title: Virulence of Mycobacterium avium complex strains isolated from immunocompetent patients.
abstract: Mycobacterium avium complex (MAC) disease has been increasing worldwide not only in immunocompromised but also in immunocompetent humans. However, the relationship between mycobacterial strain virulence and disease progression in immunocompetent humans is unclear. In this study, we isolated 6 strains from patients with pulmonary MAC disease. To explore the virulence, we examined the growth in human THP-1 macrophages and pathogenicity in C57BL/6 mice. We found that one strain, designated 198, which was isolated from a patient showing the most progressive disease, persisted in THP-1 cells. In addition, strain 198 grew to a high bacterial load with strong inflammation in mouse lungs and spleens 16 weeks after infection. To our knowledge, strain 198 is the first isolated MAC strain that exhibits hypervirulence consistently for the human patient, human macrophages in vitro, and even for immunocompetent mice. Other strains showed limited survival and weak virulence both in macrophages and in mice, uncorrelated to disease progression in human patients. We demonstrated that there is a hypervirulent clinical MAC strain whose experimental virulence corresponds to the serious disease progression in the patients. The existence of such strain suggests the involvement of bacterial virulence in the pathogenesis of pulmonary MAC disease in immunocompetent status.
authors.affiliation: Department of Bacteriology, Osaka City University Graduate School of Medicine, and Department of Internal Medicine, National Hospital Organization Toneyama National Hospital, 5-1-1 Toneyama, Toyonaka, Osaka 560-8552, Japan. y-tateishi@med.osaka-cu.ac.jp
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Tateishi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hirayama
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Ozeki
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nishiuchi
authors.forename: Mamiko
authors.initials: M
authors.lastname: Yoshimura
authors.forename: Jing
authors.initials: J
authors.lastname: Kang
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shibata
authors.forename: Kazuto
authors.initials: K
authors.lastname: Hirata
authors.forename: Seigo
authors.initials: S
authors.lastname: Kitada
authors.forename: Ryoji
authors.initials: R
authors.lastname: Maekura
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ogura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Sohkichi
authors.initials: S
authors.lastname: Matsumoto
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D006801:Humans; D007121:Immunocompetence; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology / Q000382:microbiology; D015269:Mycobacterium avium Complex / Q000254:growth & development / Q000302:isolation & purification* / Q000472:pathogenicity*; D015270:Mycobacterium avium-intracellulare Infection / Q000382:microbiology / Q000473:pathology*; D014397:Tuberculosis, Pulmonary / Q000382:microbiology / Q000473:pathology*; D014774:Virulence