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Interspecies recombination, not de novo mutation, maintains virulence after β-lactam resistance acquisition in Streptococcus pneumoniae

As opposed to de novo mutation, β-lactam resistance in S. pneumoniae is often conferred via homologous recombination during horizontal gene transfer. We hypothesize that β-lactam resistance in pathogenic streptococci is restricted to naturally competent species via intra-/interspecies recombination...

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Autores principales: Nishimoto, Andrew T., Dao, Tina H., Jia, Qidong, Ortiz-Marquez, Juan C., Echlin, Haley, Vogel, Peter, van Opijnen, Tim, Rosch, Jason W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9850807/
https://www.ncbi.nlm.nih.gov/pubmed/36516783
http://dx.doi.org/10.1016/j.celrep.2022.111835
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author Nishimoto, Andrew T.
Dao, Tina H.
Jia, Qidong
Ortiz-Marquez, Juan C.
Echlin, Haley
Vogel, Peter
van Opijnen, Tim
Rosch, Jason W.
author_facet Nishimoto, Andrew T.
Dao, Tina H.
Jia, Qidong
Ortiz-Marquez, Juan C.
Echlin, Haley
Vogel, Peter
van Opijnen, Tim
Rosch, Jason W.
author_sort Nishimoto, Andrew T.
collection PubMed
description As opposed to de novo mutation, β-lactam resistance in S. pneumoniae is often conferred via homologous recombination during horizontal gene transfer. We hypothesize that β-lactam resistance in pathogenic streptococci is restricted to naturally competent species via intra-/interspecies recombination due to in vivo fitness trade-offs of de novo penicillin-binding protein (PBP) mutations. We show that de novo mutant populations have abrogated invasive disease capacity and are difficult to evolve in vivo. Conversely, serially transformed recombinant strains efficiently integrate resistant oral streptococcal DNA, gain penicillin resistance and tolerance, and retain virulence in mice. Large-scale changes in pbp2X, pbp2B, and non-PBP-related genes occur in recombinant isolates. Our results indicate that horizontal transfer of β-lactam resistance engenders initially favorable or minimal cost changes in vivo compared with de novo mutation(s), underscoring the importance of recombination in the emergence of β-lactam resistance and suggesting why some pathogenic streptococci lacking innate competence remain universally susceptible.
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spelling pubmed-98508072023-01-19 Interspecies recombination, not de novo mutation, maintains virulence after β-lactam resistance acquisition in Streptococcus pneumoniae Nishimoto, Andrew T. Dao, Tina H. Jia, Qidong Ortiz-Marquez, Juan C. Echlin, Haley Vogel, Peter van Opijnen, Tim Rosch, Jason W. Cell Rep Article As opposed to de novo mutation, β-lactam resistance in S. pneumoniae is often conferred via homologous recombination during horizontal gene transfer. We hypothesize that β-lactam resistance in pathogenic streptococci is restricted to naturally competent species via intra-/interspecies recombination due to in vivo fitness trade-offs of de novo penicillin-binding protein (PBP) mutations. We show that de novo mutant populations have abrogated invasive disease capacity and are difficult to evolve in vivo. Conversely, serially transformed recombinant strains efficiently integrate resistant oral streptococcal DNA, gain penicillin resistance and tolerance, and retain virulence in mice. Large-scale changes in pbp2X, pbp2B, and non-PBP-related genes occur in recombinant isolates. Our results indicate that horizontal transfer of β-lactam resistance engenders initially favorable or minimal cost changes in vivo compared with de novo mutation(s), underscoring the importance of recombination in the emergence of β-lactam resistance and suggesting why some pathogenic streptococci lacking innate competence remain universally susceptible. 2022-12-13 /pmc/articles/PMC9850807/ /pubmed/36516783 http://dx.doi.org/10.1016/j.celrep.2022.111835 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Nishimoto, Andrew T.
Dao, Tina H.
Jia, Qidong
Ortiz-Marquez, Juan C.
Echlin, Haley
Vogel, Peter
van Opijnen, Tim
Rosch, Jason W.
Interspecies recombination, not de novo mutation, maintains virulence after β-lactam resistance acquisition in Streptococcus pneumoniae
title Interspecies recombination, not de novo mutation, maintains virulence after β-lactam resistance acquisition in Streptococcus pneumoniae
title_full Interspecies recombination, not de novo mutation, maintains virulence after β-lactam resistance acquisition in Streptococcus pneumoniae
title_fullStr Interspecies recombination, not de novo mutation, maintains virulence after β-lactam resistance acquisition in Streptococcus pneumoniae
title_full_unstemmed Interspecies recombination, not de novo mutation, maintains virulence after β-lactam resistance acquisition in Streptococcus pneumoniae
title_short Interspecies recombination, not de novo mutation, maintains virulence after β-lactam resistance acquisition in Streptococcus pneumoniae
title_sort interspecies recombination, not de novo mutation, maintains virulence after β-lactam resistance acquisition in streptococcus pneumoniae
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9850807/
https://www.ncbi.nlm.nih.gov/pubmed/36516783
http://dx.doi.org/10.1016/j.celrep.2022.111835
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