Abstract
A systems approach was used to explore the genome and transcriptome of Mycobacterium shigaense, 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 M. shigaense 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, M. avium, M. triplex and M. simiae. Potential virulence genes are indeed expressed by M. shigaense under culture conditions. Phenotypically, M. shigaense had similar infection and replication capacities in a macrophage model as the opportunistic species compared to M. tuberculosis. M. shigaense 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 M. tuberculosis. M. shigaense upregulated specific host response genes such as TLR7, CCL4 and CXCL5. We performed an integrated and comparative analysis of M. shigaense. Multigroup comparison indicated certain differences with typical pathogenic bacilli in terms of gene features and the macrophage response.
These authors contributed equally: Haiqin Jiang, Jiya Sun, Yanqing Chen
These authors contributed equally: Haiqin Jiang, Jiya Sun, Yanqing Chen
Acknowledgements
This work has been supported by the CAMS Initiative for Innovative Medicine (grant 2016-I2M-1-005, 2017-I2M-B&R-14), the National Natural Science Foundation of China (grant 81371751), PUMC Youth Fund (grant 2017310034), and the Fundamental Research Funds for the Central Universities (grant 2016RC310026).
Conflict of interest
The authors declare that they have no conflict of interest.
Electronic supplementary material
Supplementary Information accompanies this paper at (10.1038/s41426-018-0116-z).