Experimental reactivation of pulmonary Mycobacterium avium complex infection in a modified Cornell-like murine model

Seung Bin Cha, Bo Young Jeon, Woo Sik Kim, Jong Seok Kim, Hong Min Kim, Kee Woong Kwon, Sang Nae Cho, Sung Jae Shin, Won Jung Koh

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The latency and reactivation of Mycobacterium tuberculosis infection has been well studied. However, there have been few studies of the latency and reactivation of Mycobacterium avium complex (MAC), the most common etiological non-tuberculous Mycobacterium species next to M. tuberculosis in humans worldwide. We hypothesized that latent MAC infections can be reactivated following immunosuppression after combination chemotherapy with clarithromycin and rifampicin under experimental conditions. To this end, we employed a modified Cornell-like murine model of tuberculosis and investigated six strains consisting of two type strains and four clinical isolates of M. avium and M. intracellulare. After aerosol infection of each MAC strain, five to six mice per group were euthanized at 2, 4, 10, 18, 28 and 35 weeks post-infection, and lungs were sampled to analyze bacterial burden and histopathology. One strain of each species maintained a culture-negative state for 10 weeks after completion of 6 weeks of chemotherapy, but was reactivated after 5 weeks of immunosuppression in the lungs with dexamethasone (three out of six mice in M. avium infection) or sulfasalazine (four out of six mice in both M. avium and M. intracellulare infection). The four remaining MAC strains exhibited decreased bacterial loads in response to chemotherapy; however, they remained at detectable levels and underwent regrowth after immunosuppression. In addition, the exacerbated lung pathology demonstrated a correlation with bacterial burden after reactivation. In conclusion, our results suggest the possibility of MAC reactivation in an experimental mouse model, and experimentally demonstrate that a compromised immune status can induce reactivation and/or regrowth of MAC infection.

Original languageEnglish
Article numbere0139251
JournalPloS one
Volume10
Issue number9
DOIs
Publication statusPublished - 2015 Sep 25

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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