The antimicrobial compound reuterin (3-hydroxypropionaldehyde) induces oxidative stress via interaction with thiol groups.
Reuterin is an antimicrobial compound produced by Lactobacillus reuteri, and has been proposed to mediate, in part, the probiotic health benefits ascribed to this micro-organism. Despite 20 years of investigation, the mechanism of action by which reuterin exerts its antimicrobial effects has remained elusive. Here we provide evidence that reuterin induces oxidative stress in cells, most likely by modifying thiol groups in proteins and small molecules. Escherichia coli cells subjected to sublethal levels of reuterin expressed a set of genes that overlapped with the set of genes composing the OxyR regulon, which senses and responds to various forms of oxidative stress. E. coli cells mutated for oxyR were more sensitive to reuterin compared with wild-type cells, further supporting a role for reuterin in exerting oxidative stress. The addition of cysteine to E. coli or Clostridium difficile growth media prior to exposure to reuterin suppressed the antimicrobial effect of reuterin on these bacteria. Interestingly, interaction with E. coli stimulated reuterin production or secretion by L. reuteri, indicating that contact with other microbes in the gut increases reuterin output. Thus, reuterin inhibits bacterial growth by modifying thiol groups, which indicates that reuterin negatively affects a large number of cellular targets.
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
Laura
L
Schaefer
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
Thomas A
TA
Auchtung
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
Karley E
KE
Hermans
Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA.
Daniel
D
Whitehead
Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA.
Babak
B
Borhan
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
Robert A
RA
Britton
D000171:Acrolein / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000378:metabolism / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D005985:Glyceraldehyde / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006836:Hydro-Lyases / Q000378:metabolism; D052200:Limosilactobacillus reuteri / Q000254:growth & development / Q000378:metabolism; D050296:Microbial Viability; D018384:Oxidative Stress; D019936:Probiotics / Q000378:metabolism*; D011407:Propane / Q000378:metabolism / Q000494:pharmacology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D000890:Anti-Infective Agents; D029968:Escherichia coli Proteins; D012097:Repressor Proteins; D013438:Sulfhydryl Compounds; C499299:oxyR protein, E coli; C047158:3-hydroxypropionaldehyde; D005985:Glyceraldehyde; D000171:Acrolein; D006836:Hydro-Lyases; C020671:glycerol dehydratase; D011407:Propane