Determine the Efflux Pump Mediated Resistance Mechanism of Acinetobacter baumannii and the Effect of (+) Usnic Acid as an Efflux Pump Inhibitor with Tigecycline

This chapter explores the efflux pump mediated resistance mechanism of Acinetobacter baumannii and the effect of (+) usnic acid as an Efflux pump inhibitor with tigecycline. Among the multi-drug resistant strains, Acinetobacter baumannii is a paramount pathogen in clinical terms, particularly in hospital-acquired infections. Overall, this bacterium is the most associated with nosocomial infections, particularly in intensive care units (ICUs). The most important aspect of the infection with A. baumannii strains is their resistance to entirely known antibiotics, suggesting the need for urgent action by the global health care community. MDRAb isolates (n = 100) (preserved at-70°C in trypticase-soy broth supplemented with 30% glycerol) collected between 2017 to 2019 from two different states in India (Andhra Pradesh & Telangana). For detection of efflux pump activity of tigecycline resistant Acinetobacter baumannii isolates, micro broth dilution method and real-time quantitative reverse transcription-polymerase chain reaction methods were used. (+) usnic acid was added to tigecycline and tested by checkerboard method to evaluate the efficacy as an efflux pump inhibitor. In this study, we demonstrated the EPI activity of UA by using the EtBr agar cart wheel method and by reducing adeB gene expression using qRT-PCR, which resulted in a decrease in TGC resistance in A.baumannii. qRT-PCR analysis was done to show the down-regulation of the efflux pump in the isolates. Out of 42 tigecycline-resistant Acinetobacter baumannii isolates, 19 showed active efflux pump activity. All the 19 strains expressed adeB gene. (+) Usnic acid as adjuvant showed better efficacy in lowering the minimum inhibitory concentration when compared to conventional efflux pump inhibitor carbonyl cyanide phenylhydrazone. Plant derived compounds can act as an adjuvant to antibiotics, to increase the susceptibility to treat infectious diseases.