Horizontal gene transfer rate is not the primary determinant of observed antibiotic resistance frequencies in Streptococcus pneumoniae
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Lehtinen, Sonja
ORCID
Institute of Integrative Biology, Department of Environmental Systems Science, ETH Zurich, Zurich, Switzerland.
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Chewapreecha, Claire
ORCID
Bioinformatics and Systems Biology Program, School of Bioresource and Technology, King Mongkut’s University of Technology Thonburi, Bangkok, Thailand.
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Lees, John
ORCID
Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, UK.
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Hanage, William P.
ORCID
Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA.
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Lipsitch, Marc
ORCID
Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA.
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Croucher, Nicholas J.
ORCID
Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA.
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Bentley, Stephen D.
ORCID
Wellcome Sanger Institute, Hinxton, UK.
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Turner, Paul
ORCID
Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
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Fraser, Christophe
ORCID
Big Data Institute, University of Oxford, Oxford, UK.
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Mostowy, Rafał J.
ORCID
Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.
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Published in:
- Science Advances. - American Association for the Advancement of Science (AAAS). - 2020, vol. 6, no. 21, p. eaaz6137
English
The extent to which evolution is constrained by the rate at which horizontal gene transfer (HGT) allows DNA to move between genetic lineages is an open question, which we address in the context of antibiotic resistance in Streptococcus pneumoniae. We analyze microbiological, genomic, and epidemiological data from the largest-to-date sequenced pneumococcal carriage study in 955 infants from a refugee camp on the Thailand-Myanmar border. Using a unified framework, we simultaneously test prior hypotheses on rates of HGT and a key evolutionary covariate (duration of carriage) as determinants of resistance frequencies. We conclude that in this setting, there is little evidence of HGT playing a major role in determining resistance frequencies. Instead, observed resistance frequencies are best explained as the outcome of selection acting on a pool of variants, irrespective of the rate at which resistance determinants move between genetic lineages.
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Open access status
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gold
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Persistent URL
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https://sonar.ch/global/documents/139671
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