scholarly journals Genomic Characterization of Extensively Drug-Resistant NDM-Producing Acinetobacter baumannii Clinical Isolates With the Emergence of Novel blaADC-257

2021 ◽  
Vol 12 ◽  
Author(s):  
Mai M. Zafer ◽  
Amira F. A. Hussein ◽  
Mohamed H. Al-Agamy ◽  
Hesham H. Radwan ◽  
Samira M. Hamed
Keyword(s):  
Antimicrobial Resistance ◽  
Acinetobacter Baumannii ◽  
Resistance Genes ◽  
Strong Association ◽  
Carbapenem Resistance ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Missense Mutations ◽  
Extensively Drug Resistant ◽  
Susceptibility Profiles

Acinetobacter baumannii has become a major challenge to clinicians worldwide due to its high epidemic potential and acquisition of antimicrobial resistance. This work aimed at investigating antimicrobial resistance determinants and their context in four extensively drug-resistant (XDR) NDM-producing A. baumannii clinical isolates collected between July and October 2020 from Kasr Al-Ainy Hospital, Cairo, Egypt. A total of 20 A. baumannii were collected and screened for acquired carbapenemases (blaNDM, blaVIM and blaIMP) using PCR. Four NDM producer A. baumannii isolates were identified and selected for whole-genome sequencing, in silico multilocus sequence typing, and resistome analysis. Antimicrobial susceptibility profiles were determined using disk diffusion and broth microdilution tests. All blaNDM-positive A. baumannii isolates were XDR. Three isolates belonged to high-risk international clones (IC), namely, IC2 corresponding to ST570Pas/1701Oxf (M20) and IC9 corresponding to ST85Pas/ST1089Oxf (M02 and M11). For the first time, we report blaNDM-1 gene on the chromosome of an A. baumannii strain that belongs to sequence type ST164Pas/ST1418Oxf. Together with AphA6, blaNDM-1 was bracketed by two copies of ISAba14 in ST85Pas isolates possibly facilitating co-transfer of amikacin and carbapenem resistance. A novel blaADC allele (blaADC-257) with an upstream ISAba1 element was identified in M19 (ST/CC164Pas and ST1418Oxf/CC234Oxf). blaADC genes harbored by M02 and M11 were uniquely interrupted by IS1008. Tn2006-associated blaOXA-23 was carried by M20. blaOXA-94 genes were preceded by ISAba1 element in M02 and M11. AbGRI3 was carried by M20 hosting the resistance genes aph(3`)-Ia, aac(6`)-Ib`, catB8, ant(3``)-Ia, sul1, armA, msr(E), and mph(E). Nonsynonymous mutations were identified in the quinolone resistance determining regions (gyrA and parC) of all isolates. Resistance to colistin in M19 was accompanied by missense mutations in lpxACD and pmrABC genes. The current study provided an insight into the genomic background of XDR phenotype in A. baumannii recovered from patients in Egypt. WGS revealed strong association between resistance genes and diverse mobile genetic elements with novel insertion sites and genetic organizations.

Extensively Drug Resistant Acinetobacter baumannii ST369 Infection in Emergency Intensive Care Unit in Shandong Province, China

2020 ◽  
Author(s):  
Meijie Jiang ◽  
Lin Li ◽  
Shuang Liu ◽  
Zhijun Zhang ◽  
Ning Li ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Molecular Epidemiology ◽  
Acinetobacter Baumannii ◽  
Resistance Genes ◽  
Susceptibility Testing ◽  
Control Measures ◽  
Pulse Field ◽  
Drug Resistant ◽  
Aminoglycoside Resistance ◽  
Extensively Drug Resistant

Abstract Background: Acinetobacter baumannii is a significant nosocomial infectious pathogen worldwide. The aim of this study is to characterize the molecular epidemiology of Acinetobacter baumannii isolated from the clinical infection, providing the epidemiology data for prevention and control. Four patients hospitalized in EICU on January 31st, 2014, and then Acinetobacter baumannii infection was observed. Antimicrobial resistance and resistance genes were analyzed by antimicrobial susceptibility testing and PCR sequencing. Pulse field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were used to analyze these strains’ clonal relatedness. Results: Sixteen strains were recovered, of which 4 strains were isolated from 4 patients, and others were from environment in EICU, such as air, phone and ventilator. All strains belonged to clonal pulsotype A and ST369. Sixteen antibiotics were used to perform the susceptibility testing, and all strains were extensively drug resistant (XDR) Acinetobacter baumannii, they were only susceptible to tigecycline and polymyxin B, but resistant to others, including carbapenems and aminoglycoside antibiotics. Furthermore, all strains carried blaOXA-23-like carbapenemases gene with ISAba1 insertion sequence in the upstream, aminoglycoside resistance genes ant(3″)-I, 16S rRNA methylase gene armA and disinfectant resistant gene qacE△1, which were mainly responsible for the spread of antimicrobial resistance. Fortunately, enhanced control measures were immediately implemented after this infection, and new strains were no longer detected for consecutive three months. Conclusions: molecular epidemiology of blaOXA-23-like carbapenemase-producing Acinetobacter baumannii ST369 in EICU of a hospital was characterized. Routine monitoring should be strengthen to prevent outbreaks of this disease.

scholarly journals Complete Genome Sequences of Four Extensively Drug-Resistant Acinetobacter baumannii Isolates from Thailand

2020 ◽  
Vol 9 (40) ◽  
Author(s):  
Peechanika Chopjitt ◽  
Thidathip Wongsurawat ◽  
Piroon Jenjaroenpun ◽  
Parichart Boueroy ◽  
Rujirat Hatrongjit ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Complete Genome ◽  
Sequence Type ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Genome Sequences ◽  
Content Type ◽  
Type Isolate ◽  
Resistant Genes ◽  
Extensively Drug Resistant

ABSTRACT Here, we report the complete genome sequences of four clinical isolates of extensively drug-resistant Acinetobacter baumannii (XDRAB), isolated in Thailand. These results revealed multiple antimicrobial-resistant genes, each involving two sequence type 16 (ST16) isolates, ST2, and a novel sequence type isolate, ST1479.

scholarly journals Molecular epidemiology and antimicrobial resistance features of Acinetobacter baumannii clinical isolates from Pakistan

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Nabil Karah ◽  
Fizza Khalid ◽  
Sun Nyunt Wai ◽  
Bernt Eric Uhlin ◽  
Irfan Ahmad
Keyword(s):  
Antimicrobial Resistance ◽  
Molecular Epidemiology ◽  
Acinetobacter Baumannii ◽  
Resistance Genes ◽  
Antimicrobial Agents ◽  
Opportunistic Pathogen ◽  
Clinical Isolates ◽  
Diffusion Method ◽  
Agar Disc ◽  
Antimicrobial Resistance Genes

Abstract Background Acinetobacter baumannii is a Gram-negative opportunistic pathogen with a notorious reputation of being resistant to antimicrobial agents. The capability of A. baumannii to persist and disseminate between healthcare settings has raised a major concern worldwide. Methods Our study investigated the antibiotic resistance features and molecular epidemiology of 52 clinical isolates of A. baumannii collected in Pakistan between 2013 and 2015. Antimicrobial susceptibility patterns were determined by the agar disc diffusion method. Comparative sequence analyses of the ampC and blaOXA-51-like alleles were used to assign the isolates into clusters. The whole genomes of 25 representative isolates were sequenced using the MiSeq Desktop Sequencer. Free online applications were used to determine the phylogeny of genomic sequences, retrieve the multilocus sequence types (ST), and detect acquired antimicrobial resistance genes. Results Overall, the isolates were grouped into 7 clusters and 3 sporadic isolates. The largest cluster, Ab-Pak-cluster-1 (blaOXA-66 and ISAba1-ampC-19) included 24 isolates, belonged to ST2 and International clone (IC) II, and was distributed between two geographical far-off cities, Lahore and Peshawar. Ab-Pak-clusters-2 (blaOXA-66, ISAba1-ampC-2), and -3 (blaOXA-66, ISAba1-ampC-20) and the individual isolate Ab-Pak-Lah-01 (ISAba1-blaOXA-66, ISAba1-ampC-2) were also assigned to ST2 and IC II. On the other hand, Ab-Pak-clusters-4 (blaOXA-69, ampC-1), -5 (blaOXA-69, ISAba1-ampC-78), and -6A (blaOXA-371, ISAba1-ampC-3) belonged to ST1, while Ab-Pak-cluster-6B (blaOXA-371, ISAba1-ampC-8) belonged to ST1106, with both ST1 and ST1106 being members of IC I. Five isolates belonged to Ab-Pak-cluster-7 (blaOXA-65, ampC-43). This cluster corresponded to ST158, showed a well-delineated position on the genomic phylogenetic tree, and was equipped with several antimicrobial resistance genes including blaOXA-23 and blaGES-11. Conclusions Our study detected the occurrence of 7 clusters of A. baumannii in Pakistan. Altogether, 6/7 of the clusters and 45/52 (86.5%) of the isolates belonged to IC I (n = 9) or II (n = 36), making Pakistan no exception to the global domination of these two clones. The onset of ST158 in Pakistan marked a geographical dispersal of this clone beyond the Middle East and brought up the need for a detailed characterization.

scholarly journals Extensive antimicrobial resistance and plasmid-carrying resistance genes in mcr-1-positive E. coli sampled in swine, in Guangxi, South China

2021 ◽  
Author(s):  
Jingzhi Yuan ◽  
Xiaoye Wang ◽  
Dali Shi ◽  
Qiang Ge ◽  
Xingxing Song ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
South China ◽  
Resistance Genes ◽  
Antimicrobial Agents ◽  
Health And Safety ◽  
Carbapenem Resistance ◽  
Drug Resistant ◽  
Potential Threat ◽  
E Coli ◽  
Antimicrobial Resistance Genes

Abstract Background: The discovery of the superbug mcr-1-positive Escherichia coli (MCRPEC) has drew greet attention. Swine-origin multi-drug resistant MCRPEC has been a potential threat to public health and safety. However, there were few detailed studies have been reported on swine MCRPEC in Guangxi, South China.Results: In this study, thirty-three MCRPEC strains were detected from 142 E. coli strains from 116 samples in Guangxi in 2018. Which could be classified into eight unique STs and a total of six incompatibility plasmid groups (IncFI, IncHI1, IncY, IncN, IncI1 and IncX1). After that, the susceptibility of MCRPEC isolates to 27 antimicrobial agents belonging to 17 antimicrobial categories was tested. There were nineteen E. coli resistant to 3rd and 4th generation cephalosporins and twelve E. coli resistant to carbapenem resistan. Importantly, the MCRPEC showed high resistance highly resistance for imipenem and meropenem, which were forbidden to use in livestock production. Three MCRPEC strains were further proved to be extensively drug-resistant (XDR), and the other isolates were multi-drug-resistant (MDR). Furthermore, we found that the plasmid-carrying resistance genes coexisted with the mcr-1 gene of the MCRPEC isolates. Which were listed as follows: β-lactamase antimicrobial resistance genes e.g. ESBL genes (blaCTX-M14, blaCTX-M24, blaCTX-M123, blaOXA-1), plasmid-mediated AmpC (pAmpC) gene (blaCMY-2), the carbapenem resistance gene (blaNDM-5), and non-β-lactamase antimicrobial resistance genes (qnrA, qnrB, qnrS, aac(6’)-Ib-cr, tetA, tetB, sul1, sul2, floR, aadA).Conclusion: Thirty-three mcr-1-positive E. coli isolates in Guangxi displayed a wide profile of antimicrobial resistance. Plasmid-carrying resistance genes might be the main cause of MCRPEC multidrug resistance. This study highlighted the necessity for long-term surveillance of mcr-1-positive E. coli in pigs.

scholarly journals Multifactorial Chromosomal Variants Regulate Polymyxin Resistance in Extensively Drug-Resistant Klebsiella pneumoniae

2017 ◽  
Author(s):  
Miranda E Pitt ◽  
Alysha G Elliott ◽  
Minh Duc Cao ◽  
Devika Ganesamoorthy ◽  
Ilias Karaiskos ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Clinical Isolates ◽  
Whole Genome ◽  
Drug Resistant ◽  
Missense Mutations ◽  
Novel Mutations ◽  
Suppressor Mutations ◽  
Extensively Drug Resistant

ABSTRACTExtensively drug-resistant Klebsiella pneumoniae (XDR-KP) infections cause high mortality and are disseminating globally. Identifying the genetic basis underpinning resistance allows for rapid diagnosis and treatment. XDR isolates sourced from Greece and Brazil, including nineteen polymyxin-resistant and five polymyxin-susceptible strains, underwent whole genome sequencing. Approximately 90% of polymyxin resistance was enabled by alterations upstream or within mgrB. The most common mutation identified was an insertion at nucleotide position 75 in mgrB via an ISKpn26-like element in the ST258 lineage and ISKpn13 in one ST11 isolate. Three strains acquired an IS1 element upstream of mgrB and another strain had an ISKpn25 insertion at 133 bp. Other isolates had truncations (C28STOP, Q30STOP) or a missense mutation (D31E) affecting mgrB. Complementation assays revealed all mgrB perturbations contributed to resistance. Missense mutations in phoQ (T281M, G385C) were also found to facilitate resistance. Several variants in phoPQ co-segregating with the ISKpn26-like insertion were identified as potential partial suppressor mutations. Three ST258 samples were found to contain subpopulations with different resistance conferring mutations, including the ISKpn26-like insertion colonising with a novel mutation in pmrB (P158R), both confirmed via complementation assays. We also characterized a new multi-drug resistant Klebsiella quasipneumoniae strain ST2401 which was susceptible to polymyxins. These findings highlight the broad spectrum of chromosomal modifications which can facilitate and regulate resistance against polymyxins in K. pneumoniae.DATA SUMMARYWhole genome sequencing of the 24 clinical isolates has been deposited under BioProject PRJNA307517 (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA307517).IMPACT STATEMENTKlebsiella pneumoniae contributes to a high abundance of nosocomial infections and the rapid emergence of antimicrobial resistance hinders treatment. Polymyxins are predominantly utilized to treat multidrug-resistant infections, however, resistance to the polymyxins is arising. This increasing prevalence in polymyxin resistance is evident especially in Greece and Brazil. Identifying the genomic variations conferring resistance in clinical isolates from these regions assists with potentially detecting novel alterations and tracing the spread of particular strains. This study commonly found mutations in the gene mgrB, the negative regulator of PhoPQ, known to cause resistance in KP. In the remaining isolates, missense mutations in phoQ were accountable for resistance. Multiple novel mutations were detected to be segregating with mgrB perturbations. This was either due to a mixed heterogeneous sample of two polymyxin-resistant strains, or because of multiple mutations within the same strain. Of interest was the validation of novel mutations inphoPQ segregating with a previously known ISKpn26-like element in disrupted mgrB isolates. Complementation of these phoPQ mutations revealed a reduction in minimum inhibitory concentrations and suggests the first evidence of partial suppressor mutations in KP. This research builds upon our current understanding of heteroresistance, lineage specific mutations and regulatory variations relating to polymyxin resistance.

scholarly journals Proteogenomic characterization of antimicrobial resistance in extensively drug-resistant Acinetobacter baumannii DU202

2014 ◽  
Vol 69 (6) ◽  
pp. 1483-1491 ◽  
Author(s):  
Sang-Yeop Lee ◽  
Sung Ho Yun ◽  
Yeol Gyun Lee ◽  
Chi-Won Choi ◽  
Sun-Hee Leem ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Acinetobacter Baumannii ◽  
Drug Resistant ◽  
Extensively Drug Resistant

scholarly journals Interbacterial transfer of carbapenem resistance and large antibiotic resistance islands by natural transformation in pathogenic Acinetobacter

2021 ◽  
Author(s):  
Anne-Sophie Godeux ◽  
Elin Svedholm ◽  
Samuel Barreto ◽  
Agnese Lupo ◽  
Marisa Haenni ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Acinetobacter Baumannii ◽  
Resistance Genes ◽  
Natural Transformation ◽  
Antibiotic Resistance Genes ◽  
Carbapenem Resistance ◽  
Predatory Behavior ◽  
Clinical Isolates

Acinetobacter baumannii infection poses a major health threat with recurrent treatment failure due to antibiotic resistance, notably to carbapenems. While genomic analyses of clinical strains indicate that homologous recombination plays a major role in the acquisition of antibiotic resistance genes, the underlying mechanisms of horizontal gene transfer often remain speculative. Our understanding of the acquisition of antibiotic resistance is hampered by the lack of experimental systems able to reproduce genomic observations. We here report the detection of recombination events occurring spontaneously in mixed bacterial populations and which can result in the acquisition of resistance to carbapenems. We show that natural transformation is the main driver of intra-, but also inter-strain recombination events between A. baumannii clinical isolates and pathogenic species of Acinetobacter. We observed that interbacterial natural transformation in mixed populations is more efficient at promoting the acquisition of large resistance islands (AbaR4, AbaR1) than providing the same bacteria with high quantities of purified genomic DNA. Importantly, analysis of the genomes of the recombinant progeny revealed large recombination tracts (from 13 to 123 kb) similar to those observed in the genome of clinical isolates. Moreover, we highlight that transforming DNA availability is a key determinant of the rate of recombination and results from both spontaneous release and interbacterial predatory behavior. Natural transformation should be considered as a leading mechanism of genome recombination and horizontal gene transfer of antibiotic resistance genes in Acinetobacter baumannii.

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