Staphylococcus: Molecular Genetics
Caister Academic Press
Department of Cellular and Molecular Medicine, St George's, University of London, UK
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The staphylococci are important pathogenic bacteria responsible for a variety of diseases in humans and other animals. They are the most common cause of hospital acquired infection and antibiotic resistant strains (MRSA) have become endemic in hospitals in most countries causing major public health issues. In addition, the incidence of new strains that cause severe community-acquired infections in healthy people is increasing and MRSA strains are emerging in agricultural and domestic animals. In the race to understand staphylococcal pathogenesis the focus has been on genetics, as a bacterium can only do what its genes allow. The publication of the first staphylococcal whole genome sequence in 2001 paved the way for a greater understanding of the molecular basis of its virulence, evolution, epidemiology and drug resistance. Since then the available genomic data has mushroomed and this, coupled with the major advances in genetic know-how and the availability of better genetic tools, has allowed significant advances to be made.
This volume, the first to focus on staphylococcal genetics, brings together the expertise and enthusiasm of an international panel of leading staphylococcal researchers to provide a state-of-the art overview of the field. Topics include the sequencing projects, including spin-off microarray and systems biology tools, epidemiology, evolution, manipulation of the genome, diagnostics, gene expression due to global regulators and environmental triggers, cell-wall synthesis, coagulase-negative species, and animal pathogens. It is designed for two major audiences. Firstly, to introduce the subject to new researchers, including those unfamiliar with genetics. Secondly, for established researchers, for whom it will serve as an invaluable reference and summary of a large field, as well as presenting the latest advances and future trends written by those who are developing them.
Essential reading for anyone involved in Staphylococcus research.
"... suitable for both starting and experienced staphylococcal researchers. It is both a referral handbook as explicated by some of the chapters and an adequate introductory text in others. The mixture between "hard-core science" and clinical application also is a balanced one ... the book by Lindsay et al deserves a prominent spot in the personal library of all staphylococcologists!!" from Journal of Microbiological Methods (2008)
"This is an incredibly useful book for anyone with an interest in staphylococci. It provides a broad and in-depth synopsis of up-to-date staphylococcal research. This book is very well suited to its target audiences, researchers who are relatively new to the field and also as a suitable reference for those with greater experience. The first five chapters are particularly informative, providing an excellent overview of the staphylococcal sequencing projects, population structure and evolution of S. aureus, as well as analysis of the methods used ... The chapter on 'Global regulators of Staphylococcus aureus virulence genes' is excellent ... this chapter provides a thorough review of the literature ... We hope that this book will be regularly reviewed and updated in line with this rapidly expanding field." from Microbiology Today (2008)
"Dr Lindsay, a clearly 'rising star' in the field of molecular investigations, has assembled a diverse but highly knowledgeable group of authors ... a cohort of experienced and authoritative experts who have adroitly covered their given topics concisely and contemporaneously ... all should be complimented on the accurate relevance of this book ... it should be essential reading for all laboratories practicing in this shifting and growing field." from Expert Review of Anti-infective Therapy (December 2008)
"... the contents of this book will appeal to the many researchers and clinicians interested in the molecular genetics of this interesting group of bacteria. ... This book is easy to read and well referenced and should appeal to those researchers and clinical staff working in this interesting field." from ACM News (2008) 2: 19
Table of contents
1. Whole Genomes: Sequence, Microarray and Systems Biology
Matthew T. G. Holden and Jodi A. Lindsay
Whole genome technologies facilitate the investigation of the genetic processes that underpin bacterial cells. Whole genome sequences for twelve diverse Staphylococcus aureus isolates are available and their annotation provides enormous insight into S. aureus physiology, capabilities and virulence. Whole genome microarrays, built using the sequences, have enabled whole genome regulatory responses to environmental conditions or global regulators to be investigated. Comparative genomics by sequencing and by multi-strain microarrays have identified the S. aureus population structure and how genomes vary, as well as suggesting that invasive isolates do not carry more virulence genes than carriage isolates. Whole genomes provide the framework for other systems biology approaches such as RNomics, proteomics and metabolomics. In a rapidly changing field, this chapter summarises the major achievements so far, and what is likely to be achieved in the near future.
2. The Population Structure of Staphylococcus aureus
Mark C. Enright
Staphylococcus aureus is a major human pathogen causing a wide spectrum of diseases from minor ailments to severe life-threatening conditions. Methicillin-resistant S. aureus (MRSA) are endemic in most hospitals in many industrialized countries and they are considered the most serious hospital-acquired pathogen as they can cause large outbreaks that are frequently difficult to treat using antibiotics. A large amount of genetic information is available on several examples of this species and this, together with multilocus sequence typing (MLST) data on >1400 isolates from many countries has provided unique insights into the biology of the species and in particular, its ability to exploit a wide variety of niches. These studies show that although the great majority of S. aureus genes share a high degree of homology, virulence and antibiotic resistance genes carried on mobile genetic elements can drastically alter strain characteristics in the short-term giving the species a high degree of adaptability. These allow it to survive in many different human and animal tissues and provide the adaptability necessary to evolve resistance to new antibiotics.
3. S. aureus Evolution: Lineages and Mobile Genetic Elements (MGE)
Jodi A. Lindsay
There is enormous variation between strains of S. aureus. Evolution occurs when genomes vary and the fittest bacteria are selected. Variation occurs in three major ways: single nucleotide polymorphisms (SNP) and other minor changes in conserved core genes; variation in hundreds of genes (particularly those encoding proteins that interact with host) that are associated with lineages of S. aureus; and acquisition and loss of mobile genetic elements (MGE) which often encode virulence and resistance genes. Barriers that block horizontal transfer of DNA, such as restriction modification, influence lineages and MGE. S. aureus MGE have their own complex life-cycles that control their spread and survival. Selection of the fittest bacteria is likely being driven by mammalian host factors and antibiotic use, and new strains of S. aureus are emerging that are increasingly virulent and resistant to antibiotics, causing novel healthcare issues.
4. Rapid Diagnosis and Typing of Staphylococcus aureus
Patrice Francois and Jacques Schrenzel
5. Genetic Manipulation of Staphylococcus aureus
Peter J. McNamara
Genetic manipulation of S. aureus has provided an avenue for the discovery of new approaches to treat S. aureus infections, methods that are based on a molecular understanding of virulence and pathogenesis. This chapter provides basic information on strains of S. aureus and the tools and techniques that have been successfully employed to engineer their genome. The topics that are covered include: choosing a strain for study; the cultivation and husbandry of S. aureus; vectors and their uses; methods to introduce DNA into S. aureus, and methods for the mutagenesis of S. aureus. With the information in this chapter, it is possible to design experiments to examine a broad range of biological phenomena that will contribute to understanding the biology of S. aureus and the factors that make this bacteria such a formidable pathogen.
6. Global Regulators of Staphylococcus aureus Virulence Genes
Staphylococci cause a great diversity of infections and have thus developed sophisticated mechanisms for eliciting infection in different environments. Staphylococcal infection requires the production of various virulence factors. The expression of these virulence factor genes is co-ordinated by global regulators. These regulators help bacteria to adapt to a hostile environment by producing factors enabling them to survive and subsequently to cause infection at the appropriate time. Several of these global virulence regulators, such as the Agr system, Sar and Sae, have been well characterised. Others, such as the Arl system, Sar homologues (Rot, MgrA, SarS, SarR, SarT, SarU, SarV, SarX, SarZ and TcaR), the Srr system and TRAP, require further study to determine their exact role in the virulence regulon. Several proteins and regulators with primary functions other than the regulation of virulence, such as Clp proteins, HtrA, MsrR, aconitase and CcpA, are also involved in regulating virulence, often through interactions with major virulence regulators. Other proteins, such as SvrA, Msa, CfvA and CfvB, regulate virulence, but their main function remains unknown.
7. The Response of S. aureus to Environmental Stimuli
Malcolm J. Horsburgh
The success of S. aureus as an opportunistic human pathogen is typically ascribed to its versatility via an inherent capacity to respond to changes in its environment. The range of stimuli to which it responds are not completely characterised, however significant advances have been made in our understanding of how this bacterium modulates gene expression in response to anaerobiosis, metal ion limitation, nitrosative and oxidative stress, temperature and pH change, starvation and antibiotic-directed cell wall stress.
8. Mechanisms of β-Lactam and Glycopeptide Resistance in Staphylococcus aureus
Mariana G. Pinho
Worldwide spread of multidrug resistant Staphylococcus aureus poses serious challenges to chemotherapy, which were recently emphasized by the appearance of vancomycin resistant S. aureus (VRSA) strains. Vancomycin has become the standard therapeutic agent against methicillin-resistant S. aureus (MRSA) strains, for which the choice of treatment is limited by the accumulation of a number of other antibiotic resistance markers acquired during recent evolution of the staphylococcal genome. This chapter summarizes specific resistance mechanisms against β-lactam and glycopeptide antibiotics, as well as the mechanisms for synergism between these two classes of antibiotics, focusing on the molecular aspects as well as on the whole-cell response to the presence of antibiotics that target cell wall synthesis.
9. Staphylococcus epidermidis and other Coagulase-Negative Staphylococci
Shu Yeong Queck and Michael Otto
Over the last two decades, coagulase-negative staphylococci with the most important species Staphylococcus epidermidis have been recognized as important opportunistic pathogens. These abundant commensal organisms of the human skin and mucous membranes may cause serious infections, predominantly as biofilm-associated infections on indwelling medical devices, and are now the most frequent cause of hospital-acquired infections. More recently, the elucidation of the genomes of S. epidermidis and other coagulase-negative staphylococci, and a more pronounced interest in the molecular biology of especially S. epidermidis and its interaction with human host defenses, have provided more detailed insight into how these bacteria cause human disease. We have learned that, although definitely more limited, the repertoire and also the regulation of virulence factors in S. epidermidis may differ significantly from S. aureus. Furthermore, as a result of the increasing volume and depth of research on this pathogen, some findings have been obtained in S. epidermidis that have paradigmatic character for many staphylococci and Gram-positive pathogens.
10. Staphylococci of Animals
J. Ross Fitzgerald and José R. Penades
Several staphylococcal species are notorious as human pathogens and are the focus of worldwide intensive research efforts. However, staphylococci are also associated with a large number of animal species and cause several infections of major economic importance. In addition, the zoonotic transmission of staphylococci to humans, especially those which are antibiotic-resistant, is a growing threat to public health. In this chapter, we will summarize selected aspects of the molecular pathogenesis of staphylococci which are pathogenic to animals and discuss how researchers are starting to investigate the host-adaptive evolution of staphylococci.
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(EAN: 9781904455295 9781913652166 Subjects: [bacteriology] [microbiology] [medical microbiology] [molecular microbiology] [genomics] )