Bacterial adaptation strategies to host-derived fatty acids

Tchoupa, Arnaud Kengmo; Eijkelkamp, Bart A.; Peschel, Andreas

doi:10.1016/j.tim.2021.06.002

Cited by 33 publications

(40 citation statements)

References 80 publications

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“…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.…”

Section: Bacterial Alterations To Membrane Lipid Composition—the Phan...mentioning

confidence: 99%

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

2022

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The proposition of a post-antimicrobial era is all the more realistic with the continued rise of antimicrobial resistance. The development of new antimicrobials is failing to counter the ever-increasing rates of bacterial antimicrobial resistance. This necessitates novel antimicrobials and drug targets. The bacterial cell membrane is an essential and highly conserved cellular component in bacteria and acts as the primary barrier for entry of antimicrobials into the cell. Although previously under-exploited as an antimicrobial target, the bacterial cell membrane is attractive for the development of novel antimicrobials due to its importance in pathogen viability. Bacterial cell membranes are diverse assemblies of macromolecules built around a central lipid bilayer core. This lipid bilayer governs the overall membrane biophysical properties and function of its membrane-embedded proteins. This mini-review will outline the mechanisms by which the bacterial membrane causes and controls resistance, with a focus on alterations in the membrane lipid composition, chemical modification of constituent lipids, and the efflux of antimicrobials by membrane-embedded efflux systems. Thorough insight into the interplay between membrane-active antimicrobials and lipid-mediated resistance is needed to enable the rational development of new antimicrobials. In particular, the union of computational approaches and experimental techniques for the development of innovative and efficacious membrane-active antimicrobials is explored.

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Section: Bacterial Alterations To Membrane Lipid Composition—the Phan...mentioning

confidence: 99%

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

2022

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“…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 ). The concentration of PUFAs in the human plasma can vary considerably, from 0.1 mM to 0.6 mM, depending on dietary intake, with the shift toward western diets rapidly decreasing their accumulation within the host ( 23 , 24 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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“…Production of free fatty acids (FFAs) are known as a natural protection strategy against bacterial infections in humans, animals, and plants ( Kengmo Tchoupa et al, 2021 ). In humans, FFAs are present in multiple areas, such as the skin and the gastrointestinal tract, where their antimicrobial properties protect the host against bacterial infections ( Chatterjee et al, 2007 ; Kohler et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

“…In general, FFAs are thought to interfere with biological processes in the membrane, causing reduced nutrient uptake, cell lysis, leakage of cell metabolites, or disruption of the electron transport chain ( Desbois and Smith, 2010 ). To cope with antimicrobial FFAs in FFA-rich environments, bacteria have evolved various strategies to avoid FFA toxicity ( Kengmo Tchoupa et al, 2021 ). Those strategies primarily involve repulsion of FFAs from the bacterial surface, detoxification of the FFAs, or efflux of FFAs from the cytosol to the extracellular environment ( Kengmo Tchoupa et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Absence of N-Acetylglucosamine Glycosylation on Listeria monocytogenes Wall Teichoic Acids Promotes Fatty Acid Tolerance by Repulsion From the Bacterial Surface

et al. 2022

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Free fatty acids (FFAs) have strong antimicrobial properties against pathogenic bacteria and are known as natural protective agents against bacterial infections. Growth of the foodborne pathogen Listeria monocytogenes is highly affected by the presence of antimicrobial FFAs, however, the response of L. monocytogenes toward FFAs is not fully understood. Here, we explore how L. monocytogenes gains tolerance toward FFAs and present a novel mechanism conferring bacterial protection against FFA toxicity. Strains tolerant against the antimicrobial FFA palmitoleic acid were isolated and whole genome sequenced, and mutations were found in genes involved in wall teichoic acid (WTA) glycosylations. We show that mutation or deletion of lmo1079, which is essential for N-acetylglucosamine (GlcNAc) glycosylation of WTAs, confer tolerance against several antimicrobial FFAs. The FFA tolerant strains are lacking GlcNAc on their WTAs, which result in a more hydrophilic surface. In line with this, we observed a reduced binding of FFAs to the surface of the FFA tolerant strains. Additionally, lack of GlcNAc on WTAs confers tolerance toward acid stress. Altogether, these findings support that GlcNAc modification of WTA plays an important role in the response of L. monocytogenes toward stress conditions encountered during growth as a saprophyte and pathogen, including FFA-rich environments. Most importantly, our data revealed that L. monocytogenes strains lacking GlcNAc on their WTAs are protected against FFA toxicity, because the FFAs are repulsed from the bacterial surface of GlcNAc-deficient strains.

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Bacterial adaptation strategies to host-derived fatty acids

Cited by 33 publications

References 80 publications

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

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

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

Absence of N-Acetylglucosamine Glycosylation on Listeria monocytogenes Wall Teichoic Acids Promotes Fatty Acid Tolerance by Repulsion From the Bacterial Surface

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