Original Investigation

Medical Microbiology and Immunology

, Volume 200, Issue 3, pp 177-191

First online:

Conversion of Mycobacterium smegmatis to a pathogenic phenotype via passage of epithelial cells during macrophage infection

  • Su-Young KimAffiliated withDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine
  • , Hosung SohnAffiliated withDepartment of Microbiology and Infectious Signaling Network Research Center, Research Institute for Medical Sciences, College of Medicine, Chungnam National University
  • , Go-Eun ChoiAffiliated withDepartment of Laboratory Medicine, School of Medicine and Medical Research Institute, Pusan National University
  • , Sang-Nae ChoAffiliated withDepartment of Microbiology and Institute of Immunology and Immunological Diseases, Yonsei University College of Medicine
  • , Taegwon OhAffiliated withDepartment of Microbiology and Institute of Immunology and Immunological Diseases, Yonsei University College of Medicine
  • , Hwa-Jung KimAffiliated withDepartment of Microbiology and Infectious Signaling Network Research Center, Research Institute for Medical Sciences, College of Medicine, Chungnam National University
  • , Jake WhangAffiliated withDepartment of Microbiology and Infectious Signaling Network Research Center, Research Institute for Medical Sciences, College of Medicine, Chungnam National University
  • , Jong-Seok KimAffiliated withDepartment of Microbiology and Infectious Signaling Network Research Center, Research Institute for Medical Sciences, College of Medicine, Chungnam National University
  • , Eui-Hong ByunAffiliated withDepartment of Microbiology and Infectious Signaling Network Research Center, Research Institute for Medical Sciences, College of Medicine, Chungnam National University
    • , Woo Sik KimAffiliated withDepartment of Microbiology and Infectious Signaling Network Research Center, Research Institute for Medical Sciences, College of Medicine, Chungnam National University
    • , Ki-Nam MinAffiliated withDepartment of Microbiology and Infectious Signaling Network Research Center, Research Institute for Medical Sciences, College of Medicine, Chungnam National University
    • , Jin Man KimAffiliated withDepartment of Pathology, College of Medicine, Chungnam National University
    • , Sung Jae ShinAffiliated withDepartment of Microbiology and Infectious Signaling Network Research Center, Research Institute for Medical Sciences, College of Medicine, Chungnam National University Email author 

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Abstract

Mycobacteria encounter many different cells during infection within their hosts. Although alveolar epithelial cells play an essential role in host defense as the first cells to be challenged upon contact with mycobacteria, they may contribute to the acquisition of mycobacterial virulence by increasing the expression of virulence or adaptation factors prior to being ingested by macrophages on the side of pathogens. From this aspect, the enhanced virulence of nonpathogenic Mycobacterium smegmatis (MSM) passed through human alveolar A549 epithelial cells (A-MSM) was compared to the direct infection of MSM (D-MSM) in THP-1 macrophages and mouse models. The intracellular growth rate and cytotoxicity of A-MSM were significantly increased in THP-1 macrophages. In addition, compared to D-MSM, A-MSM induced relatively greater interleukin (IL)-1β, IL-6, IL-8, IL-12, TNF-α, MIP-1α, and MCP-1 in THP-1 macrophages. As a next step, a more persistent A-MSM infection was observed in a murine infection model with the development of granulomatous inflammation. Finally, 58 genes induced specifically in A-MSM were partially identified by differential expression using a customized amplification library. These gene expressions were simultaneously maintained in THP-1 infection but no changes were observed in D-MSM. Bioinformatic analysis revealed that these genes are involved mainly in bacterial metabolism including energy production and conversion, carbohydrate, amino acid, and lipid transport, and metabolisms. Conclusively, alveolar epithelial cells promoted the conversion of MSM to the virulent phenotype prior to encountering macrophages by activating the genes required for intracellular survival and presenting its pathogenicity.

Keywords

Mycobacterium smegmatis Enhanced virulence Epithelial cell Pathogenicity Induced gene