Germinants and Their Receptors in Clostridia

Abstract

Many anaerobic spore-forming clostridial species are pathogenic, and some are industrially useful. Although many are strict anaerobes, the bacteria persist under aerobic and growth-limiting conditions as multilayered metabolically dormant spores. For many pathogens, the spore form is what most commonly transmits the organism between hosts. After the spores are introduced into the host, certain proteins (germinant receptors) recognize specific signals (germinants), inducing spores to germinate and subsequently grow into metabolically active cells. Upon germination of the spore into the metabolically active vegetative form, the resulting bacteria can colonize the host and cause disease due to the secretion of toxins from the cell. Spores are resistant to many environmental stressors, which make them challenging to remove from clinical environments. Identifying the conditions and the mechanisms of germination in toxin-producing species could help develop affordable remedies for some infections by inhibiting germination of the spore form. Unrelated to infectious disease, spore formation in species used in the industrial production of chemicals hinders the optimum production of the chemicals due to the depletion of the vegetative cells from the population. Understanding spore germination in acetone-butanol-ethanol-producing species can help boost the production of chemicals, leading to cheaper ethanol-based fuels. Until recently, clostridial spore germination is assumed to be similar to that of Bacillus subtilis. However, recent studies in Clostridium difficile shed light on a mechanism of spore germination that has not been observed in any endospore-forming organisms to date. In this review, we focus on the germinants and the receptors recognizing these germinants in various clostridial species.

Dipicolinic Acid Release by Germinating Clostridium difficile Spores Occurs through a Mechanosensing Mechanism

“…The absence of germinant receptor in the inner spore membrane simplifies the mechanism of DPA release but may result in less specificity and a tendency for an increased amount of spontaneous DPA release. Interestingly, Clostridium perfringens encodes a spoVA system similar to that of C. difficile and also encodes functional germinant receptors (5, 41, 50, 51). How DPA release is signaled in this organism is unknown, but understanding its role would be of important value for understanding how the SpoVAD, SpoVAC, and SpoVAE proteins interact in such a system.…”

“…Spores are metabolically dormant forms of bacteria that are resistant to many harsh conditions (e.g., heat, desiccation, antibiotics) (5, 6). The spore structure is conserved across most spore-forming, Gram-positive bacteria and is important for maintaining the spore’s resistance properties.…”

“…C. difficile spore germination is triggered by a combination of certain bile acids and amino acids (5, 17–20). In contrast to the mechanisms of germination observed in Bacilli and most Clostridia , C. difficile does not encode the Ger-type germinant receptors (21).…”

“…Instead, C. difficile uses the germination-specific, pseudoprotease CspC as the bile acid germinant receptor (22). In Clostridium perfringens , CspA, CspB, and CspC are active proteases with the potential to cleave the SCLE, pro-SleC, to its active form (5, 23–28). Interestingly, C. difficile CspA and CspC are pseudoproteases, as their catalytic triads are not complete.…”

Sporulation: how to survive on planet Earth (and beyond)

“…Proteomic studies on B. subtilis spores show that spores harbor proteins required for stress resistance, anabolism, and cell signaling -- all consistent with the idea that spores resist environmental insults and are poised for rapid growth in response to germination signals (Liu et al 2004; Mao et al 2011). These classes of protein components of spores appear to be fairly consistent across diverse bacterial species; however, the nature and efficacy of conditions and compounds that provide the signal to germinate vary widely, as do the molecular components used to sense and signal germination (Setlow 2013; Paredes-Sabja et al 2014; Bhattacharjee et al 2016). Even among individual spores within the same population, there can be significant heterogeneity in the time taken to germinate when stimulated by nutrients, varying from minutes to hours or even days (Stewart and Setlow 2013).…”