title: The Type of Growth Medium Affects the Presence of a Mycobacterial Capsule and Is Associated With Differences in Protective Efficacy of BCG Vaccination Against Mycobacterium tuberculosis.
abstract: Bacillus Calmette-Guerin (BCG) vaccine is widely used for the prevention of tuberculosis, despite limited efficacy. Most immunological studies of BCG or Mycobacterium tuberculosis strains grow bacteria in the presence of detergent, which also strips the mycobacterial capsule. The impact of the capsule on vaccine efficacy has not been explored.
  
  
  
  We tested the influence of detergent in cultures of BCG and M. tuberculosis strains on the outcome of vaccination experiments on mice and transcriptional responses on M. tuberculosis
  
  
  
  Vaccination of mice with encapsulated BCG promoted a more potent immune response relative to vaccination with unencapsulated BCG, including higher polysaccharide-specific capsule antibody titers, higher interferon γ and interleukin 17 splenic responses, and more multifunctional CD4(+) T cells. These differences correlated with variability in the bacterial burden in lung and spleen of mice infected with encapsulated or unencapsulated M. tuberculosis The combination of vaccination and challenge with encapsulated strains resulted in the greatest protection efficacy. The transcriptome of encapsulated M. tuberculosis was similar to that of starvation, hypoxia, stationary phase, or nonreplicating persistence.
  
  
  
  The presence of detergent in growth media and a capsule on BCG were associated with differences in the outcome of vaccination, implying that these are important variables in immunological studies.
authors.affiliation: Department of Microbiology and Immunology CIC bioGUNE, Bizkaia Technology Park, Derio, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Prados-Rosales
authors.affiliation: Department of Microbiology and Immunology Millennium Institute on Immunology and Immunotherapy, Programa Disciplinario de Inmunologia, Facultad de Medicina, Universidad de Chile, Santiago.
authors.forename: Leandro J
authors.initials: LJ
authors.lastname: Carreño
authors.affiliation: Department of Microbiology and Immunology Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Brian
authors.initials: B
authors.lastname: Weinrick
authors.affiliation: Department of Microbiology and Immunology.
authors.forename: Ana
authors.initials: A
authors.lastname: Batista-Gonzalez
authors.affiliation: Department of Pediatrics, and Department of Family and Community Medicine, New York Medical College, Valhalla, New York.
authors.forename: Aarona
authors.initials: A
authors.lastname: Glatman-Freedman
authors.affiliation: Department of Microbiology and Immunology Department of Medicine.
authors.forename: Jiayong
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Microbiology and Immunology Department of Medicine.
authors.forename: John
authors.initials: J
authors.lastname: Chan
authors.affiliation: Department of Microbiology and Immunology Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: William R
authors.initials: WR
authors.lastname: Jacobs
authors.affiliation: Department of Microbiology and Immunology.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Porcelli
authors.affiliation: Department of Microbiology and Immunology Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Arturo
authors.initials: A
authors.lastname: Casadevall
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001500:BCG Vaccine / Q000276:immunology*; D016667:Bacterial Capsules / Q000276:immunology* / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003470:Culture Media / Q000737:chemistry*; D005260:Female; D020869:Gene Expression Profiling; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000254:growth & development / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001500:BCG Vaccine; D003470:Culture Media; D020381:Interleukin-17; D007371:Interferon-gamma
keywords: BCG; Mycobacterium tuberculosis; capsule; vaccine