An Evolutionary Paradigm Favoring Cross Talk between Bacterial Two-Component Signaling Systems

Area of Science:

• Microbiology
• Systems Biology
• Evolutionary Biology

Background:

• Bacteria utilize two-component signaling systems (TCSs) to perceive and react to environmental shifts.
• The established view of TCSs emphasizes specificity, where histidine kinases (HKs) exclusively activate their cognate response regulators (RRs), with cross talk considered disadvantageous.
• However, observed cross talk in various bacteria challenges this paradigm.

Purpose of the Study:

• To propose and investigate an alternative paradigm where cross talk in bacterial TCSs can be evolutionarily advantageous.
• To explore the role of programmed environments with sequential signals in promoting beneficial cross talk.
• To reconcile the observed specificity and cross talk in bacterial signaling.

Main Methods:

• Mathematical modeling of TCS signaling networks.
• Stochastic evolutionary dynamics simulations incorporating diverse cross talk patterns and signaling environments.
• Analysis of existing TCS data from Mycobacterium tuberculosis.

Main Results:

• Simulations predicted that in programmed environments, bacterial phenotypes with cross talk facilitating priming outperform those without.
• In random environments, bacteria without cross talk were predicted to dominate, aligning with observed specificity.
• A key prediction was that selected cross talk patterns in programmed environments would be unidirectional, facilitating priming.

Conclusions:

• Cross talk in bacterial TCSs can be advantageous in programmed environments by priming responses to upcoming signals.
• Specificity is favored in random environments, reconciling the presence of both specificity and cross talk.
• The study's findings, supported by Mycobacterium tuberculosis data, offer insights into bacterial adaptation and potential intervention strategies.