Catabolite repression and inducer control in Gram-positive bacteria.
Results currently available clearly indicate that the metabolite-activated protein kinase-mediated phosphorylation of Ser-46 in HPr plays a key role in catabolite repression and the control of inducer levels in low-GC Gram-positive bacteria. This protein kinase is not found in enteric bacteria such as E. coli and Salmonella typhimurium where an entirely different PTS-mediated regulatory mechanism is responsible for catabolite repression and inducer concentration control. In Table 2 these two mechanistically dissimilar but functionally related processes are compared (Saier et al., 1995b). In Gram-negative enteric bacteria, an external sugar is sensed by the sugar-recognition constituent of an Enzyme II complex of the PTS (IIC), and a dephosphorylating signal is transmitted via the Enzyme IIB/HPr proteins to the central regulatory protein, IIAGlc. Targets regulated include (1) permeases specific for lactose, maltose, melibiose and raffinose, (2) catabolic enzymes such as glycerol kinase that generate cytoplasmic inducers, and (3) the cAMP biosynthetic enzyme, adenylate cyclase that mediates catabolite repression (Saier, 1989, 1993). In low-GC Gram-positive bacteria, cytoplasmic phosphorylated sugar metabolites are sensed by the HPr kinase which is allostericlaly activated. HPr becomes phosphorylated on Ser-46, and this phosphorylated derivative regulates the activities of its target proteins. These targets include (1) the PTS, (2) non-PTS permeases (both of which are inhibited) and (3) a cytoplasmic sugar-P phosphatase which is activated to reduce cytoplasmic inducer levels. Other important targets of HPr(ser-P) action are (4) the CcpA protein and probably (5) the CepB transcription factor. These two proteins together are believed to determine the intensity of catabolite repression. Their relative importance depends on physiological conditions. Both proteins may respond to the cytoplasmic concentration of HPr(ser-P) and appropriate metabolites. CepA possibly binds sugar metabolites such as FBP as well as HPr(ser-P). Because HPr(his-P, ser-P) does not bind to CepA, the regulatory cascade is also sensitive to the external PTS sugar concentration. Mutational analyses (unpublished results) suggest that CepA may bind to a site that includes His-15. Interestingly, both the CepA protein in the Gram-positive bacterium, B. subtilis, and glycerol kinase in the Gram-negative bacterium, E. coli, sense both a PTS protein and a cytoplasmic metabolic intermediate. The same may be true of target permeases and enzymes in both types of organisms, but this possibility has not yet been tested. The parallels between the Gram-negative and Gram-positive bacterial regulatory systems are superficial at the mechanistic level but fundamental at the functional level. Thus, the PTS participates in regulation in both cases, and phosphorylation of its protein constituents plays key roles. However, the stimuli sensed, the transmission mechanisms, the central PTS regulatory proteins that effect allosteric regulation, and some of the target proteins are completely different. It seems clear that these two transmission mechanisms evolved independently. They provide a prime example of functional convergence.
Saier
Milton H
MH
Department of Biology, University of California at San Diego, La Jolla, CA 92093-0116, USA.
Chauvaux
Sylvie
S
Department of Biology, University of California at San Diego, La Jolla, CA 92093-0116, USA.
Cook
Gregory M
GM
Department of Biology, University of California at San Diego, La Jolla, CA 92093-0116, USA.
Deutscher
Josef
J
Department of Biology, University of California at San Diego, La Jolla, CA 92093-0116, USA.
Paulsen
Ian T
IT
Department of Biology, University of California at San Diego, La Jolla, CA 92093-0116, USA.
Reizer
Jonathan
J
Department of Biology, University of California at San Diego, La Jolla, CA 92093-0116, USA.
Ye
Jing-Jing
JJ
Department of Biology, University of California at San Diego, La Jolla, CA 92093-0116, USA.
D000255:Adenosine Triphosphate / Q000378:metabolism; D001412:Bacillus subtilis / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins; D004734:Energy Metabolism; D006094:Gram-Positive Bacteria / Q000235:genetics / Q000378:metabolism*; D017045:Lactococcus / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013291:Streptococcus / Q000378:metabolism
D001426:Bacterial Proteins; D000255:Adenosine Triphosphate; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System; C030182:phosphocarrier protein HPr