Antimicrobial medium- and long-chain free fatty acids prevent PrfA-dependent activation of virulence genes in Listeria monocytogenes.
The foodborne pathogen Listeria monocytogenes is the causative agent of the invasive disease listeriosis. Infection by L. monocytogenes involves bacterial crossing of the intestinal barrier and intracellular replication in a variety of host cells. The PrfA protein is the master regulator of virulence factors required for bacterial entry, intracellular replication and cell-to-cell spread. PrfA-dependent activation of virulence genes occurs primarily in the blood and during intracellular infection. In contrast, PrfA does not play a significant role in regulation of virulence gene expression in the intestinal environment. In the gastrointestinal phase of infection, the bacterium encounters a variety of antimicrobial agents, including medium- and long-chain free fatty acids that are commonly found in our diet and as active components of bile. Here we show that subinhibitory concentrations of specific antimicrobial free fatty acids act to downregulate transcription of PrfA-activated virulence genes. Interestingly, the inhibitory effect is also evident in cells encoding a constitutively active variant of PrfA. Collectively, our data suggest that antimicrobial medium- and long-chain free fatty acids may act as signals to prevent PrfA-mediated activation of virulence genes in environments where PrfA activation is not required, such as in food and the gastrointestinal tract.
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark. Electronic address: emsl@bmb.sdu.dk.
Eva Maria
EM
Sternkopf Lillebæk
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark. Electronic address: sln1990@hotmail.com.
Stine
S
Lambert Nielsen
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark. Electronic address: rthom13@student.sdu.dk.
Rikke
R
Scheel Thomasen
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark. Electronic address: nils.f@bmb.sdu.dk.
Nils J
NJ
Færgeman
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark. Electronic address: bhk@bmb.sdu.dk.
Birgitte H
BH
Kallipolitis
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial; D008089:Listeria monocytogenes / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity*; D010454:Peptide Termination Factors / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects*; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005230:Fatty Acids, Nonesterified; D010454:Peptide Termination Factors; C545356:PrfA protein, Listeria monocytogenes; D015534:Trans-Activators; D037521:Virulence Factors
Antimicrobial free fatty acids; Listeria monocytogenes; PrfA; Transcription regulation