- Email: [email protected]
Challenges and excitement at all levels
133
Cell regulation Challenges and excitement at all levels Editorial overview Victor J DiRita and Bernt Eric Uhlin Current Opinion in Microbiology 2002, 5:133–134 1369-5274/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved
Victor J DiRita Department of Microbiology and Immunology, University of Michigan Medical School, 5641 Medical Science Building II, 1150 West Medical Center Drive, Ann Arbor, Michigan 48109-0620, USA; e-mail: [email protected]
Victor’s research interests include understanding mechanisms of gene regulation and virulence in bacterial pathogens. His lab currently investigates Vibrio cholerae, the agent of human cholera, Streptococcus pyogenes, which causes necrotizing skin disease, and Campylobacter jejuni, a leading cause of gastroenteritis throughout the world. Bernt Eric Uhlin Department of Microbiology, Umeå University, S-901 87 Umeå, Sweden; e-mail: [email protected]
Bernt Eric’s research topics include molecular mechanisms of virulenceassociated gene expression and the role of nucleoid proteins in gene regulation in Escherichia coli and other enterobacteria.
In this issue of Current Opinion in Microbiology, we include authors whose work spans the range of regulatory possibilities from transcriptional control, through post-transcription and translation control to regulation of organelle function. In the first review, Kenney (pp 135–141) highlights new knowledge of transcription control mechanisms used by winged helix-turn-helix proteins, using OmpR as a paradigm. Recent structural and biochemical data on this widely dispersed family of activators has allowed for a better understanding of how these proteins are controlled by regulatory events that lead to DNA binding and transcription activation. In the second review, Varughese (pp 142–148) looks in great molecular detail at the phosphotransfer and phosphorelay mechanism used by many signal transduction proteins in bacteria. In so doing, he addresses the essential question of how signal specificity can be attained through the use of highly conserved domains. With the completion of genome sequencing projects for an ever-increasing number of bacteria, gene regulation research has been enhanced by computational approaches to identify regulatory elements and to characterize regulatory interactions within the virtual whole cell. Stormo and Tan (pp 149–153) provide a primer on methods currently being used to serve these goals. As they point out, these methods are primarily aimed at transcription regulation, because identifying post-transcription regulatory mechanisms currently remains a challenge to the field of bioinformatics. Certainly, one of the most fascinating post-transcriptional regulatory mechanisms identified recently in both Gram-negative and Gram-positive bacteria uses the tmRNA molecule, which exhibits features of both transfer RNA and messenger RNA in a process called trans-translation. Withey and Friedman (pp 154–159) postulate at least two different roles for this mechanism in the cell — tagging of aberrently truncated proteins for degradation, in a process reminiscent of eukaryotic ubiquitination, and removal of stalled ribosomes from mRNA. They also consider the possibility that trans-translation is a mechanism for fine-tuning gene expression in certain cases. The elegance of economy of gene expression in prokaryotes is perhaps no better exemplified than in the temporally ordered expression of genes related to flagellar assembly. Aldridge and Hughes (pp 160–165) break the process down into transcriptional and translational regulatory events, highlighting the latter. Furthermore, they point out similarities with the more recently identified but extensively researched type III secretion systems required for the pathogenicity of numerous Gram-negative bacteria. Regulatory cues and components of type III secretion are covered by Francis, Wolf-Watz and Forsberg (pp 166–172), who describe a number of intriguing regulatory features in the assembly of these complex machines, including the recently identified, surprising role for secretion chaperones in gene activation. Another extracellular organelle often associated with bacterial pathogens is the type IV pilus (Tfp). Unlike other pili, whose principal role is in adherence, these
134
Cell regulation
unusual structures also control the fascinating process of twitching motility, which results from alternating extension and retraction of the pilus. Winther-Larsen and Koomey (pp 173–178) compare regulatory mechanisms in different Tfp systems, and advance the fascinating hypothesis that twitching motility may also be regulated by chemosensory proteins similar to those that govern flagellar motility. Flagella, type III secretions and type IV pili are among the variety of structures that microbes assemble on their surfaces for a variety of purposes. It is clear that microbes are polarized; flagella are often at only one pole and we now know that other specialized structures exhibit polarity as well [1,2]. How does a simple unicellular organism establish polarity? Saccharomyces cerevisiae is a wonderful model to study this problem, and Casamayor and Snyder (pp 179–186) explain the most recent developments in this important area of cell regulation. Investigation into questions of basic cellular physiology, structure and function continues to be a rich vein for uncovering intriguing regulatory mechanisms. A simple example is in the phosphotransferase system (PTS) involved in sugar uptake and central to bacterial metabolism. As Plumbridge (pp 187–193) describes, de-repression of glucose-regulated genes seems to occur when the Mlc repressor becomes sequestered to the membrane as a consequence of de-phosphorylation of a key PTS protein. As with new structural data on the two-component regulatory systems addressed by Kenney and Varughese in their reviews, crystal structure data has become a key element in understanding how Fe3+–siderophore transport is controlled in Escherichia coli. Braun and Braun (pp 194–201) discuss the structural consequences of iron binding by two different transport proteins and how one of these, FhuA, also serves to transport antibiotics into the cell as well. Crystallographic data for antibiotic binding may be
instrumental for designing new and more efficiently transported antimicrobials. The principal purpose of regulation is adaptation to the challenges of new environmental conditions. An essential element of all cells is membrane fluidity, which is radically affected by growth temperature and other environmental parameters. As pointed out by Cronan (pp 202–205), three basic mechanisms for regulating the fluidity of the membrane are understood to occur. He discusses two of these — cyclopropanation and cis–trans isomerization — and notes how the former has recently been identified as a potent survival mechanism for the persistent pathogen Mycobacterium tuberculosis. The third prominent mechanism for lipid modification is desaturation, addition of a double bond into the acyl chain of phospholipids. The regulation of desaturation and the factors and signals that influence this important process as it occurs in cyanobacteria and Bacillus subtilis are presented by Sakamoto and Murata (pp 206–210). The topics selected for inclusion in this issue of Current Opinion in Microbiology were identified as model systems for processes that occur in virtually all cells. We have tried to identify a range of levels at which cell regulation can occur, and authors were selected for their own contributions to each research topic as well as for their broad perspective in their fields. Each author has done an excellent job — in short space — of highlighting the most exciting new aspects of the topic at hand, and we trust that you will enjoy reading this issue as much as we have enjoyed putting it together.
References 1.
Scott ME, Dossani ZY, Sandkvist M: Directed polar secretion of protease from single cells of Vibrio cholerae via the type II secretion pathway. Proc Natl Acad Sci USA 2001, 98:13978-13983.
2.
Charles M, Perez M, Kobil JH, Goldberg MB: Polar targeting of Shigella virulence factor IcsA in Enterobacteriaceae and Vibrio. Proc Natl Acad Sci USA 2001, 98:9871-9876.
Cell regulation Challenges and excitement at all levels Editorial overview Victor J DiRita and Bernt Eric Uhlin Current Opinion in Microbiology 2002, 5:133–134 1369-5274/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved
Victor J DiRita Department of Microbiology and Immunology, University of Michigan Medical School, 5641 Medical Science Building II, 1150 West Medical Center Drive, Ann Arbor, Michigan 48109-0620, USA; e-mail: [email protected]
Victor’s research interests include understanding mechanisms of gene regulation and virulence in bacterial pathogens. His lab currently investigates Vibrio cholerae, the agent of human cholera, Streptococcus pyogenes, which causes necrotizing skin disease, and Campylobacter jejuni, a leading cause of gastroenteritis throughout the world. Bernt Eric Uhlin Department of Microbiology, Umeå University, S-901 87 Umeå, Sweden; e-mail: [email protected]
Bernt Eric’s research topics include molecular mechanisms of virulenceassociated gene expression and the role of nucleoid proteins in gene regulation in Escherichia coli and other enterobacteria.
In this issue of Current Opinion in Microbiology, we include authors whose work spans the range of regulatory possibilities from transcriptional control, through post-transcription and translation control to regulation of organelle function. In the first review, Kenney (pp 135–141) highlights new knowledge of transcription control mechanisms used by winged helix-turn-helix proteins, using OmpR as a paradigm. Recent structural and biochemical data on this widely dispersed family of activators has allowed for a better understanding of how these proteins are controlled by regulatory events that lead to DNA binding and transcription activation. In the second review, Varughese (pp 142–148) looks in great molecular detail at the phosphotransfer and phosphorelay mechanism used by many signal transduction proteins in bacteria. In so doing, he addresses the essential question of how signal specificity can be attained through the use of highly conserved domains. With the completion of genome sequencing projects for an ever-increasing number of bacteria, gene regulation research has been enhanced by computational approaches to identify regulatory elements and to characterize regulatory interactions within the virtual whole cell. Stormo and Tan (pp 149–153) provide a primer on methods currently being used to serve these goals. As they point out, these methods are primarily aimed at transcription regulation, because identifying post-transcription regulatory mechanisms currently remains a challenge to the field of bioinformatics. Certainly, one of the most fascinating post-transcriptional regulatory mechanisms identified recently in both Gram-negative and Gram-positive bacteria uses the tmRNA molecule, which exhibits features of both transfer RNA and messenger RNA in a process called trans-translation. Withey and Friedman (pp 154–159) postulate at least two different roles for this mechanism in the cell — tagging of aberrently truncated proteins for degradation, in a process reminiscent of eukaryotic ubiquitination, and removal of stalled ribosomes from mRNA. They also consider the possibility that trans-translation is a mechanism for fine-tuning gene expression in certain cases. The elegance of economy of gene expression in prokaryotes is perhaps no better exemplified than in the temporally ordered expression of genes related to flagellar assembly. Aldridge and Hughes (pp 160–165) break the process down into transcriptional and translational regulatory events, highlighting the latter. Furthermore, they point out similarities with the more recently identified but extensively researched type III secretion systems required for the pathogenicity of numerous Gram-negative bacteria. Regulatory cues and components of type III secretion are covered by Francis, Wolf-Watz and Forsberg (pp 166–172), who describe a number of intriguing regulatory features in the assembly of these complex machines, including the recently identified, surprising role for secretion chaperones in gene activation. Another extracellular organelle often associated with bacterial pathogens is the type IV pilus (Tfp). Unlike other pili, whose principal role is in adherence, these
134
Cell regulation
unusual structures also control the fascinating process of twitching motility, which results from alternating extension and retraction of the pilus. Winther-Larsen and Koomey (pp 173–178) compare regulatory mechanisms in different Tfp systems, and advance the fascinating hypothesis that twitching motility may also be regulated by chemosensory proteins similar to those that govern flagellar motility. Flagella, type III secretions and type IV pili are among the variety of structures that microbes assemble on their surfaces for a variety of purposes. It is clear that microbes are polarized; flagella are often at only one pole and we now know that other specialized structures exhibit polarity as well [1,2]. How does a simple unicellular organism establish polarity? Saccharomyces cerevisiae is a wonderful model to study this problem, and Casamayor and Snyder (pp 179–186) explain the most recent developments in this important area of cell regulation. Investigation into questions of basic cellular physiology, structure and function continues to be a rich vein for uncovering intriguing regulatory mechanisms. A simple example is in the phosphotransferase system (PTS) involved in sugar uptake and central to bacterial metabolism. As Plumbridge (pp 187–193) describes, de-repression of glucose-regulated genes seems to occur when the Mlc repressor becomes sequestered to the membrane as a consequence of de-phosphorylation of a key PTS protein. As with new structural data on the two-component regulatory systems addressed by Kenney and Varughese in their reviews, crystal structure data has become a key element in understanding how Fe3+–siderophore transport is controlled in Escherichia coli. Braun and Braun (pp 194–201) discuss the structural consequences of iron binding by two different transport proteins and how one of these, FhuA, also serves to transport antibiotics into the cell as well. Crystallographic data for antibiotic binding may be
instrumental for designing new and more efficiently transported antimicrobials. The principal purpose of regulation is adaptation to the challenges of new environmental conditions. An essential element of all cells is membrane fluidity, which is radically affected by growth temperature and other environmental parameters. As pointed out by Cronan (pp 202–205), three basic mechanisms for regulating the fluidity of the membrane are understood to occur. He discusses two of these — cyclopropanation and cis–trans isomerization — and notes how the former has recently been identified as a potent survival mechanism for the persistent pathogen Mycobacterium tuberculosis. The third prominent mechanism for lipid modification is desaturation, addition of a double bond into the acyl chain of phospholipids. The regulation of desaturation and the factors and signals that influence this important process as it occurs in cyanobacteria and Bacillus subtilis are presented by Sakamoto and Murata (pp 206–210). The topics selected for inclusion in this issue of Current Opinion in Microbiology were identified as model systems for processes that occur in virtually all cells. We have tried to identify a range of levels at which cell regulation can occur, and authors were selected for their own contributions to each research topic as well as for their broad perspective in their fields. Each author has done an excellent job — in short space — of highlighting the most exciting new aspects of the topic at hand, and we trust that you will enjoy reading this issue as much as we have enjoyed putting it together.
References 1.
Scott ME, Dossani ZY, Sandkvist M: Directed polar secretion of protease from single cells of Vibrio cholerae via the type II secretion pathway. Proc Natl Acad Sci USA 2001, 98:13978-13983.
2.
Charles M, Perez M, Kobil JH, Goldberg MB: Polar targeting of Shigella virulence factor IcsA in Enterobacteriaceae and Vibrio. Proc Natl Acad Sci USA 2001, 98:9871-9876.