OBJECTIVES: To obtain an expanded understanding of antibiotic resistance evolution in vivo, particularly in the context of vancomycin exposure. METHODS: The whole genomes of six consecutive methicillin-resistant Staphylococcus aureus blood culture isolates (ST239-MRSA-III) from a single patient exposed to various antimicrobials (over a 77 day period) were sequenced and analysed. RESULTS: Variant analysis revealed the existence of non-susceptible sub-populations derived from a common susceptible ancestor, with the predominant circulating clone(s) selected for by type and duration of antimicrobial exposure. CONCLUSIONS: This study highlights the dynamic nature of bacterial evolution and that non-susceptible sub-populations can emerge from clouds of variation upon antimicrobial exposure. Diagnostically, this has direct implications for sample selection when using whole-genome sequencing as a tool to guide clinical therapy. In the context of bacteraemia, deep sequencing of bacterial DNA directly from patient blood samples would avoid culture 'bias' and identify mutations associated with circulating non-susceptible sub-populations, some of which may confer cross-resistance to alternate therapies.
OBJECTIVES: To obtain an expanded understanding of antibiotic resistance evolution in vivo, particularly in the context of vancomycin exposure. METHODS: The whole genomes of six consecutive methicillin-resistant Staphylococcus aureus blood culture isolates (ST239-MRSA-III) from a single patient exposed to various antimicrobials (over a 77 day period) were sequenced and analysed. RESULTS: Variant analysis revealed the existence of non-susceptible sub-populations derived from a common susceptible ancestor, with the predominant circulating clone(s) selected for by type and duration of antimicrobial exposure. CONCLUSIONS: This study highlights the dynamic nature of bacterial evolution and that non-susceptible sub-populations can emerge from clouds of variation upon antimicrobial exposure. Diagnostically, this has direct implications for sample selection when using whole-genome sequencing as a tool to guide clinical therapy. In the context of bacteraemia, deep sequencing of bacterial DNA directly from patient blood samples would avoid culture 'bias' and identify mutations associated with circulating non-susceptible sub-populations, some of which may confer cross-resistance to alternate therapies.
Authors: Catherine Liu; Arnold Bayer; Sara E Cosgrove; Robert S Daum; Scott K Fridkin; Rachel J Gorwitz; Sheldon L Kaplan; Adolf W Karchmer; Donald P Levine; Barbara E Murray; Michael J Rybak; David A Talan; Henry F Chambers Journal: Clin Infect Dis Date: 2011-01-04 Impact factor: 9.079
Authors: Michael M Mwangi; Shang Wei Wu; Yanjiao Zhou; Krzysztof Sieradzki; Herminia de Lencastre; Paul Richardson; David Bruce; Edward Rubin; Eugene Myers; Eric D Siggia; Alexander Tomasz Journal: Proc Natl Acad Sci U S A Date: 2007-05-21 Impact factor: 11.205
Authors: Tanya Golubchik; Elizabeth M Batty; Ruth R Miller; Helen Farr; Bernadette C Young; Hanna Larner-Svensson; Rowena Fung; Heather Godwin; Kyle Knox; Antonina Votintseva; Richard G Everitt; Teresa Street; Madeleine Cule; Camilla L C Ip; Xavier Didelot; Timothy E A Peto; Rosalind M Harding; Daniel J Wilson; Derrick W Crook; Rory Bowden Journal: PLoS One Date: 2013-05-01 Impact factor: 3.240
Authors: Anton Y Peleg; Spiros Miyakis; Doyle V Ward; Ashlee M Earl; Aileen Rubio; David R Cameron; Satish Pillai; Robert C Moellering; George M Eliopoulos Journal: PLoS One Date: 2012-01-06 Impact factor: 3.240
Authors: Benjamin P Howden; Christopher R E McEvoy; David L Allen; Kyra Chua; Wei Gao; Paul F Harrison; Jan Bell; Geoffrey Coombs; Vicki Bennett-Wood; Jessica L Porter; Roy Robins-Browne; John K Davies; Torsten Seemann; Timothy P Stinear Journal: PLoS Pathog Date: 2011-11-10 Impact factor: 6.823
Authors: Patrick R Secor; Lia A Michaels; Anina Ratjen; Laura K Jennings; Pradeep K Singh Journal: Proc Natl Acad Sci U S A Date: 2018-10-01 Impact factor: 11.205
Authors: Xavier Didelot; A Sarah Walker; Tim E Peto; Derrick W Crook; Daniel J Wilson Journal: Nat Rev Microbiol Date: 2016-01-19 Impact factor: 60.633
Authors: Jorunn Pauline Cavanagh; Erik Hjerde; Matthew T G Holden; Tim Kahlke; Claus Klingenberg; Trond Flægstad; Julian Parkhill; Stephen D Bentley; Johanna U Ericson Sollid Journal: J Antimicrob Chemother Date: 2014-07-17 Impact factor: 5.790