Iron regulated genes of Salmonella enterica serovar Typhimurium in response to norepinephrine and the requirement of fepDGC for norepinephrine-enhanced growth

• Published in: Microbes and infection 2008-06, Vol.10 (7), p.807-816
• Main Authors: Bearson, Bradley L., Bearson, Shawn M.D., Uthe, Jolita J., Dowd, Scot E., Houghton, John O., Lee, InSoo, Toscano, Michael J., Lay, Donald C.
• Format: Article
• Language: English
• Subjects: Animals; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; Biological and medical sciences; DNA Transposable Elements; Female; Fundamental and applied biological sciences. Psychology; Gastrointestinal Tract - microbiology; Gene Expression Profiling; Iron; Iron - metabolism; Male; Membrane Transport Proteins - genetics; Membrane Transport Proteins - metabolism; Microbiology; Miscellaneous; Mutagenesis, Insertional; Norepinephrine; Norepinephrine - metabolism; Oligonucleotide Array Sequence Analysis; Salmonella enterica; Salmonella enterica serovar Typhimurium; Salmonella Infections, Animal - microbiology; Salmonella typhimurium; Salmonella typhimurium - genetics; Salmonella typhimurium - growth & development; Salmonella typhimurium - metabolism; Swine; Swine - microbiology; Virulence
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2008.04.011

Catecholamines may stimulate enteric bacteria including the foodborne pathogen Salmonella enterica serovar Typhimurium ( Salmonella Typhimurium) by two mechanisms in vivo: as a quorum sensing signal and a supplier of iron. To identify genes of Salmonella Typhimurium that respond to norepinephrine, transposon mutagenesis and DNA microarray analysis were performed. Insertional mutations in the following genes decreased norepinephrine-enhanced growth: degS, entE, entF, fes, gpmA, hfq, STM3846. DNA microarray and real-time RT-PCR analyses revealed a decrease in the expression of several genes involved in iron acquisition and utilization during norepinephrine exposure, signifying the iron-limiting conditions of serum-SAPI minimal medium and the siderophore-like activity of norepinephrine. Unlike the wild-type parent strain, growth of neither a fepA iroN cirA mutant nor a fepC mutant, harboring deletional mutations in the outer and inner membrane transporters of enterochelin, respectively, was enhanced by norepinephrine. However, growth of the fepC and the fepA iroN cirA mutants could be rescued by an alternative siderophore, ferrioxamine E, further validating the role of norepinephrine in supplying the organism with iron via the catecholate-specific iron transport system. Contrary to previous reports using small animal models, the fepA iroN cirA mutant of Salmonella Typhimurium colonized the swine gastrointestinal tract, as did the fepC mutant.