- Email: [email protected]
Editorial overview: Cell regulation: Microbial cell regulation — looking in from the outside
Available online at www.sciencedirect.com
ScienceDirect Editorial overview: Cell regulation: Microbial cell regulation — looking in from the outside Cecı´lia Maria Arraiano and Gregory M Cook Current Opinion in Microbiology 2014, 18:v–vii This review comes from a themed issue on Cell regulation Edited by Cecı´lia Maria Arraiano and Gregory M Cook For a complete overview see the Issue and the Editorial Available online 2nd April 2014 1369-5274/$ – see front matter, # 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.mib.2014.03.001
Cecı´lia Maria Arraiano Laboratory of Control of Gene Expression, Instituto de Tecnologia Quı´mica e Biolo´gica (ITQB), Universidade Nova de Lisboa, Apt 127, 2781-901 Oeiras, Portugal e-mail: [email protected] Cecı´lia M Arraiano is a Coordinating Investigator (Full Professor) at ITQB, Universidade Nova de Lisboa, Portugal. She is an elected member of the European Molecular Biology Organization (EMBO), Fellow of the American Academy of Microbiology and Fellow of the Portuguese Academy of Sciences. The research in her laboratory focuses on the control of gene expression in many organisms. The overall goal is to study mechanisms of RNA processing/degradation/ quality control and characterize ribonucleases, the enzymes that mediate decay. They have also investigated the regulation of small noncoding RNAs. Other interests are stress, microbial growth and persistence, and synthetic biology. This work has many applications in Biotechnology and Health. http://www.itqb.unl.pt/research/biology/coge
Gregory M Cook Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin 9054, New Zealand e-mail: [email protected] Gregory M Cook is a Professor and James Cook Fellow in the Department of Microbiology and Immunology at the University of Otago. The research in his laboratory focuses on the cellular and molecular physiology of pathogenic and environmental microorganisms. The overall goal of his research is to understand at a cellular and molecular level how microorganisms adapt their metabolism and energetics to different environments. Through increased understanding we are exploring metabolism as a potential drug target to control the growth of bacterial pathogens in host tissues. http:// micro.otago.ac.nz/our-people/gregorycook www.sciencedirect.com
The physiological and molecular responses of the bacterial cell to changing environmental conditions have fascinated scientists for decades. Central in this adaptation is cellular homeostasis, an essential capability of all living cells mediated by complex and diverse regulatory networks. The overarching focus of this current issue is to highlight the many levels at which cellular regulation and sensing takes place, and the mechanisms by which regulation occurs. A major focus of our contributors has been linking this sensing/regulation to the physiological output of the microbial cell. The responses of the bacterial cell to changing environmental conditions can be coordinated with neighbours to accomplish cooperative activities such as bioluminescence production, biofilm development and secretion of enzymes. Coordination can occur through a mechanism of cell-to-cell communication called quorum sensing. Lasa and co-authors cover the interesting mechanisms involved in biofilm dispersion and quorum sensing. Bacteria and higher organisms are also modulated by a rhythmically changing environment due to the rotation of the planet on its axis. Many organisms have developed endogenous timing systems called circadian clocks, which generate near24 hour rhythms in behavior and physiology. Pattanayak and Rust have focused on the Cyanobacterial clock and metabolism and describe how these endogenous rhythms are self-sustaining and persist even in constant environments. Dietrich and colleagues highlight cellular regulation at a morphological level. The captivating patterns (e.g. wrinkling) of many bacterial colonies have remained a relatively overlooked area for cell regulation. New studies show that wrinkling is a redox-driven adaptation to maximize oxygen accessibility hinting at critical mechanistic links between environmental sensing and community behavior, providing an exciting new context within which to interpret the molecular details of biofilm structure determination. A key factor in redox homeostasis is the ability of the bacterial cell to sense electron donor availability. A largely overlooked electron donor that is available to aerobic bacteria is molecular hydrogen. Greening and Cook highlight the importance of hydrogen and hydrogenases in environmental and pathogenic bacteria. Hydrogen metabolism is a facultative trait that is tightly regulated in response to both external factors (e.g. gas concentrations) and internal factors (e.g. redox state). Regulation of hydrogen utilization is achieved through integration of these chemical changes to match the physiological needs of the cell. Considerable diversity exists in how and why hydrogen metabolism is regulated between organisms of different phyla, ecosystems, and metabolisms. Despite decades of investigation, there is still incomplete understanding of the Current Opinion in Microbiology 2014, 18:v–vii
vi Cell regulation
molecular details of hydrogenase regulation in even the more sophisticated models explored in this work. Several of our authors deal with membrane proteins and their role(s) in the signaling and regulation of cellular metabolism. Va¨stermark and Saier highlight the interconnectivity of diverse transport systems as regulatory systems to coordinate different metabolic processes to achieve efficiency of growth. The phosphoenolpyruvatedependent phosphotransferase system (PTS), major facilitator superfamily UhpC and the ABC transporter PstSABC control diverse activities such as carbon, exogenous hexosephosphate and phosphorous metabolism respectively. While the PTS participates in multiple regulatory processes through its major components (HPr, IIAGlc and IIBCGlc), the UhpC (receptor role) and the Pst (phosphate) transporters (transduce independently of transport) exemplify differing strategies. Another class of membrane proteins, mechanosensitive channels (MscL and MscS) are critical for cellular homeostasis in preventing structural perturbation during transitions from high osmolarity to low osmolarity environments. Booth covers the question of channel diversity and plurality in bacterial species and proposes that channel diversity is a reflection of the cells response to hypoosmotic stress and that cells have evolved mechanosensitive channels that reflect their biological niche. Structural diversity may reflect roles additional to the observed function of protection of structural integrity during water fluxes across the lipid bilayer. Integral to the control of water flux in bacteria is the cell wall. Cava and de Pedro highlight the role of peptidoglycan as a dynamic cell constituent involved in every aspect of bacterial physiology. The plasticity of peptidoglycan composition plays a fundamental role in adaptation to different kinds of environmental stresses; immune response; intra- and inter-specific signaling and antibiotics. Cells must control their division cycle in order to divide faster or slower, depending on the growth conditions. Jonas highlights how these mechanisms can be diverse but they often involve small molecule-based signaling, regulated proteolysis, as well as protein-protein interactions. For instance (p)ppGpp and UDP-glucose modulate cell cycle processes in response to nutrient availability. Most mechanisms affect replication initiation or septum formation by targeting DnaA or FtsZ. In budding yeast cell division encompasses asymmetric inheritance of several aging factors including toxic species. Age is reset in the process of cell division and daughter cell rejuvenation includes filtering and restoration of organelle function. Nystro¨m and Liu describe what is known regarding the mystery of aging and rejuvenation in Saccharomyces cerevisiae. If we look into the bacterial cell we can observe that gene expression is highly affected by the environmental conditions. Both transcriptional and post-transcriptional mechanisms are highly controlled to rapidly adapt to a Current Opinion in Microbiology 2014, 18:v–vii
changing environment. Several of our authors deal with regulation of cellular metabolism through CRP, allosteric control and compartmentalization. The Escherichia coli cyclic-AMP receptor protein (CRP) is a paradigm of gene regulation and recent work discussed by Green and coworkers demonstrate the repurposing of CRP through cAMP affinity and DNA binding to function in the specific niches occupied by the bacteria. It appears that the cyclic-AMP-CRP regulatory system has been adapted to respond to distinct external and internal inputs across a broad sensitivity range that is, at least in part, determined by bacterial lifestyles. Eoh and Rhee focus on two widely recognized regulatory mechanisms, allostery and subcellular compartmentalization, and highlights the fact that these mechanisms have largely failed to penetrate many physiological models of cellular regulation. Moreover, subcellular compartmentalization, a cornerstone of eukaryotic cell biology, has failed to penetrate the thinking of most microbiologists due to the apparent lack of lipid bound organelles. Growing evidence suggests that bacteria can indeed achieve the same functional compartmentalization through the regulated formation and/or activity of protein localization and pseudo-organelles, such as protein microcompartments and the periplasm. Eoh and Rhee highlight existing knowledge of these processes in the human pathogen Mycobacterium tuberculosis. RNA is an important regulatory molecule and during RNA synthesis the performance of RNA polymerases can be regulated by transcription factors. Yakhnin and Babitzke cover the functions of NusG/Spt5 which seems to be the only universally conserved transcription elongation factor. NusG and its paralog RfaH recognize specific sequences in the nontemplate DNA strand and regulate transcription elongation. NusG/Spt5 may partially release the transcription-associated stress on genome stability and it is probable that NusG becomes especially important under genotoxic conditions. Arraiano and collaborators describe the characteristics of ribonucleases (RNases), the enzymes that are involved in the maturation, turnover and quality control of all types of RNA. Namely RNases can act as controllers of sRNA networks affecting their targets and modifying gene expression. The authors have compiled many publications, which focus on the role of different bacterial ribonucleases in the regulation of small noncoding RNAs. Quek and Beemon focus on virus and describe the retroviral Strategy to stabilize Viral RNA. Namely, the unspliced RNA of Rous sarcoma virus (RSV), a well-studied avian retrovirus, is very stable, suggesting the virus has evolved a means to overcome degradation by RNA surveillance systems such as nonsense mediated decay (NMD). The study of different RNAs has led to the discovery of CRISPR RNAs. The clustered regularly interspaced short palindromic repeat (CRISPR) arrays and their www.sciencedirect.com
Editorial overview: Cell regulation: Microbial cell regulation — looking in from the outside Arraiano vii
CRISPR associated (Cas) proteins constitute adaptive immune systems in bacteria and archaea. They provide a range of mechanisms to confer protection from bacteriophages, plasmids and other mobile genetic elements. Fineran and Dy review small RNA-based CRISPR-Cas systems and describe how they can be directed to DNA in a sequence-specific manner. These new technologies have a great potential for the manipulation of gene expression in bacteria and eukaryotes. Großkopf and Soyer highlight how synthetic microbial communities can be engineered for the generation of defined systems
www.sciencedirect.com
with reduced complexity. Besides their value as model systems to understand the structure, function and evolution of microbial communities synthetic communities can also open up new avenues for biotechnological applications. All our contributors have connected the sensing/ regulation to the physiological output of the microbial cell. The responses of the bacterial cell to changing environmental conditions will have to be understood in the context of synthetic microbial communities. Certainly, these mechanisms will continue to fascinate scientists for the years to come.
Current Opinion in Microbiology 2014, 18:v–vii
ScienceDirect Editorial overview: Cell regulation: Microbial cell regulation — looking in from the outside Cecı´lia Maria Arraiano and Gregory M Cook Current Opinion in Microbiology 2014, 18:v–vii This review comes from a themed issue on Cell regulation Edited by Cecı´lia Maria Arraiano and Gregory M Cook For a complete overview see the Issue and the Editorial Available online 2nd April 2014 1369-5274/$ – see front matter, # 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.mib.2014.03.001
Cecı´lia Maria Arraiano Laboratory of Control of Gene Expression, Instituto de Tecnologia Quı´mica e Biolo´gica (ITQB), Universidade Nova de Lisboa, Apt 127, 2781-901 Oeiras, Portugal e-mail: [email protected] Cecı´lia M Arraiano is a Coordinating Investigator (Full Professor) at ITQB, Universidade Nova de Lisboa, Portugal. She is an elected member of the European Molecular Biology Organization (EMBO), Fellow of the American Academy of Microbiology and Fellow of the Portuguese Academy of Sciences. The research in her laboratory focuses on the control of gene expression in many organisms. The overall goal is to study mechanisms of RNA processing/degradation/ quality control and characterize ribonucleases, the enzymes that mediate decay. They have also investigated the regulation of small noncoding RNAs. Other interests are stress, microbial growth and persistence, and synthetic biology. This work has many applications in Biotechnology and Health. http://www.itqb.unl.pt/research/biology/coge
Gregory M Cook Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin 9054, New Zealand e-mail: [email protected] Gregory M Cook is a Professor and James Cook Fellow in the Department of Microbiology and Immunology at the University of Otago. The research in his laboratory focuses on the cellular and molecular physiology of pathogenic and environmental microorganisms. The overall goal of his research is to understand at a cellular and molecular level how microorganisms adapt their metabolism and energetics to different environments. Through increased understanding we are exploring metabolism as a potential drug target to control the growth of bacterial pathogens in host tissues. http:// micro.otago.ac.nz/our-people/gregorycook www.sciencedirect.com
The physiological and molecular responses of the bacterial cell to changing environmental conditions have fascinated scientists for decades. Central in this adaptation is cellular homeostasis, an essential capability of all living cells mediated by complex and diverse regulatory networks. The overarching focus of this current issue is to highlight the many levels at which cellular regulation and sensing takes place, and the mechanisms by which regulation occurs. A major focus of our contributors has been linking this sensing/regulation to the physiological output of the microbial cell. The responses of the bacterial cell to changing environmental conditions can be coordinated with neighbours to accomplish cooperative activities such as bioluminescence production, biofilm development and secretion of enzymes. Coordination can occur through a mechanism of cell-to-cell communication called quorum sensing. Lasa and co-authors cover the interesting mechanisms involved in biofilm dispersion and quorum sensing. Bacteria and higher organisms are also modulated by a rhythmically changing environment due to the rotation of the planet on its axis. Many organisms have developed endogenous timing systems called circadian clocks, which generate near24 hour rhythms in behavior and physiology. Pattanayak and Rust have focused on the Cyanobacterial clock and metabolism and describe how these endogenous rhythms are self-sustaining and persist even in constant environments. Dietrich and colleagues highlight cellular regulation at a morphological level. The captivating patterns (e.g. wrinkling) of many bacterial colonies have remained a relatively overlooked area for cell regulation. New studies show that wrinkling is a redox-driven adaptation to maximize oxygen accessibility hinting at critical mechanistic links between environmental sensing and community behavior, providing an exciting new context within which to interpret the molecular details of biofilm structure determination. A key factor in redox homeostasis is the ability of the bacterial cell to sense electron donor availability. A largely overlooked electron donor that is available to aerobic bacteria is molecular hydrogen. Greening and Cook highlight the importance of hydrogen and hydrogenases in environmental and pathogenic bacteria. Hydrogen metabolism is a facultative trait that is tightly regulated in response to both external factors (e.g. gas concentrations) and internal factors (e.g. redox state). Regulation of hydrogen utilization is achieved through integration of these chemical changes to match the physiological needs of the cell. Considerable diversity exists in how and why hydrogen metabolism is regulated between organisms of different phyla, ecosystems, and metabolisms. Despite decades of investigation, there is still incomplete understanding of the Current Opinion in Microbiology 2014, 18:v–vii
vi Cell regulation
molecular details of hydrogenase regulation in even the more sophisticated models explored in this work. Several of our authors deal with membrane proteins and their role(s) in the signaling and regulation of cellular metabolism. Va¨stermark and Saier highlight the interconnectivity of diverse transport systems as regulatory systems to coordinate different metabolic processes to achieve efficiency of growth. The phosphoenolpyruvatedependent phosphotransferase system (PTS), major facilitator superfamily UhpC and the ABC transporter PstSABC control diverse activities such as carbon, exogenous hexosephosphate and phosphorous metabolism respectively. While the PTS participates in multiple regulatory processes through its major components (HPr, IIAGlc and IIBCGlc), the UhpC (receptor role) and the Pst (phosphate) transporters (transduce independently of transport) exemplify differing strategies. Another class of membrane proteins, mechanosensitive channels (MscL and MscS) are critical for cellular homeostasis in preventing structural perturbation during transitions from high osmolarity to low osmolarity environments. Booth covers the question of channel diversity and plurality in bacterial species and proposes that channel diversity is a reflection of the cells response to hypoosmotic stress and that cells have evolved mechanosensitive channels that reflect their biological niche. Structural diversity may reflect roles additional to the observed function of protection of structural integrity during water fluxes across the lipid bilayer. Integral to the control of water flux in bacteria is the cell wall. Cava and de Pedro highlight the role of peptidoglycan as a dynamic cell constituent involved in every aspect of bacterial physiology. The plasticity of peptidoglycan composition plays a fundamental role in adaptation to different kinds of environmental stresses; immune response; intra- and inter-specific signaling and antibiotics. Cells must control their division cycle in order to divide faster or slower, depending on the growth conditions. Jonas highlights how these mechanisms can be diverse but they often involve small molecule-based signaling, regulated proteolysis, as well as protein-protein interactions. For instance (p)ppGpp and UDP-glucose modulate cell cycle processes in response to nutrient availability. Most mechanisms affect replication initiation or septum formation by targeting DnaA or FtsZ. In budding yeast cell division encompasses asymmetric inheritance of several aging factors including toxic species. Age is reset in the process of cell division and daughter cell rejuvenation includes filtering and restoration of organelle function. Nystro¨m and Liu describe what is known regarding the mystery of aging and rejuvenation in Saccharomyces cerevisiae. If we look into the bacterial cell we can observe that gene expression is highly affected by the environmental conditions. Both transcriptional and post-transcriptional mechanisms are highly controlled to rapidly adapt to a Current Opinion in Microbiology 2014, 18:v–vii
changing environment. Several of our authors deal with regulation of cellular metabolism through CRP, allosteric control and compartmentalization. The Escherichia coli cyclic-AMP receptor protein (CRP) is a paradigm of gene regulation and recent work discussed by Green and coworkers demonstrate the repurposing of CRP through cAMP affinity and DNA binding to function in the specific niches occupied by the bacteria. It appears that the cyclic-AMP-CRP regulatory system has been adapted to respond to distinct external and internal inputs across a broad sensitivity range that is, at least in part, determined by bacterial lifestyles. Eoh and Rhee focus on two widely recognized regulatory mechanisms, allostery and subcellular compartmentalization, and highlights the fact that these mechanisms have largely failed to penetrate many physiological models of cellular regulation. Moreover, subcellular compartmentalization, a cornerstone of eukaryotic cell biology, has failed to penetrate the thinking of most microbiologists due to the apparent lack of lipid bound organelles. Growing evidence suggests that bacteria can indeed achieve the same functional compartmentalization through the regulated formation and/or activity of protein localization and pseudo-organelles, such as protein microcompartments and the periplasm. Eoh and Rhee highlight existing knowledge of these processes in the human pathogen Mycobacterium tuberculosis. RNA is an important regulatory molecule and during RNA synthesis the performance of RNA polymerases can be regulated by transcription factors. Yakhnin and Babitzke cover the functions of NusG/Spt5 which seems to be the only universally conserved transcription elongation factor. NusG and its paralog RfaH recognize specific sequences in the nontemplate DNA strand and regulate transcription elongation. NusG/Spt5 may partially release the transcription-associated stress on genome stability and it is probable that NusG becomes especially important under genotoxic conditions. Arraiano and collaborators describe the characteristics of ribonucleases (RNases), the enzymes that are involved in the maturation, turnover and quality control of all types of RNA. Namely RNases can act as controllers of sRNA networks affecting their targets and modifying gene expression. The authors have compiled many publications, which focus on the role of different bacterial ribonucleases in the regulation of small noncoding RNAs. Quek and Beemon focus on virus and describe the retroviral Strategy to stabilize Viral RNA. Namely, the unspliced RNA of Rous sarcoma virus (RSV), a well-studied avian retrovirus, is very stable, suggesting the virus has evolved a means to overcome degradation by RNA surveillance systems such as nonsense mediated decay (NMD). The study of different RNAs has led to the discovery of CRISPR RNAs. The clustered regularly interspaced short palindromic repeat (CRISPR) arrays and their www.sciencedirect.com
Editorial overview: Cell regulation: Microbial cell regulation — looking in from the outside Arraiano vii
CRISPR associated (Cas) proteins constitute adaptive immune systems in bacteria and archaea. They provide a range of mechanisms to confer protection from bacteriophages, plasmids and other mobile genetic elements. Fineran and Dy review small RNA-based CRISPR-Cas systems and describe how they can be directed to DNA in a sequence-specific manner. These new technologies have a great potential for the manipulation of gene expression in bacteria and eukaryotes. Großkopf and Soyer highlight how synthetic microbial communities can be engineered for the generation of defined systems
www.sciencedirect.com
with reduced complexity. Besides their value as model systems to understand the structure, function and evolution of microbial communities synthetic communities can also open up new avenues for biotechnological applications. All our contributors have connected the sensing/ regulation to the physiological output of the microbial cell. The responses of the bacterial cell to changing environmental conditions will have to be understood in the context of synthetic microbial communities. Certainly, these mechanisms will continue to fascinate scientists for the years to come.
Current Opinion in Microbiology 2014, 18:v–vii