Landscape of the genome and host cell response of <i>Mycobacterium shigaense</i> reveals pathogenic features

A systems approach was used to explore the genome and transcriptome of <i>Mycobacterium shigaense</i>, a new opportunistic pathogen isolated from a patient with a skin infection, and the host response transcriptome was assessed using a macrophage infection model. The <i>M</i>. <i>shigaense</i> genome comprises 5,207,883 bp, with 67.2% G+C content and 5098 predicted coding genes. Evolutionarily, the bacterium belongs to a cluster in the phylogenetic tree along with three target opportunistic pathogenic strains, namely, <i>M</i>. <i>avium</i>, <i>M</i>. <i>triplex</i> and <i>M</i>. <i>simiae</i>. Potential virulence genes are indeed expressed by <i>M</i>. <i>shigaense</i> under culture conditions. Phenotypically, <i>M</i>. <i>shigaense</i> had similar infection and replication capacities in a macrophage model as the opportunistic species compared to <i>M</i>. <i>tuberculosis</i>. <i>M</i>. <i>shigaense</i> activated NF-κB, TNF, cytokines and chemokines in the host innate immune-related signaling pathways and elicited an early response shared with pathogenic bacilli except <i>M</i>. <i>tuberculosis</i>. <i>M</i>. <i>shigaense</i> upregulated specific host response genes such as <i>TLR7</i>, <i>CCL4</i> and <i>CXCL5</i>. We performed an integrated and comparative analysis of <i>M</i>. <i>shigaense</i>. Multigroup comparison indicated certain differences with typical pathogenic bacilli in terms of gene features and the macrophage response.