To Make or Take: Bacterial Lipid Homeostasis during Infection

Abstract

Acinetobacter baumannii is one of the world’s most problematic superbugs and is associated with significant morbidity and mortality in the hospital environment. The critical need for new antimicrobial strategies is recognized, but our understanding of its behavior and adaptation to a changing environment during infection is limited.

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

“…This observation displays similarity to the enhanced resistance of Streptococcus pneumoniae to the antimicrobial peptide LL-37 following AA treatment ( 31 ). Considering the profound impact of fatty acids on antibiotic activity and their ubiquitous presence at the host-pathogen interface, compared to standard laboratory media ( 19 ), the supplementation of fatty acids based on niche-specific profiles ( 21 ) in in vitro resistance assays should be considered. Exactly how host fatty acids impact macrolide- A. baumannii interactions during infection remains unknown, but the work presented here underscores the importance of administering the appropriate antibiotic during treatment, because failed erythromycin treatment may compromise the efficacy of treatment with other antibiotics, such as tetracycline.…”

“…Antimicrobial resistance is mostly studied in standard laboratory media, and the impact of host molecules is thus overlooked. Fatty acids are highly abundant in most host niches, they are nearly indiscriminately acquired by A. baumannii , and they can impact A. baumannii physiology ( 18 – 21 ). The nearly universal antimicrobial activity of the long-chain polyunsaturated fatty acids (PUFAs) (with ≥16 carbons and ≥2 double bonds) that belong to the omega-3 and omega-6 groups has been well established ( 19 , 22 ).…”

Lipid-mediated antimicrobial resistance: a phantom menace or a new hope?

“…Both Gram-negative and Gram-positive pathogens can alter their membrane composition to adapt to their biological niche (Adams et al 2021 ) or evade antimicrobials and host immune mechanisms (Epand and Epand 2009b ; Hewelt-Belka et al 2016 ; Hines et al 2017 ; Sperandeo et al 2019 ). These changes in their membranes are induced via transcriptional control of lipid synthesis, or through alterations to the active transport of lipids between membrane leaflets, and also between the inner and outer membranes of Gram-negative bacteria.…”

“…For example, mutations in pgsA, resulting in decreased PG content, can also result in upstream accumulation of fatty acids and subsequent remodelling of bacterial lipid fatty acid profiles (Hines et al 2017 ). The acyl tail profile of some pathogens is also influenced by the availability of exogenous fatty acids, such as host-derived long-chain polyunsaturated fatty acids which have antimicrobial properties (Yao and Rock 2015 ; Churchward et al 2018 ; Adams et al 2021 ; Kengmo Tchoupa et al 2021 ). Acyl-tail remodelling induced by exogenous fatty acids has been associated with reduced fitness and increased antimicrobial susceptibility in several pathogens (Kengmo Tchoupa et al 2021 ), raising the possibility of combining membrane-active antimicrobial therapy with exogenous fatty acids for increased efficacy.…”

123I-BMIPP, a Radiopharmaceutical for Myocardial Fatty Acid Metabolism Scintigraphy, Could Be Utilized in Bacterial Infection Imaging

“…The development and application of radiopharmaceuticals, such as 99m Tc-based derivatives, 99m Tc-labeled antibiotics, 11 C-labeled D-amino acids, and 2-deoxy-2-[ 18 F]fluoro- d -glucose ( 18 F-FDG), which target components of the bacterial cell wall, are still in progress [ 6 , 8 ]. These compounds include not only carbon sources (D-glucose), nitrogen sources (amino acids), and minerals but also fatty acids, which are essential for bacterial growth [ 9 , 10 ]. However, to date, no radiopharmaceutical for bacterial infection imaging that targets fatty acid metabolism has been developed.…”