- Email: [email protected]
Involvement of the bacterial phosphotransferase system in diverse mechanisms of transcriptional regulation
(~ II~STITUTPASTEUR/ELsEVIER Paris 1989
Res. MicrobioL 1989, 140~ 349-354
TIMES A N D TRENDS
INVOLVEMENT OF T H E BACTERIAL P H O S P H O T R A N S F E R A S E SYSTEM IN DIVERSE M E C H A N I S M S OF T R A N S C R I P T I O N A L REGULATION M . H . Saier, Jr Department o f Biology, C-016, University o f California, San Diego, La Jol!a, CA 92093 (USA)
"'Vere scire, esse per causas scire. ""
Francis Bacon
Genes encoding proteins of the bacterial phosphotransferase system (PTS) have long been thought to be regulated by complex mechanisms (Saier, 1985). Additionally, the PTS appears to indirectly (Saier, 1989) or directly (Clan e~ aL, 1987; Chin et al., i989) regulate the transcription of nvmerous genes encoding non-PTS proteins involved in carbohydrate transport and metabolism, gluconeogenesis, oxidative metabolism, electron flow and bacterial pathogenesis. In this Times and Trends article salient features of current studies concerned with these various regulatory mechanisms are briefly summarized. Early studies (reviewed in Saier, 1985), led to the suggestion that the soluble, lactose-specific energy coupling component of the lactose permease of Staphylococcus aureus (enzyme IIIlac of the PTS or IlPac) might function in the transcriptional regulation of the lac operon. While still not proven, this possibility is strengthened by recent evidence suggesting that other enzymes III of the PTS function directly cr indirectly in transcriptional regulation. Thus, in Escherichia coil the glucose enzyme III (IIIs~c) regulates non-PTS inducer uptake and cycfic AMP synthesis (Saier, 1989), and consequently it indirectly regulates the transcription of hundreds of genes. III•c may also play a role in the transcriptional regulation of thepts operon (Saier, 1985). The fructose enzyme III (III fru) and the glucitol enzyme |I1 (IIIsut) apparently can regulate transcription of genes encoding enzynies of glucon~genesis, the glyoxylate shunt and oxidative metabolism (Chin et ai., 1987; Chin et al., 1989; Yam~.da and Saler, 1987). How this regulation is effected is not clear, but the involvement of the repressor of the fructose operon, Fn'O~ has been suggested (Geerse t a/., 1986). The recent sequencing of the IIIfru structural gene (Geerse et al., 1989) as anowed this anu other PTS protein sequences (Saier et al., 1988) to be searched for consensus motifs to the transmitter and receiver components of the two-component
350
TIMES AND TRENDS
systems which sense environmental stimuli and regulate transcriptional events in bacteria (Kofoid and Parkinson, 1988). Of the many PTS protein sequences examined, III fru showed a region with the highest degree of sequence identity to the receiver module (score of 4.02; M.H. Saier, Jr and J.S. Parkinson, unpublished results). This observation increases the likelihood that it plays a role in transcriptional regulation. Previous arguments have been put forth to suggest that the enzyme III components of the PTS permeases may have arisen during evolutionary history by the introduction of no'.~nse mutations into the structural genes encoding the intact PTS permeases (Saier et al., 1985; Saler et aL, 1988). The evolutionary pressure for these events to occur may have been the need for structural independence so that these proteins (or permease fragments) could assume the regulatory functions that they are frequently found to possess. It is possible that a number of additional regulatory roles for these proteins will be discovered. The ~-glucoside (bgl) operon of E. coil and. the sucrose. (sac~)regulon o¢ Bacillus s,tbtilis are both regulated by anti-terminaUon (Aymench and Steinmetz, 1987; Mahadevan and Wright, 1987; Mahadevan et al., 1987; Schnetz and Rak, 1988). In both cases, anti-termination is inducer (~-giucoside and sucrose, respectively)dependent, and the promoters are not subject to inducer-dependent regulation. Thus, induced synthesis of the encoded catabolic enzymes is due to suppression of a transcriptional termination event which occurs before initiation of the first structural gene. Current evidence favours a protein vhosphorylation/dephosphorylation mechanism in which only the free (dephospho~lated) anti-terminator is active. In the case of the [3-giucoside system, the [~-glucoside-specific enzyme II (IIbs~)probably mediates the phosphorylation/dephosphorylation of the anti-terminator, but in the s,Tc regulon~ a distinct gene product showing extea~ive sequence identity with the sucrose-specific enzyme II (IIscr) may be responsible (see Klier and Rapoport, 1988 for a consideration of the evidence). The two anti-terminators, which are encoded within the bgl and sac regulons, are homologous proteins which presumab!v function by simila~ mechanisms. The sac regulon of B. subtilis is additionally contr'oll~ by a two-component sensor-regulator system (Kunst et al., 1988) while the bgl operon is additionally controlled by cn~¢~rnent (Mahadevan et ¢!., 1987; Schuetz and Rak, 1988). Other operons encoding PTS proteins a iso appear to be regulated by comolex mechanisms. Thus, the E. coil glucitol (gut) operon is regulated by both positive~and negative transcriptional regulators, both of which probably bind to the operatorpromoter region of the gut operon (Yamada and Saier, 1988). The pts operon of E. coil, encoding the general energy-coupling proteins of the PTS, enzyme I, HPr and llIOc, is subject to complex regulation giving rise to three distinct but major mRNA species (De Reuse and Danchin, 1988). The possible involvement of an antistrand RNA or an anti-strand-encoded protein in the transcriptional regulation of tbJs operon has been suggested but not proven (Gonzy-Tr6boul et al., 1989; L~vy et al., 1989; Schnieron et al., 1989). Complex transcriptional regulation has also been demonstrated for the N-acetylgiucosamine (nag) operon in E. cog (Peri and Waygood, 1988; Rogers et al., 1988), the fructose (fru/operon in Salmonella typhimurium (D.A. Feldheim, A.M. Chin and M.H. S~ier, Jr, unpublished results) and the lactose (lac) operon in Staphylococcus aureus (G.C. Stewart, personal communication). It therefore appears that the proteins and genetic apparatus of the phosphotransferase system will provide exciting material for the detection and elucidation of diverse transcriptional regulatory mechanisms for many years to come.
SUMMARY A large ,.:umber of genes in bacteria appear to be expressed in processes regulated by very different mechanisms dependent on the acttvities of the proteins of the phosphoenolpyruvate/sugar phosphotransferase sytem. These mechanisms include
TIMES AND
TRENDS
351
protein phosphorylation, antitermination, enhancement, antagonistic repression/activation, sensory detection involving two component systems, and other processes not yet understood. MoTS-Ct~: Transcriptional reg~flation, Opcron, Phosphotransferase system, Protein phosphorylation; Anti-terminatio:i, Enha.~.cement. Antazonistic revression/activation, Bacteria. " --
REFERENCES A'~alcH, S. & STermlaTZ, M. (1987), Cloning and preliminary characterization of the sacs locus from Bacillus subtilis which controls the regulation of the exocnzyme levansucrase. Mol. gen. Genetics, ~08, 114-120. CHV~, A.M., FEuctrr, B.U. & S^lea, M.H., Jr (1987), Evidence for the regulation of gluconeogenesis by the fructose phosphotr~nsferase system in Salmonella typhimurium. J. Bact., 169, 897-899. CHIN, A.M.. FELDHEIM,D.A. & S~Eg, M.H., Jr (1989), Altered transcriptional patterns attecting severm metabolic patllways in strains of Salmonella typhimurium which overexpress the fructose regulon. J. Bact., 171, 2424-2434. De ReusE, H. & DAKcm~, A. (1988), The ptsH, ptsl, and crr genes of the Escherichia coil phosphocnolpyruyate-d.el.X,ndent pbosphotransferase system: a complex operon with several mooes of transcnption. J. Boct., 170, 3827-3837. GEeRS~, R.H., RuIo, C.R., ScmJrreMA,A.R.J. & POSTMA,P.W. (1986), Relationship between pseudo-HPr and the PEP: fructose phosphotransgerase system in Salmonella typiffmurium and Escherichia coll. Moi. gen. Geneacs, 203, ~,35-444. G~RSe, R:I-I., Izzo, F. & P..o~'y~,.P.W. (1989), The PEP: ~'uctc~ phosphotransferase ~wstem m ~lmonella t~phlmunum: FPr combines enzynie IIVm and pseudo-HPr activities. ~ol. gen. t~enetics, 216, 517-525. GONzv-T~noUL,G., ZAOOREC,M.. RAIN-GuIoN,M ~:. ~ STI~.n~l.ETZ,M..(1989), P..hosphoenol-
K:~oR~A E ' ing proteins. J'rc~. nat. Aca'~. Sci. (Wash.), SS, 4981-4985. Ku.,Jsx, F., DeesneOUILLe,M., MSAO~, T., You^o, M., MAUEL~C., KARAMATA,D~, KLWR,A., P-o~...pp.XT, G. & I)~m~.R, R. (1988), Deduced polypeptides encoded by the Bac///us SUbtlfiS sacU locus share homology with two-component sensor-regulator systems. J. Bact., 170, 5093-5101. L~w, S., DE Reuse, H. & D^NCHm, A. (1989), Antisense expression at the ptsH-ptsl locus of Escherichia coll. FEM3 MicrobioL letters, 57, 35-38. Mm-~.DevAs, S. & W monT, A. (1987), A bacterial gene involv~ in transc~in0~n antitermination: regulation at a rho-independent terminator in the bgl oper'on of E. coli Ceil, 50, 485-494. 1Vb,w~Ev~, S., Re~oLDs, A.E. & Winos, A. (1987), Positive and negativeregulation of the ogi operon in Escherichia coil J. Boct., 169, 2570-2578. P~m, K.G. & W^~c,ooD, E.B. (1988), Sequence of cloned enzyme II ~ - ' ~ of the phosphoenolpyruvate: N-acetylglucosamine phosphotransferase system of E~cher/ch/a coll. Biochemistry, 27, 6054-6061. Roo~as, M.J., OHO~, T., PLt~mmm~, J. & SOLe, D. (1988), Nuclcotide sequences of the E,.~cherich.ia coil nagE and nagB genes: the structural genes for the N-acetyl~,cosamme ~.7:',portprotein of the .bacterial phosphoenolpyruvate: sng~r p.hosphotransterase s~st~_=: -"~ tor gmcosamme-o-pnospnate ocammme, oene, o~, l~/-~/. SA~eR,M.H., Jr (1985), "Me~aanisms and regulation of carbohydrate transport in bacteria" Academic Press, New York. S^~e~, M.H.: Jr (1989), Protein pi~osphorylation .and allosteric control of inducer exclusion ano ¢ata~olite repression oy the oacterim pnospnoenolpyruvate: sugar phosphotransferase system. Microbioi. Rev., 53, 109-120.
352
TIMES AND TRENDS
S^~Ea, M.H., Jr, GRENIER,F.C., LEE,C.A. & WAYGOOD,E.B. (1985), Evidence for the evolutionary relatedness of the proteins of the bacterial phosphoenolpyruvate: sugar phosphotransferase system. J. Cell. Biochem., 27, 43-56. SAmX, M.H., Jr, YAMADA,M., LENOE'EX,J., EgNt, B., SUDA,K., Agoos, P., SCHNETZ,K., RAK, B., LP~E_,C.A., STEWART,G.C., PEah K.G. & WAYOOOD,E,IL (1988), Sugar permeases or the bacterial phosphoenolpyruvate-dependent phosphotransferase system: sequence comparisons. FASEB J., 2, 199-208. ~HN~rz, K. & RAg, B. (1988), Regulation of the bgl operon of Escherichia coil by transcriptional antiteimination. EMBO J., 7, 3271-3277. S.'HNIEXOW,B.~ YAMADA,M. & SALES,M.H., Jr (1989), Partial nucleotide seoue,:lce o~ thepts operon in Salmonella typhiraurium: comparative analyses in five bacterial genera Mol. Microbiol., 3, 113-118. " Y~,~Av^, M. & S^lsn, M.H., Jr (1987), The regulation of gluconeogenesis via the enzyme III of :he glucitol phosphotransferase system in Escherichia coli. J. Bact., 169, 5416-5422. YAM^D^, M. & SAIEg, M.H., Jr (1988), Positive and negative regulators for glucitol (gu0 operon expression in Escherichia coil J. mol. Biol.. 203, 569-583.
BIOLOGY AND PATHOGENICITY OF TREPONEMES
C.W. P e n n ?chool o f !~iological Sciences, University o f Birmit~gham, PO Box 363, Birmingham B15 2 T T (UK)
An international workshop on treponemes was held in Birmingham, UK, in April 1989. Over 100 delegates from 12 countries discussed aspects of the new information and l~rogress in research on t ~ s group of organisms, which has largely arisen from tiic application of molecular methodologies to a poorly characterized and fastidious group of pathogens. As well as the agents of the classical treponematoses - Treponem¢t~llidum (syphilis) and its subspecies pertenue (yaws) - . the organisms covered included T. hyodysenteriae, agent of swine dysentery, intestinal isolates from other species, and -also ora! greponemes including. T. denticola, implicated in the aetiology of periodontal disease. Application of molecular techonelogies ha~ le.d to advances in three mean areas. First, because of the difficulty of cul,::~ring or , ~ b t a ~ g f.'om in vivo sources any substantial amounts of material for an~lyais, traditional methods of fractionation, purification and characterization of individual antigens of the orsanisms have never been possible. This difficulty has been circumvented by the application of immunoblotting, with its immense powe~ to characterize and semi-quantRate numerous antigenic components in the complex mixture representing whole organisms applied to SDSPAGE gels. During the past decade information has accumulated rapidly on a variety ot prominent antigenic polypeptides of T. pailidum analysed by this method. Unfortunately however, many of them have been unidentified in terms of function or location in the intact organism, and much confusion between laboratories has resulteci from ut,¢ of different experimental conditions. A major benefit to the field has resulted from multiple comparisons of reagents supplied by a number of groups, producing an excellent ~cheme defining the most prominent components (Norris et al., 1987). This was extended at the meeting to include 2-dimensional gel analysis.
Res. MicrobioL 1989, 140~ 349-354
TIMES A N D TRENDS
INVOLVEMENT OF T H E BACTERIAL P H O S P H O T R A N S F E R A S E SYSTEM IN DIVERSE M E C H A N I S M S OF T R A N S C R I P T I O N A L REGULATION M . H . Saier, Jr Department o f Biology, C-016, University o f California, San Diego, La Jol!a, CA 92093 (USA)
"'Vere scire, esse per causas scire. ""
Francis Bacon
Genes encoding proteins of the bacterial phosphotransferase system (PTS) have long been thought to be regulated by complex mechanisms (Saier, 1985). Additionally, the PTS appears to indirectly (Saier, 1989) or directly (Clan e~ aL, 1987; Chin et al., i989) regulate the transcription of nvmerous genes encoding non-PTS proteins involved in carbohydrate transport and metabolism, gluconeogenesis, oxidative metabolism, electron flow and bacterial pathogenesis. In this Times and Trends article salient features of current studies concerned with these various regulatory mechanisms are briefly summarized. Early studies (reviewed in Saier, 1985), led to the suggestion that the soluble, lactose-specific energy coupling component of the lactose permease of Staphylococcus aureus (enzyme IIIlac of the PTS or IlPac) might function in the transcriptional regulation of the lac operon. While still not proven, this possibility is strengthened by recent evidence suggesting that other enzymes III of the PTS function directly cr indirectly in transcriptional regulation. Thus, in Escherichia coil the glucose enzyme III (IIIs~c) regulates non-PTS inducer uptake and cycfic AMP synthesis (Saier, 1989), and consequently it indirectly regulates the transcription of hundreds of genes. III•c may also play a role in the transcriptional regulation of thepts operon (Saier, 1985). The fructose enzyme III (III fru) and the glucitol enzyme |I1 (IIIsut) apparently can regulate transcription of genes encoding enzynies of glucon~genesis, the glyoxylate shunt and oxidative metabolism (Chin et ai., 1987; Chin et al., 1989; Yam~.da and Saler, 1987). How this regulation is effected is not clear, but the involvement of the repressor of the fructose operon, Fn'O~ has been suggested (Geerse t a/., 1986). The recent sequencing of the IIIfru structural gene (Geerse et al., 1989) as anowed this anu other PTS protein sequences (Saier et al., 1988) to be searched for consensus motifs to the transmitter and receiver components of the two-component
350
TIMES AND TRENDS
systems which sense environmental stimuli and regulate transcriptional events in bacteria (Kofoid and Parkinson, 1988). Of the many PTS protein sequences examined, III fru showed a region with the highest degree of sequence identity to the receiver module (score of 4.02; M.H. Saier, Jr and J.S. Parkinson, unpublished results). This observation increases the likelihood that it plays a role in transcriptional regulation. Previous arguments have been put forth to suggest that the enzyme III components of the PTS permeases may have arisen during evolutionary history by the introduction of no'.~nse mutations into the structural genes encoding the intact PTS permeases (Saier et al., 1985; Saler et aL, 1988). The evolutionary pressure for these events to occur may have been the need for structural independence so that these proteins (or permease fragments) could assume the regulatory functions that they are frequently found to possess. It is possible that a number of additional regulatory roles for these proteins will be discovered. The ~-glucoside (bgl) operon of E. coil and. the sucrose. (sac~)regulon o¢ Bacillus s,tbtilis are both regulated by anti-terminaUon (Aymench and Steinmetz, 1987; Mahadevan and Wright, 1987; Mahadevan et al., 1987; Schnetz and Rak, 1988). In both cases, anti-termination is inducer (~-giucoside and sucrose, respectively)dependent, and the promoters are not subject to inducer-dependent regulation. Thus, induced synthesis of the encoded catabolic enzymes is due to suppression of a transcriptional termination event which occurs before initiation of the first structural gene. Current evidence favours a protein vhosphorylation/dephosphorylation mechanism in which only the free (dephospho~lated) anti-terminator is active. In the case of the [3-giucoside system, the [~-glucoside-specific enzyme II (IIbs~)probably mediates the phosphorylation/dephosphorylation of the anti-terminator, but in the s,Tc regulon~ a distinct gene product showing extea~ive sequence identity with the sucrose-specific enzyme II (IIscr) may be responsible (see Klier and Rapoport, 1988 for a consideration of the evidence). The two anti-terminators, which are encoded within the bgl and sac regulons, are homologous proteins which presumab!v function by simila~ mechanisms. The sac regulon of B. subtilis is additionally contr'oll~ by a two-component sensor-regulator system (Kunst et al., 1988) while the bgl operon is additionally controlled by cn~¢~rnent (Mahadevan et ¢!., 1987; Schuetz and Rak, 1988). Other operons encoding PTS proteins a iso appear to be regulated by comolex mechanisms. Thus, the E. coil glucitol (gut) operon is regulated by both positive~and negative transcriptional regulators, both of which probably bind to the operatorpromoter region of the gut operon (Yamada and Saier, 1988). The pts operon of E. coil, encoding the general energy-coupling proteins of the PTS, enzyme I, HPr and llIOc, is subject to complex regulation giving rise to three distinct but major mRNA species (De Reuse and Danchin, 1988). The possible involvement of an antistrand RNA or an anti-strand-encoded protein in the transcriptional regulation of tbJs operon has been suggested but not proven (Gonzy-Tr6boul et al., 1989; L~vy et al., 1989; Schnieron et al., 1989). Complex transcriptional regulation has also been demonstrated for the N-acetylgiucosamine (nag) operon in E. cog (Peri and Waygood, 1988; Rogers et al., 1988), the fructose (fru/operon in Salmonella typhimurium (D.A. Feldheim, A.M. Chin and M.H. S~ier, Jr, unpublished results) and the lactose (lac) operon in Staphylococcus aureus (G.C. Stewart, personal communication). It therefore appears that the proteins and genetic apparatus of the phosphotransferase system will provide exciting material for the detection and elucidation of diverse transcriptional regulatory mechanisms for many years to come.
SUMMARY A large ,.:umber of genes in bacteria appear to be expressed in processes regulated by very different mechanisms dependent on the acttvities of the proteins of the phosphoenolpyruvate/sugar phosphotransferase sytem. These mechanisms include
TIMES AND
TRENDS
351
protein phosphorylation, antitermination, enhancement, antagonistic repression/activation, sensory detection involving two component systems, and other processes not yet understood. MoTS-Ct~: Transcriptional reg~flation, Opcron, Phosphotransferase system, Protein phosphorylation; Anti-terminatio:i, Enha.~.cement. Antazonistic revression/activation, Bacteria. " --
REFERENCES A'~alcH, S. & STermlaTZ, M. (1987), Cloning and preliminary characterization of the sacs locus from Bacillus subtilis which controls the regulation of the exocnzyme levansucrase. Mol. gen. Genetics, ~08, 114-120. CHV~, A.M., FEuctrr, B.U. & S^lea, M.H., Jr (1987), Evidence for the regulation of gluconeogenesis by the fructose phosphotr~nsferase system in Salmonella typhimurium. J. Bact., 169, 897-899. CHIN, A.M.. FELDHEIM,D.A. & S~Eg, M.H., Jr (1989), Altered transcriptional patterns attecting severm metabolic patllways in strains of Salmonella typhimurium which overexpress the fructose regulon. J. Bact., 171, 2424-2434. De ReusE, H. & DAKcm~, A. (1988), The ptsH, ptsl, and crr genes of the Escherichia coil phosphocnolpyruyate-d.el.X,ndent pbosphotransferase system: a complex operon with several mooes of transcnption. J. Boct., 170, 3827-3837. GEeRS~, R.H., RuIo, C.R., ScmJrreMA,A.R.J. & POSTMA,P.W. (1986), Relationship between pseudo-HPr and the PEP: fructose phosphotransgerase system in Salmonella typiffmurium and Escherichia coll. Moi. gen. Geneacs, 203, ~,35-444. G~RSe, R:I-I., Izzo, F. & P..o~'y~,.P.W. (1989), The PEP: ~'uctc~ phosphotransferase ~wstem m ~lmonella t~phlmunum: FPr combines enzynie IIVm and pseudo-HPr activities. ~ol. gen. t~enetics, 216, 517-525. GONzv-T~noUL,G., ZAOOREC,M.. RAIN-GuIoN,M ~:. ~ STI~.n~l.ETZ,M..(1989), P..hosphoenol-
K:~oR~A E ' ing proteins. J'rc~. nat. Aca'~. Sci. (Wash.), SS, 4981-4985. Ku.,Jsx, F., DeesneOUILLe,M., MSAO~, T., You^o, M., MAUEL~C., KARAMATA,D~, KLWR,A., P-o~...pp.XT, G. & I)~m~.R, R. (1988), Deduced polypeptides encoded by the Bac///us SUbtlfiS sacU locus share homology with two-component sensor-regulator systems. J. Bact., 170, 5093-5101. L~w, S., DE Reuse, H. & D^NCHm, A. (1989), Antisense expression at the ptsH-ptsl locus of Escherichia coll. FEM3 MicrobioL letters, 57, 35-38. Mm-~.DevAs, S. & W monT, A. (1987), A bacterial gene involv~ in transc~in0~n antitermination: regulation at a rho-independent terminator in the bgl oper'on of E. coli Ceil, 50, 485-494. 1Vb,w~Ev~, S., Re~oLDs, A.E. & Winos, A. (1987), Positive and negativeregulation of the ogi operon in Escherichia coil J. Boct., 169, 2570-2578. P~m, K.G. & W^~c,ooD, E.B. (1988), Sequence of cloned enzyme II ~ - ' ~ of the phosphoenolpyruvate: N-acetylglucosamine phosphotransferase system of E~cher/ch/a coll. Biochemistry, 27, 6054-6061. Roo~as, M.J., OHO~, T., PLt~mmm~, J. & SOLe, D. (1988), Nuclcotide sequences of the E,.~cherich.ia coil nagE and nagB genes: the structural genes for the N-acetyl~,cosamme ~.7:',portprotein of the .bacterial phosphoenolpyruvate: sng~r p.hosphotransterase s~st~_=: -"~ tor gmcosamme-o-pnospnate ocammme, oene, o~, l~/-~/. SA~eR,M.H., Jr (1985), "Me~aanisms and regulation of carbohydrate transport in bacteria" Academic Press, New York. S^~e~, M.H.: Jr (1989), Protein pi~osphorylation .and allosteric control of inducer exclusion ano ¢ata~olite repression oy the oacterim pnospnoenolpyruvate: sugar phosphotransferase system. Microbioi. Rev., 53, 109-120.
352
TIMES AND TRENDS
S^~Ea, M.H., Jr, GRENIER,F.C., LEE,C.A. & WAYGOOD,E.B. (1985), Evidence for the evolutionary relatedness of the proteins of the bacterial phosphoenolpyruvate: sugar phosphotransferase system. J. Cell. Biochem., 27, 43-56. SAmX, M.H., Jr, YAMADA,M., LENOE'EX,J., EgNt, B., SUDA,K., Agoos, P., SCHNETZ,K., RAK, B., LP~E_,C.A., STEWART,G.C., PEah K.G. & WAYOOOD,E,IL (1988), Sugar permeases or the bacterial phosphoenolpyruvate-dependent phosphotransferase system: sequence comparisons. FASEB J., 2, 199-208. ~HN~rz, K. & RAg, B. (1988), Regulation of the bgl operon of Escherichia coil by transcriptional antiteimination. EMBO J., 7, 3271-3277. S.'HNIEXOW,B.~ YAMADA,M. & SALES,M.H., Jr (1989), Partial nucleotide seoue,:lce o~ thepts operon in Salmonella typhiraurium: comparative analyses in five bacterial genera Mol. Microbiol., 3, 113-118. " Y~,~Av^, M. & S^lsn, M.H., Jr (1987), The regulation of gluconeogenesis via the enzyme III of :he glucitol phosphotransferase system in Escherichia coli. J. Bact., 169, 5416-5422. YAM^D^, M. & SAIEg, M.H., Jr (1988), Positive and negative regulators for glucitol (gu0 operon expression in Escherichia coil J. mol. Biol.. 203, 569-583.
BIOLOGY AND PATHOGENICITY OF TREPONEMES
C.W. P e n n ?chool o f !~iological Sciences, University o f Birmit~gham, PO Box 363, Birmingham B15 2 T T (UK)
An international workshop on treponemes was held in Birmingham, UK, in April 1989. Over 100 delegates from 12 countries discussed aspects of the new information and l~rogress in research on t ~ s group of organisms, which has largely arisen from tiic application of molecular methodologies to a poorly characterized and fastidious group of pathogens. As well as the agents of the classical treponematoses - Treponem¢t~llidum (syphilis) and its subspecies pertenue (yaws) - . the organisms covered included T. hyodysenteriae, agent of swine dysentery, intestinal isolates from other species, and -also ora! greponemes including. T. denticola, implicated in the aetiology of periodontal disease. Application of molecular techonelogies ha~ le.d to advances in three mean areas. First, because of the difficulty of cul,::~ring or , ~ b t a ~ g f.'om in vivo sources any substantial amounts of material for an~lyais, traditional methods of fractionation, purification and characterization of individual antigens of the orsanisms have never been possible. This difficulty has been circumvented by the application of immunoblotting, with its immense powe~ to characterize and semi-quantRate numerous antigenic components in the complex mixture representing whole organisms applied to SDSPAGE gels. During the past decade information has accumulated rapidly on a variety ot prominent antigenic polypeptides of T. pailidum analysed by this method. Unfortunately however, many of them have been unidentified in terms of function or location in the intact organism, and much confusion between laboratories has resulteci from ut,¢ of different experimental conditions. A major benefit to the field has resulted from multiple comparisons of reagents supplied by a number of groups, producing an excellent ~cheme defining the most prominent components (Norris et al., 1987). This was extended at the meeting to include 2-dimensional gel analysis.