Herrero-Fresno, Ana4; Wallrodt, Inke4; Leekitcharoenphon, Pimlapas2; Olsen, John Elmerdahl4; Aarestrup, Frank Møller2; Hendriksen, Rene S.2
1 Comparative Microbial Genomics, Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark2 National Food Institute, Technical University of Denmark3 Division of Epidemiology and Microbial Genomics, National Food Institute, Technical University of Denmark4 University of Copenhagen
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.
Plos One, 2014, Vol 9, Issue 1
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  cattle common; Facultatively Anaerobic Gram-Negative Rods Eubacteria Bacteria Microorganisms (Bacteria, Eubacteria, Microorganisms) - Enterobacteriaceae  Salmonella genus strain-Dublin Salmonella enterica species pathogen serovar-Typhimurium ST313; Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae  human common host; Rodentia Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Mammals, Nonhuman Vertebrates, Nonhuman Mammals, Rodents, Vertebrates) - Muridae  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