Entry into host cells is an essential feature in the pathogenicity of Salmonella spp. The inv locus of Salmonella typhimurium encodes several proteins which are components of a type III protein secretion system required for these organisms to gain access to host cells. We report here the identification of several proteins whose secretion into the culture supernatant of S. typhimurium is dependent on the function of the inv-encoded translocation apparatus. Nucleotide sequence analysis of the genes encoding two of these secreted proteins, SipB and SipC, indicated that they are homologous to the Shigella sp. invasins IpaB and IpaC, respectively. An additional gene was identified, sicA, which encodes a protein homologous to IpgC, a Shigella protein that serves as a molecular chaperone for the invasins IpaB and IpaC. Nonpolar mutations in sicA, sipB, and sipC rendered S. typhimurium unable to enter cultured epithelial cells, indicating that these genes are required for bacterial internalization.
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http://dx.doi.org/10.1128/jb.177.14.3965-3971.1995 | DOI Listing |
Lancet Microbe
October 2024
Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Department of Immunology and Infectious Diseases, Harvard T H Chan School of Public Health, Boston, MA, USA.
Background: Shigella is the third leading global cause of moderate or severe diarrhoea among children younger than 5 years globally, and is the leading cause in children aged 24-59 months. The mechanism of protection against Shigella infection and disease in endemic areas is uncertain. We aimed to compare the Shigella-specific antibody responses in individuals living in Shigella-endemic and non-endemic areas, and to identify correlates of protection in a Shigella-endemic location.
View Article and Find Full Text PDFInfect Immun
January 2024
Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA.
Infection by the enteric pathogen requires transit through the gastrointestinal tract and invasion of and replication within the cells of the host colonic epithelium. This process exposes the pathogen to a range of diverse microenvironments. Furthermore, the unique composition and physical environment of the eukaryotic cell cytosol represents a stressful environment for , and extensive physiological adaptations are needed for the bacterium to thrive.
View Article and Find Full Text PDFACS Omega
December 2023
Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Marbacher Weg 8, D-35037 Marburg, Germany.
The pathogenicity factor IpgC belongs to the class II of type III secretion system chaperones, whose members are characterized by a tetratricopeptide repeat (TPR) domain consisting of three and a half TPR motifs. Since IpgC is essential for virulence, we determined a high-resolution crystal structure of this chaperone to facilitate its use as a target for the structure-based design of anti-shigellosis compounds. The crystal structure revealed two possible homodimer assemblies, which strongly differ from the homodimer architectures so far known for IpgC and orthologues thereof.
View Article and Find Full Text PDFFoodborne Pathog Dis
November 2023
Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
is considered a major public health concern, especially for children younger than 5 years of age in developing countries. The pathogenicity of is a complex process that involves the interplay of multiple genes located on a large, unstable virulence plasmid as well as chromosomal pathogenicity islands. Since various factors (including virulence and antibiotic resistance genes) are associated with the severity and duration of shigellosis, in this article, we aim to evaluate whether the invasion of HeLa cells is affected by spp.
View Article and Find Full Text PDFmSphere
August 2023
Department of Diarrheal Disease Research, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
The artificial invasin complex (Invaplex) vaccine is a subunit approach that effectively induces robust immunogenicity directed to serotype-specific lipopolysaccharide and the broadly conserved IpaB and IpaC proteins. One advantage of the vaccine approach is the ability to adjust the constituents to address suboptimal immunogenicity and to change the serotype targeted by the vaccine. As the vaccine moves through the product development pipeline, substantial modifications have been made to address manufacturing feasibility, acceptability to regulatory authorities, and developing immunogenic and effective products for an expanded list of serotypes.
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