Maximizing bacterial survival: integrating sense-and-respond and bet-hedging mechanisms

Two-component systems allow bacteria to respond to specific environmental signals with defined adaptive phenotypic changes, a process that requires time and may be inadequate for contending with rapidly changing environments. In contrast, phase variation generates baseline levels of phenotypic heterogeneity that helps to ensure survival of the population as a whole. This strategy may be better suited to confront abrupt environmental changes but may produce transiently less-fit subpopulations. Many bacteria have integrated phase variation and two-component signaling - how combining these stochastic and deterministic mechanisms affects bacterial fitness is unclear. Here, we identify three distinct schemes for integration of phase variation and two-component signaling. Using well-characterized examples, we speculate the circumstances in which each integration scheme confers a fitness advantage.