Pathogenic diversification of the gut commensal Providencia alcalifaciens via acquisition of a second type III secretion system.

Autor: Klein JA; Paul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA., Predeus AV; Wellcome Sanger Institute, Hinxton, Cambridgeshire, United Kingdom., Greissl AR; Paul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA., Clark-Herrera MM; Paul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA., Cruz E; Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA., Cundiff JA; Paul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA., Haeberle AL; Paul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA., Howell M; Paul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA., Lele A; Paul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA., Robinson DJ; Paul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA., Westerman TL; Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.; Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA., Wrande M; Paul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA., Wright SJ; Paul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA., Green NM; Public Health Laboratory, Los Angeles County Department of Public Health, Downey, California, USA., Vallance BA; Division of Gastroenterology, Hepatology and Nutrition, BC Children's Hospital and the University of British Columbia, Vancouver, British Columbia, Canada., McClelland M; Department of Microbiology and Molecular Genetics, University of California, Irvine, California, USA., Mejia A; Comparative Pathology Laboratory, Research Animal Resources and Compliance, University of Wisconsin-Madison, Madison, Wisconsin, USA., Goodman AG; Paul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.; School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA., Elfenbein JR; Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.; Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA., Knodler LA; Paul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.; Department of Microbiology and Molecular Genetics, Robert Larner College of Medicine at The University of Vermont, Burlington, Vermont, USA.
Jazyk: angličtina
Zdroj: Infection and immunity [Infect Immun] 2024 Oct 15; Vol. 92 (10), pp. e0031424. Date of Electronic Publication: 2024 Sep 10.
DOI: 10.1128/iai.00314-24
Abstrakt: Providencia alcalifaciens is a Gram-negative bacterium found in various water and land environments and organisms, including insects and mammals. Some P. alcalifaciens strains encode gene homologs of virulence factors found in pathogenic Enterobacterales members, such as Salmonella enterica serovar Typhimurium and Shigella flexneri . Whether these genes are pathogenic determinants in P. alcalifaciens is not known. In this study, we investigated P. alcalifaciens -host interactions at the cellular level, focusing on the role of two type III secretion systems (T3SS) belonging to the Inv-Mxi/Spa family. T3SS 1b is widespread in Providencia spp. and encoded on the chromosome. A large plasmid that is present in a subset of P. alcalifaciens strains, primarily isolated from diarrheal patients, encodes for T3SS 1a . We show that P. alcalifaciens 205/92 is internalized into eukaryotic cells, lyses its internalization vacuole, and proliferates in the cytosol. This triggers caspase-4-dependent inflammasome responses in gut epithelial cells. The requirement for the T3SS 1a in entry, vacuole lysis, and cytosolic proliferation is host cell type-specific, playing a more prominent role in intestinal epithelial cells than in macrophages or insect cells. In a bovine ligated intestinal loop model, P. alcalifaciens colonizes the intestinal mucosa and induces mild epithelial damage with negligible fluid accumulation in a T3SS 1a - and T3SS 1b -independent manner. However, T3SS 1b was required for the rapid killing of Drosophila melanogaster . We propose that the acquisition of two T3SS has allowed P. alcalifaciens to diversify its host range, from a highly virulent pathogen of insects to an opportunistic gastrointestinal pathogen of animals.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE
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