The Ger receptor family from sporulating bacteria

Abstract

Bacterial spores are specialized cells that are exceptionally resistant to environmental stress. Spores convert back to actively growing cells, a process called germination, upon nutrient detection. The most common, initial step in the germination process is the recognition of small molecule germinants by germination (Ger) receptors. Ger receptors are inner-membrane heterocomplexes formed by three distinct protein products, the A-, B-, and C-subunits. In this review, we discuss and contrast published reports on representative Ger receptors from different Bacilli and Clostridia. We also present evidence for unrecognized germination pathways independent of Ger receptors. We further emphasize the function of L-alanine as a universal germinant. We also comment on biochemical aspects of germinant recognition and interaction between Ger receptor proteins. We propose that there are six general strategies used by Bacilli and Clostridia to integrate multiple germination signals. The use of different germinant recognition strategies results in germination response flexibility. Consequently, sporulating bacterial species that use the same biomolecules as germination signals can have different germination profiles. Finally, we discuss future directions for understanding the function of Ger receptors.

Figure 1

Model of the quintessential germination receptor GerA from B. subtilis. Suggested topology and localization of the GerAA, GerAB, and GerAC proteins are shown. All other Ger receptors are believed to fold in a similar fashion (adapted from Moir et al., 2002).

Figure 2

Idealized B. anthracis germination kinetics analysis. (a) B. anthracis spores were treated with increasing amounts of inosine at a fixed L-alanine concentration (Akoachere et al., 2007). Germination rates were calculated from the change in optical density over time (grey bar). (b) Plotting germination rate vs. inosine concentration gave a hyperbolic curve indicating saturation of specific receptor sites. (c) Double reciprocal plots were used to calculate inosine's apparent binding constant (K_m) and the maximal apparent rate (V_max). (d) This process was repeated at different fix L-alanine concentrations to obtain a family of double reciprocal plots. V_max increased with increasing L-alanine concentrations indicating that inosine and alanine bind to separate sites (Segel, 1993). The spore's affinity for inosine also increased with increasing L-alanine concentration revealing cooperativity between their receptors. The intersection of the curve family at a single point strongly supports the notion that both germinants are present simultaneously on their receptor(s).

Figure 3

Strategies for spore germination. Boxed letters represent germinants. White and black hourglasses represent Ger receptors that recognize a single germinant. Grey hourglasses represent Ger receptors that recognize multiple germinants. Arrows represent germination. (a) A single germinant triggers germination by activating its cognate Ger receptor. (b) A single germinant can trigger germination through multiple independent Ger receptors. (c) A single germinant must activate different Ger receptors simultaneously. (d) Multiple germinants must interact individually with their cognate receptors. (e) A single Ger receptor can be independently activated by different germinants. (f) A single Ger receptor must interact with multiple germinants to be activated.