Salmonella: Molecular Biology and Pathogenesis Chapter Abstracts
Chapter 1
Current Trends in the Spread and Occurrence of Human Salmonellosis: Molecular Typing and Emerging Antibiotic Resistance
Fiona J. Cooke, John Wain, E. John Threlfall
Abstract
At a global level, salmonella infections continue to have a large impact on human and animal health. The traditional division of human clinical syndromes into those due to the non-typhoidal salmonella serotypes and the serotypes causing enteric fever is becoming less absolute. Antibiotic resistance, due to both the spread of pre-existing resistant organisms and the appearance of new resistance mechanisms, such as the qnr genes, is an increasing concern. Resistance already results in treatment problems in both developed and developing countries, and the detection of integrons opens up the theoretical possibility of many resistance genes transferring to many salmonella serovars. New techniques for classifying and typing salmonella have been described, such as Multi Locus Sequence Typing, Variable Number of Tandem repeats and Microarray analysis, but we do not yet have a universally applicable and acceptable scheme. Usually a combination of phenotypic and genotypic approaches are most appropriate for typing, but do not reflect true classification. Effective epidemiological surveillance using classification-based typing schemes will allow us to understand the basic biology of the salmonella and thus develop rational, practical control strategies.
Chapter 2
The Intestinal Phase of Salmonella Infections
Manuela Raffatellu, Çagla Tükel, Daniela Chessa, R. Paul Wilson and Andreas J. Bäumler
Abstract
The two most common disease manifestations associated with human Salmonella infections are gastroenteritis and typhoid fever. Gastroenteritis is a diarrheal illness caused by zoonotic Salmonella serovars, with Salmonella enterica serovars Typhimurium and Enteritidis being isolated most frequently. The intestinal pathology during gastroenteritis is dominated by a neutrophil infiltrate that is triggered by toll-like receptor (TLR)-mediated innate immune recognition of bacterial penetration of the intestinal epithelial barrier. Typhoid fever is a severe systemic infection caused by human adapted Salmonella serovars, most importantly S. enterica serovar Typhi. Penetration of the intestinal epithelium by S. Typhi does not result in marked neutrophil infiltration but is characterized by an inflammatory infiltrate that is dominated by mononuclear cells. This review will summarize our current knowledge of virulence mechanisms important for the pathologic changes that characterize the intestinal phase of gastroenteritis and typhoid fever.
Chapter 3
Adhesins of Salmonella and Their Putative Roles in Infection
Timo K. Korhonen
Abstract
As a species, Salmonella enterica exhibits a repertoire of fimbrial and nonfimbrial adhesins that bind to intestinal epithelial surfaces and cell lines, to glycoproteins of the mammalian extracellular matrices, to intestinal mucins, and that interact with circulating proteins. The type-1 fimbria, the long polar fimbria, and the plasmid-encoded fimbriae, as well as the SEF14 fimbria have been implicated in adhesion of S. enterica to intestinal epithelia but, excepting the role of SEF14 in serovar Enteritidis infection in the mouse, these fimbriae have only revealed a modest role in the virulence of S. enterica. The genome sequences of serovars Typhimurium and Typhi show the presence of several novel fimbriae gene operons, yet many of these appear to be expressed selectively inside the host and their functions remain largely unknown. Fimbrial and several outer membrane proteins of S. enterica bind to laminin and/or fibronectin, which may enhance persistent colonization at damaged tissue sites and establishment of systemic infection. The binding of type-1 fimbria to chicken intestinal mucin may promote bacterial growth within the mucus layer, and interaction of the type-1 and the curli fimbria with the plasminogen system as well as binding of the curli fimbria to contact phase proteins, may promote spread of S. enterica in host tissues. Our knowledge on the molecular and cell-binding specificities of the individual adhesins in S. enterica is limited, but the over-all picture emerging is that the multiple adhesins of the bacterium affect the infectious processes at various stages.
Chapter 4
Salmonella Pathogenicity Islands
Eirwen Morgan,
Abstract
The disease outcomes of infections caused by Salmonella enterica vary depending on the serovar and the nature of the infected host. Many of the major components required by S. enterica to cause infections are carried on discrete regions of the chromosome called Salmonella Pathogenicity Islands (SPI); fourteen SPIs have been identified to date. The variations in structure, function and distribution of these SPIs between different subspecies and serovars of S. enterica influence the characteristics of the different serovars and may contribute to the host-specificity of Salmonella. In this review, the characteristics of the different SPIs are described and the role of SPIs in the evolution of Salmonella host-specificity is discussed.
Chapter 5
The Salmonella enterica Virulence Plasmid and the spv Gene Cluster
Dilek Tezcan-Merdol, Sofia Eriksson Ygberg and Mikael Rhen
Abstract
The spv gene cluster was originally described as a virulence-associated locus carried by selected serovars of Salmonella enterica subspecies I. More recently, chromosomal spv genes have been detected in subspecies II, IIIa, IV and V of S. enterica, and the available sequence data suggest that the spv genes have in fact evolved from a chromosomal determinant. The plasmid-carried spv gene cluster divides into two transcriptional units, one coding for the transcriptional activator SpvR, and the other coding for the SpvABCD proteins. SpvB acts as a mono(ADP-ribosyl)transferase whereas the SpvACD proteins have not been assigned any specific functions, although it remains possible that some of these Spv proteins assist translocation of SpvB out from the Salmonella-containing host cell vacuole to the cytosol. Besides the spv determinant, a number of other loci on the virulence plasmid do code for virulence-associated characters, such as serum resistance or invasion factor homologues. Furthermore, growth conditions that mimic in vivo conditions induce the expression of several regions of the serovar Typhimurium plasmid, implying the existence of additional virulence-associated functions.
Chapter 6
Virulence Gene Regulation in Salmonella enterica serovar Typhimurium.
Charles J. Dorman, Tadhg Ó Cróinín, and Michael W. Mangan
Abstract
The virulence genes of Salmonella enterica serovar Typhimurium are subject to complex regulation. This is thought to reflect the complexity of the environments in which the bacterium finds itself during the infection process and the need to optimize virulence gene expression to the benefit of the pathogen. This chapter concentrates on the control of gene expression at the level of transcription and considers both global and specific aspects of the regulatory process. Themes such as the roles of nucleoid-associated proteins and DNA topology are addressed together with the contributions of more conventional transcription factors. There is an emphasis on coordination of gene expression within regulatory networks with discussion of specific examples in which the molecular details have been elucidated. The regulation of genes that form part of the ancestral chromosome and of those carried within horizontally-acquired genetic elements are both described. Although the focus of the chapter is on S. Typhimurium gene regulation, the principles covered are generally applicable to most bacteria.
Chapter 7
Biofilms of Salmonella enterica
Ute Rmling, Devrim Pesen and Sima Yaron
Abstract
It is well established that Salmonella enterica (S. enterica) can form multicellular structures, commonly called biofilms, on various occasions. Biofilms can be formed on diverse surfaces/interfaces such as at the epithelial cell layer of a vertebrate host, on plant surfaces, or on abiotic surfaces, at the air-liquid interface and on gallstones. In this way, S. enterica is thought to achieve environmental persistence, transmission, and colonization of host organisms. Characterization of biofilm formation on the molecular level revealed different types of biofilms that have common and distinct regulatory and structural components. The so-called "rdar morphotype", a multicellular behaviour of S. enterica on agar plates is characterized by the expression of the master regulator CsgD, which controls expression of the extracellular matrix components curli fimbriae, the large surface-associated protein BapA, the exopolysaccharide cellulose and a capsular polysaccharide. Colonisation of abiotic surfaces, plant surfaces and epithelial cell layers partly require the same factors as rdar morphotype formation, while the biofilm formed by Salmonella on gall stones seems to be substantially distinct from rdar morphotype formation.
Chapter 8
Innate Host Defenses in Salmonellosis
Jessica Jones-Carson and Andres Vazquez-Torres
Abstract
The intracellular pathogen Salmonella is a frequent cause of gastrointestinal and systemic infections. The innate host response to this bacterium is complex, involving humoral and cellular defenses in stomach, gut and systemic organs. Non-specific barriers such as gastric acidity and mucus are some of the first obstacles encountered by Salmonella in the gastrointestinal tract. Interaction with the intestinal epithelium triggers innate responses that mobilize and activate innate effector cells of myeloid and lymphoid origin. Salmonella come into contact with phagocytic cells strategically situated in lamina propria and lymphoid tissue underlying Peyer's patches. Innate responses of phagocytic cells are of critical importance to the pathogenesis of Salmonella. On one hand, some populations of phagocytic cells promote the expression of virulence factors and the intracellular replication of Salmonella. On the other hand, phagocytes can exert direct anti-Salmonella activity through oxygen-dependent and -independent mechanisms, while providing signals that facilitate the initiation of acquired immunity. A variety of Salmonella virulence factors such as a couple of type III secretion systems allow Salmonella to surmount some of the challenges encounter by this enteric bacteria in the diverse niches offered by the host. The balance between innate host defenses and Salmonella virulence factors dictate in great part the overall outcome of Salmonella infection.
Chapter 9
Revealing the Mosaic Nature of Salmonella Genomes Using Microarrays
Muna F. Anjum
Abstract
The accumulation of whole genome sequences has truly brought forth the strength of microarray technology. Thereby, DNA microarray technologies have gained the ability to generate and provide efficient access to vast genetic information suited not only for comparative genomics, but also for the identification and sub-classification of microbes. Furthermore, DNA-microarrays have opened the possibility to probe bacterial transcriptomes at a whole genome level. This review describes the application of DNA microarrays to define the genome content within the genus Salmonella. Also, the review will discuss the diagnostic potential of the array technology in terms of use in routine reference laboratory for sero- and genotyping.
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