Major Human Pathogen (major + human_pathogen)

Distribution by Scientific Domains


Selected Abstracts


Growth-induced changes in the proteome of Helicobacter pylori

ELECTROPHORESIS, Issue 5-6 2006
Christina Uwins
Abstract Helicobacter pylori is a major human pathogen that is responsible for a number of gastrointestinal infections. We have used 2-DE to characterise protein synthesis in bacteria grown either on solid agar-based media or in each of two broth culture media (Brucella and brain heart infusion (BHI) broth). Significant differences were observed in the proteomes of bacteria grown either on agar-based or in broth media. Major changes in protein abundance were identified using principal component analysis (PCA), which delineated the profiles derived for the three key growth conditions (i.e. agar plates, Brucella and BHI broth). Proteins detected across the gel series were identified by peptide mass mapping and Edman sequencing. A number of proteins associated with protein synthesis in general as well as specific amino acid synthesis were depressed in broth-grown bacteria compared to plate-grown bacteria. A similar reduction was also observed in the abundance of proteins involved in detoxification. Two of the most abundant spots, identified as UreB and GroEL, in plate-grown bacteria showed a >140-fold drop in abundance in bacteria grown in Brucella broth compared to bacteria grown on agar plates. Two protein spots induced in bacteria grown in broth culture were both identified as glyceraldehyde 3-phosphate dehydrogenase based on their N -terminal amino acid sequences derived by Edman degradation. The underlying causes of the changes in the proteins abundance were not clear, but it was likely that a significant proportion of the changes were due to the alkaline pH of the broth culture media. [source]


Role of apoptosis and cytokines in influenza virus morbidity

FEMS MICROBIOLOGY REVIEWS, Issue 4 2005
Edward W.A. Brydon
Abstract Influenza virus is a major human pathogen that causes epidemics and pandemics with increased morbidity and, especially in the elderly and those with pre-existing medical conditions, increased mortality. Influenza is characterised by respiratory symptoms and constitutional symptoms. Whilst knowledge of the mechanisms underlying host and tissue specificity has advanced considerably of late we still know relatively little about other aspects of influenza virus virulence. In this review, we will explore what is known about the role of apoptosis in respiratory epithelial cell damage and the role of cytokines in inflammation and constitutional symptoms with particular emphasis on the link between apoptosis, inflammation, fever and cytokine production. [source]


Does cytomegalovirus play a causative role in the development of various inflammatory diseases and cancer?

JOURNAL OF INTERNAL MEDICINE, Issue 3 2006
C. SÖDERBERG-NAUCLÉR
Abstract. Human cytomegalovirus (HCMV) is a herpes virus that infects and is carried by 70,100% of the world's population. During its evolution, this virus has developed mechanisms that allow it to survive in an immunocompetent host. For many years, HCMV was not considered to be a major human pathogen, as it appeared to cause only rare cases of HCMV inclusion disease in neonates. However, HCMV is poorly adapted for survival in the immunosuppressed host and has emerged as an important human pathogen in AIDS patients and in patients undergoing immunosuppressive therapy following organ or bone marrow transplantation. HCMV-mediated disease in such patients has highlighted the possible role of this virus in the development of other diseases, in particular inflammatory diseases such as vascular diseases, autoimmune diseases and, more recently, with certain forms of cancers. Current research is focused on determining whether HCMV plays a causative role in these diseases or is merely an epiphenomenon of inflammation. Inflammation plays a central role in the pathogenesis of HCMV. This virus has developed a number of mechanisms that enable it to hide from the cells of the immune system and, at the same time, reactivation of a latent infection requires immune activation. Numerous products of the HCMV genome are devoted to control central functions of the innate and adaptive immune responses. By influencing the regulation of various cellular processes including the cell cycle, apoptosis and migration as well as tumour invasiveness and angiogenesis, HCMV may participate in disease development. Thus, the various drugs now available for treatment of HCMV disease (e.g. ganciclovir, acyclovir and foscarnet), may also prove to be useful in the treatment of other, more widespread diseases. [source]


Improved accuracy of cell surface shaving proteomics in Staphylococcus aureus using a false-positive control

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 10 2010
Nestor Solis
Abstract Proteolytic treatment of intact bacterial cells is an ideal means for identifying surface-exposed peptide epitopes and has potential for the discovery of novel vaccine targets. Cell stability during such treatment, however, may become compromised and result in the release of intracellular proteins that complicate the final analysis. Staphylococcus aureus is a major human pathogen, causing community and hospital-acquired infections, and is a serious healthcare concern due to the increasing prevalence of multiple antibiotic resistances amongst clinical isolates. We employed a cell surface "shaving" technique with either trypsin or proteinase- K combined with LC-MS/MS. Trypsin-derived data were controlled using a "false-positive" strategy where cells were incubated without protease, removed by centrifugation and the resulting supernatants digested. Peptides identified in this fraction most likely result from cell lysis and were removed from the trypsin-shaved data set. We identified 42 predicted S. aureus COL surface proteins from 260 surface-exposed peptides. Trypsin and proteinase- K digests were highly complementary with ten proteins identified by both, 16 specific to proteinase- K treatment, 13 specific to trypsin and three identified in the control. The use of a subtracted false-positive strategy improved enrichment of surface-exposed peptides in the trypsin data set to approximately 80% (124/155 peptides). Predominant surface proteins were those associated with methicillin resistance,surface protein SACOL0050 (pls) and penicillin-binding protein 2, (mecA), as well as bifunctional autolysin and the extracellular matrix-binding protein Ebh. The cell shaving strategy is a rapid method for identifying surface-exposed peptide epitopes that may be useful in the design of novel vaccines against S. aureus. [source]


Simply and reliably integrating micro heaters/sensors in a monolithic PCR-CE microfluidic genetic analysis system

ELECTROPHORESIS, Issue 8 2009
Runtao Zhong
Abstract A novel fabrication process was presented to construct a monolithic integrated PCR-CE microfluidic DNA analysis system as a step toward building a total genetic analysis microsystem. Microfabricated Titanium/Platinum (Ti/Pt) heaters and resistance temperature detectors (RTDs) were integrated on the backside of a bonded glass chip to provide good thermal transfer and precise temperature detection for the drilled PCR-wells. This heater/RTD integration procedure was simple and reliable, and the resulting metal layer can be easily renewed when the Ti/Pt layer was damaged in later use or novel heater/RTD design was desired. A straightforward "RTD-calibration" method was employed to optimize the chip-based thermal cycling conditions. This method was convenient and rapid, comparing with a conventional RTD-calibration/temperature adjustment method. The highest ramping rates of 14°C/s for heating and 5°C/s for cooling in a 3-,L reaction volume allow 30 complete PCR cycles in about 33,min. After effectively passivating the PCR-well surface, successful ,-phage DNA amplifications were achieved using a two- or three-temperature cycling protocol. The functionality and performance of the integrated microsystem were demonstrated by successful amplification and subsequent on-line separation/sizing of ,-phage DNA. A rapid assay for Hepatitis B virus, one of the major human pathogens, was performed in less than 45,min, demonstrating that the developed PCR-CE microsystem was capable of performing automatic and high-speed genetic analysis. [source]


Genome dynamics in major bacterial pathogens

FEMS MICROBIOLOGY REVIEWS, Issue 3 2009
Ole Herman Ambur
Abstract Pathogenic bacteria continuously encounter multiple forms of stress in their hostile environments, which leads to DNA damage. With the new insight into biology offered by genome sequences, the elucidation of the gene content encoding proteins provides clues toward understanding the microbial lifestyle related to habitat and niche. Campylobacter jejuni, Haemophilus influenzae, Helicobacter pylori, Mycobacterium tuberculosis, the pathogenic Neisseria, Streptococcus pneumoniae, Streptococcus pyogenes and Staphylococcus aureus are major human pathogens causing detrimental morbidity and mortality at a global scale. An algorithm for the clustering of orthologs was established in order to identify whether orthologs of selected genes were present or absent in the genomes of the pathogenic bacteria under study. Based on the known genes for the various functions and their orthologs in selected pathogenic bacteria, an overview of the presence of the different types of genes was created. In this context, we focus on selected processes enabling genome dynamics in these particular pathogens, namely DNA repair, recombination and horizontal gene transfer. An understanding of the precise molecular functions of the enzymes participating in DNA metabolism and their importance in the maintenance of bacterial genome integrity has also, in recent years, indicated a future role for these enzymes as targets for therapeutic intervention. [source]