Dataset Information

Comparative proteomic investigation of multiple methicillin-resistant Staphylococcus aureus strains generated through adaptive laboratory evolution.

ABSTRACT: Recent discoveries indicate that tolerance and resistance could rapidly evolve in bacterial populations under intermittent antibiotic treatment. In the present study, we applied antibiotic combinations in laboratory experiments to generate novel methicillin-resistant Staphylococcus aureus strains with distinct phenotypes (tolerance, resistance, and suppressed tolerance), and compared their proteome profiles to uncover the adaptation mechanisms. While the tolerant strains have very different proteomes than the susceptible ancestral strain, the resistant strain largely resembles the ancestral in terms of their proteomes. Our proteomics data and other assays support the connection between the detected mutations to the observed phenotypes, confirming the general understanding of tolerance and resistance mechanisms. While resistance directly counteracts the action mechanism of the antibiotic, tolerance involves complex substantial changes in the cells' biological process to achieve survival advantages. Overall, this study provides insights into the existence of diverse evolutionary pathways for tolerance and resistance development under different treatment scenarios.

SUBMITTER: Sulaiman JE

PROVIDER: S-EPMC8377494 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Comparative proteomic investigation of multiple methicillin-resistant <i>Staphylococcus aureus</i> strains generated through adaptive laboratory evolution.

Sulaiman Jordy Evan JE Long Lexin L Wu Long L Qian Pei-Yuan PY Lam Henry H

iScience 20210806 9

Recent discoveries indicate that tolerance and resistance could rapidly evolve in bacterial populations under intermittent antibiotic treatment. In the present study, we applied antibiotic combinations in laboratory experiments to generate novel methicillin-resistant <i>Staphylococcus aureus</i> strains with distinct phenotypes (tolerance, resistance, and suppressed tolerance), and compared their proteome profiles to uncover the adaptation mechanisms. While the tolerant strains have very differe ...[more]

PMID: 34458699

Similar Datasets

Project description:It has been shown recently in a number of in vitro laboratory evolution experiments that under repetitive antibiotic exposure, bacterial populations can adapt quickly to the treatment condition by becoming tolerant and/or resistant to the drug. The repeated killing and regrowth cycles hasten the selection for tolerant/resistant mutants with survival advantages. Due to the random nature of mutagenesis and the large target size of tolerance mutations, this dynamic evolutionary process appears to be highly unpredictable, generating distinct mutants even under identical, well-controlled laboratory conditions. Here, we utilized an adaptive laboratory evolution (ALE) experiment to hunt for novel tolerance and resistance mutations by subjecting multiple lineages of methicillin-resistant Staphylococcus aureus (MRSA) to repetitive daptomycin treatment. By sequencing multiple isolates along the course of evolution, we obtained three tolerant mutants that have different tolerance levels and identified novel daptomycin resistance mutations in the mprF gene. In addition, we found that tolerance/resistance development is more rapid if the population is treated in the exponential phase than if it is treated in the stationary phase, which is likely attributable to the more effective killing of growing cells by the antibiotic. Through competition assays, we found that whether or not the resistant mutants can take over the population heavily depends on the relative survival advantages conferred by the tolerance and resistance mutations. This study reports novel daptomycin resistance and tolerance mutations and offers new insights into the dynamics of the development of tolerance and resistance in bacterial populations under antibiotic exposure. IMPORTANCE Although the phenotype of increased tolerance and/or resistance was commonly observed in evolved populations from typical adaptive laboratory evolution (ALE) experiments, a wide variety of mutations that underlie those phenotypes have been discovered. Therefore, performing ALE experiments in multiple populations in parallel would serve the purpose of mining for different tolerant/resistant mutants and would be useful to explore the diverse population dynamics of evolution. In this study, we performed in vitro evolution in a clinically relevant methicillin-resistant Staphylococcus aureus (MRSA) pathogen, using a lethal concentration of a drug that is frequently used in the clinic, daptomycin. Using this strategy, we obtained three distinct daptomycin-tolerant mutants and identified six daptomycin resistance mutations in different locations on the mprF gene, collectively adding to our current knowledge of this important pathogen. In addition, we found out that in most cases, the daptomycin-resistant mutant outcompetes other susceptible and tolerant mutants and becomes established in the final population. Follow-up competition experiments offered an explanation; the resistant mutant cannot invade populations of tolerant mutants that confer higher survival advantages than itself. In summary, we demonstrated an experimental strategy to explore the landscape and dynamics of the evolution of tolerance and resistance in MRSA toward daptomycin and made observations that will guide future ALE experiments.

Dataset Information

Comparative proteomic investigation of multiple methicillin-resistant Staphylococcus aureus strains generated through adaptive laboratory evolution.

Publications

Comparative proteomic investigation of multiple methicillin-resistant <i>Staphylococcus aureus</i> strains generated through adaptive laboratory evolution.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets