89809 20210902121818.0 doi 10.1080/21505594.2020.1764173 sideral 118275 ART-2020-118275 eng Arenas, J. Universidad de Zaragoza (orcid)0000-0002-8134-0693 Identification of conditionally essential genes for Streptococcus suis infection in pigs 2020 Access copy available to the general public Unrestricted Streptococcus suis is a Gram-positive bacterium and zoonotic pathogen that causes meningitis and sepsis in pigs and humans. The aim of this study was to identify genes required for S. suis infection. We created Tn-Seq libraries in a virulent S. suis strain 10, which was used to inoculate pigs in an intrathecal experimental infection. Comparative analysis of the relative abundance of mutants recovered from different sites of infection (blood, cerebrospinal fluid, and meninges of the brain) identified 361 conditionally essential genes, i.e. required for infection, which is about 18% of the genome. The conditionally essential genes were primarily involved in metabolic and transport processes, regulation, ribosomal structure and biogenesis, transcription, and cell wall membrane and envelope biogenesis, stress defenses, and immune evasion. Directed mutants were created in a set of 10 genes of different genetic ontologies and their role was determined in ex vivo models. Mutants showed different levels of sensitivity to survival in whole blood, serum, cerebrospinal fluid, thermic shock, and stress conditions, as compared to the wild type. Additionally, the role of three selected mutants was validated in co-infection experiments in which pigs were infected with both wild type and isogenic mutant strains. The genetic determinants of infection identified in this work contribute to novel insights in S. suis pathogenesis and could serve as targets for novel vaccines or antimicrobial drugs. info:eu-repo/grantAgreement/EC/H2020/727966/EU/Program for Innovative Global Prevention of Streptococcus suis/PIGSs This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 727966-PIGSs info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 5.882 2020 INFECTIOUS DISEASES 12 / 92 = 0.13 2020 Q1 T1 MICROBIOLOGY 23 / 136 = 0.169 2020 Q1 T1 IMMUNOLOGY 44 / 162 = 0.272 2020 Q2 T1 1.927 2020 Immunology 2020 Q1 Infectious Diseases 2020 Q1 Parasitology 2020 Q1 Microbiology (medical) 2020 Q1 Microbiology 2020 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Zomer, A. Harders-Westerveen, J. Bootsma, H.J. De Jonge, M.I. Stockhofe-Zurwieden, N. Smith, H.E. De Greeff, A. 1009 773 Universidad de Zaragoza Dpto. Patología Animal Área Sanidad Animal 11, 1 (2020), 446-464 VIRULENCE Virulence 2150-5594 4999030 http://zaguan.unizar.es/record/89809/files/texto_completo.pdf Versión publicada 227713 http://zaguan.unizar.es/record/89809/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:89809 articulos driver 2021-09-02-10:06:14 ARTICLE