GASPing for Life in Stationary Phase

Harvard Medical School now recognized as players in widely used mechanisms Boston, Massachusetts 02115 for sensing cell numbers among gram-negative bacteria, the role of acylated HSLs as signal molecules was first discovered in the studies of the high cell density induc-Microbial Differentiation in Response tion of bioluminescence in the marine bacterium Vibrio to Starvation fischeri. The machinery for luminescence is composed For metazoans cellular differentiation starts as part of of luciferase and the enzymes that produce a fatty alde-the developmental programs set in motion by the forma-hyde that is oxidized with the concomitant release of tion of a zygote, but for unicellular microorganisms dif-light. Regulation of the transcription of the genes encod-ferentiation is almost invariably a response to starvation. ing these enzymes is the key process that results in cell While supplies of essential nutrients are plentiful, micro-density–dependent production of light. There are two bial populations grow exponentially, but when one or key regulatory proteins involved: LuxR is an apo-activa-more of these nutrients is exhausted growth necessarily tor of the luciferase genes and requires 3-oxo-hexanoyl-slows down and the population enters the so-called HSL as a coactivator. LuxI, encoded by a gene cotrans-" stationary phase. " Starvation results in profound devel-cribed with the luciferase genes, is in turn required for opmental changes, perhaps the most dramatic example the synthesis of 3-oxo-hexanoyl-HSL. At low cell densi-of which is the generation of dormant spores by many ties, there is only low level transcription of the operon species of gram-positive bacteria. In contrast, many encoding LuxI and luciferase and thus only small gram-negative bacteria, among them Escherichia coli, amounts of LuxI to make 3-oxo-hexanoyl-HSL. Because respond to starvation by developing increased resis-of the acyl side chain, this molecule diffuses rapidly tance to different environmental stresses without be-across membranes, and its concentration is therefore a coming dormant. These cells maintain a low level of function of the density of cells in a culture. Once enough metabolism which, under the right conditions, allows 3-oxo-hexanoyl-HSL is made, it can bind LuxR, generat-the cells to remain viable for many years as well. ing an activator that induces transcription of the operon, Starved E. coli cells are much smaller than their rapidly resulting in the increased synthesis of 3-oxo-hexanoyl-growing counterparts, their cell wall is more highly HSL. This in turn will lead to further increase in the cross-linked, their cytoplasm is condensed, and their transcription of the operon. The …