Human serum induces daptomycin tolerance in Enterococcus faecalis and viridans group streptococci
File(s)
Published version
Author(s)
Tickle, Alicia RH
Ledger, Elizabeth VK
Edwards, Andrew M
Type
Journal Article
Abstract
Daptomycin is a membrane-targeting lipopeptide antibiotic used in the treatment of infective endocarditis caused by multidrug-resistant Gram-positive bacteria such as Staphylococcus aureus , enterococci and viridans group streptococci. Despite demonstrating excellent in vitro 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 S. aureus , but it was not clear if a similar phenotype occurred in other major infective endocarditis pathogens. We found that Enterococcus faecalis , Streptococcus gordonii or Streptococcus mutans 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 d-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 E. faecalis 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.
Date Issued
2022-12
Date Acceptance
2022-11-24
Citation
Microbiology, 2022, 168 (12)
ISSN
1350-0872
Publisher
Microbiology Society
Journal / Book Title
Microbiology
Volume
168
Issue
12
Copyright Statement
© 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.
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.
License URL
Subjects
antibiotic tolerance
daptomycin
Enterococcus
Life Sciences & Biomedicine
Microbiology
peptidoglycan
Science & Technology
Streptococcus
Publication Status
Published
Article Number
001282
Date Publish Online
2022-12-16