Correlation of Ciprofloxacin Resistance with the AdeABC Efflux System in Acinetobacter baumannii Clinical Isolates
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Background: Acinetobacter baumannii is one of the most important pathogens capable of colonization in burn patients, leading to drug-resistant wound infections. This study evalu- ated the distribution of the AdeABC efflux system genes and their relationship to ciproflox- acin resistance in A. baumannii isolates collected from burn patients. Methods: A total of 68 A. baumannii clinical strains were isolated from patients hospital- ized in Motahari Burns Center in Tehran, Iran. Ciprofloxacin susceptibility was tested by the disk diffusion and agar dilution methods. PCR amplification of the adeRS-adeB drug efflux genes was performed for all resistant and susceptible isolates. To assess the role of the drug efflux pump in ciprofloxacin susceptibility, carbonyl cyanide 3-chlorophenylhy- drazone (CCCP) was used as an efflux pump inhibitor (EPI). Results: Approximately 95.6% of the Acinetobacter isolates were resistant to ciprofloxacin, with minimum inhibitory concentration (MIC) values ranging from 4 to ≥128 µg/mL. The susceptibility of 86.1% of the resistant isolates increased by factors of 2 to 64 in the pres- ence of CCCP. All resistant isolates were positive for the adeRS-adeB genes, and 73.2% of them had mutations in the AdeRS regulatory system. Conclusions: The results showed that AdeABC genes are common in A. baumannii , which might be associated with ciprofloxacin non-susceptibility, as indicated by the observed link- age to the presence of the genes essential for the activity of the AdeABC, several single mutations occurring in the adeRS regulatory system, and an increase of ciprofloxacin sus- ceptibility in the presence of a CCCP EPI.
Abstract
Background: Acinetobacter baumannii is one of the most important pathogens capable of colonization in burn patients, leading to drug-resistant wound infections. This study evalu- ated the distribution of the AdeABC efflux system genes and their relationship to ciproflox- acin resistance in A. baumannii isolates collected from burn patients. Methods: A total of 68 A. baumannii clinical strains were isolated from patients hospital- ized in Motahari Burns Center in Tehran, Iran. Ciprofloxacin susceptibility was tested by the disk diffusion and agar dilution methods. PCR amplification of the adeRS-adeB drug efflux genes was performed for all resistant and susceptible isolates. To assess the role of the drug efflux pump in ciprofloxacin susceptibility, carbonyl cyanide 3-chlorophenylhy- drazone (CCCP) was used as an efflux pump inhibitor (EPI). Results: Approximately 95.6% of the Acinetobacter isolates were resistant to ciprofloxacin, with minimum inhibitory concentration (MIC) values ranging from 4 to ≥128 µg/mL. The susceptibility of 86.1% of the resistant isolates increased by factors of 2 to 64 in the pres- ence of CCCP. All resistant isolates were positive for the adeRS-adeB genes, and 73.2% of them had mutations in the AdeRS regulatory system. Conclusions: The results showed that AdeABC genes are common in A. baumannii , which might be associated with ciprofloxacin non-susceptibility, as indicated by the observed link- age to the presence of the genes essential for the activity of the AdeABC, several single mutations occurring in the adeRS regulatory system, and an increase of ciprofloxacin sus- ceptibility in the presence of a CCCP EPI.
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