Growth productivity as a determinant of the inoculum effect for bactericidal antibiotics.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
14 12 2022
14 12 2022
Historique:
entrez:
14
12
2022
pubmed:
15
12
2022
medline:
17
12
2022
Statut:
ppublish
Résumé
Understanding the mechanisms by which populations of bacteria resist antibiotics has implications in evolution, microbial ecology, and public health. The inoculum effect (IE), where antibiotic efficacy declines as the density of a bacterial population increases, has been observed for multiple bacterial species and antibiotics. Several mechanisms to account for IE have been proposed, but most lack experimental evidence or cannot explain IE for multiple antibiotics. We show that growth productivity, the combined effect of growth and metabolism, can account for IE for multiple bactericidal antibiotics and bacterial species. Guided by flux balance analysis and whole-genome modeling, we show that the carbon source supplied in the growth medium determines growth productivity. If growth productivity is sufficiently high, IE is eliminated. Our results may lead to approaches to reduce IE in the clinic, help standardize the analysis of antibiotics, and further our understanding of how bacteria evolve resistance.
Identifiants
pubmed: 36516248
doi: 10.1126/sciadv.add0924
pmc: PMC9750144
doi:
Substances chimiques
Anti-Bacterial Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
eadd0924Subventions
Organisme : NIAID NIH HHS
ID : R15 AI159902
Pays : United States
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