Journal article
The Role of the st313-td Gene in Virulence of Salmonella Typhimurium ST313
University of Copenhagen1
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
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.
Language: | English |
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Publisher: | Public Library of Science |
Year: | 2014 |
Pages: | e84566 |
ISSN: | 15537358 , 1553734x and 19326203 |
Types: | Journal article |
DOI: | 10.1371/journal.pone.0084566 |
ORCIDs: | 0000-0001-5026-7852 , 0000-0001-6225-6587 , Leekitcharoenphon, Pimlapas , Aarestrup, Frank Møller and Hendriksen, Rene S. |
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 ANIMAL MODELS Africa Ethiopian region Palearctic region Artiodactyla Mammalia Vertebrata Chordata Animalia (Animals, Artiodactyls, Chordates, Mammals, Nonhuman Vertebrates, Nonhuman Mammals, Vertebrates) - Bovidae [85715] cattle common BACTEREMIA BIOFILM FORMATION Belarus Europe Palearctic region Biochemistry and Molecular Biophysics CHROMOSOMAL GENES China Asia Palearctic region ENTERICA SEROVAR TYPHIMURIUM FOOD SAFETY Facultatively Anaerobic Gram-Negative Rods Eubacteria Bacteria Microorganisms (Bacteria, Eubacteria, Microorganisms) - Enterobacteriaceae [06702] Salmonella genus strain-Dublin Salmonella enterica species pathogen serovar-Typhimurium ST313 GENES GENETICS HOST-CELLS Human Medicine Hygiene and toxicology IN-VIVO INFECTIONS INVASIVE NONTYPHOIDAL SALMONELLA Infection MULTIDISCIPLINARY MULTIDRUG-RESISTANCE Medical Sciences Microbiological aspects Molecular Genetics Nepal Asia Oriental region PCR PRODUCTS 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 SALMONELLA TYPHIMURIUM SDG 3 - Good Health and Well-being Salmonella enterica serovar Typhimurium ST313 infection bacterial disease etiology Salmonella enterica st313-td gene [Enterobacteriaceae] expression VIRULENCE comparative genomics laboratory techniques, genetic techniques epithelial cell genomic island genomic structure macrophage immune system, blood and lymphatics
Animals Bacterial Proteins Epithelial Cells Female Gene Deletion Gene Expression Gene Order Genome, Bacterial Genomic Islands Humans Macrophages Medicine Mice Multilocus Sequence Typing Polymorphism, Single Nucleotide Q R Salmonella Infections Salmonella typhimurium Science Virulence Virulence Factors