RESEARCH HIGHLIGHTS BACTERIAL PHYSIOLOGY New alarm call for spores Dormant endospores can survive simply release them into the environ- Fractionation of a tagged protein tough conditions over prolonged ment. Because B. subtilis supernatants proved that PrkCBs is localized to periods of time, but what cues were more efficient germinants than the spore inner membrane, and is reactivate them from their torpor? E. coli supernatants, the authors therefore ideally positioned to bind Nutrients are a well-characterized proposed that liberated peptidoglycan small peptidoglycan fragments that signal for germination of spores fragments might induce germination. can penetrate the spore coat. To but now muropeptides released by Tiny amounts of purified and test if PrkC discriminates amongst growing bacteria have been identified digested B. subtilis peptidoglycan muropeptide signals, the authors as a general signal for germination, were sufficient to induce spore replaced the B. subtilis PrkCBs with according to a paper published in germination, and high-performance the S. aureus PrkCSa homologue. Cell. liquid chromatography was used S. aureus peptidoglycan has L-Lys in STOCKBYTE Reasoning that the growth of to pinpoint disaccharide tripeptide the third position of the stem pep- bacteria could serve as a marker as the smallest molecule that could tide. Spores of the B. subtilis mutant of an environment that is conducive induce germination. Purification of that expressed PrkCSa responded to growth, the authors set out to peptidoglycan from a selection of to both meso-diaminopimelic acid probe whether growing bacteria Gram-positive and Gram-negative and L-Lys-containing peptidogly- produced signals that could induce bacteria confirmed that only pepti- can. Finally, the ability of a kinase spore germination. Filtered bac- doglycan with a meso-diaminopimelic activator (bryostatin) and repressor terial culture supernatants from acid residue in the third position of (staurosporine) to regulate germina- Bacillus subtilis and Escherichia the stem peptide induced germina- tion provided clear evidence that the coli, but not Staphylococcus tion, which explained why S. aureus kinase activity of PrkC is essential for aureus, induced spore germi- supernatant (L-Lys in the third peptidoglycan signalling. nation. Intriguingly, only position of the stem peptide) failed to Innate immune responses depend growing cells produced induce germination. on the recognition of specific the spore-germination The ~55 amino-acid PASTA bacteria-derived molecules such as signal. During growth, (penicillin and Ser or Thr peptidoglycan. Research into how enzymes lyse the kinase-associated) domain has spores of the humble soil bacterium mature peptidoglycan previously been proposed to bind B. subtilis germinate has unexpectedly sac that maintains peptidoglycan. Many (if not all) revealed a new interspecies signal bacterial cell shape Gram-positive bacteria and all (peptidoglycan fragments) that might to allow insertion of bacterial spore formers have at least have common functions in awakening new peptidoglycan one Ser or Thr membrane kinase dormant bacteria. monomers, releas- with multiple PASTA repeats in Susan Jones ing muropeptides in their extracellular domains, and the process. Gram- in B. subtilis this protein is PrkC . Bs ORIGINAL RESEARCH PAPER Shah, I. M., negative bacteria can Spores of a mutant lacking PrkCBs Laaberki, M-H., Popham, D. L. & Dworkin, J. recycle muropeptides, failed to respond to muropeptides A eukaryotic-like Ser/Thr kinase signals bacteria to exit dormancy in response to peptidoglycan whereas Gram- or culture supernatants, but could fragments. Cell 135, 486–496 (2008) positive bacteria germinate in response to nutrients. NATURE REVIEWS | MICROBIOLOGY VOLUME 7 | JANUARY 2009 © 2009 Macmillan Publishers Limited. All rights reserved.