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Volume 168, Issue 12

Human serum induces daptomycin tolerance in and viridans group streptococci Open Access

Abstract

Daptomycin is a membrane-targeting lipopeptide antibiotic used in the treatment of infective endocarditis caused by multidrug-resistant Gram-positive bacteria such as , enterococci and viridans group streptococci. Despite demonstrating excellent activity and a low prevalence of resistant isolates, treatment failure is a significant concern, particularly for enterococcal infection. We have shown recently that human serum triggers daptomycin tolerance in , but it was not clear if a similar phenotype occurred in other major infective endocarditis pathogens. We found that , or grown under standard laboratory conditions were efficiently killed by daptomycin, whereas bacteria pre-incubated in human serum survived exposure to the antibiotic, with >99 % cells remaining viable. Incubation of enterococci or streptococci in serum led to peptidoglycan accumulation, as shown by increased incorporation of the fluorescent -amino acid analogue HADA. Inhibition of peptidoglycan accumulation using the antibiotic fosfomycin resulted in a >tenfold reduction in serum-induced daptomycin tolerance, demonstrating the important contribution of the cell wall to the phenotype. We also identified a small contribution to daptomycin tolerance in from cardiolipin synthases, although this may reflect the inherent increased susceptibility of cardiolipin-deficient mutants. In summary, serum-induced daptomycin tolerance is a consistent phenomenon between Gram-positive infective endocarditis pathogens, but it may be mitigated using currently available antibiotic combination therapy.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): antibiotic tolerance , daptomycin , Enterococcus , peptidoglycan and Streptococcus
Funding
This study was supported by the:
  • National Institute for Health Research Health Protection Research Unit (Award Imperial College London)
    • Principle Award Recipient: AndrewM Edwards
  • Wellcome Trust (Award 203812/Z/16/Z)
    • Principle Award Recipient: ElizabethVK Ledger
© 2022 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2022-12-16
2024-04-20
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Human serum induces daptomycin tolerance in Enterococcus faecalis and viridans group streptococci
Microbiology 168, 001282 (2022); https://doi.org/10.1099/mic.0.001282
/content/journal/micro/10.1099/mic.0.001282
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