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Microbes Infect. 2017 Jan;19(1):5-17. doi: 10.1016/j.micinf.2016.09.001. Epub 2016 Sep 13.

Mycobacterium abscessus ESX-3 plays an important role in host inflammatory and pathological responses during infection.

Author information

1
Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea; Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea.
2
Department of Molecular and Life Science, Hanyang University, Ansan 426-791, South Korea.
3
Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, South Korea.
4
Department of Pathology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea; Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea.
5
Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea; Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea; Molecular Mechanism of Antibiotics, Division of Life Science, Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, South Korea. Electronic address: jichanjang@gnu.ac.kr.

Abstract

Mycobacterial ESX systems are often related to pathogenesis during infection. However, little is known about the function of ESX systems of Mycobacterium abscessus (Mab). This study focuses on the Mab ESX-3 cluster, which contains major genes such as esxH (Rv0288, low molecular weight protein antigen 7; CFP-7) and esxG (Rv0287, ESAT-6 like protein). An esx-3 (MAB 2224c-2234c)-deletional mutant of Mab (Δesx) was constructed and used to infect murine and human macrophages. We then investigated whether Mab Δesx modulated innate host immune responses in macrophages. Mab Δesx infection resulted in less pathological and inflammatory responses. Additionally, Δesx resulted in significantly decreased activation of inflammatory signaling and cytokine production in macrophages compared to WT. Moreover, recombinant EsxG·EsxH (rEsxGH) proteins encoded by the ESX-3 region showed synergistic enhancement of inflammatory cytokine generation in macrophages infected with Δesx. Taken together, our data suggest that Mab ESX-3 plays an important role in inflammatory and pathological responses during Mab infection.

KEYWORDS:

ESX-3; Host inflammation; Mycobacterium abscessus

PMID:
27637463
DOI:
10.1016/j.micinf.2016.09.001
[Indexed for MEDLINE]

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