Unraveling the hydroxypropionaldehyde (HPA) system: an active antimicrobial agent against human pathogens.
The hydroxypropionaldehyde (HPA) system is a natural defense system synthesized by the probiotic bacterium Lactobacillus reuteri. To elucidate which of the molecules composing the HPA system (3-hydroxypropionaldehyde (3-HPA), reuterin (HPA dimer), and HPA hydrate) is responsible for the potent antimicrobial activity in biological systems, a combination of biochemical, genetic, and proteomic assays was used. The HPA system reacts with sulfhydryl-containing compounds such as cysteine and reduced glutathione (GSH) in solution. In situ, GSH knock-out Escherichia coli is significantly more susceptible to HPA-mediated cell death than E. coli wild type; GSH supplementation protects either bacteria from HPA attack. Proteomic analysis of HPA-treated bacteria ( Haemophilus influenzae ) revealed induction of redox- and heat shock-related proteins. A new antimicrobial mechanism of HPA is proposed, whereby the activity of HPA leads to depletion of free SH- groups in GSH and proteins through the action of 3-hydroxypropionaldehyde, causing an imbalance of the cellular redox status, ultimately resulting in cell death.
Vollenweider
Sabine
S
Laboratory of Food Biotechnology, Institute of Food, Nutrition and Health, 8092 ETH Zurich, Switzerland. sabine.vollenweider@ilw.agrl.ethz.ch
Evers
Stefan
S
Zurbriggen
Karin
K
Lacroix
Christophe
C
D000447:Aldehydes / Q000494:pharmacology; D000890:Anti-Infective Agents; D001426:Bacterial Proteins / Q000032:analysis; D003545:Cysteine / Q000737:chemistry; D019281:Dimerization; D004926:Escherichia coli / Q000187:drug effects; D005978:Glutathione / Q000737:chemistry / Q000494:pharmacology; D005985:Glyceraldehyde / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006193:Haemophilus influenzae / Q000187:drug effects; D006801:Humans; D011407:Propane / Q000737:chemistry / Q000494:pharmacology*; D012996:Solutions
D000447:Aldehydes; D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D012996:Solutions; C047158:3-hydroxypropionaldehyde; D005985:Glyceraldehyde; C005556:propionaldehyde; D005978:Glutathione; D003545:Cysteine; D011407:Propane