Microscale insights into pneumococcal antibiotic mutant selection windows

Robin A. Sorg and Jan-Willem Veening ()
Additional contact information
Robin A. Sorg: Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen
Jan-Willem Veening: Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: Abstract The human pathogen Streptococcus pneumoniae shows alarming rates of antibiotic resistance emergence. The basic requirements for de novo resistance emergence are poorly understood in the pneumococcus. Here we systematically analyse the impact of antibiotics on S. pneumoniae at concentrations that inhibit wild type cells, that is, within the mutant selection window. We identify discrete growth-inhibition profiles for bacteriostatic and bactericidal compounds, providing a predictive framework for distinction between the two classifications. Cells treated with bacteriostatic agents show continued gene expression activity, and real-time mutation assays link this activity to the development of genotypic resistance. Time-lapse microscopy reveals that antibiotic-susceptible pneumococci display remarkable growth and death bistability patterns in response to many antibiotics. We furthermore capture the rise of subpopulations with decreased susceptibility towards cell wall synthesis inhibitors (heteroresisters). We show that this phenomenon is epigenetically inherited, and that heteroresistance potentiates the accumulation of genotypic resistance.

Date: 2015
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms9773 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9773

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms9773

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().