Unique genomic sequences in a novel Mycobacterium avium subsp. hominissuis lineage enable fine scale transmission route tracing during pig movement
Tetsuya Komatsu,
Kenji Ohya,
Atsushi Ota,
Yukiko Nishiuchi,
Hirokazu Yano,
Kayoko Matsuo,
Justice Opare Odoi,
Shota Suganuma,
Kotaro Sawai,
Akemi Hasebe,
Tetsuo Asai,
Tokuma Yanai,
Hideto Fukushi,
Takayuki Wada,
Shiomi Yoshida,
Toshihiro Ito,
Kentaro Arikawa,
Mikihiko Kawai,
Manabu Ato,
Anthony D. Baughn,
Tomotada Iwamoto,
Fumito Maruyama
Affiliations
Tetsuya Komatsu
Aichi Prefectural Tobu Livestock Hygiene Service Center, Toyohashi, Aichi, Japan
Kenji Ohya
Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan; United Graduate School of Veterinary Sciences, Gifu University, Gifu, Japan; Education and Research Center for Food Animal Health, Gifu University (GeFAH), Gifu, Japan
Atsushi Ota
Data Science Center, Division of Biological Science, Nara Institute of Science and Technology, Ikoma, Nara, Japan
Yukiko Nishiuchi
Office of Academic Research and Industry-Government Collaboration, Hiroshima University, Higashi-Hiroshima, Hiroshima, Japan
Hirokazu Yano
Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi, Japan
Kayoko Matsuo
Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan; Kumamoto Prefectural Aso Public Health Center, Aso, Kumamoto, Japan
Justice Opare Odoi
United Graduate School of Veterinary Sciences, Gifu University, Gifu, Japan
Shota Suganuma
Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan
Kotaro Sawai
Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan; Division of Transboundary Animal Disease Research, National Institute of Animal Health, National Agriculture Research Organization, Tsukuba, Ibaraki, Japan
Akemi Hasebe
Toyama Prefectural Meat Inspection Center, Imizu, Toyama, Japan
Tetsuo Asai
United Graduate School of Veterinary Sciences, Gifu University, Gifu, Japan; Education and Research Center for Food Animal Health, Gifu University (GeFAH), Gifu, Japan
Tokuma Yanai
Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan; United Graduate School of Veterinary Sciences, Gifu University, Gifu, Japan; Hiwa Natural History Museum, Shobara, Hiroshima, Japan
Hideto Fukushi
Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan; United Graduate School of Veterinary Sciences, Gifu University, Gifu, Japan
Takayuki Wada
Graduate School of Human Life and Ecology, Osaka Metropolitan University, Osaka, Japan
Shiomi Yoshida
Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, Osaka, Japan
Toshihiro Ito
Laboratory of Proteome Research, Proteome Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan
Kentaro Arikawa
Department of Infectious Diseases, Kobe Institute of Health, Kobe, Hyogo, Japan
Mikihiko Kawai
Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan
Manabu Ato
Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Tokyo, Japan
Anthony D. Baughn
Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN, USA
Tomotada Iwamoto
Department of Infectious Diseases, Kobe Institute of Health, Kobe, Hyogo, Japan
Fumito Maruyama
Office of Academic Research and Industry-Government Collaboration, Hiroshima University, Higashi-Hiroshima, Hiroshima, Japan; Project Research Center for Holobiome and Built Environment (CHOBE), Hiroshima University, Higashi-Hiroshima, Hiroshima, Japan; Scientific and Technological Bioresource Nucleus, Universidad de La Frontera, Temuco, Chile; Corresponding author at: The IDEC Institute, Hiroshima University, Higashi-Hiroshima, Hiroshima, Japan.
Mycobacterium avium subsp. hominissuis (MAH) is one of the most prevalent mycobacteria causing non-tuberculous mycobacterial disease in humans and animals. Of note, MAH is a major cause of mycobacterial granulomatous mesenteric lymphadenitis outbreaks in pig populations. To determine the precise source of infection of MAH in a pig farm and to clarify the epidemiological relationship among pig, human and environmental MAH lineages, we collected 50 MAH isolates from pigs reared in Japan and determined draft genome sequences of 30 isolates. A variable number of tandem repeat analysis revealed that most pig MAH isolates in Japan were closely related to North American, European and Russian human isolates but not to those from East Asian human and their residential environments. Historical recombination analysis revealed that most pig isolates could be classified into SC2/4 and SC3, which contain MAH isolated from pig, European human and environmental isolates. Half of the isolates in SC2/4 had many recombination events with MAH lineages isolated from humans in East Asia. To our surprise, four isolates belonged to a new lineage (SC5) in the global MAH population. Members of SC5 had few footprints of inter-lineage recombination in the genome, and carried 80 unique genes, most of which were located on lineage specific-genomic islands. Using unique genetic features, we were able to trace the putative transmission route via their host pigs. Together, we clarify the possibility of species-specificity of MAH in addition to local adaptation. Our results highlight two transmission routes of MAH, one exposure on pig farms from the environment and the other via pig movement. Moreover, our study also warns that the evolution of MAH in pigs is influenced by MAH from patients and their residential environments, even if the MAH are genetically distinct.
