FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3033136082> ?p ?o ?g. }

• W3033136082 abstract "ABSTRACT Cefotaxime (CTX) is a commonly used third-generation cephalosporin (3GC) to treat infections caused by Escherichia coli . Two genetic mechanisms have been associated with 3GC resistance in E. coli . The first is the conjugative transfer of a plasmid harboring antibiotic resistance genes. The second is the introduction of mutations in the promoter region of the ampC β-lactamase gene that cause chromosomal-encoded β-lactamase hyperproduction. A wide variety of promoter mutations related to AmpC hyperproduction have been described. However, their link to a specific 3GC such as CTX resistance has not been reported. Here, we measured CTX MICs in 172 cefoxitin resistant E. coli isolates and performed genome-wide analysis of homoplastic mutations associated with CTX resistance by comparing Illumina whole-genome sequencing data of all isolates to a PacBio tailored-made reference chromosome. We mapped the mutations on the reference chromosome and determined their occurrence in the phylogeny, revealing extreme homoplasy at the −42 position of the ampC promoter. The 24 occurrences of a “T” at the −42 position rather than the wild type “C”, resulted from 18 independent C>T mutations in 5 phylogroups. The −42 C>T mutation was only observed in E. coli lacking a plasmid-encoded ampC gene. The association of the −42 C>T mutation with CTX resistance was confirmed to be significant (FDR < 0.05). To conclude, genome-wide analysis of homoplasy in combination with CTX resistance identifies the −42 C>T mutation of the ampC promotor as significantly associated with CTX resistance and underline the role of recurrent mutations in the spread of antibiotics resistance. Impact Statement In the past decades, the worldwide spread of extended spectrum beta-lactamases (ESBLs) has led to a substantial increase in the prevalence of resistant common pathogens, thereby restricting available treatment options. Although acquired resistance genes, e.g. ESBLs, get most attention, chromosome-encoded resistance mechanisms may play an important role as well. In E. coli chromosome-encoded β-lactam resistance can be caused by alterations in the promoter region of the ampC gene. To improve our understanding of how frequently these alterations occur, a comprehensive interpretation of the evolution of these mutations is essential. This study is the first to apply genome-wide homoplasy analysis to better perceive adaptation of the E. coli genome to antibiotics. Thereby, this study grants insights into how chromosomal-encoded antibiotic resistance evolves and, by combining genome-wide association studies with homoplasy analyses, provides potential strategies for future association studies into the causes of antibiotics resistance. Data summary All data is available under BioProject: PRJNA592140. Raw Illumina sequencing data and metadata of all 171 E. coli isolates used in this study is available from the Sequence Read Archive database under accession no. SAMN15052485 to SAMN15052655. Full reference chromosome of ampC_0069 is available via GenBank accession no. CP046396.1 and NCBI Reference Sequence: NZ_CP046396.1." @default.
• W3033136082 created "2020-06-12" @default.
• W3033136082 creator A5002180109 @default.
• W3033136082 creator A5004742977 @default.
• W3033136082 creator A5005551299 @default.
• W3033136082 creator A5025916989 @default.
• W3033136082 creator A5049689837 @default.
• W3033136082 creator A5053049764 @default.
• W3033136082 creator A5054237610 @default.
• W3033136082 creator A5054798761 @default.
• W3033136082 creator A5059615290 @default.
• W3033136082 creator A5085258368 @default.
• W3033136082 date "2020-06-02" @default.
• W3033136082 modified "2023-10-07" @default.
• W3033136082 title "Genome-wide analysis in Escherichia coli unravels an unprecedented level of genetic homoplasy associated with cefotaxime resistance" @default.
• W3033136082 cites W1936021896 @default.
• W3033136082 cites W1967551369 @default.
• W3033136082 cites W1972145956 @default.
• W3033136082 cites W2001783515 @default.
• W3033136082 cites W2004745913 @default.
• W3033136082 cites W2019385975 @default.
• W3033136082 cites W2031611770 @default.
• W3033136082 cites W2038662463 @default.
• W3033136082 cites W2051072617 @default.
• W3033136082 cites W2053940732 @default.
• W3033136082 cites W2055043387 @default.
• W3033136082 cites W2058935505 @default.
• W3033136082 cites W2082581672 @default.
• W3033136082 cites W2093323099 @default.
• W3033136082 cites W2095824770 @default.
• W3033136082 cites W2099303284 @default.
• W3033136082 cites W2109339376 @default.
• W3033136082 cites W2110150994 @default.
• W3033136082 cites W2112874950 @default.
• W3033136082 cites W2120902911 @default.
• W3033136082 cites W2131081634 @default.
• W3033136082 cites W2133187353 @default.
• W3033136082 cites W2148050511 @default.
• W3033136082 cites W2151958462 @default.
• W3033136082 cites W2152215229 @default.
• W3033136082 cites W2155476515 @default.
• W3033136082 cites W2158266834 @default.
• W3033136082 cites W2158804744 @default.
• W3033136082 cites W2327639708 @default.
• W3033136082 cites W2470052926 @default.
• W3033136082 cites W2580631853 @default.
• W3033136082 cites W2597477442 @default.
• W3033136082 cites W2766648240 @default.
• W3033136082 cites W2789695063 @default.
• W3033136082 cites W2791094870 @default.
• W3033136082 cites W2891625489 @default.
• W3033136082 cites W2913512063 @default.
• W3033136082 cites W2927961455 @default.
• W3033136082 cites W2949182334 @default.
• W3033136082 cites W2949660875 @default.
• W3033136082 cites W2950681580 @default.
• W3033136082 cites W2952167528 @default.
• W3033136082 cites W2952170484 @default.
• W3033136082 cites W2970413854 @default.
• W3033136082 cites W2986177632 @default.
• W3033136082 cites W2993005136 @default.
• W3033136082 doi "https://doi.org/10.1101/2020.06.01.128843" @default.
• W3033136082 hasPublicationYear "2020" @default.
• W3033136082 type Work @default.
• W3033136082 sameAs 3033136082 @default.
• W3033136082 citedByCount "0" @default.
• W3033136082 crossrefType "posted-content" @default.
• W3033136082 hasAuthorship W3033136082A5002180109 @default.
• W3033136082 hasAuthorship W3033136082A5004742977 @default.
• W3033136082 hasAuthorship W3033136082A5005551299 @default.
• W3033136082 hasAuthorship W3033136082A5025916989 @default.
• W3033136082 hasAuthorship W3033136082A5049689837 @default.
• W3033136082 hasAuthorship W3033136082A5053049764 @default.
• W3033136082 hasAuthorship W3033136082A5054237610 @default.
• W3033136082 hasAuthorship W3033136082A5054798761 @default.
• W3033136082 hasAuthorship W3033136082A5059615290 @default.
• W3033136082 hasAuthorship W3033136082A5085258368 @default.
• W3033136082 hasBestOaLocation W30331360821 @default.
• W3033136082 hasConcept C104317684 @default.
• W3033136082 hasConcept C141231307 @default.
• W3033136082 hasConcept C176944494 @default.
• W3033136082 hasConcept C22744801 @default.
• W3033136082 hasConcept C2776124114 @default.
• W3033136082 hasConcept C2778719061 @default.
• W3033136082 hasConcept C2779489039 @default.
• W3033136082 hasConcept C30481170 @default.
• W3033136082 hasConcept C501734568 @default.
• W3033136082 hasConcept C523546767 @default.
• W3033136082 hasConcept C54355233 @default.
• W3033136082 hasConcept C547475151 @default.
• W3033136082 hasConcept C86803240 @default.
• W3033136082 hasConceptScore W3033136082C104317684 @default.
• W3033136082 hasConceptScore W3033136082C141231307 @default.
• W3033136082 hasConceptScore W3033136082C176944494 @default.
• W3033136082 hasConceptScore W3033136082C22744801 @default.
• W3033136082 hasConceptScore W3033136082C2776124114 @default.
• W3033136082 hasConceptScore W3033136082C2778719061 @default.
• W3033136082 hasConceptScore W3033136082C2779489039 @default.
• W3033136082 hasConceptScore W3033136082C30481170 @default.
• W3033136082 hasConceptScore W3033136082C501734568 @default.

• next