Overexpression of the <i>adeB</i> Efflux Pump Gene in Tigecycline-Resistant <i>Acinetobacter baumannii</i> Clinical Isolates and Its Inhibition by (+)Usnic Acid as an Adjuvant

Abstract

Acinetobacter species are among the most life-threatening Gram-negative bacilli, causing hospital-acquired infections, and they are associated with high morbidity and mortality. They show multidrug resistance that acts via various mechanisms. In Acinetobacter baumannii, efflux pump-mediated resistance to many antimicrobial compounds, including tigecycline, has been widely reported. Natural compounds have been used for their various pharmacological properties, including anti-efflux pump activity. The present study aimed to evaluate the efflux pump-mediated resistance mechanism of Acinetobacter baumannii and the effect of (+)Usnic acid as an efflux pump inhibitor with tigecycline. For detecting the efflux pump activity of tigecycline-resistant Acinetobacter baumannii isolates, microbroth dilution method and real-time quantitative reverse transcription–polymerase chain reaction was used. (+)Usnic acid was added to tigecycline and tested by the checkerboard method to evaluate its efficacy as an efflux pump inhibitor. qRT-PCR analysis was carried out to show the downregulation of the efflux pump in the isolates. Out of 42 tigecycline-resistant Acinetobacter baumannii isolates, 19 showed efflux pump activity. All 19 strains expressed the adeB gene. (+)Usnic acid as an adjuvant showed better efficacy in lowering the minimum inhibitory concentration compared with the conventional efflux pump inhibitor, carbonyl cyanide phenylhydrazone.

Keywords

• multidrug resistance
• <i>Acinetobacter</i> <i>baumannii</i>
• efflux pumps
• <i>adeB</i>
• (+)Usnic acid