Sensing When Happy Days Are Here Again

Science Signaling  04 Nov 2008:
Vol. 1, Issue 44, pp. ec374
DOI: 10.1126/scisignal.144ec374

Bacillus bacteria respond to unfavorable environmental conditions by forming spores, a dormant state in which they can survive for years, and germinating when conditions become more propitious. One mechanism for sensing that conditions have become favorable for growth depends on the perception of specific nutrients through germination receptors (see Setlow); Shah et al. explored the intriguing possibility that germination might also be triggered by signals from actively dividing bacteria. Cell-free supernatants from Bacillus subtilis cultures stimulated germination of B. subtilis spores; supernatants from Escherichia coli cultures were less effective, and supernatants from Staphylococcus aureus cultures failed to trigger B. subtilis germination. Noting that actively growing bacteria release muropeptides (fragments of cell wall peptidoglycan), the authors showed that purified B. subtilis peptidoglycan hydrolyzed into muropeptides elicited germination. Analysis of peptidoglycans purified from various species indicated that the ability to elicit B. subtilis germination depended on the presence of meso-diaminopimelate as the third position of the peptidoglycan stem peptide. Mutant spores missing the eukaryotic-like serine/threonine membrane protein kinase PrkC failed to germinate in response to B. subtilis supernatant or peptidoglycan fragments but did germinate in response to the nutrient L-alanine. Moreover, a form of PrkC with a phosphorylation-inactivating mutation failed to promote germination. The PrkC extracellular domain contains three PASTA repeats (thought to bind peptidoglycans), and the tagged extracellular domain indeed bound B. subtilis peptidoglycan. Moreover, spores expressing S. aureus PrkC germinated in response to peptidoglycan with L-lysine in the stem peptide amino acid three position, and the S. aureus PrkC extracellular domain bound S. aureus peptidoglycan. Bryostatin, a small molecule that activates eukaryotic serine/threonine kinases, stimulated PrkC-dependent B. subtilis germination, whereas staurosporine, which inhibits eukaryotic serine/threonine kinases, inhibited peptidoglycan-dependent germination. The authors conclude that peptidoglycan fragments released from growing bacteria signal dormant spores to germinate through PrkC.

I. M. Shah, M.-H. Laaberki, D. L. Popham, J. Dworkin, A eukaryotic-like Ser/Thr kinase signals bacteria to exit dormancy in response to peptidoglycan fragments. Cell 135, 486-496 (2008). [Online Journal]

P. Setlow, Dormant spores receive an unexpected wake-up call. Cell 135, 410-412 (2008). [Online Journal]