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Gene expression profile analysis and target gene discovery of Mycobacterium tuberculosis biofilm

  • Genomics, Transcriptomics, Proteomics
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Abstract

Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tuberculosis) is a fatal infectious disease to human health, and the drug tolerance and immune evasion of M. tuberculosis were reported to be related to its biofilm formation; however, the difficulty of M. tuberculosis biofilm culture and its unknown global mechanism impede its further research. Here, we developed a modified in vitro M. tuberculosis biofilm model with shorter culture time. Then we used Illumina RNA-seq technology to determine the global gene expression profile of M. tuberculosis H37Rv biofilms. Over 437 genes are expressed at significantly different levels in biofilm cells than in planktonic cells; among them, 153 were downregulated and 284 were upregulated. Go enrichment analysis and KEGG pathway analysis showed that genes involved in biosynthesis and metabolism of sulfur metabolism, steroid degradation, atrazine degradation, mammalian cell entry protein complex, etc. are involved in M. tuberculosis biofilm cells. Especially, ATP-binding cassette (ABC) transporters Rv1217c and Rv1218c were significantly upregulated in biofilm, whereas efflux pump inhibitors (EPIs) piperine and 1-(1-naphthylmethyl)-piperazine (NMP) inhibited biofilm formation and the expression of the Rv1217c and Rv1218c genes in a concentration-dependent manner, respectively, indicating Rv1217c and Rv1218c are potential target genes of M. tuberculosis biofilm. This study is the first RNA-Seq-based transcriptome profiling of M. tuberculosis biofilms and provides insights into a potential strategy for M. tuberculosis biofilm inhibition.

Key points

• Characterize M. tuberculosis transcriptomes in biofilm cells by RNA-seq.

• Inhibit the expression of Rv1217c and Rv1218c repressed biofilm formation.

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Acknowledgements

The Fund for Science and Technology Development of Jilin Province approved this study development.

Funding

This work was supported by the State’s Key Project of Research and Development Plan (2016YFD0501302; 2017YFD0502200); the National Natural Science Foundation of China (No. 81801972; 31172364); the Fund for Science and Technology Development of Jilin Province (20150101108JC); and the Project of the Education Department of Jilin Province (No. 2016444). Science and Technology Research Project of Jilin Provincial Department of Education (JKH20211179).

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Author notes

  1. Fangxue Ma, Hong Zhou and Zhiqiang Yang contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory for Zoonoses Research, Ministry of Education, Institute of Zoonosis, Department of Infectious Diseases, First Hospital of Jilin University, College of Veterinary Medicine, Jilin University, Changchun, 130062, China

    Fangxue Ma, Hong Zhou, Lihui Ni, Mingyuan Liu, Yang Wang & Lu Yu

  2. Institute of Biomedical Sciences, School of Life Science, Shanxi University, Taiyuan, 030006, China

    Zhiqiang Yang

  3. Department of Immunology, Binzhou Medical University, Yantai, 264000, China

    Chao Wang

  4. Department of Physiology, Binzhou Medical University, Yantai, 264000, China

    Yanan An

  5. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, China

    Mingyuan Liu

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  1. Fangxue Ma
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  2. Hong Zhou
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  3. Zhiqiang Yang
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  4. Chao Wang
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  8. Yang Wang
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  9. Lu Yu
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Contributions

FM and HZ conceived and carried out the experiments; FM wrote the manuscript; ZY and CW provide the part of experiments design; CW and AY made the data collection; FM made the data analysis; LN perform the figure making; FM performed the cell cultivation; FM and HZ designed study and guide the experiments.

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Correspondence to Yang Wang or Lu Yu.

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Ma, F., Zhou, H., Yang, Z. et al. Gene expression profile analysis and target gene discovery of Mycobacterium tuberculosis biofilm. Appl Microbiol Biotechnol 105, 5123–5134 (2021). https://doi.org/10.1007/s00253-021-11361-4

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