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Non‐invasive Salmonella typhimurium mutants are avirulent because of an inability to enter and destroy M cells of ileal Peyer's patches
Author(s) -
Penheiter Kristi L.,
Mathur Nitin,
Giles Dobie,
Fahlen Thomas,
Jones Bradley D.
Publication year - 1997
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.1997.3741745.x
Subject(s) - biology , virulence , secretion , microbiology and biotechnology , mutant , salmonella , gentamicin protection assay , phenotype , enterobacteriaceae , pathogenicity island , secretory protein , gene , bacteria , genetics , escherichia coli , western blot , biochemistry
Salmonella typhimurium initiates infection of a host by invading M cells of Peyer’s patches within the small intestine. The ability of the bacteria to invade mammalian cells has been shown to be regulated by environmental conditions, including oxygen concentrations, osmolarity, and growth phase. We have previously created oxygen‐regulated Tn 5lacZY S. typhimurium mutants that are defective in invasion. We have now identified the invasion genes disrupted by eight of the transposon insertions. These genes encode transcriptional regulators ( hilA and invF ), type III secretory components ( orgA , invG and spaR ) and secreted proteins ( invC and invD ). Examination of the protein‐secretion profiles of the non‐invasive mutants indicated that each of the mutants was defective in secretion of between one and six proteins. We have also demonstrated that the loss of tissue culture cell invasiveness corresponds to an inability to invade and destroy M cells of Peyer's patches in a murine ligated loop model. Virulence studies, performed in mice, demonstrated that these defects significantly reduced the ability of the mutants to cause murine typhoid fever by an oral route of infection. Virulence by an intraperitoneal route of infection was unaffected. The data indicate that in vitro invasiveness, invasion‐protein secretion, and M‐cell invasion are critical indicators of S. typhimurium virulence.