Pub Date : 2024-09-03DOI: 10.1016/j.mib.2024.102538
Bryan Lakey , François Alberge , Timothy J Donohue
The cell envelope is at the center of many processes essential for bacterial lifestyles. In addition to giving bacteria shape and delineating it from the environment, it contains macromolecules important for energy transduction, cell division, protection against toxins, biofilm formation, or virulence. Hence, many systems coordinate different processes within the cell envelope to ensure function and integrity. Two-component systems have been identified as crucial regulators of cell envelope functions over the last few years. In this review, we summarize the new information obtained on the regulation of cell envelope biosynthesis and homeostasis in α-proteobacteria, as well as newly identified targets that coordinate the processes in the cell envelope.
{"title":"Insights into Alphaproteobacterial regulators of cell envelope remodeling","authors":"Bryan Lakey , François Alberge , Timothy J Donohue","doi":"10.1016/j.mib.2024.102538","DOIUrl":"10.1016/j.mib.2024.102538","url":null,"abstract":"<div><p>The cell envelope is at the center of many processes essential for bacterial lifestyles. In addition to giving bacteria shape and delineating it from the environment, it contains macromolecules important for energy transduction, cell division, protection against toxins, biofilm formation, or virulence. Hence, many systems coordinate different processes within the cell envelope to ensure function and integrity. Two-component systems have been identified as crucial regulators of cell envelope functions over the last few years. In this review, we summarize the new information obtained on the regulation of cell envelope biosynthesis and homeostasis in α-proteobacteria<em>,</em> as well as newly identified targets that coordinate the processes in the cell envelope.</p></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"81 ","pages":"Article 102538"},"PeriodicalIF":5.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142129993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1016/j.mib.2024.102540
Madeleine Delbeau , Ruby Froom , Robert Landick , Seth A Darst , Elizabeth A Campbell
RNA polymerase (RNAP), the central enzyme of transcription, intermittently pauses during the elongation stage of RNA synthesis. Pausing provides an opportunity for regulatory events such as nascent RNA folding or the recruitment of transregulators. NusG (Spt5 in eukaryotes and archaea) regulates RNAP pausing and is the only transcription factor conserved across all cellular life. NusG is a multifunctional protein: its N-terminal domain (NGN) binds to RNAP, and its C-terminal KOW domain in bacteria interacts with transcription regulators such as ribosomes and termination factors. In Escherichia coli, NusG acts as an antipausing factor. However, recent studies have revealed that NusG has distinct transcriptional regulatory roles specific to bacterial clades with clinical implications. Here, we focus on NusG’s dual roles in the regulation of pausing.
{"title":"The yin and yang of the universal transcription factor NusG","authors":"Madeleine Delbeau , Ruby Froom , Robert Landick , Seth A Darst , Elizabeth A Campbell","doi":"10.1016/j.mib.2024.102540","DOIUrl":"10.1016/j.mib.2024.102540","url":null,"abstract":"<div><p>RNA polymerase (RNAP), the central enzyme of transcription, intermittently pauses during the elongation stage of RNA synthesis. Pausing provides an opportunity for regulatory events such as nascent RNA folding or the recruitment of transregulators. NusG (Spt5 in eukaryotes and archaea) regulates RNAP pausing and is the only transcription factor conserved across all cellular life. NusG is a multifunctional protein: its N-terminal domain (NGN) binds to RNAP, and its C-terminal KOW domain in bacteria interacts with transcription regulators such as ribosomes and termination factors. In <em>Escherichia coli</em>, NusG acts as an antipausing factor. However, recent studies have revealed that NusG has distinct transcriptional regulatory roles specific to bacterial clades with clinical implications. Here, we focus on NusG’s dual roles in the regulation of pausing.</p></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"81 ","pages":"Article 102540"},"PeriodicalIF":5.9,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-30DOI: 10.1016/j.mib.2024.102536
Megan KM Young, Jue D Wang
Bacteria thrive in diverse environments and must withstand various stresses. A key stress response mechanism is the reprogramming of macromolecular biosynthesis and metabolic processes through alarmones — signaling nucleotides that accumulate intracellularly in response to metabolic stress. Diadenosine tetraphosphate (Ap4A), a putative alarmone, is produced in a noncanonical reaction by universally conserved aminoacyl-tRNA synthetases. Ap4A is ubiquitous across all domains of life and accumulates during heat and oxidative stress. Despite its early discovery in 1966, Ap4A’s alarmone status remained inconclusive. Recent discoveries identified Ap4A as a precursor to RNA 5′ caps in Escherichia coli. Additionally, Ap4A was found to directly bind to and allosterically inhibit the purine biosynthesis enzyme inosine 5′-monophosphate dehydrogenase, regulating guanosine triphosphate levels and enabling heat resistance in Bacillus subtilis. These findings, along with previous research, strongly suggest that Ap4A plays a crucial role as an alarmone, warranting further investigation to fully elucidate its functions.
{"title":"From dusty shelves toward the spotlight: growing evidence for Ap4A as an alarmone in maintaining RNA stability and proteostasis","authors":"Megan KM Young, Jue D Wang","doi":"10.1016/j.mib.2024.102536","DOIUrl":"10.1016/j.mib.2024.102536","url":null,"abstract":"<div><p>Bacteria thrive in diverse environments and must withstand various stresses. A key stress response mechanism is the reprogramming of macromolecular biosynthesis and metabolic processes through alarmones — signaling nucleotides that accumulate intracellularly in response to metabolic stress. Diadenosine tetraphosphate (Ap4A), a putative alarmone, is produced in a noncanonical reaction by universally conserved aminoacyl-tRNA synthetases. Ap4A is ubiquitous across all domains of life and accumulates during heat and oxidative stress. Despite its early discovery in 1966, Ap4A’s alarmone status remained inconclusive. Recent discoveries identified Ap4A as a precursor to RNA 5′ caps in <em>Escherichia coli</em>. Additionally, Ap4A was found to directly bind to and allosterically inhibit the purine biosynthesis enzyme inosine 5′-monophosphate dehydrogenase, regulating guanosine triphosphate levels and enabling heat resistance in <em>Bacillus subtilis</em>. These findings, along with previous research, strongly suggest that Ap4A plays a crucial role as an alarmone, warranting further investigation to fully elucidate its functions.</p></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"81 ","pages":"Article 102536"},"PeriodicalIF":5.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142095703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26DOI: 10.1016/j.mib.2024.102525
Alice X Wen , Christophe Herman
Membrane vesicles (MVs) are produced in all domains of life. In eukaryotes, extracellular vesicles have been shown to mediate the horizontal transfer of biological material between cells [1]. Therefore, bacterial MVs are also thought to mediate horizontal material transfer to host cells and other bacteria, especially in the context of cell stress. In this review, we discuss the mechanisms of bacterial MV production, evidence that their contents can be trafficked to host cells and other bacteria, and the biological relevance of horizontal material transfer by bacterial MVs.
{"title":"Horizontal gene transfer and beyond: the delivery of biological matter by bacterial membrane vesicles to host and bacterial cells","authors":"Alice X Wen , Christophe Herman","doi":"10.1016/j.mib.2024.102525","DOIUrl":"10.1016/j.mib.2024.102525","url":null,"abstract":"<div><p>Membrane vesicles (MVs) are produced in all domains of life. In eukaryotes, extracellular vesicles have been shown to mediate the horizontal transfer of biological material between cells [1]. Therefore, bacterial MVs are also thought to mediate horizontal material transfer to host cells and other bacteria, especially in the context of cell stress. In this review, we discuss the mechanisms of bacterial MV production, evidence that their contents can be trafficked to host cells and other bacteria, and the biological relevance of horizontal material transfer by bacterial MVs.</p></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"81 ","pages":"Article 102525"},"PeriodicalIF":5.9,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142077455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-23DOI: 10.1016/j.mib.2024.102526
Gengtan Li , Madison Newman , Houlin Yu , Maryam Rashidzade , Domingo Martínez-Soto , Ana Caicedo , Kelly S Allen , Li-Jun Ma
Fungal effector proteins function at the interfaces of diverse interactions between fungi and their plant and animal hosts, facilitating interactions that are pathogenic or mutualistic. Recent advancements in protein structure prediction have significantly accelerated the identification and functional predictions of these rapidly evolving effector proteins. This development enables scientists to generate testable hypotheses for functional validation using experimental approaches. Research frontiers in effector biology include understanding pathways through which effector proteins are secreted or translocated into host cells, their roles in manipulating host microbiomes, and their contribution to interacting with host immunity. Comparative effector repertoires among different fungal–host interactions can highlight unique adaptations, providing insights for the development of novel antifungal therapies and biocontrol strategies.
{"title":"Fungal effectors: past, present, and future","authors":"Gengtan Li , Madison Newman , Houlin Yu , Maryam Rashidzade , Domingo Martínez-Soto , Ana Caicedo , Kelly S Allen , Li-Jun Ma","doi":"10.1016/j.mib.2024.102526","DOIUrl":"10.1016/j.mib.2024.102526","url":null,"abstract":"<div><p>Fungal effector proteins function at the interfaces of diverse interactions between fungi and their plant and animal hosts, facilitating interactions that are pathogenic or mutualistic. Recent advancements in protein structure prediction have significantly accelerated the identification and functional predictions of these rapidly evolving effector proteins. This development enables scientists to generate testable hypotheses for functional validation using experimental approaches. Research frontiers in effector biology include understanding pathways through which effector proteins are secreted or translocated into host cells, their roles in manipulating host microbiomes, and their contribution to interacting with host immunity. Comparative effector repertoires among different fungal–host interactions can highlight unique adaptations, providing insights for the development of novel antifungal therapies and biocontrol strategies.</p></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"81 ","pages":"Article 102526"},"PeriodicalIF":5.9,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1369527424001024/pdfft?md5=92a5fec3391cf18a402141961b4ad94d&pid=1-s2.0-S1369527424001024-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142049608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D-galactonate, a widely prevalent sugar acid, was first reported as a nutrient source for enteric bacteria in the 1970s. Since then, decades of research enabled a description of the modified Entner-Doudoroff pathway involved in its degradation and reported the structural and biochemical features of its metabolic enzymes, primarily in Escherichia coli K-12. However, only in the last few years, the D-galactonate transporter has been characterized, and the regulation of the dgo operon, encoding the structural genes for the transporter and enzymes of D-galactonate metabolism, has been detailed. Notably, in recent years, multiple evolutionary studies have identified the dgo operon as a dominant target for adaptation of E. coli in the mammalian gut. Despite considerable research on dgo operon, numerous fundamental questions remain to be addressed. The emerging relevance of the dgo operon in host–bacterial interactions further necessitates the study of D-galactonate metabolism in other enterobacterial strains.
{"title":"D-galactonate metabolism in enteric bacteria: a molecular and physiological perspective","authors":"Swati Singh , Chetna Gola , Bhupinder Singh , Vishal Agrawal , Rachna Chaba","doi":"10.1016/j.mib.2024.102524","DOIUrl":"10.1016/j.mib.2024.102524","url":null,"abstract":"<div><p><span>D</span>-galactonate, a widely prevalent sugar acid, was first reported as a nutrient source for enteric bacteria in the 1970s. Since then, decades of research enabled a description of the modified Entner-Doudoroff pathway involved in its degradation and reported the structural and biochemical features of its metabolic enzymes, primarily in <em>Escherichia coli</em> K-12. However, only in the last few years, the <span>D</span>-galactonate transporter has been characterized, and the regulation of the <em>dgo</em> operon, encoding the structural genes for the transporter and enzymes of <span>D</span>-galactonate metabolism, has been detailed. Notably, in recent years, multiple evolutionary studies have identified the <em>dgo</em> operon as a dominant target for adaptation of <em>E. coli</em> in the mammalian gut. Despite considerable research on <em>dgo</em> operon, numerous fundamental questions remain to be addressed. The emerging relevance of the <em>dgo</em> operon in host–bacterial interactions further necessitates the study of <span>D</span>-galactonate metabolism in other enterobacterial strains.</p></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"81 ","pages":"Article 102524"},"PeriodicalIF":5.9,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fungal biofilms are a multilayered community of cells attached to mucosal or abiotic surfaces enclosed in a coating of self-produced extracellular polymeric matrix. The sheer density of cells protected by a polymeric shield not only makes the biofilm impermeable to antimicrobials or immune cells but also hidden from host recognition. Biofilms also serve as a reservoir of drug-resistant persister cells and dispersal cells armored with virulence factors adept at evading the immune system. Here, we summarize the latest knowledge on the immunomodulatory properties of biofilms formed by Candida species and by other biofilm-forming fungal pathogens such as Aspergillus and Cryptococcus. Finally, we deliberate on promising strategies to help activate the immune system for combating fungal biofilms.
{"title":"Host immune response against fungal biofilms","authors":"Mohammad Mannan , Sunna Nabeela , Reetakshi Mishra , Priya Uppuluri","doi":"10.1016/j.mib.2024.102520","DOIUrl":"10.1016/j.mib.2024.102520","url":null,"abstract":"<div><p>Fungal biofilms are a multilayered community of cells attached to mucosal or abiotic surfaces enclosed in a coating of self-produced extracellular polymeric matrix. The sheer density of cells protected by a polymeric shield not only makes the biofilm impermeable to antimicrobials or immune cells but also hidden from host recognition. Biofilms also serve as a reservoir of drug-resistant persister cells and dispersal cells armored with virulence factors adept at evading the immune system. Here, we summarize the latest knowledge on the immunomodulatory properties of biofilms formed by <em>Candida</em> species and by other biofilm-forming fungal pathogens such as <em>Aspergillus</em> and <em>Cryptococcus</em>. Finally, we deliberate on promising strategies to help activate the immune system for combating fungal biofilms.</p></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"81 ","pages":"Article 102520"},"PeriodicalIF":5.9,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1369527424000961/pdfft?md5=d1b3631d18ad1cf50b233ae1db6be79e&pid=1-s2.0-S1369527424000961-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-07DOI: 10.1016/j.mib.2024.102522
Toni Gabaldón , Luiz Pedro Sório de Carvalho
{"title":"Editorial overview: emerging avenues in antimicrobial research","authors":"Toni Gabaldón , Luiz Pedro Sório de Carvalho","doi":"10.1016/j.mib.2024.102522","DOIUrl":"10.1016/j.mib.2024.102522","url":null,"abstract":"","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"81 ","pages":"Article 102522"},"PeriodicalIF":5.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1016/j.mib.2024.102521
Matthew R James, Katherine E Doss, Robert A Cramer
Aspergillus fumigatus is a filamentous fungus abundant in the environment and the most common causative agent of a spectrum of human diseases collectively termed aspergillosis. Invasive pulmonary aspergillosis is caused by deficiencies in innate immune function that result in the inability of the host to clear inhaled Aspergillus conidia that then germinate and form invasive hyphae. Myeloid cells, and their ability to generate reactive oxygen species (ROS), are essential for conidia clearance from the host. To combat ROS, A. fumigatus employs an expansive antioxidant system, though how these canonical antioxidant mechanisms contribute to infection initiation and disease progression remain to be fully defined. Recent research has identified noncanonical pathways in the A. fumigatus ROS response and new host populations with ROS deficiencies that are at-risk for invasive aspergillosis. Here, we highlight recent developments in the understanding of ROS at the interface of the dynamic A. fumigatus–host interaction.
{"title":"New developments in Aspergillus fumigatus and host reactive oxygen species responses","authors":"Matthew R James, Katherine E Doss, Robert A Cramer","doi":"10.1016/j.mib.2024.102521","DOIUrl":"10.1016/j.mib.2024.102521","url":null,"abstract":"<div><p><em>Aspergillus fumigatus</em> is a filamentous fungus abundant in the environment and the most common causative agent of a spectrum of human diseases collectively termed aspergillosis. Invasive pulmonary aspergillosis is caused by deficiencies in innate immune function that result in the inability of the host to clear inhaled <em>Aspergillus</em> conidia that then germinate and form invasive hyphae. Myeloid cells, and their ability to generate reactive oxygen species (ROS), are essential for conidia clearance from the host. To combat ROS, <em>A. fumigatus</em> employs an expansive antioxidant system, though how these canonical antioxidant mechanisms contribute to infection initiation and disease progression remain to be fully defined. Recent research has identified noncanonical pathways in the <em>A. fumigatus</em> ROS response and new host populations with ROS deficiencies that are at-risk for invasive aspergillosis. Here, we highlight recent developments in the understanding of ROS at the interface of the dynamic <em>A. fumigatus</em>–host interaction.</p></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"80 ","pages":"Article 102521"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}