Virulence and immunogenicity of genetically defined human and porcine isolates of M. avium subsp. hominissuis in an experimental mouse infection.
Mycobacterium avium subsp. hominissuis (Mah) represents a health concern for humans and to a lesser extent for pigs, but its zoonotic potential remains elusive. Using multispacer sequence typing (MST) we previously identified 49 different genotypes of Mah among Belgian clinical and porcine isolates, with 5 MSTs shared by both hosts. Using experimental intranasal infection of BALB/c mice, we compared the virulence and immunogenicity of porcine and clinical human isolates with shared genotype or with a genotype only found in humans or pigs. Bacterial replication was monitored for 20 weeks in lungs, spleen and liver and mycobacteria specific spleen cell IFN-γ, IL-10 and IL-17 production as well as serum antibody responses were analyzed. Isolates varied in virulence, with human and porcine isolates sharing MST22 genotype showing a thousand fold higher bacterial replication in lungs and more dissemination to spleen and liver than the human and porcine MST91 isolates. Virulent MST22 type was also associated with progressive suppression of IFN-γ and IL-17 responses, and increased IL-10 production. Whole genome sequencing of the two virulent isolates with MST22 genotype and two avirulent isolates of genotype MST91 and comparison with two well-studied M. avium subsp. hominissuis reference strains i.e. Mah 104 and Mah TH135, identified in the two MST22 isolates nine specific virulence factors of the mammalian cell entry family, that were identical with Mah 104 strain. Despite the obvious limitations of the mouse model, a striking link of virulence and identity at the genome level of porcine and human isolates with the same multisequence type, for which no correlation of place of residence (humans) or farm of origin (pigs) was observed, seems to point to the existence in the environment of certain genotypes of Mah which may be more infectious both for humans and pigs than other genotypes.
Service Immunology, Operational Direction Communicable and infectious Diseases, Scientific Institute of Public Health, Brussels, Belgium.
Nicolas
http://orcid.org/0000-0001-6310-9140
N
Bruffaerts
Service Bacterial diseases, Operational Direction Communicable and infectious Diseases, Scientific Institute of Public Health, Brussels, Belgium.
Christelle
C
Vluggen
Unit Bacterial Zoonoses of livestock, Operational Direction Bacterial Diseases, Veterinary and Agrochemical Research Centre, Brussels, Belgium.
Virginie
V
Roupie
Unit Bacterial Zoonoses of livestock, Operational Direction Bacterial Diseases, Veterinary and Agrochemical Research Centre, Brussels, Belgium.|Research Unit in Epidemiology and Risk Analysis applied to Veterinary Sciences, Fundamental and Applied Research for Animal and Health, Université of Liège, Liège, Belgium.
Lucille
L
Duytschaever
Service Immunology, Operational Direction Communicable and infectious Diseases, Scientific Institute of Public Health, Brussels, Belgium.
Christophe
C
Van den Poel
Research Unit in Epidemiology and Risk Analysis applied to Veterinary Sciences, Fundamental and Applied Research for Animal and Health, Université of Liège, Liège, Belgium.
Joseph
J
Denoël
Service Protéomique et Microbiologie, Université de Mons, Mons, Belgium.
Ruddy
R
Wattiez
Unité de Recherche en Biologie des Microorganismes, Université de Namur, Namur, Belgium.
Jean-Jacques
JJ
Letesson
Unit Bacterial Zoonoses of livestock, Operational Direction Bacterial Diseases, Veterinary and Agrochemical Research Centre, Brussels, Belgium.
David
D
Fretin
Department Biomedical Sciences, University of Antwerp, Antwerp, Belgium.|Unit Mycobacteriology, Institute of Tropical Medicine, Antwerp, Belgium.
Leen
L
Rigouts
Service bioinformatique, Genoscreen, Lille, France.
Ophélie
O
Chapeira
Service Bacterial diseases, Operational Direction Communicable and infectious Diseases, Scientific Institute of Public Health, Brussels, Belgium.
Vanessa
V
Mathys
Research Unit in Epidemiology and Risk Analysis applied to Veterinary Sciences, Fundamental and Applied Research for Animal and Health, Université of Liège, Liège, Belgium.
Claude
C
Saegerman
Service Immunology, Operational Direction Communicable and infectious Diseases, Scientific Institute of Public Health, Brussels, Belgium.
Kris
K
Huygen
D000328:Adult; D000818:Animals; D002675:Child, Preschool; D005260:Female; D016680:Genome, Bacterial; D005838:Genotype; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009162:Mycobacterium avium / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity; D013154:Spleen / Q000382:microbiology; D013552:Swine; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology* / Q000662:veterinary; D014774:Virulence / Q000235:genetics
D007378:Interleukins; D007371:Interferon-gamma