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Metabolic changes associated with adaptive resistance to daptomycin in Streptococcus mitis-oralis

BACKGROUND: Viridans group streptococci of the Streptococcus mitis-oralis subgroup are important endovascular pathogens. They can rapidly develop high-level and durable non-susceptibility to daptomycin both in vitro and in vivo upon exposure to daptomycin. Two consistent genetic adaptations associat...

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Autores principales: Parrett, Allison, Reed, Joseph M., Gardner, Stewart G., Mishra, Nagendra N., Bayer, Arnold S., Powers, Robert, Somerville, Greg A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296729/
https://www.ncbi.nlm.nih.gov/pubmed/32539684
http://dx.doi.org/10.1186/s12866-020-01849-w
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author Parrett, Allison
Reed, Joseph M.
Gardner, Stewart G.
Mishra, Nagendra N.
Bayer, Arnold S.
Powers, Robert
Somerville, Greg A.
author_facet Parrett, Allison
Reed, Joseph M.
Gardner, Stewart G.
Mishra, Nagendra N.
Bayer, Arnold S.
Powers, Robert
Somerville, Greg A.
author_sort Parrett, Allison
collection PubMed
description BACKGROUND: Viridans group streptococci of the Streptococcus mitis-oralis subgroup are important endovascular pathogens. They can rapidly develop high-level and durable non-susceptibility to daptomycin both in vitro and in vivo upon exposure to daptomycin. Two consistent genetic adaptations associated with this phenotype (i.e., mutations in cdsA and pgsA) lead to the depletion of the phospholipids, phosphatidylglycerol and cardiolipin, from the bacterial membrane. Such alterations in phospholipid biosynthesis will modify carbon flow and change the bacterial metabolic status. To determine the metabolic differences between daptomycin-susceptible and non-susceptible bacteria, the physiology and metabolomes of S. mitis-oralis strains 351 (daptomycin-susceptible) and 351-D10 (daptomycin non-susceptible) were analyzed. S. mitis-oralis strain 351-D10 was made daptomycin non-susceptible through serial passage in the presence of daptomycin. RESULTS: Daptomycin non-susceptible S. mitis-oralis had significant alterations in glucose catabolism and a re-balancing of the redox status through amino acid biosynthesis relative to daptomycin susceptible S. mitis-oralis. These changes were accompanied by a reduced capacity to generate biomass, creating a fitness cost in exchange for daptomycin non-susceptibility. CONCLUSIONS: S. mitis-oralis metabolism is altered in daptomycin non-susceptible bacteria relative to the daptomycin susceptible parent strain. As demonstrated in Staphylococcus aureus, inhibiting the metabolic changes that facilitate the transition from a daptomycin susceptible state to a non-susceptible one, inhibits daptomycin non-susceptibility. By preventing these metabolic adaptations in S. mitis-oralis, it should be possible to deter the formation of daptomycin non-susceptibility.
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spelling pubmed-72967292020-06-16 Metabolic changes associated with adaptive resistance to daptomycin in Streptococcus mitis-oralis Parrett, Allison Reed, Joseph M. Gardner, Stewart G. Mishra, Nagendra N. Bayer, Arnold S. Powers, Robert Somerville, Greg A. BMC Microbiol Research Article BACKGROUND: Viridans group streptococci of the Streptococcus mitis-oralis subgroup are important endovascular pathogens. They can rapidly develop high-level and durable non-susceptibility to daptomycin both in vitro and in vivo upon exposure to daptomycin. Two consistent genetic adaptations associated with this phenotype (i.e., mutations in cdsA and pgsA) lead to the depletion of the phospholipids, phosphatidylglycerol and cardiolipin, from the bacterial membrane. Such alterations in phospholipid biosynthesis will modify carbon flow and change the bacterial metabolic status. To determine the metabolic differences between daptomycin-susceptible and non-susceptible bacteria, the physiology and metabolomes of S. mitis-oralis strains 351 (daptomycin-susceptible) and 351-D10 (daptomycin non-susceptible) were analyzed. S. mitis-oralis strain 351-D10 was made daptomycin non-susceptible through serial passage in the presence of daptomycin. RESULTS: Daptomycin non-susceptible S. mitis-oralis had significant alterations in glucose catabolism and a re-balancing of the redox status through amino acid biosynthesis relative to daptomycin susceptible S. mitis-oralis. These changes were accompanied by a reduced capacity to generate biomass, creating a fitness cost in exchange for daptomycin non-susceptibility. CONCLUSIONS: S. mitis-oralis metabolism is altered in daptomycin non-susceptible bacteria relative to the daptomycin susceptible parent strain. As demonstrated in Staphylococcus aureus, inhibiting the metabolic changes that facilitate the transition from a daptomycin susceptible state to a non-susceptible one, inhibits daptomycin non-susceptibility. By preventing these metabolic adaptations in S. mitis-oralis, it should be possible to deter the formation of daptomycin non-susceptibility. BioMed Central 2020-06-15 /pmc/articles/PMC7296729/ /pubmed/32539684 http://dx.doi.org/10.1186/s12866-020-01849-w Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Parrett, Allison
Reed, Joseph M.
Gardner, Stewart G.
Mishra, Nagendra N.
Bayer, Arnold S.
Powers, Robert
Somerville, Greg A.
Metabolic changes associated with adaptive resistance to daptomycin in Streptococcus mitis-oralis
title Metabolic changes associated with adaptive resistance to daptomycin in Streptococcus mitis-oralis
title_full Metabolic changes associated with adaptive resistance to daptomycin in Streptococcus mitis-oralis
title_fullStr Metabolic changes associated with adaptive resistance to daptomycin in Streptococcus mitis-oralis
title_full_unstemmed Metabolic changes associated with adaptive resistance to daptomycin in Streptococcus mitis-oralis
title_short Metabolic changes associated with adaptive resistance to daptomycin in Streptococcus mitis-oralis
title_sort metabolic changes associated with adaptive resistance to daptomycin in streptococcus mitis-oralis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296729/
https://www.ncbi.nlm.nih.gov/pubmed/32539684
http://dx.doi.org/10.1186/s12866-020-01849-w
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