Evolutionary Aspects

Based on in vitro data, all Listeria species are regarded as normally noncompetent 71 . It was therefore totally unexpected to find genes in L. monocytogenes and L. innocua coding for putative DNA uptake systems, homologous to B. subtilis competence genes 2, 71 . The uptake apparatus may either not be functional any more, or its regulation or the signals that induce competence may differ from those of B. subtilis and the inducing conditions have not yet been met during laboratory culture....

Comparison of Gene Expression Profiles of Macrophages and Dendritic Cells In Vitro Upon Infection with Different

Several studies 1-3 compared the responses of macrophages or dendritic cells upon infection with different pathogens. Huang et al. 1 determined the gene expression profiles of human monocyte-derived dendritic cells in response to Escherichia coli SD54, Candida albicans, and influenzavirus as well as to their molecular components by using oligonucleotide arrays representing 6800 genes. While 166 genes were found to be regulated in common by all these pathogens, 118 genes were specifically...

Info

To further elucidate the genetic differences that might be responsible for the differences in the pathogenic potential of different N. meningitidis isolates, the genomes of two nonpathogenic isolates of N. meningitidis (ST-53 and ST-136 strains) 7 have been sequenced and their annotation is still in progress (H. Claus et al., 2005). A comparison of these genomes with the already sequenced genomes of the virulent N. meningitidis isolates will not only reveal these subtle differences, and hence...

Pathogenicity Island of Efaecalis

The E.faecalis pathogenicity island is 153 kbp and encodes 129 predicted ORFs. Present on this element are genes encoding for virulence factors, transposases, transcriptional regulators, and other proteins potentially involved in adaptation to diverse environments. Spread across the pathogenicity island are 11 transposases and insertion elements, with homology to ORFs from other low G+C gram-positive organisms such as E. faecium, S. aureus, Listeria innocua, L. monocytogenes, S. pneumoniae, and...

Subspecies I Signature Genes

While the genomic features that differentiate Salmonella serotypes and their closest relative E. coli nicely fit the differences in metabolism and pathogenicity that have been historically described in the literature, the relationship between genetic and phenotypic differences within the species S. enterica are less clearly defined. The species S. enterica contains six subspecies, and all of these are capable of causing disease in mammals 1 . However, the overwhelming majority of cases of...

Proteomes of Nongrowing Cells Proteomic Signatures of Stress Starvation Stimuli

The transition from a growing to a nongrowing state is accompanied by a dramatic reprogramming of the protein synthesis profile. Vegetative proteins no longer required at high concentrations are no longer synthesized in nongrowing cells, and in some cases are even degraded in a specific manner 8, 9 . Other proteins with specific and nonspecific adaptive functions are strongly induced on a time-dependent scale. On the basis of proteomic studies, three main groups of stress starvation proteins...

Targeting the Resistance Mechanism

Instead of searching for a novel antibiotic free of cross-resistance, an alternative strategy would be to combine an existing drug with a compound that overcomes or at least reduces the resistance against that particular antibiotic. This approach is especially appealing because it would restore the power of a previously valuable class, and because it has already been clinically validated by the very successful combination of b-lactams with b-lactamase inhibitors capable of protecting the active...

The Present

The deciphering of the complete genome of Haemophilus influenzae in 1995 11 heralded a flood of unprecedented prokaryotic sequence information and triggered a paradigm shift in antibacterial drug discovery. It therefore seems appropriate to define this event as the starting point of the present era of antibiotic discovery strategies. Since that time, more than 190 complete bacterial genomic sequences have become available. That large collection of fully sequenced bacterial genomes includes...

References

Middendorf, G. Schneider, C. Buchrieser, G. Gottschalk, and U. Dobrindt. 2004. Pathogenomics of mobile genetic elements of toxigenic bacteria. Int. J. Med. Microbiol. 293 453-461. 2 Hacker, J., U. Hentschel, and U. Dobrindt. 2003. Prokaryotic chromosomes and disease. Science 301 790-793. 3 Sorsa, L. J., S. Dufke, and S. Schubert. 2004. Identification of novel virulence-associated loci in uropathogenic Escherichia coli by suppression subtractive hybridization. FEMS...

MenB Vaccine Approach by Reverse Vaccinology

The first example in which genomic technology has been used for the identification of potential vaccine candidates is the vaccine against the human pathogen Neisseria meningitidis serogroup B (MenB), the major cause of sepsis and meningitis in children and young adults. In the last forty years, conventional vaccinology approaches failed to provide an effective and universal vaccine against MenB. Although for other meningococcal serogroups (A, C, Y, and W135) conjugate vaccines based on the...

Salmonella Signature Genes

What genetic features set Salmonella serotypes apart from closely related organisms such as E. coli Comparison of bacterial genomes shows that Salmonella-specific DNA regions encode many of the biological properties that distinguish Salmonella serotypes from other members of the family Enterobacteriaceae. An alignment of the chromosomes of S. enterica serotype Typhimurium and E.coli K-12 provided the first evidence that their collinear genetic maps are interrupted by large DNA segments that are...

Genetic Polymorphisms and Mutations Affect Gene Expression Impact on Infection Susceptibility and Infection Course

Gene expression profiles help us to understand the complexity of immune response mechanisms, and animal models including gene-targeted mice help to prove the biological relevance of particular genes for defense against pathogens. The impact of such genes for human disease is apparent in primary immunodeficiency due to genomic deletions or null mutations of single genes. Furthermore, point mutations in important genes of the immune system are often sufficient to affect the severity and the...

Strategies for Reducing Virulence andor Influencing Pathogenesis

The general progress in bacterial physiology combined with the rapidly increasing knowledge of the molecular biology of infection and bacterial genomics have given an enormous boost to our understanding of the bacterial infection process. As a consequence we have gained deeper insight into the factors that enable certain bacteria to induce disease in particular hosts, while others behave as innocent bystanders or are even beneficial for the host. The recent literature and the present volume are...

Impact of Genomics on Vaccine Design

Despite advances in the treatment of infectious diseases, pathogenic microorganisms are the single most important threat to health worldwide. Approaches to vaccine development have made remarkable progress in the last 200 years, and vaccination has prevented illness and death for millions of individuals every year. However, there are many infectious diseases still waiting for efficacious formulations, and many emerging pathogens. For these reasons, novel vaccines together with new ways to...

Pathogenomic Tools Microarrays in the Diagnosis of Microbiologic Agents as Bioweapons

There is increasing concern within both the scientific and security communities that the ongoing revolution in biology has great potential to be misused in offensive biological weapons programs 75-77 . Interdisciplinary and international efforts to increase the monitoring, surveillance, identification, and reporting of disease agents and to better understand the potential dynamics of disease transmission within human and animal populations in both industrialized and developing country settings...

Detection of Antibiotic Resistance in Microbial Pathogens Using Microarray Technology

DNA microarray technologies offer a promising method for detection of antimicrobial resistance genes and point mutations in resistance-related sequences (rRNA, katG, gyrA) 9 . Detection and identification of multiple tetracycline resistance genes by a glass-based DNA microarray were recently described 46 . In this study, microarray probes for 17 tet genes, the b-lactamase blaTEM-1 gene, and a 16S-rDNA gene (E. coli) were generated and successfully applied to clinical isolates. Recently, the...

Scc476

SaGIm 14 SaPI3 25 SaPIm1 14 SaPI2 25 SaPIm2 14 SaPIm3 14 Gene symbols bsa, bacteriocin gene cluster ccrA,B, cassette chromosome recombinase A,B far, fusidic acid resistance geh, lipase lpl, lipoproteins lukDE, components of toxin leukocidin DE lukS-PV, lukF-PV, Panton-Valentine leukocidin components S and F mecA, penicillin binding protein 2a sak, staphylococcal kinase set, staphylococcal exotoxins splA-F, serine protease sea, seb, sec3, sec4, seg, seg2, sek2, sel, sem, sen, seo, sep,...

Internalins and Other Surface Proteins

A large number of internalin-related proteins in addition to the well-studied InlA and InlB proteins were identified in the different L. monocytogenes genome sequences 2, 3, 65, 70 . However, so far only those of them already identified in the pregenomic era InlC, InlE, InlF, InlG, and InlH 7, 8, 79 have been studied in any detail, and it was shown that none of them is able to induce phagocytosis in mammalian cells on its own, although at least some of them may play a role in virulence 8 ....

Environmental Adaptation and Stress Response

Environmental adaptation traits and stress resistance mechanisms have been linked to virulence, as bacterial survival in the host is often reliant on these factors. Disruption of genes encoding such traits often leads to attenuation of the organism in an animal model 32-35 . As mentioned previously, E.faecalis is a very robust organism able to survive in many harsh environments. E.faecalis V583 contains a V-type and F -type ATPase responsible for regulating the intracellular pH and proton...

Mobile Genetic Elements and Evolution of Pathogenic E coli

Mobilizable plasmids and bacteriophages represent key elements to enable bacteria to exchange genetic information by conjugation and transduction. During recent years, genomic research revealed that pathogenicity islands PAIs have also played a major role for the transformation of avirulent into virulent bacteria. Only limited knowledge exists about the origin of PAIs, but it has been speculated that they may derive from integrating plasmids or phages that have lost the genes required for...

Gene Expression In Vivo IVETand STM

Growing a pathogenic organism in vitro and studying its gene expression pattern may not tell us which genes are important for causing pathogenicity in a living organism. Genes involved in these processes can only be determined in vivo. A genetic system termed IVET in vivo expression technology was developed to identify bacterial genes that are induced when a pathogen infects its host 20 . A subset of these induced genes should include those that encode virulence factors - products specifically...

Helicobacter pylori

H. pylori, which adheres to the luminal surface of gastric epithelial cells, is the causative agent of gastritis and possesses a number of virulence factors that modulate its interaction with the host 10, 11 . These virulence factors include the secreted cytotoxin VacA and the gene products of the pathogenicity island cagPAl. The cagPAl encodes a type IV secretion system that facilitates the injection of bacterial proteins into host cells 10, 11 . One of these proteins, CagA, undergoes tyrosine...

Genomic Islands Pathogenicity Islands

Many virulence-associated genes of pathogenic E. coli are frequently located on formerly mobile genetic elements such as bacteriophages, plasmids, and geno-mic islands. A variety of pathogenic E. coli isolates have been analyzed with respect to the presence and spread of virulence-associated genes. The presence of distinct genomic islands GEIs encoding virulence determinants, designated pathogenicity islands PAIs , has been shown for a broad variety of bacteria including various strains of the...