, and the rate of resistance genes was sul1 in 71%, followed by sul2 (43%), dfr (29%), and sul3 (7%). The most common aminoglycoside resistance genes were ant3Ia, aac6Ib, aph3Ib, and APHs in 44%, 32%, 32%, and 31.4%, respectively. The most frequent resistance gene to fosfomycin was fosA (40%) and fosX (40%) followed by fosC (20%). Conclusion. The results of this study indicate the high frequency of drug resistance among K. pneumoniae isolated from hospitals of Azerbaijan state. The present study shows the presence of high levels of drug-resistant genes in various antibiotics, which are usually used in the treatment of infections due to K. pneumoniae.

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Evolution of a clade of Acinetobacter baumannii global clone 1, lineage 1 via acquisition of carbapenem- and aminoglycoside-resistance genes and dispersion of ISAba1

Microbial Genomics ◽

10.1099/mgen.0.000242 ◽

2019 ◽

Vol 5 (1) ◽

Cited By ~ 9

Author(s):

Mohammad Hamidian ◽

Jane Hawkey ◽

Ryan Wick ◽

Kathryn E. Holt ◽

Ruth M. Hall

Keyword(s):

Acinetobacter Baumannii ◽

Resistance Genes ◽

Aminoglycoside Resistance ◽

Aminoglycoside Resistance Genes

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Prevalence of Aminoglycoside Resistance Genes and Molecular Characterization of a Novel Gene, aac(3)-IIg, among Clinical Isolates of the Enterobacter cloacae Complex from a Chinese Teaching Hospital

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00852-20 ◽

2020 ◽

Vol 64 (9) ◽

Author(s):

Xinyi Zhu ◽

Peizhen Li ◽

Changrui Qian ◽

Hongmao Liu ◽

Hailong Lin ◽

...

Keyword(s):

Teaching Hospital ◽

Resistance Genes ◽

High Throughput Sequencing ◽

Enterobacter Cloacae ◽

Human Pathogens ◽

Aminoglycoside Resistance ◽

Class 1 Integron ◽

Content Type ◽

Novel Gene ◽

Aminoglycoside Resistance Genes

ABSTRACT Members of the Enterobacter cloacae complex are important opportunistic human pathogens capable of causing a wide variety of infections. During recent decades, aminoglycoside-resistant E. cloacae complex isolates have increasingly been reported and have become a major concern. Here, we employed high-throughput sequencing in combination with specific PCR assays to investigate the prevalence of aminoglycoside resistance genes among 170 isolates of the E. cloacae complex collected from a teaching hospital in Wenzhou, China. A total of 12 known genes [aphA-1, strA, strB, aac(6′)-IIc, aadA2, aac(3)-IId, aadB, aadA1, rmtB, armA, aadA5, and aac(6′)-Ie–aph(2′')-Ia] and 1 novel gene [aac(3)-IIg] were identified, with aphA-1 (71.18%), strA (55.29%), and strB (52.35%) being the most prevalent, and aac(3)-IIg was detected with a positive rate of 21.76% (37/170). The aac(3)-IIg gene was 810 bp in length and encoded a protein that shared 72 to 78% identities with previously known AAC(3)-II aminoglycoside 3-N-acetyltransferases. The MICs of gentamicin and tobramycin were 512 μg/ml and 64 μg/ml, respectively, when aac(3)-IIg was cloned into Escherichia coli DH5α. All aac(3)-IIg-positive isolates exerted broad aminoglycoside resistance profiles, mediated by the coexistence of multiple resistance genes. Moreover, aminoglycoside resistance and resistance genes were found to be transferable in most strains (24/37). Nevertheless, pulsed-field gel electrophoresis (PFGE) and dendrogram analysis showed clonal diversity among these isolates. S1 nuclease PFGE, Southern hybridization, and whole-genome sequencing indicated that aac(3)-IIg was located on transferable as well as nontransferable plasmids of various sizes. The analysis of the genetic environment suggested that aac(3)-IIg is embedded within a class 1 integron, with IS26 playing an important role in its mobility.

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Prevalence of Genes Encoding Aminoglycoside-Modifying Enzymes and armA among Acinetobacter baumannii Clinical Isolates in Alexandria, Egypt

Infectious Disorders - Drug Targets ◽

10.2174/1871526521666210225113041 ◽

2021 ◽

Vol 21 ◽

Author(s):

Amel ELsheredy ◽

Zainab Yousif ◽

Ebtesam Elghazzawi ◽

Ahmed Elmenshawy ◽

Abeer Ghazal

Keyword(s):

Acinetobacter Baumannii ◽

Resistance Genes ◽

Antimicrobial Agents ◽

Clinical Isolates ◽

Aminoglycoside Resistance ◽

High Propensity ◽

Genes Encoding ◽

Resistance Patterns ◽

Aminoglycoside Resistance Genes ◽

High Level

Introduction: Acinetobacter baumannii (A.baumannii ) is a ubiquitous pathogen responsible for serious infections in hospitalized patients with a high propensity to develop resistance to antimicrobial agents. The study aimed to determine the antimicrobial resistance patterns and the prevalence of aminoglycoside resistance genes among A. baumannii clinical isolates from patients in different intensive care units (ICUs) in Alexandria, Egypt. Methods: A total of 100 A. baumannii isolates collected from ICU patients were confirmed as A. baumannii by VITEK 2 and the presence of the blaOXA-51 gene has been reported. Antimicrobial susceptibility testing was performed and Multiplex PCR was done for the detection of aminoglycoside resistance genes. Results: Most of the isolates (82%) were resistant to all tested aminoglycosides; resistance was higher for kanamycin and neomycin, followed by amikacin. The predominant AMEs were aphA6 and aphA1 in 86% and 67% of the isolates, respectively; aacA4 and aacC1 were detected in 37% and 8%, respectively, while aadA1 and aadB were present in 34% and 4%, respectively. Furthermore, armA gene was detected in 83% of the isolates. Conclusion: The results of this study revealed a high level carriage of armA and AMEs which limit the usage of aminoglycoside as a treatment option for A. baumannii and makes treatment extremely difficult.

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Genetic identity of aminoglycoside-resistance genes in Escherichia coli isolates from human and animal sources

Journal of Medical Microbiology ◽

10.1099/jmm.0.015032-0 ◽

2010 ◽

Vol 59 (6) ◽

pp. 702-707 ◽

Cited By ~ 30

Author(s):

Pak-Leung Ho ◽

River C. Wong ◽

Stephanie W. Lo ◽

Kin-Hung Chow ◽

Samson S. Wong ◽

...

Keyword(s):

Escherichia Coli ◽

Hong Kong ◽

Molecular Epidemiology ◽

Resistance Genes ◽

Genetic Identity ◽

Aminoglycoside Resistance ◽

Aminoglycoside Resistance Genes ◽

Animal Isolates

A bacterial collection (n=249) obtained in Hong Kong from 2002 to 2004 was used to investigate the molecular epidemiology of aminoglycoside resistance among Escherichia coli isolates from humans and food-producing animals. Of these, 89 isolates were gentamicin-sensitive (human n=60, animal n=29) and 160 isolates were gentamicin-resistant (human n=107, animal n=53). Overall, 84.1 % (90/107) and 75.5 % (40/53) of the gentamicin-resistant isolates from human and animal sources, respectively, were found to possess the aacC2 gene. The aacC2 gene for 20 isolates (10 each for human and animal isolates) was sequenced. Two alleles were found that were equally distributed in human and animal isolates. PFGE showed that the gentamicin-resistant isolates exhibited diverse patterns with little clonality. In some isolates, the aacC2 gene was encoded on large transferable plasmids of multiple incompatibility groups (IncF, IncI1 and IncN). An IncFII plasmid of 140 kb in size was shared by one human and three animal isolates. In summary, this study showed that human and animal isolates share the same pool of resistance genes.

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