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Editorial overview: Cell regulation: New insights into the versatile regulatory processes governing bacterial life
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ScienceDirect Editorial overview: Cell regulation: New insights into the versatile regulatory processes governing bacterial life Petra Dersch and Michael Laub Current Opinion in Microbiology 2017, 36:v–viii For a complete overview see the Issue http://dx.doi.org/10.1016/j.mib.2017.07.002 1369-5274/# 2017 Elsevier Ltd. All rights reserved.
Petra Dersch
Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany e-mail: [email protected] Petra Dersch is a professor of Microbiology and Molecular Infection Biology at the Helmholtz Centre for Infection Research and the Technical University Braunschweig. Her long-standing interest is the molecular analysis of pathogenicity mechanisms, in particular colonization factors and toxins of enteric bacteria. Another major and more recent research concerns the regulation of virulence-relevant factors of enteropathogens, for example, by sensory and regulatory RNA elements, in response to environmental and host signals, and their role during infection.
Michael Laub
The lifestyle of bacteria can be viewed as the relationships that they establish with other species and their environment over short and long periods of time. These relationships are one of the strongest driving forces that contribute to the evolution of sophisticated regulatory mechanisms underlying adaptive processes. One reason why bacteria are among the most successful life-forms on our planet is that small bacterial cells are able to sense and respond very rapidly to individual and global changes in their surroundings and efficiently adjust their cellular functions and physiological reactions accordingly. The recent development of novel deep-sequencing approaches and other powerful technologies have allowed us to probe molecular phenomena at a global scale and have provided spectacular new insights into the complexity of bacterial regulatory strategies and networks. These insights include the discoveries of novel regulatory principles associated with RNA, including the identification of a plethora of new regulatory RNA elements and RNA-based control concepts, and novel detailed knowledge about the global rewiring of bacterial transcriptomes in response to environmental and host stresses. Consequently, a significant part of this volume of ‘Cell regulation’ addresses new aspects and recent advances in our knowledge on riboregulation and complex post-transcriptional regulatory processes required to maintain bacterial fitness and adjust virulence-relevant properties. Another focus is how post-transcriptional control strategies modulate signaling and inter-cellular communications to help control pivotal processes, such as protein degradation and the subcellular localization of proteins. An increasingly higher degree of complexity is also seen in bacterial signal transduction pathways, implemented by protein kinases and small second messenger molecules. These regulatory mechanisms ultimately enable some sophisticated new cellular-level controls, including the ability of bacteria to react to emerging danger in the presence of competitors and enemies and to mechanical perturbations via direct contact with other cells or abiotic surfaces.
All about RNA: synthesis and modulation of its function
Department of Biology, Massachusetts Institute of Technology and Howard Hughes Medical Institute, 31 Ames St. 68-580A, Cambridge, MA, USA e-mail: [email protected] www.sciencedirect.com
RNA synthesis by transcription is the first strongly regulated step in gene expression. The induction of gene expression programs characterized by distinct transcriptional patterns is generally mediated by sigma factors, a reversibly interacting subunit of the RNA polymerase (RNAP) that targets the enzyme to specific promoters, melts the region of the double-stranded promoter DNA, and interacts with other transcription factors that modulate the transcription process. One class of sigma factors, the extracytoplasmic function (ECF) sigma factor family, has recently emerged as a large, phylogenetically distinct subfamily of s70-like factors. They are responsible for regulating a wide range of Current Opinion in Microbiology 2017, 36:v–viii
vi Cell regulation
Michael Laub is a professor of Biology at the Massachusetts Institute of Technology and an investigator of the Howard Hughes Medical Institute. His lab has focused on understanding the specificity and evolution of two-component signal transduction pathways in bacteria. Additionally, his lab has studied the regulatory mechanisms underlying the bacterial cell cycle, including efforts to elucidate the structure and organization of bacterial chromosomes.
functions, involved in sensing and reacting to conditions in the membrane, or extracellular environment. Recent advances in our understanding of their individual features, and the signal pathways governing their activities are reviewed by Sineva et al. The authors highlight that despite their considerable diversity, the ECF sigma factors all seem controlled by individual antisigma factors. Many previous studies addressed the global transcriptional responses of single bacterial species upon changes to individual environmental and virulence-relevant signals, such as temperature, reactive oxygen species, and iron starvation. However, transcription reprogramming by pathogens in response to stresses experienced during the course of an infection is highly complex and depends on a myriad of different parameters sensed by the bacteria in the different colonized host niches. Use of new refined RNA sequencing techniques presented in the overview by Colgan et al. has revolutionized the analysis of gene expression in infection systems. These approaches enable simultaneous detection, fine scale mapping, and quantification of all transcripts of multiple species at the same time and provide a powerful tool to reveal the most relevant infection-specific stimuli, host pathogen responses, and underlying regulatory processes. Over the past years it further became evident that stochastic fluctuations and regulatory feedback mechanisms, as well as differences in host environments, provoke different responses in individual bacterial cells, leading to heterogeneous populations. This strategy can provide a selective advantage particularly in rapidly changing environments, for example, during the course of an infection. Using single cell approaches reviewed by Mills and Avraham, researchers have now started to uncover the extent of heterogeneity within bacterial populations. The phenomena triggering this diversity and their biological relevance are described. Not only the control of transcription initiation, but also the intrinsic ability of RNAs to fold into versatile secondary motifs or tertiary motifs plays a pivotal role in governing protein synthesis. Systematic probing of the bacterial RNA structurome presented by Ignatova and Narberhaus has revealed an unexpected and manifold structural complexity affecting RNA function (e.g. translation) and stability. The review on this topic addresses probing of single RNAs and on the systems level, and highlights current challenges in the attempt to determine global structure–function relationships and their impact on diverse cellular processes.
Post-transcriptional regulation implicating non-coding RNAs, small proteins and proteases Recent discoveries have revealed that most bacteria encode a large repertoire of RNA-based regulatory mechanisms, including non-coding small regulatory RNAs, riboswitches, and small proteins. Some of these processes respond to environmental stresses and metabolites as well as signaling molecules and are involved in the maintenance of cellular homeostasis. The article by Dar and Sorek discusses new results showing that cis-acting non-coding RNA elements located upstream of antibiotic resistance genes can sense the presence of translation-inhibiting antibiotics. Antibioticpromoted blockage of the translation of short open reading frames encoded within these regulatory RNA elements leads to ribosome arrest, which changes the RNA structure and allows efficient expression of the antibiotic resistance genes located downstream. In addition, as outlined in the review by Hall et al., six types of toxin-antitoxin systems exist, that encompass noncoding RNAs and/or small proteins and act as stress response systems. They were shown to manipulate general cell processes such as DNA replication Current Opinion in Microbiology 2017, 36:v–viii
www.sciencedirect.com
Editorial overview Dersch and Laub vii
and membrane homeostasis, and are implicated in the formation of non-growing persister cells that can efficiently evade extinction by antibiotics. Activation of the individual toxins and their mode of action are well understood, but relatively little information is available about the reawakening of growth-arrested bacterial cells. New evidence exists and is discussed that indicates reversibility of the intoxication. A phenomenon, called conditional cooperativity allows cells to replenish antitoxin levels to resume growth. Although it is now universally acknowledged that noncoding sensory and regulatory RNAs are ubiquitous regulators, their molecular targets, physiological role, and individual molecular functions in different bacteria are often still unknown. The review by Soutourina focuses on the function and role of non-coding RNAs of Clostridium difficile causing nosocomial diarrhea and severe gut inflammation. The article accentuates the magnitude and variety of non-coding RNAs present in a single pathogen and highlights how they are involved in virulence relevant processes such as biofilm formation, cell adhesion, and host stress defenses. Non-coding RNAs also play a crucial role in the control of type III secretion systems (T3SS) of plants and animal pathogens serving as antihost defense tool. Schulmeyer and Yahr describe recent studies demonstrating that global RNA-binding proteins such as Hfq and CsrA/RsmA controlling the function of non-coding RNAs have a strong influence on the control of T3SS components in multiple Gram-negative pathogens. Moreover, components of the RNA degradosome alter the stability and translation of T3SS component or transcriptional regulator transcripts. This adds another level of control to the highly complex regulatory network of T3SS gene expression. Finally, Kuhlmann and Chien emphasize the importance of controlled proteolysis in cell regulation and explain how protein degradation by oligomeric AAA+ proteases is controlled by selective adaptors. Adaptors can modulate recognition of the substrate by the active protease, or alter protease assembly or activity of the protease complex. They further describe how this process affects fundamental biological processes, in particular bacterial cell proliferation.
Signaling/inter-cellular communication In addition to sophisticated mechanisms for regulating the expression and abundance of proteins, bacteria also employ a wide range of regulatory mechanisms at the post-translational level that help modulate and control various cellular processes. One well established mechanism involves changes in the subcellular localization of proteins. However, despite great progress in documenting these patterns of localization, we are still in the early stages of understanding www.sciencedirect.com
exactly how proteins are targeted to specific locations within the cell. One major mechanism, as reviewed by Updegrove and Ramamurthi, is through the inherent ability of some proteins to recognize specific geometric cues within cells such as the cell poles or nascent sites of division. The localization and activity of various membrane proteins is also likely to be strongly influenced by the composition of the membrane, which may differ at cell poles, sites of division, and along the length of cells. In addition, as Lopez and Koch describe, there is a growing body of evidence that bacterial membranes may be subdivided into microdomains, including lipid rafts comprising specific lipids and scaffolding proteins. These microdomains promote the clustering and oligomerization of some proteins, and likely the exclusion of others, with potentially profound consequences to the operation and function of membrane proteins and protein complexes. Post-translational control mechanisms in bacteria also frequently involve signaling pathways that modulate the phosphorylation of specific proteins or the production of second messengers. The classic and most frequent form of signaling in bacteria involves two-component signal transduction, typically comprising a sensor histidine kinase and its cognate response regulator. Although well characterized, and previously well reviewed, there is an increasing appreciation that two-component signaling pathways come in a variety of forms with specific or unusual properties. One such variety involves the socalled HWE/HisKA2-family sensor kinases. As described by Herrou et al., these kinases are structurally different from canonical HisKA-family histidine kinases, and they frequently participate in branched pathways wherein a given kinase has not just one, but several response regulator substrates. A second major form of signaling in bacteria involves proteins that synthesize or degrade the second messenger c-di-GMP. There have been major recent advances in understanding how c-di-GMP impacts cellular physiology through the identification and characterization of new c-di-GMP effector proteins, as well as the regulatory proteins that integrate various cues and signals into c-di-GMP-controlled processes. Yildiz and colleagues describe some of these recent advances in the context of Vibrio cholerae, an important pathogen that seems to rely heavily on c-di-GMP for its pathogenic lifestyle. In addition to the control of individual proteins and their individual activities, bacterial cells also must tightly regulate the functions and activities of large, multi-component protein complexes, which may be best characterized as molecular machines. One amazing such machine is that driving peptidoglycan synthesis. Although many, perhaps most, of the enzymes and proteins involved in the critical process of cell wall synthesis have been known for years, how they work together as a unit to build the Current Opinion in Microbiology 2017, 36:v–viii
viii Cell regulation
peptidoglycan meshwork surrounding cells has remained poorly understood. However, with major recent advances in imaging, significant new insights into the proteinprotein interactions and protein dynamics critical to peptidoglycan synthesis are rapidly emerging, as summarized in the review from Pazos et al. Bacterial cell division also requires specialized peptidoglycan synthesis, and the coordinated constriction of cell membranes. Additionally, cell division must be tightly regulated in space, to ensure that it occurs at or near mid-cell, and in time to ensure that it is appropriately coordinated with cell growth and the DNA replication cycle. In a provocative and forwardlooking review, Hamoen et al. describe the state of our understanding of bacterial cell division 25 years after the initial discovery of FtsZ and some prospects of what lies ahead in the coming years. Finally, this issue closes with two reviews describing two relatively new but exciting phenomena in bacteria involving fascinating cellular-level regulatory processes. The first, from Persat, describes the remarkable ability of cells to sense and respond to a range of mechanical cues and signals. Although signaling pathways are often envisioned as having small molecule ligands as input signals, it is increasingly clear that bacteria can respond to mechanical perturbations, including interactions with biotic and
Current Opinion in Microbiology 2017, 36:v–viii
abiotic surfaces. We are only just beginning to understand how such mechanical interactions are sensed at a molecular level, but the recent results summarized by Persat indicate that this is likely to be an active area of investigation in the near future. The second phenomenon, reviewed by Westhoff et al., centers on the ability of many bacteria to sense danger and the presence of potentially harmful neighbors. How cells recognize the presence of other cells may involve volatile compounds, diffusible molecules, or direct contact, and the type of signal may help convey the distance of a competitor and, consequently, the appropriate response, including defensive measures like changes in growth and permeability or offensive measures like the release of toxins. As with mechanotransduction, danger sensing is an intriguing new area that will likely garner significant attention in the coming years. In sum, the collection of reviews in this issue highlight the amazing and sophisticated regulatory processes that allow bacterial cells to respond to an impressive and sometimes intense set of environmental challenges and cellular perturbations. The individual reviews each provide both an outstanding summary of recent results in specific areas and a palpably exciting sense of what future discoveries and breakthroughs may lie ahead.
www.sciencedirect.com
ScienceDirect Editorial overview: Cell regulation: New insights into the versatile regulatory processes governing bacterial life Petra Dersch and Michael Laub Current Opinion in Microbiology 2017, 36:v–viii For a complete overview see the Issue http://dx.doi.org/10.1016/j.mib.2017.07.002 1369-5274/# 2017 Elsevier Ltd. All rights reserved.
Petra Dersch
Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany e-mail: [email protected] Petra Dersch is a professor of Microbiology and Molecular Infection Biology at the Helmholtz Centre for Infection Research and the Technical University Braunschweig. Her long-standing interest is the molecular analysis of pathogenicity mechanisms, in particular colonization factors and toxins of enteric bacteria. Another major and more recent research concerns the regulation of virulence-relevant factors of enteropathogens, for example, by sensory and regulatory RNA elements, in response to environmental and host signals, and their role during infection.
Michael Laub
The lifestyle of bacteria can be viewed as the relationships that they establish with other species and their environment over short and long periods of time. These relationships are one of the strongest driving forces that contribute to the evolution of sophisticated regulatory mechanisms underlying adaptive processes. One reason why bacteria are among the most successful life-forms on our planet is that small bacterial cells are able to sense and respond very rapidly to individual and global changes in their surroundings and efficiently adjust their cellular functions and physiological reactions accordingly. The recent development of novel deep-sequencing approaches and other powerful technologies have allowed us to probe molecular phenomena at a global scale and have provided spectacular new insights into the complexity of bacterial regulatory strategies and networks. These insights include the discoveries of novel regulatory principles associated with RNA, including the identification of a plethora of new regulatory RNA elements and RNA-based control concepts, and novel detailed knowledge about the global rewiring of bacterial transcriptomes in response to environmental and host stresses. Consequently, a significant part of this volume of ‘Cell regulation’ addresses new aspects and recent advances in our knowledge on riboregulation and complex post-transcriptional regulatory processes required to maintain bacterial fitness and adjust virulence-relevant properties. Another focus is how post-transcriptional control strategies modulate signaling and inter-cellular communications to help control pivotal processes, such as protein degradation and the subcellular localization of proteins. An increasingly higher degree of complexity is also seen in bacterial signal transduction pathways, implemented by protein kinases and small second messenger molecules. These regulatory mechanisms ultimately enable some sophisticated new cellular-level controls, including the ability of bacteria to react to emerging danger in the presence of competitors and enemies and to mechanical perturbations via direct contact with other cells or abiotic surfaces.
All about RNA: synthesis and modulation of its function
Department of Biology, Massachusetts Institute of Technology and Howard Hughes Medical Institute, 31 Ames St. 68-580A, Cambridge, MA, USA e-mail: [email protected] www.sciencedirect.com
RNA synthesis by transcription is the first strongly regulated step in gene expression. The induction of gene expression programs characterized by distinct transcriptional patterns is generally mediated by sigma factors, a reversibly interacting subunit of the RNA polymerase (RNAP) that targets the enzyme to specific promoters, melts the region of the double-stranded promoter DNA, and interacts with other transcription factors that modulate the transcription process. One class of sigma factors, the extracytoplasmic function (ECF) sigma factor family, has recently emerged as a large, phylogenetically distinct subfamily of s70-like factors. They are responsible for regulating a wide range of Current Opinion in Microbiology 2017, 36:v–viii
vi Cell regulation
Michael Laub is a professor of Biology at the Massachusetts Institute of Technology and an investigator of the Howard Hughes Medical Institute. His lab has focused on understanding the specificity and evolution of two-component signal transduction pathways in bacteria. Additionally, his lab has studied the regulatory mechanisms underlying the bacterial cell cycle, including efforts to elucidate the structure and organization of bacterial chromosomes.
functions, involved in sensing and reacting to conditions in the membrane, or extracellular environment. Recent advances in our understanding of their individual features, and the signal pathways governing their activities are reviewed by Sineva et al. The authors highlight that despite their considerable diversity, the ECF sigma factors all seem controlled by individual antisigma factors. Many previous studies addressed the global transcriptional responses of single bacterial species upon changes to individual environmental and virulence-relevant signals, such as temperature, reactive oxygen species, and iron starvation. However, transcription reprogramming by pathogens in response to stresses experienced during the course of an infection is highly complex and depends on a myriad of different parameters sensed by the bacteria in the different colonized host niches. Use of new refined RNA sequencing techniques presented in the overview by Colgan et al. has revolutionized the analysis of gene expression in infection systems. These approaches enable simultaneous detection, fine scale mapping, and quantification of all transcripts of multiple species at the same time and provide a powerful tool to reveal the most relevant infection-specific stimuli, host pathogen responses, and underlying regulatory processes. Over the past years it further became evident that stochastic fluctuations and regulatory feedback mechanisms, as well as differences in host environments, provoke different responses in individual bacterial cells, leading to heterogeneous populations. This strategy can provide a selective advantage particularly in rapidly changing environments, for example, during the course of an infection. Using single cell approaches reviewed by Mills and Avraham, researchers have now started to uncover the extent of heterogeneity within bacterial populations. The phenomena triggering this diversity and their biological relevance are described. Not only the control of transcription initiation, but also the intrinsic ability of RNAs to fold into versatile secondary motifs or tertiary motifs plays a pivotal role in governing protein synthesis. Systematic probing of the bacterial RNA structurome presented by Ignatova and Narberhaus has revealed an unexpected and manifold structural complexity affecting RNA function (e.g. translation) and stability. The review on this topic addresses probing of single RNAs and on the systems level, and highlights current challenges in the attempt to determine global structure–function relationships and their impact on diverse cellular processes.
Post-transcriptional regulation implicating non-coding RNAs, small proteins and proteases Recent discoveries have revealed that most bacteria encode a large repertoire of RNA-based regulatory mechanisms, including non-coding small regulatory RNAs, riboswitches, and small proteins. Some of these processes respond to environmental stresses and metabolites as well as signaling molecules and are involved in the maintenance of cellular homeostasis. The article by Dar and Sorek discusses new results showing that cis-acting non-coding RNA elements located upstream of antibiotic resistance genes can sense the presence of translation-inhibiting antibiotics. Antibioticpromoted blockage of the translation of short open reading frames encoded within these regulatory RNA elements leads to ribosome arrest, which changes the RNA structure and allows efficient expression of the antibiotic resistance genes located downstream. In addition, as outlined in the review by Hall et al., six types of toxin-antitoxin systems exist, that encompass noncoding RNAs and/or small proteins and act as stress response systems. They were shown to manipulate general cell processes such as DNA replication Current Opinion in Microbiology 2017, 36:v–viii
www.sciencedirect.com
Editorial overview Dersch and Laub vii
and membrane homeostasis, and are implicated in the formation of non-growing persister cells that can efficiently evade extinction by antibiotics. Activation of the individual toxins and their mode of action are well understood, but relatively little information is available about the reawakening of growth-arrested bacterial cells. New evidence exists and is discussed that indicates reversibility of the intoxication. A phenomenon, called conditional cooperativity allows cells to replenish antitoxin levels to resume growth. Although it is now universally acknowledged that noncoding sensory and regulatory RNAs are ubiquitous regulators, their molecular targets, physiological role, and individual molecular functions in different bacteria are often still unknown. The review by Soutourina focuses on the function and role of non-coding RNAs of Clostridium difficile causing nosocomial diarrhea and severe gut inflammation. The article accentuates the magnitude and variety of non-coding RNAs present in a single pathogen and highlights how they are involved in virulence relevant processes such as biofilm formation, cell adhesion, and host stress defenses. Non-coding RNAs also play a crucial role in the control of type III secretion systems (T3SS) of plants and animal pathogens serving as antihost defense tool. Schulmeyer and Yahr describe recent studies demonstrating that global RNA-binding proteins such as Hfq and CsrA/RsmA controlling the function of non-coding RNAs have a strong influence on the control of T3SS components in multiple Gram-negative pathogens. Moreover, components of the RNA degradosome alter the stability and translation of T3SS component or transcriptional regulator transcripts. This adds another level of control to the highly complex regulatory network of T3SS gene expression. Finally, Kuhlmann and Chien emphasize the importance of controlled proteolysis in cell regulation and explain how protein degradation by oligomeric AAA+ proteases is controlled by selective adaptors. Adaptors can modulate recognition of the substrate by the active protease, or alter protease assembly or activity of the protease complex. They further describe how this process affects fundamental biological processes, in particular bacterial cell proliferation.
Signaling/inter-cellular communication In addition to sophisticated mechanisms for regulating the expression and abundance of proteins, bacteria also employ a wide range of regulatory mechanisms at the post-translational level that help modulate and control various cellular processes. One well established mechanism involves changes in the subcellular localization of proteins. However, despite great progress in documenting these patterns of localization, we are still in the early stages of understanding www.sciencedirect.com
exactly how proteins are targeted to specific locations within the cell. One major mechanism, as reviewed by Updegrove and Ramamurthi, is through the inherent ability of some proteins to recognize specific geometric cues within cells such as the cell poles or nascent sites of division. The localization and activity of various membrane proteins is also likely to be strongly influenced by the composition of the membrane, which may differ at cell poles, sites of division, and along the length of cells. In addition, as Lopez and Koch describe, there is a growing body of evidence that bacterial membranes may be subdivided into microdomains, including lipid rafts comprising specific lipids and scaffolding proteins. These microdomains promote the clustering and oligomerization of some proteins, and likely the exclusion of others, with potentially profound consequences to the operation and function of membrane proteins and protein complexes. Post-translational control mechanisms in bacteria also frequently involve signaling pathways that modulate the phosphorylation of specific proteins or the production of second messengers. The classic and most frequent form of signaling in bacteria involves two-component signal transduction, typically comprising a sensor histidine kinase and its cognate response regulator. Although well characterized, and previously well reviewed, there is an increasing appreciation that two-component signaling pathways come in a variety of forms with specific or unusual properties. One such variety involves the socalled HWE/HisKA2-family sensor kinases. As described by Herrou et al., these kinases are structurally different from canonical HisKA-family histidine kinases, and they frequently participate in branched pathways wherein a given kinase has not just one, but several response regulator substrates. A second major form of signaling in bacteria involves proteins that synthesize or degrade the second messenger c-di-GMP. There have been major recent advances in understanding how c-di-GMP impacts cellular physiology through the identification and characterization of new c-di-GMP effector proteins, as well as the regulatory proteins that integrate various cues and signals into c-di-GMP-controlled processes. Yildiz and colleagues describe some of these recent advances in the context of Vibrio cholerae, an important pathogen that seems to rely heavily on c-di-GMP for its pathogenic lifestyle. In addition to the control of individual proteins and their individual activities, bacterial cells also must tightly regulate the functions and activities of large, multi-component protein complexes, which may be best characterized as molecular machines. One amazing such machine is that driving peptidoglycan synthesis. Although many, perhaps most, of the enzymes and proteins involved in the critical process of cell wall synthesis have been known for years, how they work together as a unit to build the Current Opinion in Microbiology 2017, 36:v–viii
viii Cell regulation
peptidoglycan meshwork surrounding cells has remained poorly understood. However, with major recent advances in imaging, significant new insights into the proteinprotein interactions and protein dynamics critical to peptidoglycan synthesis are rapidly emerging, as summarized in the review from Pazos et al. Bacterial cell division also requires specialized peptidoglycan synthesis, and the coordinated constriction of cell membranes. Additionally, cell division must be tightly regulated in space, to ensure that it occurs at or near mid-cell, and in time to ensure that it is appropriately coordinated with cell growth and the DNA replication cycle. In a provocative and forwardlooking review, Hamoen et al. describe the state of our understanding of bacterial cell division 25 years after the initial discovery of FtsZ and some prospects of what lies ahead in the coming years. Finally, this issue closes with two reviews describing two relatively new but exciting phenomena in bacteria involving fascinating cellular-level regulatory processes. The first, from Persat, describes the remarkable ability of cells to sense and respond to a range of mechanical cues and signals. Although signaling pathways are often envisioned as having small molecule ligands as input signals, it is increasingly clear that bacteria can respond to mechanical perturbations, including interactions with biotic and
Current Opinion in Microbiology 2017, 36:v–viii
abiotic surfaces. We are only just beginning to understand how such mechanical interactions are sensed at a molecular level, but the recent results summarized by Persat indicate that this is likely to be an active area of investigation in the near future. The second phenomenon, reviewed by Westhoff et al., centers on the ability of many bacteria to sense danger and the presence of potentially harmful neighbors. How cells recognize the presence of other cells may involve volatile compounds, diffusible molecules, or direct contact, and the type of signal may help convey the distance of a competitor and, consequently, the appropriate response, including defensive measures like changes in growth and permeability or offensive measures like the release of toxins. As with mechanotransduction, danger sensing is an intriguing new area that will likely garner significant attention in the coming years. In sum, the collection of reviews in this issue highlight the amazing and sophisticated regulatory processes that allow bacterial cells to respond to an impressive and sometimes intense set of environmental challenges and cellular perturbations. The individual reviews each provide both an outstanding summary of recent results in specific areas and a palpably exciting sense of what future discoveries and breakthroughs may lie ahead.
www.sciencedirect.com