Research

The Role of the st313-td Gene in Virulence of Salmonella Typhimurium ST313

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Abstract

Multidrug-resistant Salmonella enterica serovar Typhimurium ST313 has emerged in sub-Saharan Africa causing severe infections in humans. Therefore, it has been speculated that this specific sequence type, ST313, carries factors associated with increased pathogenicity. We assessed the role in virulence of a gene with a yet unknown function, st313-td, detected in ST313 through comparative genomics. Additionally, the structure of the genomic island ST313-GI, harbouring the gene was determined. The gene st313-td was cloned into wild type S. Typhimurium 4/74 (4/74-C) as well as knocked out in S. Typhimurium ST313 02-03/002 (Delta st313-td) followed by complementation (02-03/002-C). Delta st313-td was less virulent in mice following i.p. challenge than the wild type and this phenotype could be partly complemented in trans, indicating that st313td plays a role during systemic infection. The gene st313-td was shown not to affect invasion of cultured epithelial cells, while the absence of the gene significantly affects uptake and intracellular survival within macrophages. The gene st313-td was proven to be strongly associated to invasiveness, harboured by 92.5% of S. Typhimurium blood isolates (n = 82) and 100% of S. Dublin strains (n = 50) analysed. On the contrary, S. Typhimurium isolates of animal and food origin (n = 82) did not carry st313-td. Six human, non-blood isolates of S. Typhimurium from Belarus, China and Nepal harboured the gene and belonged to sequence types ST398 and ST19. Our data showed a global presence of the st313-td gene and in other sequence types than ST313. The gene st313-td was shown to be expressed during logarithmic phase of growth in 14 selected Salmonella strains carrying the gene. This study reveals that st313-td plays a role in S. Typhimurium ST313 pathogenesis and adds another chapter to understanding of the virulence of S. Typhimurium and in particular of the emerging sequence type ST313.

ANIMAL MODELS FOOD SAFETY GENES GENETICS SALMONELLA SALMONELLA TYPHIMURIUM VIRULENCE Hygiene and toxicology Microbiological aspects MULTIDISCIPLINARY ENTERICA SEROVAR TYPHIMURIUM INVASIVE NONTYPHOIDAL SALMONELLA MULTIDRUG-RESISTANCE CHROMOSOMAL GENES BIOFILM FORMATION PCR PRODUCTS HOST-CELLS IN-VIVO INFECTIONS BACTEREMIA Africa Ethiopian region Palearctic region Belarus Europe Palearctic region China Asia Palearctic region Nepal Asia Oriental region Artiodactyla Mammalia Vertebrata Chordata Animalia (Animals Artiodactyls Chordates Mammals Nonhuman Vertebrates Nonhuman Mammals Vertebrates) - Bovidae [85715] cattle common Facultatively Anaerobic Gram-Negative Rods Eubacteria Bacteria Microorganisms (Bacteria Eubacteria Microorganisms) - Enterobacteriaceae [06702] Salmonella genus strain-Dublin Salmonella enterica species pathogen serovar-Typhimurium ST313 Primates Mammalia Vertebrata Chordata Animalia (Animals Chordates Humans Mammals Primates Vertebrates) - Hominidae [86215] human common host Rodentia Mammalia Vertebrata Chordata Animalia (Animals Chordates Mammals Nonhuman Vertebrates Nonhuman Mammals Rodents Vertebrates) - Muridae [86375] J774 cell line cell_line mouse macrophage cells mouse common host female strain-C57/BL6 Salmonella enterica st313-td gene [Enterobacteriaceae] expression genomic island 02506 Cytology - Animal 02508 Cytology - Human 03502 Genetics - General 03506 Genetics - Animal 03508 Genetics - Human 12502 Pathology - General 15002 Blood - Blood and lymph studies 15004 Blood - Blood cell studies 31000 Physiology and biochemistry of bacteria 31500 Genetics of bacteria and viruses 34502 Immunology - General and methods 36002 Medical and clinical microbiology - Bacteriology Human Medicine Infection Molecular Genetics genomic structure Salmonella enterica serovar Typhimurium ST313 infection bacterial disease etiology Biochemistry and Molecular Biophysics Medical Sciences epithelial cell macrophage immune system blood and lymphatics comparative genomics laboratory techniques genetic techniques