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Comparative proteomic investigation unravels the pathobiology of Mycobacterium fortuitum biofilm

  • Genomics, Transcriptomics, Proteomics
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Biofilm formation by Mycobacterium fortuitum causes serious threats to human health due to its increased contribution to nosocomial infections. In this study, the first comprehensive global proteome analysis of M. fortuitum was reported under planktonic and biofilm growth states. A label-free Q Exactive Quadrupole-Orbitrap tandem mass spectrometry analysis was performed on the protein lysates. The differentially abundant proteins were functionally characterized and re-annotated using Blast2GO and CELLO2GO. Comparative analysis of the proteins among two growth states provided insights into the phenotypic switch, and fundamental pathways associated with pathobiology of M. fortuitum biofilm, such as lipid biosynthesis and quorum-sensing. Interaction network generated by the STRING database revealed associations between proteins that endure M. fortuitum during biofilm growth state. Hypothetical proteins were also studied to determine their functional alliance with the biofilm phenotype. CARD, VFDB, and PATRIC analysis further showed that the proteins upregulated in M. fortuitum biofilm exhibited antibiotic resistance, pathogenesis, and virulence. Heatmap and correlation analysis provided the biomarkers associated with the planktonic and biofilm growth of M. fortuitum. Proteome data was validated by qPCR analysis. Overall, the study provides insights into previously unexplored biochemical pathways that can be targeted by novel inhibitors, either for shortened treatment duration or for eliminating biofilm of M. fortuitum and related nontuberculous mycobacterial pathogens.

Key points

Proteomic analyses of M. fortuitum reveals novel biofilm markers.

Acetyl-CoA acetyltransferase acts as the phenotype transition switch.

The study offers drug targets to combat M. fortuitum biofilm infections.

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Data availability

All data generated or analyzed during this study are included in the manuscript (and its supplemental material). The mass spectrometry (MS) proteomics data are available via the ProteomeXchange Consortium (PRIDE partner repository) with the data set identifier PXD023784. Further information are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to acknowledge the administration of Jaypee University of Information Technology, Waknaghat, Solan (Himachal Pradesh), India for providing the research facility, and a fellowship to Dr. Ayushi Sharma. The authors are also grateful to Central Drug Research Institute (CDRI), Lucknow, India, for providing the mycobacterial strain.

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Authors and Affiliations

Authors

Contributions

AS and RS conceived and designed research. AS conducted experiments. AS, SB, and NK analyzed data. JV and RS supervised the study. AS wrote the manuscript. All authors read and approved the manuscript.

Corresponding author

Correspondence to Rahul Shrivastava.

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The article does not contain any studies with human participants or animals performed by any of the authors.

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The authors declare no competing interests.

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Sharma, A., Bansal, S., Kumari, N. et al. Comparative proteomic investigation unravels the pathobiology of Mycobacterium fortuitum biofilm. Appl Microbiol Biotechnol 107, 6029–6046 (2023). https://doi.org/10.1007/s00253-023-12705-y

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  • DOI: https://doi.org/10.1007/s00253-023-12705-y

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