Pub Date : 2024-12-12Epub Date: 2024-06-12DOI: 10.1128/ecosalplus.esp-0001-2022
Sonya K Royzenblat, Lydia Freddolino
Escherichia coli has been a vital model organism for studying chromosomal structure, thanks, in part, to its small and circular genome (4.6 million base pairs) and well-characterized biochemical pathways. Over the last several decades, we have made considerable progress in understanding the intricacies of the structure and subsequent function of the E. coli nucleoid. At the smallest scale, DNA, with no physical constraints, takes on a shape reminiscent of a randomly twisted cable, forming mostly random coils but partly affected by its stiffness. This ball-of-spaghetti-like shape forms a structure several times too large to fit into the cell. Once the physiological constraints of the cell are added, the DNA takes on overtwisted (negatively supercoiled) structures, which are shaped by an intricate interplay of many proteins carrying out essential biological processes. At shorter length scales (up to about 1 kb), nucleoid-associated proteins organize and condense the chromosome by inducing loops, bends, and forming bridges. Zooming out further and including cellular processes, topological domains are formed, which are flanked by supercoiling barriers. At the megabase-scale both large, highly self-interacting regions (macrodomains) and strong contacts between distant but co-regulated genes have been observed. At the largest scale, the nucleoid forms a helical ellipsoid. In this review, we will explore the history and recent advances that pave the way for a better understanding of E. coli chromosome organization and structure, discussing the cellular processes that drive changes in DNA shape, and what contributes to compaction and formation of dynamic structures, and in turn how bacterial chromatin affects key processes such as transcription and replication.
大肠杆菌一直是研究染色体结构的重要模式生物,这部分归功于它的小而圆的基因组(460 万碱基对)和特征良好的生化途径。过去几十年来,我们在了解大肠杆菌核团结构及其功能方面取得了长足的进步。在最小尺度上,DNA 在没有物理约束的情况下,其形状让人联想到随机扭曲的电缆,形成的线圈大部分是随机的,但部分受到其硬度的影响。这种面条球状的形状形成了一个大数倍的结构,无法装入细胞。一旦加上细胞的生理限制,DNA 就会形成过度扭曲(负超卷)的结构,这种结构是由许多执行重要生物过程的蛋白质错综复杂地相互作用形成的。在较短的长度范围内(最多约 1 kb),核团相关蛋白通过诱导环、弯曲和形成桥来组织和凝结染色体。进一步放大,包括细胞过程在内,拓扑结构域形成,其两侧是超卷曲屏障。在巨碱基尺度上,既观察到了大型、高度自我相互作用的区域(宏域),也观察到了相距遥远但共同调控的基因之间的强烈接触。在最大尺度上,核团形成一个螺旋椭圆体。在这篇综述中,我们将探讨为更好地了解大肠杆菌染色体组织和结构铺平道路的历史和最新进展,讨论驱动 DNA 形状变化的细胞过程、促成压实和动态结构形成的因素,以及细菌染色质如何反过来影响转录和复制等关键过程。
{"title":"Spatio-temporal organization of the <i>E. coli</i> chromosome from base to cellular length scales.","authors":"Sonya K Royzenblat, Lydia Freddolino","doi":"10.1128/ecosalplus.esp-0001-2022","DOIUrl":"10.1128/ecosalplus.esp-0001-2022","url":null,"abstract":"<p><p><i>Escherichia coli</i> has been a vital model organism for studying chromosomal structure, thanks, in part, to its small and circular genome (4.6 million base pairs) and well-characterized biochemical pathways. Over the last several decades, we have made considerable progress in understanding the intricacies of the structure and subsequent function of the <i>E. coli</i> nucleoid. At the smallest scale, DNA, with no physical constraints, takes on a shape reminiscent of a randomly twisted cable, forming mostly random coils but partly affected by its stiffness. This ball-of-spaghetti-like shape forms a structure several times too large to fit into the cell. Once the physiological constraints of the cell are added, the DNA takes on overtwisted (negatively supercoiled) structures, which are shaped by an intricate interplay of many proteins carrying out essential biological processes. At shorter length scales (up to about 1 kb), nucleoid-associated proteins organize and condense the chromosome by inducing loops, bends, and forming bridges. Zooming out further and including cellular processes, topological domains are formed, which are flanked by supercoiling barriers. At the megabase-scale both large, highly self-interacting regions (macrodomains) and strong contacts between distant but co-regulated genes have been observed. At the largest scale, the nucleoid forms a helical ellipsoid. In this review, we will explore the history and recent advances that pave the way for a better understanding of <i>E. coli</i> chromosome organization and structure, discussing the cellular processes that drive changes in DNA shape, and what contributes to compaction and formation of dynamic structures, and in turn how bacterial chromatin affects key processes such as transcription and replication.</p>","PeriodicalId":11500,"journal":{"name":"EcoSal Plus","volume":" ","pages":"eesp00012022"},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11636183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-12Epub Date: 2024-07-18DOI: 10.1128/ecosalplus.esp-0004-2023
Garima Bansal, Mostafa Ghanem, Khandra T Sears, James E Galen, Sharon M Tennant
Salmonella enterica is a diverse species that infects both humans and animals. S. enterica subspecies enterica consists of more than 1,500 serovars. Unlike typhoidal Salmonella serovars which are human host-restricted, non-typhoidal Salmonella (NTS) serovars are associated with foodborne illnesses worldwide and are transmitted via the food chain. Additionally, NTS serovars can cause disease in livestock animals causing significant economic losses. Salmonella is a well-studied model organism that is easy to manipulate and evaluate in animal models of infection. Advances in genetic engineering approaches in recent years have led to the development of Salmonella vaccines for both humans and animals. In this review, we focus on current progress of recombinant live-attenuated Salmonella vaccines, their use as a source of antigens for parenteral vaccines, their use as live-vector vaccines to deliver foreign antigens, and their use as therapeutic cancer vaccines in humans. We also describe development of live-attenuated Salmonella vaccines and live-vector vaccines for use in animals.
{"title":"Genetic engineering of <i>Salmonella</i> spp. for novel vaccine strategies and therapeutics.","authors":"Garima Bansal, Mostafa Ghanem, Khandra T Sears, James E Galen, Sharon M Tennant","doi":"10.1128/ecosalplus.esp-0004-2023","DOIUrl":"10.1128/ecosalplus.esp-0004-2023","url":null,"abstract":"<p><p><i>Salmonella enterica</i> is a diverse species that infects both humans and animals. <i>S. enterica</i> subspecies <i>enterica</i> consists of more than 1,500 serovars. Unlike typhoidal <i>Salmonella</i> serovars which are human host-restricted, non-typhoidal <i>Salmonella</i> (NTS) serovars are associated with foodborne illnesses worldwide and are transmitted via the food chain. Additionally, NTS serovars can cause disease in livestock animals causing significant economic losses. <i>Salmonella</i> is a well-studied model organism that is easy to manipulate and evaluate in animal models of infection. Advances in genetic engineering approaches in recent years have led to the development of <i>Salmonella</i> vaccines for both humans and animals. In this review, we focus on current progress of recombinant live-attenuated <i>Salmonella</i> vaccines, their use as a source of antigens for parenteral vaccines, their use as live-vector vaccines to deliver foreign antigens, and their use as therapeutic cancer vaccines in humans. We also describe development of live-attenuated <i>Salmonella</i> vaccines and live-vector vaccines for use in animals.</p>","PeriodicalId":11500,"journal":{"name":"EcoSal Plus","volume":" ","pages":"eesp00042023"},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11636237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-12Epub Date: 2024-01-31DOI: 10.1128/ecosalplus.esp-0003-2023
Janay I Little, Pradip K Singh, Jinlei Zhao, Shakeera Dunn, Hanover Matz, Michael S Donnenberg
Type IV pili (T4Ps) are surface filaments widely distributed among bacteria and archaea. T4Ps are involved in many cellular functions and contribute to virulence in some species of bacteria. Due to the diversity of T4Ps, different properties have been observed for homologous proteins that make up T4Ps in various organisms. In this review, we highlight the essential components of T4Ps, their functions, and similarities to related systems. We emphasize the unique T4Ps of enteric pathogens within the Enterobacteriaceae family, which includes pathogenic strains of Escherichia coli and Salmonella. These include the bundle-forming pilus (BFP) of enteropathogenic E. coli (EPEC), longus (Lng) and colonization factor III (CFA/III) of enterotoxigenic E. coli (ETEC), T4P of Salmonella enterica serovar Typhi, Colonization Factor Citrobacter (CFC) of Citrobacter rodentium, T4P of Yersinia pseudotuberculosis, a ubiquitous T4P that was characterized in enterohemorrhagic E. coli (EHEC), and the R64 plasmid thin pilus. Finally, we highlight areas for further study.
{"title":"Type IV pili of <i>Enterobacteriaceae</i> species.","authors":"Janay I Little, Pradip K Singh, Jinlei Zhao, Shakeera Dunn, Hanover Matz, Michael S Donnenberg","doi":"10.1128/ecosalplus.esp-0003-2023","DOIUrl":"10.1128/ecosalplus.esp-0003-2023","url":null,"abstract":"<p><p>Type IV pili (T4Ps) are surface filaments widely distributed among bacteria and archaea. T4Ps are involved in many cellular functions and contribute to virulence in some species of bacteria. Due to the diversity of T4Ps, different properties have been observed for homologous proteins that make up T4Ps in various organisms. In this review, we highlight the essential components of T4Ps, their functions, and similarities to related systems. We emphasize the unique T4Ps of enteric pathogens within the <i>Enterobacteriaceae</i> family, which includes pathogenic strains of <i>Escherichia coli</i> and <i>Salmonella</i>. These include the bundle-forming pilus (BFP) of enteropathogenic <i>E. coli</i> (EPEC), longus (Lng) and colonization factor III (CFA/III) of enterotoxigenic <i>E. coli</i> (ETEC), T4P of <i>Salmonella enterica</i> serovar Typhi, Colonization Factor Citrobacter (CFC) of <i>Citrobacter rodentium</i>, T4P of <i>Yersinia pseudotuberculosis</i>, a ubiquitous T4P that was characterized in enterohemorrhagic <i>E. coli</i> (EHEC), and the R64 plasmid thin pilus. Finally, we highlight areas for further study.</p>","PeriodicalId":11500,"journal":{"name":"EcoSal Plus","volume":" ","pages":"eesp00032023"},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11636386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139641811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-12Epub Date: 2024-05-20DOI: 10.1128/ecosalplus.esp-0025-2022
Selene F H Shore, Florian H Leinberger, Elizabeth M Fozo, Bork A Berghoff
Toxin-antitoxin systems are ubiquitous in the prokaryotic world and widely distributed among chromosomes and mobile genetic elements. Several different toxin-antitoxin system types exist, but what they all have in common is that toxin activity is prevented by the cognate antitoxin. In type I toxin-antitoxin systems, toxin production is controlled by an RNA antitoxin and by structural features inherent to the toxin messenger RNA. Most type I toxins are small membrane proteins that display a variety of cellular effects. While originally discovered as modules that stabilize plasmids, chromosomal type I toxin-antitoxin systems may also stabilize prophages, or serve important functions upon certain stress conditions and contribute to population-wide survival strategies. Here, we will describe the intricate RNA-based regulation of type I toxin-antitoxin systems and discuss their potential biological functions.
毒素-抗毒素系统在原核生物中无处不在,广泛分布于染色体和移动遗传因子中。毒素-抗毒素系统有几种不同的类型,但它们的共同点都是毒素活性被同源的抗毒素所阻止。在 I 型毒素-抗毒素系统中,毒素的产生受 RNA 抗毒素和毒素信使 RNA 固有结构特征的控制。大多数 I 型毒素都是小型膜蛋白,能产生多种细胞效应。虽然最初是作为稳定质粒的模块被发现的,但染色体 I 型毒素-抗毒素系统也可能稳定原生质粒,或在某些应激条件下发挥重要功能,并有助于整个种群的生存策略。在这里,我们将描述 I 型毒素-抗毒素系统基于 RNA 的复杂调控,并讨论其潜在的生物学功能。
{"title":"Type I toxin-antitoxin systems in bacteria: from regulation to biological functions.","authors":"Selene F H Shore, Florian H Leinberger, Elizabeth M Fozo, Bork A Berghoff","doi":"10.1128/ecosalplus.esp-0025-2022","DOIUrl":"10.1128/ecosalplus.esp-0025-2022","url":null,"abstract":"<p><p>Toxin-antitoxin systems are ubiquitous in the prokaryotic world and widely distributed among chromosomes and mobile genetic elements. Several different toxin-antitoxin system types exist, but what they all have in common is that toxin activity is prevented by the cognate antitoxin. In type I toxin-antitoxin systems, toxin production is controlled by an RNA antitoxin and by structural features inherent to the toxin messenger RNA. Most type I toxins are small membrane proteins that display a variety of cellular effects. While originally discovered as modules that stabilize plasmids, chromosomal type I toxin-antitoxin systems may also stabilize prophages, or serve important functions upon certain stress conditions and contribute to population-wide survival strategies. Here, we will describe the intricate RNA-based regulation of type I toxin-antitoxin systems and discuss their potential biological functions.</p>","PeriodicalId":11500,"journal":{"name":"EcoSal Plus","volume":" ","pages":"eesp00252022"},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11636113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-12Epub Date: 2024-02-12DOI: 10.1128/ecosalplus.esp-0039-2020
Stephen J W Busby, Douglas F Browning
Promoter-specific activation of transcript initiation provides an important regulatory device in Escherichia coli and Salmonella. Here, we describe the different mechanisms that operate, focusing on how they have evolved to manage the "housekeeping" bacterial transcription machinery. Some mechanisms involve assisting the bacterial DNA-dependent RNA polymerase or replacing or remodeling one of its subunits. Others are directed to chromosomal DNA, improving promoter function, or relieving repression. We discuss how different activators work together at promoters and how the present complex network of transcription factors evolved.
在大肠杆菌和沙门氏菌中,启动子特异性激活转录本启动是一种重要的调控手段。在这里,我们描述了不同的运作机制,重点是它们是如何进化来管理 "看家 "细菌转录机制的。一些机制涉及辅助细菌的 DNA 依赖性 RNA 聚合酶,或替换或重塑其一个亚基。其他机制则针对染色体 DNA、改善启动子功能或缓解抑制。我们将讨论不同的激活因子如何在启动子上协同工作,以及目前复杂的转录因子网络是如何演变而来的。
{"title":"Transcription activation in <i>Escherichia coli</i> and <i>Salmonella</i>.","authors":"Stephen J W Busby, Douglas F Browning","doi":"10.1128/ecosalplus.esp-0039-2020","DOIUrl":"10.1128/ecosalplus.esp-0039-2020","url":null,"abstract":"<p><p>Promoter-specific activation of transcript initiation provides an important regulatory device in <i>Escherichia coli</i> and <i>Salmonella</i>. Here, we describe the different mechanisms that operate, focusing on how they have evolved to manage the \"housekeeping\" bacterial transcription machinery. Some mechanisms involve assisting the bacterial DNA-dependent RNA polymerase or replacing or remodeling one of its subunits. Others are directed to chromosomal DNA, improving promoter function, or relieving repression. We discuss how different activators work together at promoters and how the present complex network of transcription factors evolved.</p>","PeriodicalId":11500,"journal":{"name":"EcoSal Plus","volume":" ","pages":"eesp00392020"},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11636354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-11DOI: 10.1128/ecosalplus.esp-0006-2023
Sudhir Doranga, K. A. Krogfelt, Paul S. Cohen, Tyrrell Conway
ABSTRACT In this chapter, we update our 2004 review of “The Life of Commensal Escherichia coli in the Mammalian Intestine” (https://doi.org/10.1128/ecosalplus.8.3.1.2), with a change of title that reflects the current focus on “Nutrition of E. coli within the Intestinal Microbiome.” The earlier part of the previous two decades saw incremental improvements in understanding the carbon and energy sources that E. coli and Salmonella use to support intestinal colonization. Along with these investigations of electron donors came a better understanding of the electron acceptors that support the respiration of these facultative anaerobes in the gastrointestinal tract. Hundreds of recent papers add to what was known about the nutrition of commensal and pathogenic enteric bacteria. The fact that each biotype or pathotype grows on a different subset of the available nutrients suggested a mechanism for succession of commensal colonizers and invasion by enteric pathogens. Competition for nutrients in the intestine has also come to be recognized as one basis for colonization resistance, in which colonized strain(s) prevent colonization by a challenger. In the past decade, detailed investigations of fiber- and mucin-degrading anaerobes added greatly to our understanding of how complex polysaccharides support the hundreds of intestinal microbiome species. It is now clear that facultative anaerobes, which usually cannot degrade complex polysaccharides, live in symbiosis with the anaerobic degraders. This concept led to the “restaurant hypothesis,” which emphasizes that facultative bacteria, such as E. coli, colonize the intestine as members of mixed biofilms and obtain the sugars they need for growth locally through cross-feeding from polysaccharide-degrading anaerobes. Each restaurant represents an intestinal niche. Competition for those niches determines whether or not invaders are able to overcome colonization resistance and become established. Topics centered on the nutritional basis of intestinal colonization and gastrointestinal health are explored here in detail.
{"title":"Nutrition of Escherichia coli within the intestinal microbiome","authors":"Sudhir Doranga, K. A. Krogfelt, Paul S. Cohen, Tyrrell Conway","doi":"10.1128/ecosalplus.esp-0006-2023","DOIUrl":"https://doi.org/10.1128/ecosalplus.esp-0006-2023","url":null,"abstract":"ABSTRACT In this chapter, we update our 2004 review of “The Life of Commensal Escherichia coli in the Mammalian Intestine” (https://doi.org/10.1128/ecosalplus.8.3.1.2), with a change of title that reflects the current focus on “Nutrition of E. coli within the Intestinal Microbiome.” The earlier part of the previous two decades saw incremental improvements in understanding the carbon and energy sources that E. coli and Salmonella use to support intestinal colonization. Along with these investigations of electron donors came a better understanding of the electron acceptors that support the respiration of these facultative anaerobes in the gastrointestinal tract. Hundreds of recent papers add to what was known about the nutrition of commensal and pathogenic enteric bacteria. The fact that each biotype or pathotype grows on a different subset of the available nutrients suggested a mechanism for succession of commensal colonizers and invasion by enteric pathogens. Competition for nutrients in the intestine has also come to be recognized as one basis for colonization resistance, in which colonized strain(s) prevent colonization by a challenger. In the past decade, detailed investigations of fiber- and mucin-degrading anaerobes added greatly to our understanding of how complex polysaccharides support the hundreds of intestinal microbiome species. It is now clear that facultative anaerobes, which usually cannot degrade complex polysaccharides, live in symbiosis with the anaerobic degraders. This concept led to the “restaurant hypothesis,” which emphasizes that facultative bacteria, such as E. coli, colonize the intestine as members of mixed biofilms and obtain the sugars they need for growth locally through cross-feeding from polysaccharide-degrading anaerobes. Each restaurant represents an intestinal niche. Competition for those niches determines whether or not invaders are able to overcome colonization resistance and become established. Topics centered on the nutritional basis of intestinal colonization and gastrointestinal health are explored here in detail.","PeriodicalId":11500,"journal":{"name":"EcoSal Plus","volume":"3 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139438248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-11DOI: 10.1128/ecosalplus.esp-0029-2023
J. Zulk, K. Patras, A. Maresso
ABSTRACT In the face of rising antimicrobial resistance, bacteriophage therapy, also known as phage therapy, is seeing a resurgence as a potential treatment for bacterial infections including urinary tract infection (UTI). Primarily caused by uropathogenic Escherichia coli, the 400 million UTI cases annually are major global healthcare burdens and a primary cause of antibiotic prescriptions in the outpatient setting. Phage therapy has several potential advantages over antibiotics including the ability to disrupt bacterial biofilms and synergize with antimicrobial treatments with minimal side effects or impacts on the microbiota. Phage therapy for UTI treatment has shown generally favorable results in recent animal models and human case reports. Ongoing clinical trials seek to understand the efficacy of phage therapy in individuals with asymptomatic bacteriuria and uncomplicated cystitis. A possible challenge for phage therapy is the development of phage resistance in bacteria during treatment. While resistance frequently develops in vitro and in vivo, resistance can come with negative consequences for the bacteria, leaving them susceptible to antibiotics and other environmental conditions and reducing their overall virulence. “Steering” bacteria toward phage resistance outcomes that leave them less fit or virulent is especially useful in the context of UTI where poorly adherent or slow-growing bacteria are likely to be flushed from the system. In this article, we describe the history of phage therapy in treating UTI and its current resurgence, the state of its clinical use, and an outlook on how well-designed phage therapy could be used to “steer” bacteria toward less virulent and antimicrobial-susceptible states.
{"title":"The rise, fall, and resurgence of phage therapy for urinary tract infection","authors":"J. Zulk, K. Patras, A. Maresso","doi":"10.1128/ecosalplus.esp-0029-2023","DOIUrl":"https://doi.org/10.1128/ecosalplus.esp-0029-2023","url":null,"abstract":"ABSTRACT In the face of rising antimicrobial resistance, bacteriophage therapy, also known as phage therapy, is seeing a resurgence as a potential treatment for bacterial infections including urinary tract infection (UTI). Primarily caused by uropathogenic Escherichia coli, the 400 million UTI cases annually are major global healthcare burdens and a primary cause of antibiotic prescriptions in the outpatient setting. Phage therapy has several potential advantages over antibiotics including the ability to disrupt bacterial biofilms and synergize with antimicrobial treatments with minimal side effects or impacts on the microbiota. Phage therapy for UTI treatment has shown generally favorable results in recent animal models and human case reports. Ongoing clinical trials seek to understand the efficacy of phage therapy in individuals with asymptomatic bacteriuria and uncomplicated cystitis. A possible challenge for phage therapy is the development of phage resistance in bacteria during treatment. While resistance frequently develops in vitro and in vivo, resistance can come with negative consequences for the bacteria, leaving them susceptible to antibiotics and other environmental conditions and reducing their overall virulence. “Steering” bacteria toward phage resistance outcomes that leave them less fit or virulent is especially useful in the context of UTI where poorly adherent or slow-growing bacteria are likely to be flushed from the system. In this article, we describe the history of phage therapy in treating UTI and its current resurgence, the state of its clinical use, and an outlook on how well-designed phage therapy could be used to “steer” bacteria toward less virulent and antimicrobial-susceptible states.","PeriodicalId":11500,"journal":{"name":"EcoSal Plus","volume":"11 14","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139438684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-04DOI: 10.1128/ecosalplus.esp-0001-2023
Jing Han, Nesreen H. Aljahdali, Shaohua Zhao, Hailin Tang, H. Harbottle, Maria Hoffmann, Jonathan G. Frye, S. Foley
ABSTRACT Salmonella enterica is the leading cause of bacterial foodborne illness in the USA, with an estimated 95% of salmonellosis cases due to the consumption of contaminated food products. Salmonella can cause several different disease syndromes, with the most common being gastroenteritis, followed by bacteremia and typhoid fever. Among the over 2,600 currently identified serotypes/serovars, some are mostly host-restricted and host-adapted, while the majority of serotypes can infect a broader range of host species and are associated with causing both livestock and human disease. Salmonella serotypes and strains within serovars can vary considerably in the severity of disease that may result from infection, with some serovars that are more highly associated with invasive disease in humans, while others predominantly cause mild gastroenteritis. These observed clinical differences may be caused by the genetic make-up and diversity of the serovars. Salmonella virulence systems are very complex containing several virulence-associated genes with different functions that contribute to its pathogenicity. The different clinical syndromes are associated with unique groups of virulence genes, and strains often differ in the array of virulence traits they display. On the chromosome, virulence genes are often clustered in regions known as Salmonella pathogenicity islands (SPIs), which are scattered throughout different Salmonella genomes and encode factors essential for adhesion, invasion, survival, and replication within the host. Plasmids can also carry various genes that contribute to Salmonella pathogenicity. For example, strains from several serovars associated with significant human disease, including Choleraesuis, Dublin, Enteritidis, Newport, and Typhimurium, can carry virulence plasmids with genes contributing to attachment, immune system evasion, and other roles. The goal of this comprehensive review is to provide key information on the Salmonella virulence, including the contributions of genes encoded in SPIs and plasmids during Salmonella pathogenesis.
{"title":"Infection biology of Salmonella enterica","authors":"Jing Han, Nesreen H. Aljahdali, Shaohua Zhao, Hailin Tang, H. Harbottle, Maria Hoffmann, Jonathan G. Frye, S. Foley","doi":"10.1128/ecosalplus.esp-0001-2023","DOIUrl":"https://doi.org/10.1128/ecosalplus.esp-0001-2023","url":null,"abstract":"ABSTRACT Salmonella enterica is the leading cause of bacterial foodborne illness in the USA, with an estimated 95% of salmonellosis cases due to the consumption of contaminated food products. Salmonella can cause several different disease syndromes, with the most common being gastroenteritis, followed by bacteremia and typhoid fever. Among the over 2,600 currently identified serotypes/serovars, some are mostly host-restricted and host-adapted, while the majority of serotypes can infect a broader range of host species and are associated with causing both livestock and human disease. Salmonella serotypes and strains within serovars can vary considerably in the severity of disease that may result from infection, with some serovars that are more highly associated with invasive disease in humans, while others predominantly cause mild gastroenteritis. These observed clinical differences may be caused by the genetic make-up and diversity of the serovars. Salmonella virulence systems are very complex containing several virulence-associated genes with different functions that contribute to its pathogenicity. The different clinical syndromes are associated with unique groups of virulence genes, and strains often differ in the array of virulence traits they display. On the chromosome, virulence genes are often clustered in regions known as Salmonella pathogenicity islands (SPIs), which are scattered throughout different Salmonella genomes and encode factors essential for adhesion, invasion, survival, and replication within the host. Plasmids can also carry various genes that contribute to Salmonella pathogenicity. For example, strains from several serovars associated with significant human disease, including Choleraesuis, Dublin, Enteritidis, Newport, and Typhimurium, can carry virulence plasmids with genes contributing to attachment, immune system evasion, and other roles. The goal of this comprehensive review is to provide key information on the Salmonella virulence, including the contributions of genes encoded in SPIs and plasmids during Salmonella pathogenesis.","PeriodicalId":11500,"journal":{"name":"EcoSal Plus","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139387303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-22DOI: 10.1128/ecosalplus.esp-0014-2023
D. Lewis, S. Adhya
ABSTRACT Bacteriophage λ is a paradigm in the field of gene regulation and one of the best-understood systems in genetic regulatory biology. A so-called Genetic Switch determines the mechanisms by which λ transitions to its dual lifestyles—lytic or lysogenic. When λ initiates the lysogenic lifestyle, the phage-encoded CI repressor binds cooperatively to multi-partite operators in a defined pattern that autoregulates repression of phage lytic promoters as well as activation of the lysogenic promoter. The study of this genetic switch and related earlier research on phage λ revealed the main principles of gene expression and regulation in molecular biology. This article describes the underlying molecular details of λ lysogeny, as it is currently understood.
摘要 噬菌体 λ 是基因调控领域的典范,也是基因调控生物学中最易理解的系统之一。所谓的 "基因开关"(Genetic Switch)决定了λ向其双重生活方式(溶解性或溶酶性)过渡的机制。当 λ 开始溶解生活方式时,噬菌体编码的 CI 抑制剂会以一种确定的模式与多部分操作者合作结合,从而自动调节对噬菌体溶解启动子的抑制以及对溶解启动子的激活。对这种基因开关的研究以及早期对噬菌体λ的相关研究揭示了分子生物学中基因表达和调控的主要原理。本文介绍了目前所了解的λ溶菌酶发生的基本分子细节。
{"title":"Research on phage λ: a lucky choice","authors":"D. Lewis, S. Adhya","doi":"10.1128/ecosalplus.esp-0014-2023","DOIUrl":"https://doi.org/10.1128/ecosalplus.esp-0014-2023","url":null,"abstract":"ABSTRACT Bacteriophage λ is a paradigm in the field of gene regulation and one of the best-understood systems in genetic regulatory biology. A so-called Genetic Switch determines the mechanisms by which λ transitions to its dual lifestyles—lytic or lysogenic. When λ initiates the lysogenic lifestyle, the phage-encoded CI repressor binds cooperatively to multi-partite operators in a defined pattern that autoregulates repression of phage lytic promoters as well as activation of the lysogenic promoter. The study of this genetic switch and related earlier research on phage λ revealed the main principles of gene expression and regulation in molecular biology. This article describes the underlying molecular details of λ lysogeny, as it is currently understood.","PeriodicalId":11500,"journal":{"name":"EcoSal Plus","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138946709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-12Epub Date: 2023-05-09DOI: 10.1128/ecosalplus.esp-0038-2020
François Cornet, Corentin Blanchais, Romane Dusfour-Castan, Alix Meunier, Valentin Quebre, Hicham Sekkouri Alaoui, François Boudsoq, Manuel Campos, Estelle Crozat, Catherine Guynet, Franck Pasta, Philippe Rousseau, Bao Ton Hoang, Jean-Yves Bouet
DNA segregation ensures that cell offspring receive at least one copy of each DNA molecule, or replicon, after their replication. This important cellular process includes different phases leading to the physical separation of the replicons and their movement toward the future daughter cells. Here, we review these phases and processes in enterobacteria with emphasis on the molecular mechanisms at play and their controls.
{"title":"DNA Segregation in Enterobacteria.","authors":"François Cornet, Corentin Blanchais, Romane Dusfour-Castan, Alix Meunier, Valentin Quebre, Hicham Sekkouri Alaoui, François Boudsoq, Manuel Campos, Estelle Crozat, Catherine Guynet, Franck Pasta, Philippe Rousseau, Bao Ton Hoang, Jean-Yves Bouet","doi":"10.1128/ecosalplus.esp-0038-2020","DOIUrl":"10.1128/ecosalplus.esp-0038-2020","url":null,"abstract":"<p><p>DNA segregation ensures that cell offspring receive at least one copy of each DNA molecule, or replicon, after their replication. This important cellular process includes different phases leading to the physical separation of the replicons and their movement toward the future daughter cells. Here, we review these phases and processes in enterobacteria with emphasis on the molecular mechanisms at play and their controls.</p>","PeriodicalId":11500,"journal":{"name":"EcoSal Plus","volume":"1 1","pages":"eesp00382020"},"PeriodicalIF":0.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10729935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42472568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}