Evolutionary history of Staphylococcus aureus influences antibiotic resistance evolution
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Evolutionary history of Staphylococcus aureus influences antibiotic resistance evolution. / Fait, Anaëlle; Andersson, Dan I.; Ingmer, Hanne.
I: Current Biology, Bind 33, Nr. 16, 2023, s. 3389-3397.e5.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Evolutionary history of Staphylococcus aureus influences antibiotic resistance evolution
AU - Fait, Anaëlle
AU - Andersson, Dan I.
AU - Ingmer, Hanne
N1 - Publisher Copyright: © 2023 The Authors
PY - 2023
Y1 - 2023
N2 - Antibiotic resistance often confers a fitness cost to the resistant cell and thus raises key questions of how resistance is maintained in the absence of antibiotics and, if lost, whether cells are genetically primed for re-evolving resistance. To address these questions, we have examined vancomycin-intermediate Staphylococcus aureus (VISA) strains that arise during vancomycin therapy. VISA strains harbor a broad spectrum of mutations, and they are known to be unstable both in patients and in the laboratory. Here, we show that loss of resistance in VISA strains is correlated with a fitness increase and is attributed to adaptive mutations, leaving the initial VISA-adaptive mutations intact. Importantly, upon a second exposure to vancomycin, such revertants evolve significantly faster to become VISA, and they reach higher resistance levels than vancomycin-naive cells. Further, we find that sub-lethal concentrations of vancomycin stabilize the VISA phenotype, as do the human β-defensin 3 (hBD-3) and the bacteriocin nisin that both, like vancomycin, bind to the peptidoglycan building block, lipid II. Thus, factors binding lipid II may stabilize VISA both in vivo and in vitro, and in case resistance is lost, mutations remain that predispose to resistance development. These findings may explain why VISA infections often are re-occurring and suggest that previous vancomycin adaptation should be considered a risk factor when deciding on antimicrobial chemotherapy.
AB - Antibiotic resistance often confers a fitness cost to the resistant cell and thus raises key questions of how resistance is maintained in the absence of antibiotics and, if lost, whether cells are genetically primed for re-evolving resistance. To address these questions, we have examined vancomycin-intermediate Staphylococcus aureus (VISA) strains that arise during vancomycin therapy. VISA strains harbor a broad spectrum of mutations, and they are known to be unstable both in patients and in the laboratory. Here, we show that loss of resistance in VISA strains is correlated with a fitness increase and is attributed to adaptive mutations, leaving the initial VISA-adaptive mutations intact. Importantly, upon a second exposure to vancomycin, such revertants evolve significantly faster to become VISA, and they reach higher resistance levels than vancomycin-naive cells. Further, we find that sub-lethal concentrations of vancomycin stabilize the VISA phenotype, as do the human β-defensin 3 (hBD-3) and the bacteriocin nisin that both, like vancomycin, bind to the peptidoglycan building block, lipid II. Thus, factors binding lipid II may stabilize VISA both in vivo and in vitro, and in case resistance is lost, mutations remain that predispose to resistance development. These findings may explain why VISA infections often are re-occurring and suggest that previous vancomycin adaptation should be considered a risk factor when deciding on antimicrobial chemotherapy.
KW - adaptation
KW - daptomycin
KW - hBD-3
KW - lipid IIStaphylococcus aureus
KW - stability
KW - teicoplanin
KW - vancomycin
KW - VISA
U2 - 10.1016/j.cub.2023.06.082
DO - 10.1016/j.cub.2023.06.082
M3 - Journal article
C2 - 37494936
AN - SCOPUS:85167967059
VL - 33
SP - 3389-3397.e5
JO - Current Biology
JF - Current Biology
SN - 0960-9822
IS - 16
ER -
ID: 364545341