The Impact of Omega-3 Fatty Acids on the Evolution of Acinetobacter baumannii Drug Resistance

Abstract

The global distribution of multidrug resistance in A. baumannii has necessitated seeking not only alternative therapeutic approaches but also the means to limit the development of resistance in clinical settings. Highly abundant host bioactive compounds, such as polyunsaturated fatty acids, are readily acquired by A. baumannii during infection and have been illustrated to impact the bacterium’s membrane composition and antibiotic resistance.

Mobile genetic elements in Acinetobacter antibiotic‐resistance acquisition and dissemination

“…The exact mechanism of restoring antibiotic resistance in this strain is unknown and may be related to competition for a shared metabolite used by IspB and undecaprenyl pyrophosphate synthase (UppS), which is required for cell envelope biogenesis. An in vitro study selective for erythromycin‐resistant ABUW5075 in the presence of host fatty acids identified an IS Aba13 transposition upstream of the transcriptional regulator adeN , resulting in a 13.4‐fold decrease in transcription 88 . In this study, the presence of host fatty acids promoted the development of mutations cross‐resistant to tetracycline and azithromycin.…”

“…In another example, an IS Aba1 insertion truncated and activated the expression of adeS , part of a two‐component system that activates the production of the AdeABC efflux pump and conferred tigecycline resistance 87 . An independent study found an IS Aba1 ‐encoded promoter driving transcription of adeIJK , increasing ABUW5075 resistance to erythromycin and tetracycline when supplemented with host‐derived fatty acids in vitro 88 . Similarly, IS Aba1 transposition upstream of the novel gene eptA in A. baumannii increased its expression and resulted in resistance to the polymyxin colistin 5 .…”

“… 87 An independent study found an IS Aba1 ‐encoded promoter driving transcription of adeIJK , increasing ABUW5075 resistance to erythromycin and tetracycline when supplemented with host‐derived fatty acids in vitro . 88 Similarly, IS Aba1 transposition upstream of the novel gene eptA in A. baumannii increased its expression and resulted in resistance to the polymyxin colistin. 5 eptA encodes a phosphoethanolamine transferase and is a homolog to pmrC which is also known to be associated with polymyxin resistance when overexpressed.…”

Characterizing the role of phosphatidylglycerol-phosphate phosphatases in Acinetobacter baumannii cell envelope biogenesis and antibiotic resistance

“…PgpB was found to be highly conserved across the Acinetobacter genus, however, some strains of Acinetobacter lwoffii and Acinetobacter brisouii lacked the gene encoding this phosphatase, which included both clinical and environmental isolates (The Acinetobacter-Dashboard). Although previous studies have identified pgpB mutations in A. baumannii resistance evolution studies ( Santos-Lopez et al, 2019 , Zang et al, 2021a ), this candidate was identified in > 98 % of A. baumannii strains and only a limited number of amino acid variations were seen across these 292 A. baumannii genomes ( Fig. 1 B).…”

Identification of Promoter Region Markers Associated With Altered Expression of Resistance-Nodulation-Division Antibiotic Efflux Pumps in Acinetobacter baumannii

“…Mutations affecting full translation or DNA binding in repressor proteins of RND pump operons have been associated with MIC increases to several antibiotics ( Gerson et al, 2018 ). Moreover, alterations have also been associated with resistance in upstream untranslated regions of adeIJK ( Zang et al, 2021 ).…”