Reviving the view: evidence that macromolecule synthesis fuels bacterial spore germination

Abstract

The Gram positive bacterium Bacillus subtilis and its relatives are capable of forming a durable dormant long-lasting spore. Although spores can remain dormant for years, they possess the remarkable capacity to rapidly resume life and convert into actively growing cells. This cellular transition initiates with a most enigmatic irreversible event, termed germination, lasting only for a few minutes. Germination is typified by a morphological conversion that culminates in loss of spore resilient properties. Yet, the molecular events occurring during this brief critical phase are largely unknown. The current widely accepted view considers germination to occur without the need for any macromolecule synthesis; however, accumulating data from our laboratory and others, highlighted here, provide evidence that both transcription and translation occur during germination and are required for its execution. We further underline numerous overlooked studies, conducted mainly during the 1960s-70s, reinforcing this notion. We propose to revisit the fascinating process of spore germination and redefine it as a pathway involving macromolecule synthesis. We expect our perspective to shed new light on the awakening process of a variety of spore-forming environmental, commensal and pathogenic bacteria and possibly be applicable to additional organisms displaying a quiescent life form.

Glutamate catabolism during sporulation determines the success of the future spore germination

“…These findings are in accord with previous studies showing that RNA and protein synthesis occurs very early in reviving spores, at a time coinciding with germination [e.g. ( Armstrong and Sueoka, 1968 ; Balassa and Contesse, 1965 ; Torriani and Levinthal, 1967 ; Zhou et al., 2022 )]. Still, there are gaps in our understanding of the intricate germination pathways, such as the signal transmission from germinant sensing to YwlE activation, and from the stimulated YwlE to its downstream targets.…”

“…Germination is considered independent of macromolecule synthesis ( Setlow, 2003 ; Steinberg et al., 1965 ; Vinter, 1970 ); however, in recent years, we have provided evidence that germination necessitates the activation of both transcription and translation for its completion ( Sinai and Ben-Yehuda, 2016 ; Sinai et al., 2015 ; Zhou et al., 2019 , 2022 ). This view is not collectively accepted, and other laboratories suggested alternative interpretations ( Korza et al., 2016 ; Sinai and Ben-Yehuda, 2016 ; Swarge et al., 2020 ).…”

The control of protein arginine phosphorylation facilitates proteostasis by an AAA+ chaperone protease system

“…McsB (Elsholz et al, 2012;Fuhrmann et al, 2009Fuhrmann et al, , 2013Kirstein et al, 2005Kirstein et al, , 2007Schmidt et al, 2014;Suskiewicz et al, 2019;Trentini et al, 2016). The pleiotropic influence of ywlE on B. subtilis physiology and regulatory pathways was observed (Elsholz et al, 2012;Schmidt et al, 2014), more recently an important role of YwlE in B. subtilis spore germination was discovered (Zhou et al, 2019(Zhou et al, , 2022.…”

“…YwlE is the cognate phospho-arginine phosphatase, which can counteract the McsB kinase activity, thereby controlling the extent of this protein modification in B. subtilis (Elsholz et al, 2012; Fuhrmann et al, 2009, 2013; Kirstein et al, 2005, 2007; Schmidt et al, 2014; Suskiewicz et al, 2019; Trentini et al, 2016). The pleiotropic influence of ywlE on B. subtilis physiology and regulatory pathways was observed (Elsholz et al, 2012; Schmidt et al, 2014), more recently an important role of YwlE in B. subtilis spore germination was discovered (Zhou et al, 2019, 2022).…”

“…A very pleiotropic influence of protein arginine phosphorylation in B. subtilis physiology and regulatory pathways, which includes B. subtilis spore germination ( 26, 27 ), was observed in a ywlE mutant ( 17, 20 ). However, the role and function of this protein modification system and the interplay of the respective kinase and phosphatase with the ClpC chaperone system in cellular protein homeostasis, is not well understood.…”