Matches in SemOpenAlex for { <https://semopenalex.org/work/W4384341748> ?p ?o ?g. }
- W4384341748 abstract "The ever-growing rise of antibiotic resistance among bacterial pathogens is one of the top healthcare threats today. Although combination antibiotic therapies represent a potential approach to more efficiently combat infections caused by susceptible and drug-resistant bacteria, only a few known drug pairs exhibit synergy/cooperativity in killing bacteria. Here, we discover that well-known ribosomal antibiotics, hygromycin A (HygA) and macrolides, which target peptidyl transferase center and peptide exit tunnel, respectively, can act cooperatively against susceptible and drug-resistant bacteria. Remarkably, HygA slows down macrolide dissociation from the ribosome by 60-fold and enhances the otherwise weak antimicrobial activity of the newest-generation macrolide drugs known as ketolides against macrolide-resistant bacteria. By determining a set of high-resolution X-ray crystal structures of drug-sensitive wild-type and macrolide-resistant Erm-methylated 70S ribosomes in complex with three HygA-macrolide pairs, we provide a structural rationale for the binding cooperativity of these drugs and also uncover the molecular mechanism of overcoming Erm-type resistance by macrolides acting together with hygromycin A. Altogether our structural, biochemical, and microbiological findings lay the foundation for the subsequent development of synergistic antibiotic tandems with improved bactericidal properties against drug-resistant pathogens, including those expressing erm genes." @default.
- W4384341748 created "2023-07-15" @default.
- W4384341748 creator A5015953475 @default.
- W4384341748 creator A5035595939 @default.
- W4384341748 creator A5054958328 @default.
- W4384341748 creator A5066422850 @default.
- W4384341748 creator A5072208271 @default.
- W4384341748 creator A5072287042 @default.
- W4384341748 creator A5089532497 @default.
- W4384341748 creator A5092472058 @default.
- W4384341748 date "2023-07-14" @default.
- W4384341748 modified "2023-10-18" @default.
- W4384341748 title "Structural insights into the mechanism of overcoming Erm-mediated resistance by macrolides acting together with hygromycin-A" @default.
- W4384341748 cites W1544330746 @default.
- W4384341748 cites W1587481053 @default.
- W4384341748 cites W1656338199 @default.
- W4384341748 cites W1967986998 @default.
- W4384341748 cites W1978883602 @default.
- W4384341748 cites W1984974246 @default.
- W4384341748 cites W2001351478 @default.
- W4384341748 cites W2012499642 @default.
- W4384341748 cites W2019096041 @default.
- W4384341748 cites W2039206959 @default.
- W4384341748 cites W2066757502 @default.
- W4384341748 cites W2068051461 @default.
- W4384341748 cites W2069764314 @default.
- W4384341748 cites W2087440733 @default.
- W4384341748 cites W2101010252 @default.
- W4384341748 cites W2104500040 @default.
- W4384341748 cites W2105838618 @default.
- W4384341748 cites W2109915141 @default.
- W4384341748 cites W2110803333 @default.
- W4384341748 cites W2112191861 @default.
- W4384341748 cites W2117916958 @default.
- W4384341748 cites W2119097418 @default.
- W4384341748 cites W2125776589 @default.
- W4384341748 cites W2129874158 @default.
- W4384341748 cites W2139319648 @default.
- W4384341748 cites W2145456994 @default.
- W4384341748 cites W2148134634 @default.
- W4384341748 cites W2151098242 @default.
- W4384341748 cites W2153839483 @default.
- W4384341748 cites W2159713856 @default.
- W4384341748 cites W2171076011 @default.
- W4384341748 cites W2171975065 @default.
- W4384341748 cites W2222642144 @default.
- W4384341748 cites W2398757352 @default.
- W4384341748 cites W2500609927 @default.
- W4384341748 cites W2509014851 @default.
- W4384341748 cites W2558392338 @default.
- W4384341748 cites W2613441875 @default.
- W4384341748 cites W2774722786 @default.
- W4384341748 cites W2779019546 @default.
- W4384341748 cites W2789406370 @default.
- W4384341748 cites W2789891066 @default.
- W4384341748 cites W2796092158 @default.
- W4384341748 cites W2883557242 @default.
- W4384341748 cites W2889984933 @default.
- W4384341748 cites W2912247484 @default.
- W4384341748 cites W2913672362 @default.
- W4384341748 cites W2989562929 @default.
- W4384341748 cites W2999598793 @default.
- W4384341748 cites W3011829967 @default.
- W4384341748 cites W3041403610 @default.
- W4384341748 cites W3088036532 @default.
- W4384341748 cites W3124781615 @default.
- W4384341748 cites W3185731068 @default.
- W4384341748 cites W3202017886 @default.
- W4384341748 cites W3207844981 @default.
- W4384341748 cites W3208116526 @default.
- W4384341748 cites W4212865239 @default.
- W4384341748 cites W4221006166 @default.
- W4384341748 cites W4283713157 @default.
- W4384341748 cites W4295006249 @default.
- W4384341748 cites W4297050511 @default.
- W4384341748 cites W4302010917 @default.
- W4384341748 cites W4307715805 @default.
- W4384341748 doi "https://doi.org/10.1038/s41467-023-39653-5" @default.
- W4384341748 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37452045" @default.
- W4384341748 hasPublicationYear "2023" @default.
- W4384341748 type Work @default.
- W4384341748 citedByCount "1" @default.
- W4384341748 crossrefType "journal-article" @default.
- W4384341748 hasAuthorship W4384341748A5015953475 @default.
- W4384341748 hasAuthorship W4384341748A5035595939 @default.
- W4384341748 hasAuthorship W4384341748A5054958328 @default.
- W4384341748 hasAuthorship W4384341748A5066422850 @default.
- W4384341748 hasAuthorship W4384341748A5072208271 @default.
- W4384341748 hasAuthorship W4384341748A5072287042 @default.
- W4384341748 hasAuthorship W4384341748A5089532497 @default.
- W4384341748 hasAuthorship W4384341748A5092472058 @default.
- W4384341748 hasBestOaLocation W43843417481 @default.
- W4384341748 hasConcept C104317684 @default.
- W4384341748 hasConcept C114851261 @default.
- W4384341748 hasConcept C166014724 @default.
- W4384341748 hasConcept C185592680 @default.
- W4384341748 hasConcept C2778321597 @default.
- W4384341748 hasConcept C40749294 @default.
- W4384341748 hasConcept C501593827 @default.
- W4384341748 hasConcept C523546767 @default.