Metabolic changes associated with adaptive resistance to daptomycin in Streptococcus mitis-oralis
Abstract 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...
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doaj-da469b802dd042f39bfb28149d6cd3ae2020-11-25T02:59:13ZengBMCBMC Microbiology1471-21802020-06-0120111010.1186/s12866-020-01849-wMetabolic changes associated with adaptive resistance to daptomycin in Streptococcus mitis-oralisAllison Parrett0Joseph M. Reed1Stewart G. Gardner2Nagendra N. Mishra3Arnold S. Bayer4Robert Powers5Greg A. Somerville6Department of Chemistry, University of Nebraska-LincolnSchool of Veterinary Medicine and Biomedical Sciences, University of Nebraska-LincolnSchool of Veterinary Medicine and Biomedical Sciences, University of Nebraska-LincolnDivision of Infectious Diseases, The Lundquist Institute at Harbor-UCLA Medical CenterDivision of Infectious Diseases, The Lundquist Institute at Harbor-UCLA Medical CenterDepartment of Chemistry, University of Nebraska-LincolnSchool of Veterinary Medicine and Biomedical Sciences, University of Nebraska-LincolnAbstract 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.http://link.springer.com/article/10.1186/s12866-020-01849-wStreptococcusMetabolismAntibiotic resistanceDaptomycin |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Allison Parrett Joseph M. Reed Stewart G. Gardner Nagendra N. Mishra Arnold S. Bayer Robert Powers Greg A. Somerville |
spellingShingle |
Allison Parrett Joseph M. Reed Stewart G. Gardner Nagendra N. Mishra Arnold S. Bayer Robert Powers Greg A. Somerville Metabolic changes associated with adaptive resistance to daptomycin in Streptococcus mitis-oralis BMC Microbiology Streptococcus Metabolism Antibiotic resistance Daptomycin |
author_facet |
Allison Parrett Joseph M. Reed Stewart G. Gardner Nagendra N. Mishra Arnold S. Bayer Robert Powers Greg A. Somerville |
author_sort |
Allison Parrett |
title |
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_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_sort |
metabolic changes associated with adaptive resistance to daptomycin in streptococcus mitis-oralis |
publisher |
BMC |
series |
BMC Microbiology |
issn |
1471-2180 |
publishDate |
2020-06-01 |
description |
Abstract 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. |
topic |
Streptococcus Metabolism Antibiotic resistance Daptomycin |
url |
http://link.springer.com/article/10.1186/s12866-020-01849-w |
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