Deletion of Tn AbaR23 Results in both Expected and Unexpected Antibiogram Changes in a Multidrug-Resistant Acinetobacter baumannii Strain
| Autor: | Jacqueline Z.-M. Chan, Mandira Kochar, Marialuisa Crosatti, Ewan M. Harrison, Chrystala Constantinidou, Mark J. Pallen, Kumar Rajakumar, Barbara Rieck, Hong-Yu Ou |
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| Rok vydání: | 2012 |
| Předmět: |
Acinetobacter baumannii
DNA Bacterial Transposable element Molecular Sequence Data Microbial Sensitivity Tests Drug resistance medicine.disease_cause Polymerase Chain Reaction Microbiology Antibiotic resistance Plasmid Mechanisms of Resistance Drug Resistance Multiple Bacterial Pulsed-field gel electrophoresis medicine Humans Pharmacology (medical) Pharmacology Genetics Mutation Strain (chemistry) biology Chromosome Mapping biology.organism_classification Culture Media Electrophoresis Gel Pulsed-Field Infectious Diseases Conjugation Genetic DNA Transposable Elements Gene Deletion Acinetobacter Infections Plasmids |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 56:1845-1853 |
| ISSN: | 1098-6596 0066-4804 |
| Popis: | Since the 2006 discovery of the Acinetobacter baumannii strain AYE AbaR1 resistance island, similar elements have been reported in numerous members of this species. As AbaR1 is distantly related to Tn 7 , we have renamed it Tn AbaR1 . Tn AbaR transposons are known to carry multiple antibiotic resistance- and efflux-associated genes, although none have been experimentally studied en bloc . We deleted the Tn AbaR transposon in A. baumannii A424, which we have designated Tn AbaR23 , and characterized independent deletion mutants DCO163 and DCO174. The NotI pulsed-field gel electrophoresis (PFGE) profile of strain DCO174 was consistent with targeted deletion of Tn AbaR23 alone, but strain DCO163 apparently harbored a second large genomic deletion. Nevertheless, “subtractive amplification” targeting 52 Tn AbaR and/or resistance-associated loci yielded identical results for both mutants and highlighted genes lost relative to strain A424. PCR mapping and genome sequencing revealed the entire 48.3-kb sequence of Tn AbaR23 . Consistent with Tn AbaR23 carrying two copies of sul1 , both mutants exhibited markedly increased susceptibility to sulfamethoxazole. In contrast, loss of tetAR (A) resulted in only a minor and variable increase in tetracycline susceptibility. Despite not exhibiting a growth handicap, strain DCO163 was more susceptible than strain DCO174 to 9 of 10 antibiotics associated with mutant-to-mutant variation in susceptibility, suggesting impairment of an undefined resistance-associated function. Remarkably, despite all three strains sharing identical gyrA and parC sequences, the ciprofloxacin MIC of DCO174 was >8-fold that of DCO163 and A424, suggesting a possible paradoxical role for Tn AbaR23 in promoting sensitivity to ciprofloxacin. This study highlights the importance of experimental scrutiny and challenges the assumption that resistance phenotypes can reliably be predicted from genotypes alone. |
| Databáze: | OpenAIRE |
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