Abstract
Acinetobacter baumannii is a common causative agent of hospital-acquired infections and a leading cause of infection in burns patients. Carbapenem-resistant A. baumannii is considered a major public-health threat and has been identified by the World Health Organization as the top priority organism requiring new antimicrobials. The most common mechanism for carbapenem resistance in A. baumannii is via horizontal acquisition of carbapenemase genes. In this study, we sampled 20 A. baumannii isolates from a patient with extensive burns, and characterized the evolution of carbapenem resistance over a 45 day period via Illumina and Oxford Nanopore sequencing. All isolates were multidrug resistant, carrying two genomic islands that harboured several antibiotic-resistance genes. Most isolates were genetically identical and represented a single founder genotype. We identified three novel non-synonymous substitutions associated with meropenem resistance: F136L and G288S in AdeB (part of the AdeABC efflux pump) associated with an increase in meropenem MIC to ≥8 µg ml−1; and A515V in FtsI (PBP3, a penicillin-binding protein) associated with a further increase in MIC to 32 µg ml−1. Structural modelling of AdeB and FtsI showed that these mutations affected their drug-binding sites and revealed mechanisms for meropenem resistance. Notably, one of the adeB mutations arose prior to meropenem therapy but following ciprofloxacin therapy, suggesting exposure to one drug whose resistance is mediated by the efflux pump can induce collateral resistance to other drugs to which the bacterium has not yet been exposed.
Highlights
Acinetobacter baumannii is a Gram-negative bacterium that is amongst the six most common causes of multidrug resistant (MDR) hospital-acquired infections, a group collectively known as ESKAPE pathogens [1]
During a 3 month period in 2013, 20 MDR A. baumannii isolates (A2–A20, A22) were cultured from swabs collected from the burn wound sites of a single patient with extensive burns, who was being treated in the intensive care unit (ICU) of a tertiary care hospital in Melbourne, Australia
Three additional A. baumannii isolates, cultured from wound swabs from three other patients admitted to the same ICU ward within a month of patient 1’s stay, were included in the study for comparison
Summary
Acinetobacter baumannii is a Gram-negative bacterium that is amongst the six most common causes of multidrug resistant (MDR) hospital-acquired infections, a group collectively known as ESKAPE pathogens [1]. A. baumannii is a common causative agent of pneumonia, bacteraemia, urinary tract infections, meningitis and wound infections, especially in burns patients [2]. A. baumannii is intrinsically resistant to a broad range of antibiotics; over the last three decades additional acquired resistance has emerged [3]. Resistance to these drugs has already been observed [3, 20,21,22], and in 2017 the World Health Organization named carbapenem-resistant A. baumannii as the top priority pathogen critically requiring research and development of new antibiotics [23]
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