Overexpression of the adeB Efflux Pump Gene in Tigecycline-Resistant Acinetobacter baumannii 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.

Estimation the levels of two genes expression and their effects on tetracycline resistance of Acinetobacter baumannii isolated from different sources

“…(+) Usnic acid is an efflux pump inhibitor that can be added to MDRAb as an adjuvant. To enhance the effectiveness of antibiotics in the treatment of infectious illnesses, chemicals originating from plants can be used as adjuvants (Bankan et al 2021). The results also agreed with another study that proven a correlation between the antibiotic effects of Tigecycline on AdeB gene expression and the frequency of AdeB gene in the A. baumannii isolates were 100% (Rafiei et al 2022).…”

Dissemination and prevalence of plasmid-mediated high-level tigecycline resistance gene tet (X4)

“…An active efflux pump is a protein transport system of bacteria, it can excrete antibiotics entering the bacteria from itself, reducing antibiotic concentration in bacteria, so as to promote the growth of ARB ( Venter et al, 2015 ; Bankan et al, 2021 ). There are five main efflux pump families involved in the active efflux of antibiotics, one is the ATP binding cassette (ABC) superfamily, which is the “primary active” transporter that directly uses ATP binding and hydrolysis to drive the free efflux of drugs ( Rempel et al, 2019 ).…”

Antibiotic and Nematocidal Metabolites from Two Lichen Species Collected on the Island of Lampedusa (Sicily)

“…Antiproliferative activity against some cancer cell lines [ 19 , 20 ] and in vivo anti-inflammatory [ 21 ], antiviral [ 22 ], insecticidal [ 23 , 24 ], and phytotoxic activity [ 25 , 26 ] have also been described. Lately, given its pharmacological properties, the interest in the applicability in medicine for the development of antibacterial films [ 27 ] or as adjuvant to inhibit the Gram-negative bacteria Acinetobacter baumannii [ 28 ] has increased.…”