Pseudogenization of the Secreted Effector Gene sseI Confers Rapid Systemic Dissemination of S. Typhimurium ST313 within Migratory Dendritic Cells.
Genome degradation correlates with host adaptation and systemic disease in Salmonella. Most lineages of the S. enterica subspecies Typhimurium cause gastroenteritis in humans; however, the recently emerged ST313 lineage II pathovar commonly causes systemic bacteremia in sub-Saharan Africa. ST313 lineage II displays genome degradation compared to gastroenteritis-associated lineages; yet, the mechanisms and causal genetic differences mediating these infection phenotypes are largely unknown. We find that the ST313 isolate D23580 hyperdisseminates from the gut to systemic sites, such as the mesenteric lymph nodes (MLNs), via CD11b+migratory dendritic cells (DCs). This hyperdissemination was facilitated by the loss of sseI, which encodes an effector that inhibits DC migration in gastroenteritis-associated isolates. Expressing functional SseI in D23580 reduced the number of infected migratory DCs and bacteria in the MLN. Our study reveals a mechanism linking pseudogenization of effectors with the evolution of niche adaptation in a bacterial pathogen.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Sarah E
SE
Carden
Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, CA 95616, USA.
Gregory T
GT
Walker
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Jared
J
Honeycutt
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Kyler
K
Lugo
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Trung
T
Pham
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Amanda
A
Jacobson
Department of Comparative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Donna
D
Bouley
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Juliana
J
Idoyaga
Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, CA 95616, USA.
Renee M
RM
Tsolis
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: dmonack@stanford.edu.
Denise
D
Monack
D000818:Animals; D016470:Bacteremia / Q000382:microbiology; D002465:Cell Movement; D003713:Dendritic Cells / Q000382:microbiology*; D004195:Disease Models, Animal; D005260:Female; D005759:Gastroenteritis / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D054884:Host-Pathogen Interactions; D008198:Lymph Nodes / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism; D012480:Salmonella Infections / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000235:genetics* / Q000472:pathogenicity
C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7
NTS; SrfH; T3SS effectors; evolution; genome degradation; iNTS; niche adaptation; nontyphoidal Salmonella; pathogenesis; pseudogene