Role of plasmid carrying blaNDM in mediating antibiotic resistance among Acinetobacter baumannii clinical isolates from Egypt

Acinetobacter baumannii is a Gram-negative pathogenic bacterium that often exhibits a multidrug-resistant phenotype causing infections at various sites of the body and increasingly leading to septicaemic shock. This study evaluated the role of acriflavine, a frameshift mutagen, on the movement of insertion sequence ISAba1 in clinical isolates of A. baumannii, with the focus on changes in expression levels of the bla ADC and bla OXA-51-like genes. Resistance profiles were assessed with consideration of ISAba1 acting as a promoter upstream of the bla ADC or bla OXA-51-like gene. ISAba1 movement was observed in the acriflavine mutants Ab153M and Ab1225M. Ab153M exhibited an increase in the MIC values of carbapenems and ceftazidime, with ISAba1 gained upstream of the bla ADC and bla OXA-51-like genes, correlating with an increase in gene expression. Reduced expression of the 17, 23 and 25 kDa outer-membrane proteins (OMPs) was also observed in Ab153M. There was a significant decrease in MIC values of carbapenems with the loss of ISAba1 upstream of the bla ADC and bla OXA-51-like genes in strain Ab1225M, and a significant decrease in bla OXA-51-like gene expression and, to a lesser extent, in bla ADC expression. Ab1225M and a serially subcultured Ab1225 strain (Ab1225s) exhibited overexpression of the 17, 23, 25 and 27 kDa OMPs. There was a decrease in MIC values of the carbapenems and piperacillin/tazobactam but not of ceftazidime in Ab1225s, which had ISAba1 upstream of the bla ADC and bla OXA-51-like genes. A significant decrease in bla OXA-51-like expression was observed in Ab1225s, whereas the expression of bla ADC was similar to that in the Ab1225 parental strain. The attenuation in this strain may be due to overexpression of OMPs and it is clear that, even if ISAba1 is present upstream of an antibiotic resistance gene, it may not necessarily contribute towards the overexpression of antibiotic resistance genes (bla OXA-51-like in Ab1225s). Movement of the IS element within the A. baumannii chromosome may be an important regulatory mechanism employed by the bacterium under particular stress conditions, and the ability to upregulate the expression of antibiotic resistance genes is likely to be an important factor in the pathogenicity of this bacterium.

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AB5075, a Highly Virulent Isolate of Acinetobacter baumannii, as a Model Strain for the Evaluation of Pathogenesis and Antimicrobial Treatments

mBio ◽

10.1128/mbio.01076-14 ◽

2014 ◽

Vol 5 (3) ◽

Cited By ~ 120

Author(s):

Anna C. Jacobs ◽

Mitchell G. Thompson ◽

Chad C. Black ◽

Jennifer L. Kessler ◽

Lily P. Clark ◽

...

Keyword(s):

Antibiotic Resistance ◽

Animal Models ◽

Acinetobacter Baumannii ◽

Survival Rates ◽

The United States ◽

Clinical Isolates ◽

Suitable Model ◽

Content Type ◽

Highly Virulent ◽

Model Strain

ABSTRACT Acinetobacter baumannii is recognized as an emerging bacterial pathogen because of traits such as prolonged survival in a desiccated state, effective nosocomial transmission, and an inherent ability to acquire antibiotic resistance genes. A pressing need in the field of A. baumannii research is a suitable model strain that is representative of current clinical isolates, is highly virulent in established animal models, and can be genetically manipulated. To identify a suitable strain, a genetically diverse set of recent U.S. military clinical isolates was assessed. Pulsed-field gel electrophoresis and multiplex PCR determined the genetic diversity of 33 A. baumannii isolates. Subsequently, five representative isolates were tested in murine pulmonary and Galleria mellonella models of infection. Infections with one strain, AB5075, were considerably more severe in both animal models than those with other isolates, as there was a significant decrease in survival rates. AB5075 also caused osteomyelitis in a rat open fracture model, while another isolate did not. Additionally, a Tn5 transposon library was successfully generated in AB5075, and the insertion of exogenous genes into the AB5075 chromosome via Tn7 was completed, suggesting that this isolate may be genetically amenable for research purposes. Finally, proof-of-concept experiments with the antibiotic rifampin showed that this strain can be used in animal models to assess therapies under numerous parameters, including survival rates and lung bacterial burden. We propose that AB5075 can serve as a model strain for A. baumannii pathogenesis due to its relatively recent isolation, multidrug resistance, reproducible virulence in animal models, and genetic tractability. IMPORTANCE The incidence of A. baumannii infections has increased over the last decade, and unfortunately, so has antibiotic resistance in this bacterial species. A. baumannii is now responsible for more than 10% of all hospital-acquired infections in the United States and has a >50% mortality rate in patients with sepsis and pneumonia. Most research on the pathogenicity of A. baumannii focused on isolates that are not truly representative of current multidrug-resistant strains isolated from patients. After screening of a panel of isolates in different in vitro and in vivo assays, the strain AB5075 was selected as more suitable for research because of its antibiotic resistance profile and increased virulence in animal models. Moreover, AB5075 is susceptible to tetracycline and hygromycin, which makes it amenable to genetic manipulation. Taken together, these traits make AB5075 a good candidate for use in studying virulence and pathogenicity of this species and testing novel antimicrobials.

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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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Comparative genomic analysis of Acinetobacter baumannii clinical isolates reveals extensive genomic variation and diverse antibiotic resistance determinants

BMC Genomics ◽

10.1186/1471-2164-15-1163 ◽

2014 ◽

Vol 15 (1) ◽

pp. 1163 ◽

Cited By ~ 33

Author(s):

Fei Liu ◽

Yuying Zhu ◽

Yong Yi ◽

Na Lu ◽

Baoli Zhu ◽

...

Keyword(s):

Antibiotic Resistance ◽

Acinetobacter Baumannii ◽

Genomic Analysis ◽

Comparative Genomic Analysis ◽

Genomic Variation ◽

Clinical Isolates ◽

Comparative Genomic ◽

Resistance Determinants

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Prevalence of the blaCTX-M and antibiotic resistance pattern among clinical isolates of Acinetobacter baumannii isolated from Zahedan, Southeast Iran

Gene Reports ◽

10.1016/j.genrep.2020.100626 ◽

2020 ◽

Vol 19 ◽

pp. 100626

Author(s):

Morad Ali Ranaei ◽

Shahram Shahraki-Zahedan ◽

Amir Hossein Mohagheghi-Fard ◽

Himen Salimizand ◽

Ramin Ordoni ◽

...

Keyword(s):

Antibiotic Resistance ◽

Acinetobacter Baumannii ◽

Clinical Isolates ◽

Resistance Pattern ◽

Antibiotic Resistance Pattern

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Antibiotic Resistance Profile and Distribution of Oxacillinase Genes Among Clinical Isolates of Acinetobacter baumannii in Shiraz Teaching Hospitals, 2012 - 2013

Jundishapur Journal of Microbiology ◽

10.5812/jjm.20215v2 ◽

2015 ◽

Vol 8 (8) ◽

Cited By ~ 10

Author(s):

Sara Kooti ◽

Mohammad Motamedifar ◽

Jamal Sarvari

Keyword(s):

Antibiotic Resistance ◽

Acinetobacter Baumannii ◽

Clinical Isolates ◽

Teaching Hospitals ◽

Resistance Profile ◽

Antibiotic Resistance Profile

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Colistin resistance in Acinetobacter baumannii is driven by multiple genomic traits: Evaluating the role of ISAba1-driven eptA overexpression among Indian isolates

10.1101/2021.01.07.425695 ◽

2021 ◽

Author(s):

Saranya Vijayakumar ◽

Jobin John Jacob ◽

Karthick Vasudevan ◽

Baby Abirami Shankar ◽

Maria Lincy Francis ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Lipid A ◽

Resistance Mechanisms ◽

Clinical Isolates ◽

Colistin Resistance ◽

Two Component System ◽

Synonymous Mutations ◽

Insertional Inactivation ◽

Indian Isolates

Colistin resistance in Acinetobacter baumannii is mediated by multiple mechanisms. Recently, mutations within pmrAB two component system and overexpression of eptA due to upstream insertion of ISAba1 play a major role. To characterize colistin resistance mechanisms among the clinical isolates of A. baumannii in India. A total of 224 clinical isolates of A. baumannii collected from 2016 to 2019 were included in this study. Mutations within lipid A biosynthesis and pmrAB genes were characterized by Whole Genome Shotgun sequencing. Twenty eight complete genomes were further characterized for insertional inactivation of lpx genes and the association of ISAba1-eptA using hybrid assembly approach. Non-synonymous mutations like M12I in pmrA, A138T and A444V in pmrB and E117K in lpxD were identified. Four of the five colistin resistant A. baumannii isolates had insertion of ISAba1 upstream eptA. No mcr genes were identified. Overall, the present study highlights the diversity of colistin resistance mechanisms in A. baumannii. ISAba1-driven eptA overexpression could be responsible for colistin resistance among Indian isolates of colistin resistant A. baumannii.

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Current Pattern of Antibiotic Resistance in Clinical Isolates of Acinetobacter Baumannii from Intensive Care Units of Tertiary Care Hospital

Annals of King Edward Medical University ◽

10.21649/akemu.v22i1.791 ◽

2016 ◽

Vol 22 (1) ◽

pp. 17 ◽

Cited By ~ 1

Author(s):

Ishrat Irfan Ali ◽

Irfan Ali Khan ◽

Muhammad Kashif Munir ◽

Sheikh Ajaz Rasool

Keyword(s):

Antibiotic Resistance ◽

Intensive Care ◽

Acinetobacter Baumannii ◽

Intensive Care Units ◽

Tertiary Care Hospital ◽

Tertiary Care ◽

Clinical Isolates ◽

Hospital Environment ◽

Care Hospital ◽

Acinetobacter Spp

AbstractPurpose: To determine the pattern of antibiotic resistance in clinical isolates of Acinetobacter baumannii from ICU’s of tertiary care hospital in Karachi.Study Design: A case control study.Methods: Three hundred and fifteen clinical isolates of Acinetobacter baumannii collected from different ICUs were evaluated during 1 year period. The isolates were identified by morphology, growth and biochemical characteristics, susceptibility to a panel of anti-microbial agents in disc diffusion assay and molecular characterization by PCR using glt A and gyr B genes.Results: 94% of Acinetobacter spp were detected as multi drug resistant (MDR) and sensitive to Polymixin B only. About 6% Acinetobacter spp were also MDR but sensitive to Polymixin B, Meropenem and Salbactum + Cefoperazone. All tested isolates exhibited differing resistance representation, as establish by medium incorporation – replica method, against different tested antibiotics, as follows: Amoxicillin – Cal-vulanic acid, Tazobactam, Ceftriaxone, Ceftazidime, Meropenem, Imipenem, Gentamicin, Amikacin, Chlo-ramphenicol, Cotrimoxazole, Tobramycin, Salbactam, Cefoperazone, Gentamicin and Amikacin. All the isolates of Acinetobacter baumannii were PCR positive for glt A and gyr B.Conclusions: Acinetobacter baumannii is the most frequently isolated and alarming pathogen in the health care system specifically for the patients in intensive care units (ICUs). Its survival in hospital environment is because of tolerance the antibiotics and antiseptic pressures. Multi drug resistance made this pathogen the lethal pathogen of this century to infect debilitated patients. There is a strict need to monitor the surveillance of global clones at institutional and or intra-institutional level for accurate treatment, precise prevention and batter control.

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