The biosynthesis and role of phosphorylcholine in pathogenic and nonpathogenic bacteria

Phosphorylcholine (ChoP) can be found in all life forms. Although this molecule was first thought to be uncommon in bacteria, it is now appreciated that many bacteria express ChoP on their surface. ChoP is usually attached to a glycan structure, but in some cases, it is added as a post-translational modification to proteins. Recent findings have demonstrated the role of ChoP modification and phase variation (ON/OFF switching) in bacterial pathogenesis. However, the mechanisms of ChoP synthesis are still unclear in some bacteria. Here, we review the literature and examine the recent developments in ChoP-modified proteins and glycolipids and of ChoP biosynthetic pathways. We discuss how the well-studied Lic1 pathway exclusively mediates ChoP attachment to glycans but not to proteins. Finally, we provide a review of the role of ChoP in bacterial pathobiology and the role of ChoP in modulating the immune response.     

Indole-3-acetic acid in microbial and microorganism-plant signaling

Diverse bacterial species possess the ability to produce the auxin phytohormone indole-3-acetic acid (IAA). Different biosynthesis pathways have been identified and redundancy for IAA biosynthesis is widespread among plant-associated bacteria. Interactions between IAA-producing bacteria and plants lead to diverse outcomes on the plant side, varying from pathogenesis to phyto-stimulation. Reviewing the role of bacterial IAA in different microorganism-plant interactions highlights the fact that bacteria use this phytohormone to interact with plants as part of their colonization strategy, including phyto-stimulation and circumvention of basal plant defense mechanisms. Moreover, several recent reports indicate that IAA can also be a signaling molecule in bacteria and therefore can have a direct effect on bacterial physiology. This review discusses past and recent data, and emerging views on IAA, a well-known phytohormone, as a microbial metabolic and signaling molecule.     

生物被膜在病原细菌与植物识别中的作用

生物被膜是微生物附着在生物或非生物表面所形成的一种三维结构,细胞被其自身所产生的胞外聚合物所包围,生物被膜的形成被认为是微生物应对生物和非生物胁迫时所产生的一种自我防御机制。众多微生物能够在植物叶、维管束和根等组织中生长,并在植物不同组织表面附着形成生物被膜,病原细菌的生物被膜随植物内部环境动态变化是其有效发挥致病作用的关键,研究植物病原细菌生物被膜调控机制是认识植物-病原菌互作的重要方面。文中将系统地介绍植物病原细菌生物被膜特征、组成成分、分子调控机制及最新研究进展。     

Biological conversion of cyclic alkanes and cyclic alcohols into dicarboxylic acids: biochemical and molecular basis

Biological oxidation of cyclic alkanes and cyclic alcohols normally results in formation of the corresponding dicarboxylic acids, which are further metabolized in the cell. The biochemical pathways for oxidative conversion of cyclic compounds are similar in various phylogenetically diverse bacteria. Significant progress has been made in the past 2 years in the isolation and characterization of genes involved in cyclic alkane oxidation pathways in several bacterial species. In this article, we review recent advancements in the field of cyclic alcohol oxidation with focus on the biochemical and genetic characterization of the gene functions. Phylogenetic relationships of the analogous enzymes in the pathways are analyzed. Potential biocatalysis applications of these enzymes are also discussed.     

A Tangled Web: Regulatory Connections between Quorum Sensing and Cyclic Di-GMP

Bacteria sense and respond to environmental cues to control important developmental processes. Two widely conserved and important strategies that bacteria employ to sense changes in population density and local environmental conditions are quorum sensing (QS) and cyclic di-GMP (c-di-GMP) signaling, respectively. The importance of these pathways in controlling a broad variety of functions, including virulence, biofilm formation, and motility, has been recognized in many species. Recent research has shown that these pathways are intricately intertwined. Here we review the regulatory connections between QS and c-di-GMP signaling. We propose that the integration of QS with c-di-GMP allows bacteria to assimilate information about the local bacterial population density with other physicochemical environmental signals within the broader c-di-GMP signaling network.     

c-di-AMP调控细菌生物被膜的形成

细菌生物被膜是细菌持续性致病的重要机制。研究细菌生物被膜的形成和发展可为顽固性细菌感染防治提供新的思路与策略。环二腺苷酸c-di-AMP(Cyclic diadenosine monophosphate)是继c-di-GMP之后在细菌中新发现的一种核苷酸第二信使分子。研究发现,c-di-AMP参与调节细菌多种生理功能,包括细菌生长代谢、生物被膜形成、细胞壁的合成以及细菌毒力因子等。本文综述了c-di-AMP参与调控细菌生物被膜形成的不同方式及其分子机制。鉴于c-di-AMP在调控细菌生物被膜中的重要性,其可作为抗细菌生物被膜感染新药研发的潜在靶点。     

Curli biogenesis: Order out of disorder

Many bacteria assemble extracellular amyloid fibers on their cell surface. Secretion of proteins across membranes and the assembly of complex macromolecular structures must be highly coordinated to avoid the accumulation of potentially toxic intracellular protein aggregates. Extracellular amyloid fiber assembly poses an even greater threat to cellular health due to the highly aggregative nature of amyloids and the inherent toxicity of amyloid assembly intermediates. Therefore, temporal and spatial control of amyloid protein secretion is paramount. The biogenesis and assembly of the extracellular bacterial amyloid curli is an ideal system for studying how bacteria cope with the many challenges of controlled and ordered amyloid assembly. Here, we review the recent progress in the curli field that has made curli biogenesis one of the best-understood functional amyloid assembly pathways. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey.     

Recent progress in chemical synthesis of bacterial surface glycans

With the continuing advancement of carbohydrate chemical synthesis, bacterial glycomes have become increasingly attractive and accessible synthetic targets. Although bacteria also produce carbohydrate-containing secondary metabolites, our review here will cover recent chemical synthetic efforts on bacterial surface glycans. The obtained compounds are excellent candidates for the development of improved structurally defined glycoconjugate vaccines to combat bacterial infections. They are also important probes for investigating glycan–protein interactions. Glycosylation strategies applied for the formation of some challenging glycosidic bonds of various uncommon sugars in a number of recently synthesized bacterial surface glycans are highlighted.     

New insights on molecular regulation of biofilm formation in plant-associated bacteria

Biofilms are complex bacterial assemblages with a defined three-dimensional architecture, attached to solid surfaces, and surrounded by a self-produced matrix generally composed of exopolysaccharides, proteins, lipids and extracellular DNA. Biofilm formation has evolved as an adaptive strategy of bacteria to cope with harsh environmental conditions as well as to establish antagonistic or beneficial interactions with their host. Plant-associated bacteria attach and form biofilms on different tissues including leaves, stems,vasculature, seeds and roots. In this review, we examine the formation of biofilms from the plant-associated bacterial perspective and detail the recently-described mechanisms of genetic regulation used by these organisms to orchestrate biofilm formation on plant surfaces. In addition, we describe plant host signals that bacterial pathogens recognize to activate the transition from a planktonic lifestyle to multicellular behavior.     

Patents on quorum quenching: interfering with bacterial communication as a strategy to fight infections

Numerous bacterial functions, such as virulence and biofilm formation, are controlled by a cell densitydependent communication mechanism known as Quorum Sensing (QS), in which small diffusible molecules are released, allowing bacteria to coordinate their behavior once a minimal effective quorum has been reached. The interference with these signaling systems, also known as Quorum Quenching (QQ), represents a promising strategy to tackle bacterial infections. The growing interest in this approach is reflected by the increasing number of patents within the field (45 up to now), especially in the last few years, as shown by patent applications published since 2009. The fact that biofilm formation is also controlled by QS systems expands the application of QQ to clinically-relevant biofilms such as those responsible for periodontal disease. Moreover, since biofilms increase bacterial resistance to antimicrobials, QQ could represent a new way to fight some of the most recurrent human pathogens, such as nosocomial multiresistant strains, and this deserves further exploration, especially through more proofs of concept. In this article we review the best known QS and QQ systems to date and we describe recent patents on the interference with this type of bacterial communication.     

Induction of type I interferons by bacteria

Type I interferons (IFNs) are secreted cytokines that orchestrate diverse immune responses to infection. Although typically considered to be most important in the response to viruses, type I IFNs are also induced by most, if not all, bacterial pathogens. Although diverse mechanisms have been described, bacterial induction of type I IFNs occurs upon stimulation of two main pathways: (i) Toll‐like receptor (TLR) recognition of bacterial molecules such as lipopolysaccharide (LPS); (ii) TLR‐independent recognition of molecules delivered to the host cell cytosol. Cytosolic responses can be activated by two general mechanisms. First, viable bacteria can secrete stimulatory ligands into the cytosol via specialized bacterial secretion systems. Second, ligands can be released from bacteria that lyse or are degraded. The bacterial ligands that induce the cytosolic pathways remain uncertain in many cases, but appear to include various nucleic acids. In this review, we discuss recent advances in our understanding of how bacteria induce type I interferons and the roles type I IFNs play in host immunity.     

Enteropathogenic Escherichia coli (EPEC) attachment to epithelial cells: exploiting the host cell cytoskeleton from the outside

Enteropathogenic Escherichia coli (EPEC), a leading cause of human infantile diarrhoea, is the prototype for a family of intestinal bacterial pathogens that induce attaching and effacing (A/E) lesions on host cells. A/E lesions are characterized by localized effacement of the brush border of enterocytes, intimate bacterial attachment and pedestal formation beneath the adherent bacteria. As a result of some recent breakthrough discoveries, EPEC has now emerged as a fascinating paradigm for the study of host–pathogen interactions and cytoskeletal rearrangements that occur at the host cell membrane. EPEC uses a type III secretion machinery to attach to epithelial cells, translocating its own receptor for intimate attachment, Tir, into the host cell, which then binds to intimin on the bacterial surface. Studies of EPEC-induced cytoskeletal rearrangements have begun to provide clues as to the mechanisms used by this pathogen to subvert the host cell cytoskeleton and signalling pathways. These findings have unravelled new ways by which pathogenic bacteria exploit host processes from the cell surface and have shed new light on how EPEC might cause diarrhoea.     

细菌三型分泌系统效应蛋白转运的研究进展

三型分泌系统(Type 3 secretion system,T3SS)作为存在于革兰氏阴性菌中的分泌系统之一,对革兰氏阴性菌的致病有重要作用。T3SS的致病作用体现在T3SS能直接将效应蛋白转运至宿主细胞,进而通过效应蛋白调控细胞的一系列通路,促进细菌定殖于细胞。而效应蛋白的转运受到两方面因素的调控,一方面是效应蛋白本身的信号序列,另一方面是T3SS相关蛋白的辅助。本文围绕近年来T3SS的构成、效应蛋白转运机制方面的最新进展进行概要综述。     

Candida albicans: Molecular interactions with Pseudomonas aeruginosa and Staphylococcus aureus

The fields of mycology and bacteriology have traditionally functioned independently of each other despite the fundamental actuality that fungi and bacteria not only co-exist but also interact within several niches. In the clinical context, these interactions commonly occur within biofilms, which can be composed of single-species communities or mixed-species populations and recent studies have shown that the properties of mixed-species populations differ from those of their individual components. The interacting bacteria and fungi can exert effects on microbial behavior, dissemination, survival, the response to antimicrobials and, ultimately, patient prognosis. Microbes within biofilms exhibit increased resistance to antimicrobial agents, and a significant amount of research has thus focused on gaining an understanding of how inter-domain interactions affect biofilm formation and the response to antimicrobial therapies. Candida albicans, a commensal and opportunistic pathogen of humans, is among the fungi most frequently identified in mixed-species biofilms. Here, we review interactions between C. albicans and bacterial species with which it is commonly isolated, namely Pseudomonas aeruginosa and Staphylococcus aureus in order to look into the spectrum of biologically relevant fungal–bacterial interactions that have been described.     

细菌持留与抗生素表型耐药机制

持留菌是细菌群体中一小部分具有表型耐药的细菌。自1944年被发现后,近几十年来因其在慢性持续性感染和生物膜感染中的重要作用而得到越来越多的重视。已有的研究结果表明,细菌持留的机理复杂,涉及的相关信号通路有毒素-抗毒素系统、细胞能量代谢及蛋白核酸合成等生理状态的降低、DNA保护修复系统、蛋白酶系统、反式翻译、外排泵系统等。虽然不同细菌的持留机理有一定的相似性和保守性,但不同细菌的持留机制也存在差异,如毒素-抗毒素系统在大肠埃希菌(Escherichia coli)中的过度激活可导致持留菌增加,但在金黄色葡萄球菌(Staphylococcus aureus)中却并无相同作用。本文从持留菌的研究历史出发,综述了当前对革兰氏阴性菌和阳性菌的持留机制方面的研究进展,同时探讨了在持留菌相关感染疾病方面的治疗策略,以期为更好地解决持留菌带来的问题,缩短治疗时间提供新的思路。     

Breaking the bond: recent patents on bacterial adhesins

Adhesins need to be exposed on the surface of pathogenic bacteria to properly interact with host tissues and allow establishment of the infection. This fact implies that, in theory, one could manage or avoid infection by controlling adhesins' function, and also by indirectly detecting bacteria through their surface-exposed adhesins. Besides, binding of anti-adhesin immunoglobulins on the bacterial surface tend to promote the opsonization of the pathogen. Therefore, bacterial adhesins represent a great target to develop new biopharmaceuticals, which may become commercially and medically important products. In this review, we will summarize the biological importance of bacterial adhesins, and also discuss some recent patents related to these molecules, as well as their use and possible new future developments in this area.     

Autophagosome formation in response to intracellular bacterial invasion

Autophagy is an intracellular bulk degradation system in which double‐membrane vesicles, called autophagosomes, engulf cytoplasmic components and later fuse with lysosomes to degrade the autophagosome content. Although autophagy was initially thought a non‐selective process, recent studies have clarified that it can selectively target intracellular bacteria and function as an intracellular innate immune system that suppresses bacterial survival. A key mechanism for the recognition of cytosol‐invading bacteria is ubiquitination, and the recognition of the ubiquitinated target by the autophagy machinery can be accomplished multiple ways. In this review, we discuss recent findings regarding the induction of autophagosome formation in response to intracellular bacterial invasion.     

细菌显微追踪技术在生物被膜中的应用

细菌生物被膜是粘附于物体表面的由细菌细胞及其胞外物质组成的复杂膜样物聚集体,具有很强的耐药性和免疫逃逸能力。生物被膜内细菌的代谢活性、运动状态等与浮游细菌有明显区别。近年来,先进的显微成像技术结合新型图像处理方法,在研究细菌的运动、生理等方面发挥了重要作用。本文围绕生物被膜,概述了细菌显微追踪技术在其研究中的应用。主要从细菌的运动方式和生物被膜形成过程的调控两方面出发,介绍了在单细胞水平上利用该技术研究生物被膜的进展,包括细菌的游泳、蹭行、群集运动和多种信号通路调控下生物被膜的形成过程等,并展望了该技术在生物被膜其他相关研究领域的应用前景。     

细菌群体感应及其信号分子介导的植物-细菌跨界信息交流

细菌利用群体感应(Quorum sensing,QS)系统进行细胞间的通讯联系,进而参与调控细菌多种生物学功能。近年的研究表明,细菌QS信号分子也可以被细菌的真核植物宿主感应,从而介导植物-细菌的跨界信息交流。本文综述细菌QS及其介导的植物-细菌信息交流的最新研究进展,以期为通过操纵细菌QS达到提高植物病害防治效果提供理论基础和指导。     

Cell wall structure and function in lactic acid bacteria

The cell wall of Gram-positive bacteria is a complex assemblage of glycopolymers and proteins. It consists of a thick peptidoglycan sacculus that surrounds the cytoplasmic membrane and that is decorated with teichoic acids, polysaccharides, and proteins. It plays a major role in bacterial physiology since it maintains cell shape and integrity during growth and division; in addition, it acts as the interface between the bacterium and its environment. Lactic acid bacteria (LAB) are traditionally and widely used to ferment food, and they are also the subject of more and more research because of their potential health-related benefits. It is now recognized that understanding the composition, structure, and properties of LAB cell walls is a crucial part of developing technological and health applications using these bacteria. In this review, we examine the different components of the Gram-positive cell wall: peptidoglycan, teichoic acids, polysaccharides, and proteins. We present recent findings regarding the structure and function of these complex compounds, results that have emerged thanks to the tandem development of structural analysis and whole genome sequencing. Although general structures and biosynthesis pathways are conserved among Gram-positive bacteria, studies have revealed that LAB cell walls demonstrate unique properties; these studies have yielded some notable, fundamental, and novel findings. Given the potential of this research to contribute to future applied strategies, in our discussion of the role played by cell wall components in LAB physiology, we pay special attention to the mechanisms controlling bacterial autolysis, bacterial sensitivity to bacteriophages and the mechanisms underlying interactions between probiotic bacteria and their hosts.