Macrophage killing is an essential virulence mechanism of Salmonella typhimurium.
Phagocytic cells are a critical line of defense against infection. The ability of a pathogen to survive and even replicate within phagocytic cells is a potent method of evading the defense mechanisms of the host. A number of pathogens survive within macrophages after phagocytosis and this contributes to their virulence. Salmonella is one of these pathogens. Here we report that 6-14 hr after Salmonella enters the macrophage and replicates, it resides in large vacuoles and causes the destruction of these cells. Furthermore, we identified four independently isolated MudJ-lacZ insertion mutants that no longer cause the formation of these vacuoles or kill the macrophages. All four insertions were located in the ompR/envZ regulon. These findings suggest that killing and escape from macrophages may be as important steps in Salmonella pathogenesis as are survival and replication in these host cells.
Lindgren
S W
SW
Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA.
Stojiljkovic
I
I
Heffron
F
F
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis; D002460:Cell Line; D002470:Cell Survival; D003001:Cloning, Molecular; D029968:Escherichia coli Proteins; D005816:Genetic Complementation Test; D008264:Macrophages / Q000382:microbiology* / Q000502:physiology*; D008854:Microscopy, Electron; D009097:Multienzyme Complexes; D016254:Mutagenesis, Insertional; D009876:Operon; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012486:Salmonella typhimurium / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D013997:Time Factors; D014162:Transfection; D014617:Vacuoles / Q000382:microbiology / Q000502:physiology; D014774:Virulence; D001616:beta-Galactosidase / Q000096:biosynthesis
D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D009097:Multienzyme Complexes; D011993:Recombinant Fusion Proteins; C057843:envZ protein, E coli; D001616:beta-Galactosidase