Novel Insights into Selection for Antibiotic Resistance in Complex Microbial Communities
Open Access
- 5 September 2018
- journal article
- research article
- Published by American Society for Microbiology in mBio
- Vol. 9 (4), e00969-18
- https://doi.org/10.1128/mbio.00969-18
Abstract
Recent research has demonstrated that selection for antibiotic resistance occurs at very low antibiotic concentrations in single-species experiments, but the relevance of these findings when species are embedded in complex microbial communities is unclear. We show that the strength of selection for naturally occurring resistance alleles in a complex community remains constant from low subinhibitory to above clinically relevant concentrations. Selection increases with antibiotic concentration before reaching a plateau where selection remains constant over a 2-order-magnitude concentration range. This is likely to be due to cross protection of the susceptible bacteria in the community following rapid extracellular antibiotic degradation by the resistant population, shown experimentally through a combination of chemical quantification and bacterial growth experiments. Metagenome and 16S rRNA analyses of sewage-derived bacterial communities evolved under cefotaxime exposure show preferential enrichment for blaCTX-M genes over all other beta-lactamase genes, as well as positive selection and co-selection for antibiotic resistant, opportunistic pathogens. These findings have far-reaching implications for our understanding of the evolution of antibiotic resistance, by challenging the long-standing assumption that selection occurs in a dose-dependent manner. IMPORTANCE Antibiotic resistance is one of the greatest global issues facing society. Still, comparatively little is known about selection for resistance at very low antibiotic concentrations. We show that the strength of selection for clinically important resistance genes within a complex bacterial community can remain constant across a large antibiotic concentration range (wide selective space). Therefore, largely understudied ecological compartments could be just as important as clinical environments for selection of antibiotic resistance.Keywords
Funding Information
- RCUK | Biotechnology and Biological Sciences Research Council (BB/L502509/1)
- RCUK | Natural Environment Research Council (NE/M011259/1)
This publication has 45 references indexed in Scilit:
- Bacterial cheating drives the population dynamics of cooperative antibiotic resistance plasmidsMolecular Systems Biology, 2013
- Acinetobacter baumanniiVirulence, 2012
- CTX-M Enzymes: Origin and DiffusionFrontiers in Microbiology, 2012
- FLASH: fast length adjustment of short reads to improve genome assembliesBioinformatics, 2011
- Detection of AmpC Beta-Lactamase in Escherichia coli: Comparison of Three Phenotypic Confirmation Assays and Genetic AnalysisJournal of Clinical Microbiology, 2011
- Selection of Resistant Bacteria at Very Low Antibiotic ConcentrationsPLoS Pathogens, 2011
- Metagenomic biomarker discovery and explanationGenome Biology, 2011
- Measuring dementia carers' unmet need for services - an exploratory mixed method studyBMC Health Services Research, 2010
- Complete Nucleotide Sequences of Plasmids pEK204, pEK499, and pEK516, Encoding CTX-M Enzymes in Three Major Escherichia coli Lineages from the United Kingdom, All Belonging to the International O25:H4-ST131 CloneAntimicrobial Agents and Chemotherapy, 2009
- AmpC β-LactamasesClinical Microbiology Reviews, 2009