Pathogenic Streptococci: From Genomics to Systems Biology and Control
Caister Academic Press
Yuqing Li and Xuedong Zhou
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
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Streptococcus is a diverse genus of Gram-positive bacteria commonly found in multiple locations of their human and animal hosts e.g. the oral cavity and the upper respiratory tract. Many streptococci are commensals thus play a role in colonization resistance of the host. Others, however, are pathogenic and are responsible for a range of invasive and noninvasive diseases with high morbidity and mortality worldwide. Streptococci undergo frequent and extensive horizontal gene transfer leading to the emergence of drug resistant strains. This, combined with the current lack of effective anti-streptococcal vaccines, has led to a huge amount of research into the genomics to systems biology of these important bacteria.
This timely review, edited by Yuqing Li and Xuedong Zhou, provides a comprehensive overview of the current knowledge of the most important hot-topics in streptococcal research. Topics covered include: CRISPR-Cas systems; genetic regulation by small RNAs; signal transduction by cyclic dinucleotide second messengers; the VicRK and ComDE two-component systems; mobile genetic elements; regulation of cell division; application of omics and bioinformatics tools; intrageneric and intergeneric interactions by oral streptococci; the hypervirulent M1T1 clone of GAS; Streptococcus suis; adhesion and invasion mechanisms; molecular evolution of pathogenic streptococci; novel antimicrobials; vaccine development.
This volume is essential reading for everyone working with streptococci from the PhD student to the experienced scientist, in academia, the pharmaceutical or biotechnology industries and for those working in clinical environments.
Table of contents
1. CRISPR-Cas Systems in Streptococci
Tao Gong, Miao Lu, Xuedong Zhou, Anqi Zhang, Boyu Tang, Jiamin Chen, Meiling Jing and Yuqing Li
Streptococci are one of the most important and common constituents of the host's microbiota and can colonize and live in the upper respiratory and urogenital tract of humans and animals. The CRISPR-Cas systems (i.e., clustered regularly interspaced short palindromic repeat, with CRISPR-associated proteins) found in bacteria and archaea provide sequence-based adaptive immunity against mobile genetic elements, especially in the streptococci. Here, recent research progress on CRISPR-Cas systems in the streptococci is reviewed, including their classification (mainly type I, type II, and type III), physiological function, defense mechanism (CRISPR adaptation, crRNA biogenesis, and target interference) and applications, which are useful for a better understanding of the functions of such systems. Finally, the advances that have been made in streptococci may help in the discovery of further novel CRISPR-Cas systems for use in new technologies and applications in other species.
2. Genetic Regulation of Streptococci by Small RNAs
Ye Tu, Xiaoyue Jia, Ran Yang, Xian Peng, Xuedong Zhou and Xin Xu
Streptococcal species constitute a large group of commensal and pathogenic Gram-positive bacteria that exist in a wide variety of habitats. The family of small RNAs is typically ranged in size from 50 to 300 nucleotides, and acts as regulators in bacteria. The last decade has witnessed the increasing findings of small RNAs (sRNAs), which play important regulatory roles in the variety of biological processes in streptococci. In this review, we summarized the recent achievements in the identification of streptococcal sRNAs, mainly in Streptococcus pyogenes and Streptococcus pneumoniae. In addition, we particularly focused on the functions that sRNAs exert in the regulatory networks of both phenotypical traits and pathogenicity. The fact that sRNAs act as a critical fine-tuning regulator of streptococci may not only reveal in-depth mechanisms of bacterial post-transcriptional regulations in response to environmental perturbance, but also provide promising approaches to the better management of streptococcal infections.
3. Signal Transduction of Streptococci by Cyclic Dinucleotide Second Messengers
Zhengyi Li, Xueqin Zhang, Lei Cheng, Xin Xu, Xuedong Zhou, Hui Wu and Xian Peng
Since the discovery of cyclic dimeric guanosine 3',5'-monophosphate (c-di-GMP) in 1987, the role of cyclic dinucleotides in signal pathways has been extensively studied. Many receptors and effectors of cyclic dinucleotides have been identified which play important roles in cellular processes. Example of such effectors include cyclic dimeric adenosine 3',5'-monophosphate (c-di-AMP)-binding proteins and endoplasmic reticulum membrane adaptor. Accumulating evidence indicate that cyclic dinucleotides act as second messengers that not only regulate the bacterial physiological processes but also affect host immune responses during infections. Streptococci species, which produce cyclic dinucleotides, are responsible for many human diseases. Numerous studies suggest that the cyclic dinucleotides are vital in signal transduction pathways as second messengers and influence the progression of infectious diseases. Here, we provide an overview of the molecular principles of cyclic dinucleotides synthesis and degradation and discuss recent progress on streptococcal signal transduction pathways by cyclic dinucleotide second messengers and their role in regulating host immune reaction. This review will provide a better understanding of the molecular mechanisms of streptococcal cyclic dinucleotide second messengers thereby revealing novel targets for preventing infections.
4. Mobile Genetic Elements in Streptococci
Miao Lu, Tao Gong, Anqi Zhang, Boyu Tang, Jiamin Chen, Zhong Zhang, Yuqing Li and Xuedong Zhou
Streptococci are a group of Gram-positive bacteria belonging to the family Streptococcaceae, which are responsible of multiple diseases. Some of these species can cause invasive infection that may result in life-threatening illness. Moreover, antibiotic-resistant bacteria are considerably increasing, thus imposing a global consideration. One of the main causes of this resistance is the horizontal gene transfer (HGT), associated to gene transfer agents including transposons, integrons, plasmids and bacteriophages. These agents, which are called mobile genetic elements (MGEs), encode proteins able to mediate DNA movements. This review briefly describes MGEs in streptococci, focusing on their structure and properties related to HGT and antibiotic resistance.
5. The VicRK Two-Component System Regulates Streptococcus mutans Virulence
Lei Lei, Li Long, Xin Yang, Yang Qiu, Yanglin Zeng, Tao Hu, Shida Wang and Yuqing Li
Streptococcus mutans is considered the predominant etiological agent of dental caries with the ability to form biofilm on the tooth surface. And, its abilities to obtain nutrients and metabolize fermentable dietary carbohydrates to produce acids contribute to its pathogenicity. The responses of S. mutans to environmental stresses are essential for its survival and role in cariogenesis. The VicRK system is one of the 13 putative TCS of S. mutans. The conserved functions of the VicRK signal transduction system is the key regulator of bacterial oxidative stress responses, acidification, cell wall metabolism, and biofilm formation. In this paper, it was discussed how the VicRK system regulates S. mutans virulence including bacterial physiological function, operon structure, signal transduction, and even post-transcriptional control in its regulon. Thus, this emerging subspecialty of the VicRK regulatory networks in S. mutans may strengthen our understandings aimed at providing a basis for the prevention of dental caries.
6. ComDE Two-component Signal Transduction Systems in Oral Streptococci: Structure and Function
Yue Zu, Wei Li, Qi Wang, Jiahao Chen and Qiang Guo
Oral streptococci depend on two-component signal transduction systems (TCSs), the most widespread regulatory systems in bacteria, to detect and respond to diverse stresses in oral environment. Among the larger panel of TCSs equipped by oral streptococci, ComDE TCS is thought to be one of the most classical TCSs. So far, it has been proved that ComDE TCS could play critical roles in environmental stress responses to acid, antibiotic, oxidative pressures and so on, and modulating multiple virulence traits like biofilm formation, bacteriocin production, competence, autolysis. Here, the well characterized Streptococcus mutans and Streptococcus pneumoniae are chosen as the representative species to introduce the composition, signaling pathways and regulated phenotypes of ComDE TCS in oral streptococci. The potential ComDE TCS-targeted antimicrobial applications are also discussed at last.
7. Regulation of Cell Division in Streptococci: Comparing with the Model Rods
Zhenting Xiang, Zongbo Li, Jumei Zeng, Yuqing Li and Jiyao Li
Streptococcus is a genus of oval-shaped bacteria that act as both commensals and pathogens. Streptococcal infections are relevant to high morbidity and huge socioeconomic costs, with drug resistant strains becoming an increasing threat. Cell division plays an essential role during streptococcal colonization and infection, rendering it an ideal target for antibiotics. Substantial progress has been made to uncover the molecular biology and cellular processes of cell division, favoring the target strategies. This review discusses recent advances in our understanding of streptococcal cell division and its regulatory mechanisms regarding the conserved proteins, by comparing with model rods. Peptidoglycan synthesis that involved in septum formation and the maintenance of the unique oval shape have been spatiotemporally controlled in concert with the pace of division. With newly available tools of genetic and cytological study, streptococci will become an additional model bacterial system for cytokinesis and novel therapeutic agents that target cell division.
8. Application of Omics and Bioinformatics Tools in Streptococcus Research
Min Liao, Ting Tong, Yawen Zong, Xuedong Zhou, Lei Cheng, Ruijie Huang, Biao Ren and Gil Alterovitz
Researchers used to focus on analyzing single gene or protein expression of the microbes. But recently, genome, transcriptome, proteome and metabolome have gained more and more attention. Based on technologies of omics, including genomics, transcriptomics and metabolomics, a large quantity of information about cells, microbes and human, such as the information about phylogeny, virulence, antibiotic resistance and other aspects, has been revealed. Genus Streptococcus is one of the most invasive groups of bacteria that cause both human and animal diseases, threatening public health. In this review, we summarize the application of omics to analyze this genus-Streptococcus.
9. Intrageneric and Intergeneric Interactions Developed by Oral Streptococci: Pivotal Role in the Pathogenesis of Oral Diseases
Yandi Chen, Yuqing Li and Jing Zou
Oral streptococci are among the most abundant genera present in the oral cavity. They are usually the first colonizers of oral surfaces and they develop extensive microbial interactions, playing a fundamental role in the pathogenesis of oral diseases such as dental caries and periodontitis. In addition to physical adherence, streptococcal cells also exchange messages with cells from another Streptococcus spp. and other microorganisms in the form of metabolites and signaling molecules. In this review, we focused on these intrageneric and intergeneric interactions, and their association with oral diseases.
10. The Emergence of Hypervirulent M1T1 Clone of Group A Streptococcus via Genetic Recombination and Host Selection
Streptococcus pyogenes (Group A Streptococcus, GAS) is a strictly human bacterial pathogen. Since the mid-1980s, GAS M1T1 clone has been the most prevalent and globally disseminated serotype and is the culprit causing invasive and severe streptococcal infections, urging a better understanding of the emergence of hypervirulent M1T1 clone from an evolutionary perspective. This review highlights the molecular and evolutionary events leading to pandemic M1T1 strains, and discusses the pressure driving the genetic acquisition of novel virulence genes and the selection of hypervirulent isolates in host. By understanding the evolutionary selection and pressures that select and shape the pandemic M1T1 clone, we could potentially develop new therapeutic strategies to tackle challenges when dealing with the globally disseminated M1T1 GAS clone.
11. Recent Proceedings on Prevalence and Pathogenesis of Streptococcus suis
Chen Tan, Anding Zhang, Huanchun Chen and Rui Zhou
Streptococcus suis (S. suis) is an important zoonotic pathogen that causes huge economic losses in the pig industry, as well as severe illness and even death in humans. The outbreak of human infection of S. suis in China in 2005 led to significant human morbidity and death, prompting an increase in global studies of S. suis. In recent years, important advances have been made regarding the etiology, genomics, excavation of virulence genes, and vaccine research in S. suis. A number of countries and regions have identified their predominantly serotypes. The development of genome sequencing technology has laid an important foundation for the study of pathogenic mechanisms. For example, 89K PAI was found in representative virulence strains in China, and several studies have been carried out to confirm multiple genes which carries are closely related to virulence. Also, the functions of some regulatory genes represented by the two-component signal transduction system have been analyzed. The development of inactivated vaccines, natural avirulent vaccines, gene-deletion attenuated vaccines, subunit vaccines, and glycoconjugate vaccines have greatly contributed to the prevention and control of the disease in the future. This article aims to summarize the research progress to provide directions for future research and the prevention of S. suis.
12. The Adhesion and Invasion Mechanisms of Streptococci
Qingsong Jiang, Xuedong Zhou, Lei Cheng and Mingyun Li
Streptococci are common human pathogens, colonizing multiple parts of the human body such as the upper respiratory tract, urethra, gastrointestinal tract, and oral cavity. Since they cause a variety of serious infections including heart diseases, meningitis, and oral diseases, streptococci are considered to play an important role in human diseases. Two critical steps in the pathogenesis of streptococcal infection are the adhesion to and invasion of host cells. This invasion is a strategy of streptococci to evade the host immune response and antibiotic therapy, as well as to penetrate to deeper tissues. To establish interaction between bacteria and host cells, adhesion is the initial step. To effectively adhere to host cells, streptococci express multiple adhesins, and the expression of different adhesins may lead to distinct mechanisms of subsequent invasion. The binding of streptococcal molecules to host proteins triggers downstream signal transduction in the host cells, leading to the uptake of bacteria. In this review, we present the adhesion and invasion mechanisms of different streptococci and the interaction with host cells leading to internalization.
13. Molecular Evolution of Clinical Pathogenic Streptococci
Dongdong Li and Chuanmin Tao
The genus Streptococcus comprises a wide variety of pathogenic and commensal gram-positive bacteria, many of which the pathogenic species cause severe, invasive infections that account for a high burden of morbidity and mortality. Here, we reviewed the evolution of representative virulence factors, capsule in Streptococcus pneumoniae, M protein in Streptococcus pyogenes (GAS), biofilm in Streptococcus agalactiae (GBS) and some oral Streptococcus, as well as the effect caused by evolution, antibiotic resistance and vaccine escape. Thanks to the rapid development of whole genome sequence (WGS) data, the impact of genetic recombination to the Streptococcus evolution has been proved. As to adaptive evolution caused by antibiotics, vaccine and so on, continuous surveillance is an essential to monitor evolution of Streptococcus causing disease. This knowledge is invaluable to the development of preventative and control strategies against this important pathogen.
14. Progress of Antimicrobial Discovery Against the Major Cariogenic Pathogen Streptococcus mutans
Tao Cui, Wenfu Luo, Letong Xu, Baoqiang Yang, Wen Zhao and Huaixing Cang
Dental caries, also known as tooth decay, or cavities, remains a global public health issue. Streptococcus mutans is considered the most significant contributor to dental caries. Its cariogenicity typically depends on its unique metabolic activity and lifestyle, including acid production, acid tolerance and biofilm formation. Currently used anti-caries therapies, such as fluoride and chlorhexidine, are characterized by side-effects and drug resistance. Therefore, the development of alternative inhibitors against S. mutans growth is urgently needed. In the last decade, a larger number of natural products and their derivatives from plants, marine organisms and microorganisms were studied to evaluate their antibacterial activity against S. mutans. In addition, drug-repositioning base screening and target based high-throughput screening were employed, resulting in inspiring progresses in recent years. In this review, we summarized the available evidences regarding the inhibition of S. mutans growth. We focus on the sources, structures and potential mechanism of action of these inhibitors. Beside small molecular compounds, we also considered antibacterial peptides and protein inhibitors developed in this field.
15. Recent Advances in Pathogenic Streptococcus Vaccine Development
Hongren Wang, Zhen Qin and Mingyuan Li
Streptococcus pneumoniae (Spn) and Streptococcus pyogenes (Spy) cause many invasive and noninvasive diseases responsible for high morbidity and mortality worldwide. Safe, efficacious and affordable vaccines could have a significant, positive impact on the global infectious disease burden. Since the implementation of pneumococcal vaccine in the 1980s, the incidence of Spn infection has decreased significantly. Still so, these currently used multivalent polysaccharides and conjugated pneumococcal vaccines have some limitations. For Spy, there are even no vaccines available yet. There is an urgent need of new vaccines against Spn and Spy. Encouragingly, with the hard work of many investigators worldwide, a number of new vaccines candidates are developed with promising results. Of them, many have already entered the clinical trial stage. This review will describe the current status of Spn and Spy vaccine development, with particular focus on protein-based strategy.
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(EAN: 9781912530229 9781912530236 Subjects: [bacteriology] [medical microbiology] [microbiology] [molecular microbiology] )