Sub-inhibitory concentrations of trans-cinnamaldehyde attenuate virulence in Cronobacter sakazakii in vitro.
Cronobacter sakazakii is a foodborne pathogen, which causes a life-threatening form of meningitis, necrotizing colitis and meningoencephalitis in neonates and children. Epidemiological studies implicate dried infant formula as the principal source of C. sakazakii. In this study, we investigated the efficacy of sub-inhibitory concentrations (SIC) of trans-cinnamaldehyde (TC), an ingredient in cinnamon, for reducing C. sakazakii virulence in vitro using cell culture, microscopy and gene expression assays. TC significantly (p ≤ 0.05) suppressed C. sakazakii adhesion to and invasion of human and rat intestinal epithelial cells, and human brain microvascular endothelial cells. In addition, TC inhibited C. sakazakii survival and replication in human macrophages. We also observed that TC reduced the ability of C. sakazakii to cause cell death in rat intestinal cells, by inhibiting nitric oxide production. Results from gene expression studies revealed that TC significantly downregulated the virulence genes critical for motility, host tissue adhesion and invasion, macrophage survival, and LPS (Lipopolysaccharide) synthesis in C. sakazakii. The efficacy of TC in attenuating these major virulence factors in C. sakazakii underscores its potential use in the prevention and/or control of infection caused by this pathogen.
Department of Animal Science, University of Connecticut, 3636 Horse Barn Hill Road Ext., Unit 4040, Storrs, CT 06269, USA. mary_anne.amalaradjou@uconn.edu.
Mary Anne Roshni
MA
Amalaradjou
Division of Pediatric Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore, MD 21218, USA. kwangkim@jhmi.edu.
Kwang Sik
KS
Kim
Department of Animal Science, University of Connecticut, 3636 Horse Barn Hill Road Ext., Unit 4040, Storrs, CT 06269, USA. kumar.venkitanarayanan@uconn.edu.
Kumar
K
Venkitanarayanan
D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001422:Bacterial Adhesion / Q000187:drug effects; D002460:Cell Line; D044083:Cronobacter sakazakii / Q000187:drug effects / Q000472:pathogenicity*; D015536:Down-Regulation / Q000187:drug effects; D004731:Endotoxins / Q000096:biosynthesis; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000382:microbiology; D007536:Isomerism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D008856:Microscopy, Fluorescence; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D037521:Virulence Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D004731:Endotoxins; D034741:RNA, Small Interfering; D037521:Virulence Factors; D000171:Acrolein; D052247:Nitric Oxide Synthase Type II; C012843:cinnamaldehyde