scholarly journals Staphylococcus aureus adapts to the host nutritional landscape to overcome tissue-specific branched-chain fatty acid requirement

2021 ◽  
Vol 118 (13) ◽  
pp. e2022720118
Author(s):  
Wei Ping Teoh ◽  
Xi Chen ◽  
Irina Laczkovich ◽  
Francis Alonzo

During infection, pathogenic microbes adapt to the nutritional milieu of the host through metabolic reprogramming and nutrient scavenging. For the bacterial pathogen Staphylococcus aureus, virulence in diverse infection sites is driven by the ability to scavenge myriad host nutrients, including lipoic acid, a cofactor required for the function of several critical metabolic enzyme complexes. S. aureus shuttles lipoic acid between these enzyme complexes via the amidotransferase, LipL. Here, we find that acquisition of lipoic acid, or its attachment via LipL to enzyme complexes required for the generation of acetyl-CoA and branched-chain fatty acids, is essential for bacteremia, yet dispensable for skin infection in mice. A lipL mutant is auxotrophic for carboxylic acid precursors required for synthesis of branched-chain fatty acids, an essential component of staphylococcal membrane lipids and the agent of membrane fluidity. However, the skin is devoid of branched-chain fatty acids. We showed that S. aureus instead scavenges host-derived unsaturated fatty acids from the skin using the secreted lipase, Geh, and the unsaturated fatty acid–binding protein, FakB2. Moreover, murine infections demonstrated the relevance of host lipid assimilation to staphylococcal survival. Altogether, these studies provide insight into an adaptive trait that bypasses de novo lipid synthesis to facilitate S. aureus persistence during superficial infection. The findings also reinforce the inherent challenges associated with targeting bacterial lipogenesis as an antibacterial strategy and support simultaneous inhibition of host fatty acid salvage during treatment.

2009 ◽  
Vol 191 (24) ◽  
pp. 7447-7455 ◽  
Author(s):  
Natalia Martin ◽  
Esteban Lombardía ◽  
Silvia G. Altabe ◽  
Diego de Mendoza ◽  
María C. Mansilla

ABSTRACT Lipoic acid is an essential cofactor required for the function of key metabolic pathways in most organisms. We report the characterization of a Bacillus subtilis mutant obtained by disruption of the lipA (yutB) gene, which encodes lipoyl synthase (LipA), the enzyme that catalyzes the final step in the de novo biosynthesis of this cofactor. The function of lipA was inferred from the results of genetic and physiological experiments, and this study investigated its role in B. subtilis fatty acid metabolism. Interrupting lipoate-dependent reactions strongly inhibits growth in minimal medium, impairing the generation of branched-chain fatty acids and leading to accumulation of copious amounts of straight-chain saturated fatty acids in B. subtilis membranes. Although depletion of LipA induces the expression of the Δ5 desaturase, controlled by a two-component system that senses changes in membrane properties, the synthesis of unsaturated fatty acids is insufficient to support growth in the absence of precursors for branched-chain fatty acids. However, unsaturated fatty acids generated by deregulated overexpression of the Δ5 desaturase functionally replaces lipoic acid-dependent synthesis of branched-chain fatty acids. Furthermore, we show that the cold-sensitive phenotype of a B. subtilis strain deficient in Δ5 desaturase is suppressed by isoleucine only if LipA is present.


Foods ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 471
Author(s):  
Guillermo Ripoll ◽  
María Jesús Alcalde ◽  
Anastasio Argüello ◽  
María de Guía Córdoba ◽  
Begoña Panea

Goat meat is considered healthy because it has fewer calories and fat than meat from other traditional meat species. It is also rich in branched chain fatty acids that have health advantages when consumed. We studied the effects of maternal milk and milk replacers fed to suckling kids of four breeds on the straight and branched fatty acid compositions of their muscle. In addition, the proximal and fatty acid compositions of colostrum and milk were studied. Goat colostrum had more protein and fat and less lactose than milk. Goat milk is an important source of healthy fatty acids such as C18:1 c9 and C18:2 n–6. Suckling kid meat was also an important source of C18:1c9. Dairy goat breeds had higher percentages of trans monounsaturated fatty acids (MUFAs) and most of the C18:1 isomers but lower amounts of total MUFAs than meat breeds. However, these dairy kids had meat with a lower percentage of conjugated linoleic acid (CLA) than meat kids. The meat of kids fed natural milk had higher amounts of CLA and branched chain fatty acids (BCFAs) and lower amounts of n–6 fatty acids than kids fed milk replacers. Both milk and meat are a source of linoleic, α-linolenic, docosahexaenoic, eicosapentaenoic and arachidonic fatty acids, which are essential fatty acids and healthy long-chain fatty acids.


2003 ◽  
Vol 67 (10) ◽  
pp. 2106-2114 ◽  
Author(s):  
Hirosuke OKU ◽  
Naoya FUTAMORI ◽  
Kenichi MASUDA ◽  
Yumiko SHIMABUKURO ◽  
Tomoyo OMINE ◽  
...  

1971 ◽  
Vol 26 (9) ◽  
pp. 893-901 ◽  
Author(s):  
Heinz Egge ◽  
Uwe Murawski ◽  
Wirapong Chatranon ◽  
Fritz Zilliken

The fatty acid methylesters prepared by transesterification of the total lipid extract of Staphylococcus aureus Wood 46 were analysed by gas chromatography on thin film capillaries coated with polyphenylether (OS 138), siliconerubber (SE 30) and S.C.O.T. columns coated with Diethyleneglycoladipatepolyester (DEGA) in combination with mass spectrometry. Among the branched chain fatty acids ranging from C11- C21 the iso- and anteiso-C15 acids are predominant.In the group of the C15 and C17 acids branching in position 9 and 10 was also found. No unsaturated branched chain fatty acids could be detected. Retention data and mass spectra of the branched chain fatty acids are presented.


1980 ◽  
Vol 26 (8) ◽  
pp. 893-898 ◽  
Author(s):  
Toshi Kaneda ◽  
E. J. Smith

Fatty acid compositions of lipids from six bacteria and four yeasts were determined. Fatty acid de novo synthetases were investigated with respect to chain length specificity towards acyl-CoA primers of various chain lengths.Four species of bacteria (Bacillus subtilis, Corynebacterium cyclohexanicum, Micrococcus luteus, and Pseudomonas maltophilia) possess branched-chain fatty acids of the iso and anteiso series as the major acids. De novo synthetases from these organisms exhibited specificity towards the chain length of the primer in the order butyrl-CoA > propionyl-CoA [Formula: see text] acetyl-CoA. The remainder, two bacteria and all four yeasts, have the straight-chain type of fatty acids only and fall into two groups: (1) Eschericia coli B, Pseudomonas fluorescens, and Saccharomyces cerevisiae, which utilize the primers in the order acetyl-CoA > propionyl-CoA [Formula: see text] butyryl-CoA; and (2) Candida sake, Candida tropicalis, and Rhodolorula glutinis, which show the order propionyl-CoA > acetyl-CoA [Formula: see text] butyryl-CoA.L-α-Keto-β-methylvalerate, a precursor of the branched-chain primers, can be used as a source of primer for fatty acid synthesis by the organisms with branched-chain acids but not by those with the straight-chain type.The results indicate that organisms having straight-chain fatty acids lack the branched-chain equivalents for two reasons: first, their enzymes are not active toward primers with more than three carbons, and second, they lack a system of supplying suitable branched-chain primers.It appears that activities of de novo synthetases from the organisms having straight-chain fatty acids generally have much higher activities than those from the organisms possessing branched-chain fatty acids.


2002 ◽  
Vol 68 (6) ◽  
pp. 2809-2813 ◽  
Author(s):  
David S. Nichols ◽  
Kirsty A. Presser ◽  
June Olley ◽  
Tom Ross ◽  
Tom A. McMeekin

ABSTRACT The fatty acid composition of Listeria monocytogenes Scott A was determined by close-interval sampling over the entire biokinetic temperature range. There was a high degree of variation in the percentage of branched-chain fatty acids at any given temperature. The percentage of branched C17 components increased with growth temperature in a linear manner. However, the percentages of iso-C15:0 (i15:0) and anteiso-C15:0 (a15:0) were well described by third-order and second-order polynomial curves, respectively. There were specific temperature regions where the proportion of branched-chain fatty acids deviated significantly from the trend established over the entire growth range. In the region from 12 to 13°C there were significant deviations in the percentages of both i15:0 and a15:0 together with a suggested deviation in a17:0, resulting in a significant change in the total branched-chain fatty acids. In the 31 to 33°C region the percentage of total branched-chain components exhibited a significant deviation. The observed perturbations in fatty acid composition occurred near the estimated boundaries of the normal physiological range for growth.


1983 ◽  
Vol 29 (12) ◽  
pp. 1634-1641 ◽  
Author(s):  
Toshi Kaneda ◽  
Eleanor J. Smith ◽  
Devarray N. Naik

The fatty acid compositions of three psychrophilic species of Bacillus were determined by gas–liquid chromatography. The proportions of straight-chain fatty acids, branched-chain fatty acids, and unsaturated fatty acids were found to be 13.3, 86.7, and 26.1 % of the total cellular fatty acids for Bacillus globispores, 36.6, 63.4, and 25.1 % for Bacillus insolitus, and 6.9, 93.1, and 18.4% for Bacillus psychrophilus, respectively. In all three organisms the de novo fatty acid synthetase specificity towards acyl-CoA primers was butyryl-CoA > propionyl-CoA [Formula: see text] acetyl-CoA. This shows that B. insolitus, which has an unusually large proportion of straight-chain fatty acids for Bacillus, does not possess a different de novo fatty acid synthetase than the other two organisms. Therefore, the greater proportion of straight-chain fatty acids in B. insolitus may be explained by a large supply of straight-chain primer.


Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1416
Author(s):  
Jocelijn Meijerink

Intestinal enteroendocrine cells (EECs) respond to fatty acids from dietary and microbial origin by releasing neurotransmitters and hormones with various paracrine and endocrine functions. Much has become known about the underlying signaling mechanisms, including the involvement of G-protein coupled receptors (GPCRs), like free fatty acids receptors (FFARs). This review focusses on two more recently emerging research lines: the roles of odorant receptors (ORs), and those of fatty acid conjugates in gut. Odorant receptors belong to a large family of GPCRs with functional roles that only lately have shown to reach beyond the nasal-oral cavity. In the intestinal tract, ORs are expressed on serotonin (5-HT) and glucagon-like-peptide-1 (GLP-1) producing enterochromaffin and enteroendocrine L cells, respectively. There, they appear to function as chemosensors of microbiologically produced short-, and branched-chain fatty acids. Another mechanism of fatty acid signaling in the intestine occurs via their conjugates. Among them, conjugates of unsaturated long chain fatty acids and acetate with 5-HT, N-acyl serotonins have recently emerged as mediators with immune-modulatory effects. In this review, novel findings in mechanisms and molecular players involved in intestinal fatty acid biology are highlighted and their potential relevance for EEC-mediated signaling to the pancreas, immune system, and brain is discussed.


2016 ◽  
Vol 80 (1) ◽  
pp. 6-14 ◽  
Author(s):  
XUETONG FAN ◽  
KAREN WAGNER ◽  
KIMBERLY J. B. SOKORAI ◽  
HELEN NGO

ABSTRACT Novel phenolic branched-chain fatty acids (PBC-FAs) were evaluated for their antimicrobial properties against both gram-positive (Listeria innocua, Bacillus subtilis, Enterococcus faecium) and gram-negative (Escherichia coli, Salmonella Typhimurium, and Pseudomonas tolaasii) bacteria. In addition, PBC-FA derivatives, such as PBC-FA methyl ester mixture, methyl-branched fatty acid mixtures, and trimethylsilyl–PBC-FA methyl esters, were synthesized to study the structure activity relationship. Results showed that PBC-FAs were a potent antimicrobial against gram-positive bacteria with MICs of 1.8 to 3.6 μg/ml. The compounds were less effective against gram-negative bacteria. Derivatives of PBC-FAs and an equimolar mixture of oleic acid and phenol all had MICs above 233 μg/ml against both gram-positive and gram-negative bacteria. Comparison of antimicrobial activities of the PBC-FAs with those of the derivatives suggests that the carboxylic group in the fatty acid moiety and the hydroxyl group on the phenol moiety were responsible for the antimicrobial efficacy. Growth curves of L. innocua revealed that PBC-FAs prevented bacterial growth, while MBC-FAs only delayed the onset of rapid growth of L. innocua. Our results demonstrated that the novel PBC-FAs have potential for use as antimicrobials against gram-positive bacteria.


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