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Multiple input-multiple output (MIMO) designs in two-component signalling systems of Mycobacterium tuberculosis.

Devendra Pratap Singh1, Gayathri A S1, Ramandeep Singh2

  • 1Department of Developmental Biology and Genetics, Indian Institute of Science, Bangalore 560012, India.

FEMS Microbiology Reviews
|December 13, 2025
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Summary

Bacteria use two-component systems (TCSs) for communication. This review highlights how these systems act as complex hubs, integrating multiple signals to drive bacterial adaptation and offering therapeutic targets.

Keywords:
Mycobacterium tuberculosiscross-talkhistidine kinasemultiple inputs–multiple outputsresponse regulatorserine/threonine protein kinasestwo-component signalling

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Area of Science:

  • Microbiology
  • Molecular Biology
  • Systems Biology

Background:

  • Two-component systems (TCSs) are crucial bacterial communication pathways, classically involving a histidine kinase (HK) and a response regulator (RR).
  • Emerging evidence reveals TCSs function in complex networks, sensing diverse inputs and producing modulated outputs.
  • Factors like cross-talk, posttranslational modifications, and small RNAs add layers of complexity to TCS signaling.

Purpose of the Study:

  • To review the role of mycobacterial TCSs as multiple input-multiple output (MIMO) hubs.
  • To discuss how TCSs integrate and disperse signals for complex adaptive responses.
  • To explore the therapeutic potential of targeting TCS MIMO networks.

Main Methods:

  • Literature review focusing on mycobacterial two-component systems.
  • Analysis of emerging evidence on TCS network complexity and modulation.
  • Discussion of signal integration and bacterial adaptation mechanisms.

Main Results:

  • TCSs function as MIMO hubs, integrating various signals.
  • Complex adaptive responses are generated through modulated TCS networks.
  • Mycobacterial TCSs exemplify sophisticated signal processing.

Conclusions:

  • TCSs are sophisticated signal integration and dispersion units, not just simple input-output systems.
  • The MIMO landscape of TCSs is critical for bacterial adaptation.
  • Targeting TCS MIMO networks offers promising therapeutic intervention strategies.