TY - JOUR
T1 - ldhA-induced persister in Escherichia coli is formed through accidental SOS response via intracellular metabolic perturbation
AU - Yamamoto, Naoki
AU - Ohno, Yurino
AU - Tsuneda, Satoshi
N1 - Publisher Copyright:
© 2022 The Societies and John Wiley & Sons Australia, Ltd.
PY - 2022/5
Y1 - 2022/5
N2 - Persisters are a subpopulation that exhibit growth suppression, antibiotic tolerance, and regrowth after antibiotic removal, without any genetic mutations, which causes the recalcitrance and recurrence of infectious diseases. Persisters are majorly induced through the repression of energy metabolism, but some exceptions have been reported. We have previously shown that ldhA, which encodes lactate dehydrogenase, induces Escherichia coli persisters, resulting in a state of high-energy metabolism. However, the detailed mechanism of persister formation upon ldhA expression remains elusive. In the present study, we focused on the SOS response pathway via the DNA repair pathway that consumes adenosine triphosphate and revealed that the SOS response pathway is activated upon ldhA expression even before antimicrobial treatment. Metabolome analysis of ldhA-overexpressing cells revealed that nucleotide metabolic pathways, such as de novo purine biosynthesis, were activated to prepare a nucleotide pool, as substrate for repairing ofloxacin-induced DNA damage. We provide a novel persister model that contributes to survival as a species by “accidentally” activating the SOS response even before receiving antimicrobial stress.
AB - Persisters are a subpopulation that exhibit growth suppression, antibiotic tolerance, and regrowth after antibiotic removal, without any genetic mutations, which causes the recalcitrance and recurrence of infectious diseases. Persisters are majorly induced through the repression of energy metabolism, but some exceptions have been reported. We have previously shown that ldhA, which encodes lactate dehydrogenase, induces Escherichia coli persisters, resulting in a state of high-energy metabolism. However, the detailed mechanism of persister formation upon ldhA expression remains elusive. In the present study, we focused on the SOS response pathway via the DNA repair pathway that consumes adenosine triphosphate and revealed that the SOS response pathway is activated upon ldhA expression even before antimicrobial treatment. Metabolome analysis of ldhA-overexpressing cells revealed that nucleotide metabolic pathways, such as de novo purine biosynthesis, were activated to prepare a nucleotide pool, as substrate for repairing ofloxacin-induced DNA damage. We provide a novel persister model that contributes to survival as a species by “accidentally” activating the SOS response even before receiving antimicrobial stress.
KW - Escherichia coli
KW - SOS response
KW - metabolome
KW - nucleic acid
KW - persister
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U2 - 10.1111/1348-0421.12970
DO - 10.1111/1348-0421.12970
M3 - Article
C2 - 35174526
AN - SCOPUS:85126850083
SN - 0385-5600
VL - 66
SP - 225
EP - 233
JO - Microbiology and Immunology
JF - Microbiology and Immunology
IS - 5
ER -