scholarly journals Increased resistance of a methicillin-resistant Staphylococcus aureus Δagr mutant with modified control in fatty acid metabolism

2020 ◽  
Author(s):  
Hun-Suk Song ◽  
Tae-Rim Choi ◽  
Yeong-Hoon Han ◽  
Ye-Lim Park ◽  
Jun Young Park ◽  
...  

Abstract Methicillin-resistant Staphylococcus aureus (MRSA) strains are distinct from general Staphylococcus strains with respect to the composition of the membrane, ability to form a thicker biofilm, and, importantly, ability to modify the target of antibiotics to evade their activity. The agr gene is an accessory global regulator of gram-positive bacteria that governs virulence or resistant mechanisms and therefore an important target for the control of resistant strains. However, the mechanism by which agr impacts resistance to β-lactam antibiotics remains unclear. In the present study, we found the Δagr mutant strain having higher resistance to high concentrations of b-lactam antibiotics such as oxacillin and ampicillin. To determine the influence of variation in the microenvironment of cells between the parental and mutant strains, fatty acid analysis of the supernatant, total lipids, and phospholipid fatty acids were compared. The Δagr mutant strain tended to produce fewer fatty acids and retained lower amounts of C16, C18 fatty acids in the supernatant. Phospholipid analysis showed a dramatic increase in the hydrophobic longer-chain fatty acids in the membrane. To target membrane, we applied several surfactants and found that sorbitan monolaurate (Span20) had a synergistic effect with oxacillin by decreasing biofilm formation and growth. These findings indicate that agr deletion allows for MRSA to resist antibiotics via several changes including constant expression of mecA, fatty acid metabolism, and biofilm thickening.

2020 ◽  
Author(s):  
Hun-Suk Song ◽  
Tae-Rim Choi ◽  
Yeong-Hoon Han ◽  
Ye-Lim Park ◽  
Jun Young Park ◽  
...  

Abstract Methicillin-resistant Staphylococcus aureus (MRSA) strains are distinct from general Staphylococcus strains with respect to the composition of the membrane, ability to form a thicker biofilm, and, importantly, ability to modify the target of antibiotics to evade their activity. The agr gene is an accessory global regulator of gram-positive bacteria that governs virulence or resistant mechanisms and is therefore an important target for the control of resistant strains. However, the mechanism by which agr impacts factors affecting resistance to β-lactam antibiotics remains unclear. In the present study, we found an Δagr mutant strain with higher resistance to high concentrations of b-lactam antibiotics such as oxacillin and ampicillin. To determine the influence of variation in the microenvironment of cells between the parental and mutant strains, fatty acid analysis of the supernatant, total lipids, and phospholipid fatty acids were compared. The Δagr mutant strain tended to produce fewer fatty acids and retained lower amounts of C16, C18 fatty acids in the supernatant. Phospholipid analysis showed a dramatic increase in the hydrophobic longer-chain fatty acids in the membranes. To target these differences in fatty acid distribution and membrane composition, we applied several surfactants and found that sorbitan trioleate (Span85) had a synergistic effect with oxacillin by decreasing biofilm formation and growth. These findings indicate that agr suppression allows for MRSA to antagonize antibiotics via several changes, including constant expression of mecA, fatty acid metabolism and distribution, and biofilm thickening, resulting in a strain with higher resistance to β-lactam antibiotics.


2009 ◽  
Vol 34 (3) ◽  
pp. 315-322 ◽  
Author(s):  
Gregory R. Steinberg

During moderate-intensity exercise, fatty acids are the predominant substrate for working skeletal muscle. The release of fatty acids from adipose tissue stores, combined with the ability of skeletal muscle to actively fine tune the gradient between fatty acid and carbohydrate metabolism, depending on substrate availability and energetic demands, requires a coordinated system of metabolic control. Over the past decade, since the discovery that AMP-activated protein kinase (AMPK) was increased in accordance with exercise intensity, there has been significant interest in the proposed role of this ancient stress-sensing kinase as a critical integrative switch controlling metabolic responses during exercise. In this review, studies examining the role of AMPK as a regulator of fatty acid metabolism in both adipose tissue and skeletal muscle during exercise will be discussed. Exercise induces activation of AMPK in adipocytes and regulates triglyceride hydrolysis and esterfication through phosphorylation of hormone sensitive lipase (HSL) and glycerol-3-phosphate acyl-transferase, respectively. In skeletal muscle, exercise-induced activation of AMPK is associated with increases in fatty acid uptake, phosphorylation of HSL, and increased fatty acid oxidation, which is thought to occur via the acetyl-CoA carboxylase-malony-CoA-CPT-1 signalling axis. Despite the importance of AMPK in regulating fatty acid metabolism under resting conditions, recent evidence from transgenic models of AMPK deficiency suggest that alternative signalling pathways may also be important for the control of fatty acid metabolism during exercise.


2020 ◽  
Vol 19 (2) ◽  
pp. 154
Author(s):  
Djeyne Silveira Wagmacker ◽  
Alice Miranda De Oliveira ◽  
Edna Conceição De Oliveira ◽  
Alan Carlos Nery Dos Santos ◽  
Luiz Erlon Araújo Rodrigues ◽  
...  

Introduction: Diet is a complex set of exposures that frequently interact, and whose cumulative effects influence the results of health. This includes effects on systemic inflammation markers in metabolic disturbances and cardiovascular diseases. Various studies have been presented relating the effect of physical exercise on lipids, however, the results are still controversial. Objective: To describe fatty acid metabolism and the effect of physical exercise on secondary complications. Methods: An integrative review was conducted on topics in the Medline, Pubmed, Web of Science and Scopus databases, published up to the year 2017. Results: Fatty acids, depending on their biochemical characteristics and spatial configuration, have differentiated effect on cardiovascular health, however, studies still present contradictory results about the therapeutic use of certain fatty acids. Physical exercise appears to benefit fatty acid metabolism and attenuate the complications secondary to the intake of certain fatty acids, and potentializes the positive effects of distinct fatty acids. Conclusion: However, variants of physical exercise, such as intensity, duration, time of observation of effects of the results, limit the authors to concluding, with a certain degree of certainty, about the effect of physical exercise on fatty acids and secondary complications, since the studies in the literature continue to be contradictory.Keywords: fatty acids, exercise, inflammation, oxidative stress.


1998 ◽  
Vol 84 (5) ◽  
pp. 1674-1679 ◽  
Author(s):  
Zengkui Guo ◽  
Michael D. Jensen

We evaluated the applicability of stable isotopic tracers to the study of intramuscular fatty acid metabolism by infusing both [U-13C]palmitate and [1-13C]oleate intravenously for 4 h into fasted conscious rats. Skeletal muscles were sequentially biopsied, and the concentration and13C enrichment of fatty acids were measured by gas chromatography/combustion/isotope ratio mass spectrometry. Throughout the study, the13C enrichment of plasma palmitate and oleate remained substantially greater than intramuscular nonesterified palmitate and oleate enrichment, which in turn was greater than intramuscular triglyceride palmitate and oleate enrichment. Fractional synthesis rates of intramuscular triglycerides in gastrocnemius and soleus were 0.267 ± 0.075 and 0.100 ± 0.030/h ( P = 0.04), respectively, as determined by using [U-13C]palmitate, and were 0.278 ± 0.049 and 0.075 ± 0.013/h ( P = 0.02), respectively, by using [1-13C]oleate. We conclude that plasma free fatty acids are a source for intramuscular triglycerides and nonesterified fatty acids; the latter are likely the synthetic precursors of the former. Uniformly and singly labeled [13C]fatty acid tracers will provide an important tool to study intramuscular fatty acid and triglyceride metabolism.


2019 ◽  
Vol 79 (2) ◽  
pp. 219-224 ◽  
Author(s):  
Caroline E. Childs

α-Linolenic acid (ALA) is an n-3 fatty acid found in plant-derived foods such as linseeds and linseed oil. Mammals can convert this essential fatty acid into longer-chain fatty acids including EPA, docosapentaenoic acid (DPA) and DHA. Women demonstrate greater increases in the EPA status after ALA supplementation than men, and a growing body of animal model research identifies mechanisms by which sex hormones such as oestrogen and progesterone interact with the synthesis of EPA and DHA. Alternatively, EPA, DPA and DHA can be consumed directly, with oily fish being a rich dietary source of these nutrients. However, current National Diet and Nutrition Data reveals a median oily fish intake of 0 g daily across all age ranges and in both sexes. As longer-chain n-3 fatty acids have a crucial role in fetal and neonatal brain development, advice to consume dietary ALA could prove to be a pragmatic and acceptable alternative to advice to consume fish during pregnancy, if benefits upon tissue composition and functional outcomes can be demonstrated. Further research is required to understand the effects of increasing dietary ALA during pregnancy, and will need to simultaneously address conflicts with current dietary advice to only eat ‘small amounts’ of vegetable oils during pregnancy. Improving our understanding of sex-specific differences in fatty acid metabolism and interactions with pregnancy has the potential to inform both personalised nutrition advice and public health policy.


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