FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2945130168> ?p ?o ?g. }

• W2945130168 abstract "Summary Development of fatty acid synthesis pathway (FASII) inhibitors against the major human pathogen Staphylococcus aureus hinges on the accepted but unproven postulate that an endogenously synthesized branched chain fatty acid is required to complete membrane phospholipids. Evidence for anti-FASII efficacy in animal models supported this view. However, restricted test conditions used previously to show FASII antibiotic efficacy led us to investigate these questions in a broader, host-relevant context. We report that S. aureus rapidly adapts to FASII antibiotics without FASII mutations when exposed to host environments. Treatment with a lead FASII antibiotic upon signs of infection, rather than just after inoculation as commonly practiced, failed to eliminate S. aureus from infected organs in a septicemia model. In vitro , addition of serum facilitated rapid S. aureus FASII bypass by environmental fatty acid (eFA) replacement in phospholipids. Serum lowers membrane stress, leading to increased retention of the two substrates required for exogenous fatty acid (eFA) utilization. In these conditions, eFA occupy both phospholipid positions 1 and 2, regardless of anti-FASII selection. This study revises conclusions on S. aureus fatty acid requirements by disproving the postulate of fatty acid stringency, and reveals an Achilles’ heel for using FASII antibiotics to treat infection in monotherapy. Significance statement Antibiotic discovery to overcome treatment failure has huge socio-medical and economic stakes. The fatty acid synthesis (FASII) pathway is considered an ideal druggable target against the human pathogen Staphylococcus aureus, based on evidence of anti-FASII efficacy in infection models, and the postulate that S. aureus synthesizes an irreplaceable fatty acid. We report that S. aureus alters its behavior in host-relevant conditions. Administering FASII antibiotics upon signs of infection, rather than just after inoculation as frequently practiced, failed to clear septicemic infections. In serum, S. aureus rapidly overcomes FASII antibiotics by incorporating alternative fatty acids. We conclude that previously, premature antibiotic treatments and experimental constraints masked S. aureus antibiotic adaptation capacity. These findings should help streamline future drug development programs." @default.
• W2945130168 created "2019-05-29" @default.
• W2945130168 creator A5008972939 @default.
• W2945130168 creator A5015048094 @default.
• W2945130168 creator A5017994562 @default.
• W2945130168 creator A5023219519 @default.
• W2945130168 creator A5025387449 @default.
• W2945130168 creator A5038892282 @default.
• W2945130168 creator A5044202480 @default.
• W2945130168 creator A5055793880 @default.
• W2945130168 creator A5056467193 @default.
• W2945130168 creator A5056764783 @default.
• W2945130168 creator A5079561465 @default.
• W2945130168 creator A5080692238 @default.
• W2945130168 creator A5084562464 @default.
• W2945130168 creator A5089647870 @default.
• W2945130168 date "2019-05-13" @default.
• W2945130168 modified "2023-10-10" @default.
• W2945130168 title "Permissive Fatty Acid Incorporation in Host Environments Promotes Staphylococcal Adaptation to FASII Antibiotics" @default.
• W2945130168 cites W1669810599 @default.
• W2945130168 cites W1915856409 @default.
• W2945130168 cites W1970658076 @default.
• W2945130168 cites W1971925522 @default.
• W2945130168 cites W1980792308 @default.
• W2945130168 cites W1986448105 @default.
• W2945130168 cites W1987678916 @default.
• W2945130168 cites W1993562651 @default.
• W2945130168 cites W1998378687 @default.
• W2945130168 cites W1999043967 @default.
• W2945130168 cites W2005985312 @default.
• W2945130168 cites W2008628182 @default.
• W2945130168 cites W2013519952 @default.
• W2945130168 cites W2019664080 @default.
• W2945130168 cites W2023232635 @default.
• W2945130168 cites W2028562067 @default.
• W2945130168 cites W2031951099 @default.
• W2945130168 cites W2040924145 @default.
• W2945130168 cites W2045825103 @default.
• W2945130168 cites W2056868096 @default.
• W2945130168 cites W2065554842 @default.
• W2945130168 cites W2065583035 @default.
• W2945130168 cites W2071692620 @default.
• W2945130168 cites W2079071998 @default.
• W2945130168 cites W2080588966 @default.
• W2945130168 cites W2100924623 @default.
• W2945130168 cites W2122993998 @default.
• W2945130168 cites W2127113854 @default.
• W2945130168 cites W2136246983 @default.
• W2945130168 cites W2149586621 @default.
• W2945130168 cites W2152311269 @default.
• W2945130168 cites W2155003028 @default.
• W2945130168 cites W2156937525 @default.
• W2945130168 cites W2158685996 @default.
• W2945130168 cites W2159911231 @default.
• W2945130168 cites W2160244841 @default.
• W2945130168 cites W2165240086 @default.
• W2945130168 cites W2235577322 @default.
• W2945130168 cites W2395256170 @default.
• W2945130168 cites W2440341397 @default.
• W2945130168 cites W2530376174 @default.
• W2945130168 cites W2543042368 @default.
• W2945130168 cites W2559133556 @default.
• W2945130168 cites W2591699907 @default.
• W2945130168 cites W2622651021 @default.
• W2945130168 cites W2735950380 @default.
• W2945130168 cites W2754975658 @default.
• W2945130168 cites W2766504510 @default.
• W2945130168 cites W2787033583 @default.
• W2945130168 cites W2801201490 @default.
• W2945130168 cites W2901438862 @default.
• W2945130168 cites W2902147362 @default.
• W2945130168 doi "https://doi.org/10.1101/635698" @default.
• W2945130168 hasPublicationYear "2019" @default.
• W2945130168 type Work @default.
• W2945130168 sameAs 2945130168 @default.
• W2945130168 citedByCount "0" @default.
• W2945130168 crossrefType "posted-content" @default.
• W2945130168 hasAuthorship W2945130168A5008972939 @default.
• W2945130168 hasAuthorship W2945130168A5015048094 @default.
• W2945130168 hasAuthorship W2945130168A5017994562 @default.
• W2945130168 hasAuthorship W2945130168A5023219519 @default.
• W2945130168 hasAuthorship W2945130168A5025387449 @default.
• W2945130168 hasAuthorship W2945130168A5038892282 @default.
• W2945130168 hasAuthorship W2945130168A5044202480 @default.
• W2945130168 hasAuthorship W2945130168A5055793880 @default.
• W2945130168 hasAuthorship W2945130168A5056467193 @default.
• W2945130168 hasAuthorship W2945130168A5056764783 @default.
• W2945130168 hasAuthorship W2945130168A5079561465 @default.
• W2945130168 hasAuthorship W2945130168A5080692238 @default.
• W2945130168 hasAuthorship W2945130168A5084562464 @default.
• W2945130168 hasAuthorship W2945130168A5089647870 @default.
• W2945130168 hasBestOaLocation W29451301681 @default.
• W2945130168 hasConcept C151730666 @default.
• W2945130168 hasConcept C2779343474 @default.
• W2945130168 hasConcept C2779489039 @default.
• W2945130168 hasConcept C501593827 @default.
• W2945130168 hasConcept C523546767 @default.
• W2945130168 hasConcept C543025807 @default.
• W2945130168 hasConcept C54355233 @default.
• W2945130168 hasConcept C55493867 @default.

• next