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UID:955@biology.technion.ac.il

DTSTART;TZID=Asia/Jerusalem:20210511T130000

DTEND;TZID=Asia/Jerusalem:20210511T140000

DTSTAMP:20210802T125904Z

URL:https://biology.technion.ac.il/en/seminars/phd-graduate-seminar-rotem-
 gross-2/

SUMMARY:PhD Graduate Seminar-Rotem Gross [No Categories]
DESCRIPTION:Location:   \n Affiliation: \n Host:\n \, " Evolutionary paths
  tohigh-level ampicillin resistance ""  Thewidespread use of beta-lactams
  has resulted in a growing prevalence of highlyresistant pathogens.Indeed\
 , clinical isolates can have very high resistance to beta-lactams\, mostpr
 ominently to ampicillin where resistance level could even exceed 1000 µg/
 ml. Yet\, instriking contrast\, bacteria evolved in laboratory settings\, 
 typically plateauon much lower levels of resistance. Here\, evolving Esche
 richiacoli onthe Microbial Evolution and Growth Arena (MEGA) plate\, we fo
 undthat large population sizes circumvent the previously observed saturati
 on ofresistance under ampicillin selection\, selecting for mutants resista
 nt toampicillin at over 5000 µg/mg. Whole-genome sequencing of resistant 
 isolatesrevealed that this high ampicillin resistance was acquired via a c
 ombination ofsingle-point mutations (SNP) and increasingly focused gene am
 plification ofresistant genes\, most notably the beta-lactamase enzyme Amp
 C. Importantlythough\, blocking AmpC-mediated resistance only slightly red
 uced the adaptivepotential: strains deleted for ampC were able to evolve h
 igh-level resistancethrough combinations of genetic changes in genes invol
 ved in multidrugresistance such as efflux pumps\, transcriptional regulato
 rs\, and porins. Ourresults reveal that combinations of distinct genetic m
 utations\, accessible atlarge population sizes\, can drive high-level resi
 stance to ampicillin evenindependently of beta-lactamases. " Thelink:Join
  Zoom Meeting https://technion.zoom.us/j/92305007772 Meeting ID: 923 0500 
 7772 

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