scholarly journals A Metabolic Enzyme as a Primary Virulence Factor of Mycoplasma mycoides subsp. mycoides Small Colony

2005 ◽  
Vol 187 (19) ◽  
pp. 6824-6831 ◽  
Author(s):  
Paola Pilo ◽  
Edy M. Vilei ◽  
Ernst Peterhans ◽  
Laetitia Bonvin-Klotz ◽  
Michael H. Stoffel ◽  
...  
Keyword(s):  
Host Cell ◽  
Virulence Factors ◽  
Virulence Factor ◽  
Pathogenic Bacteria ◽  
Cell Injury ◽  
Cell Damage ◽  
Metabolic Enzyme ◽  
Complex Interactions ◽  
Mycoplasma Mycoides ◽  
Small Colony

ABSTRACT During evolution, pathogenic bacteria have developed complex interactions with their hosts. This has frequently involved the acquisition of virulence factors on pathogenicity islands, plasmids, transposons, or prophages, allowing them to colonize, survive, and replicate within the host. In contrast, Mycoplasma species, the smallest self-replicating organisms, have regressively evolved from gram-positive bacteria by reduction of the genome to a minimal size, with the consequence that they have economized their genetic resources. Hence, pathogenic Mycoplasma species lack typical primary virulence factors such as toxins, cytolysins, and invasins. Consequently, little is known how pathogenic Mycoplasma species cause host cell damage, inflammation, and disease. Here we identify a novel primary virulence determinant in Mycoplasma mycoides subsp. mycoides Small Colony (SC), which causes host cell injury. This virulence factor, released in significant amounts in the presence of glycerol in the growth medium, consists of toxic by-products such as H2O2 formed by l-α-glycerophosphate oxidase (GlpO), a membrane-located enzyme that is involved in the metabolism of glycerol. When embryonic calf nasal epithelial cells are infected with M. mycoides subsp. mycoides SC in the presence of physiological amounts of glycerol, H2O2 is released inside the cells prior to cell death. This process can be inhibited with monospecific anti-GlpO antibodies.

scholarly journals Virulence factor activity relationships for hepatitis E and Cryptosporidium

2009 ◽  
Vol 7 (S1) ◽  
pp. S55-S63 ◽  
Author(s):  
Ronald Fayer ◽  
Palmer Orlandi ◽  
Michael L. Perdue
Keyword(s):  
Host Cell ◽  
Virulence Factors ◽  
Virulence Factor ◽  
Hepatitis E Virus ◽  
Animal Species ◽  
Immune Status ◽  
Hepatitis E ◽  
Host Cells ◽  
Factor Activity ◽  
Infectious Dose

The hepatitis E virus and Cryptosporidium are waterborne pathogens, each consisting of distinct taxa, genotypes and isolates that infect humans, nonhuman animal species or both. Some are associated with disease, others are not. Factors contributing to disease are extremely complicated, possibly involving differences in one or more traits associated with an organism's taxon, genotype or isolate and its infectious dose, and age or condition, as well as the host's physiology and immune status. Potential virulence factors have not yet been identified for HEV. Putative virulence factors for Cryptosporidium might be found in recently recognized genes involved in processes such as excystation, adherence to host cells, invasion, intracellular maintenance and host cell destruction.

scholarly journals A Structural Approach to Anti-Virulence: A Discovery Pipeline

2021 ◽  
Vol 9 (12) ◽  
pp. 2514
Author(s):  
Michael McCarthy ◽  
Monica Goncalves ◽  
Hannah Powell ◽  
Blake Morey ◽  
Madison Turner ◽  
...  
Keyword(s):  
Host Cell ◽  
Virulence Factors ◽  
Pathogenic Bacteria ◽  
Bacterial Virulence ◽  
Structural Approach ◽  
Multi Drug Resistance ◽  
Enzyme Active Site ◽  
Catalytic Function ◽  
Molecule Inhibitor ◽  
High Resolution Structure

The anti-virulence strategy is designed to prevent bacterial virulence factors produced by pathogenic bacteria from initiating and sustaining an infection. One family of bacterial virulence factors is the mono-ADP-ribosyltransferase toxins, which are produced by pathogens as tools to compromise the target host cell. These toxins are bacterial enzymes that exploit host cellular NAD+ as the donor substrate to modify an essential macromolecule acceptor target in the host cell. This biochemical reaction modifies the target macromolecule (often protein or DNA) and functions in a binary fashion to turn the target activity on or off by blocking or impairing a critical process or pathway in the host. A structural biology approach to the anti-virulence method to neutralize the cytotoxic effect of these factors requires the search and design of small molecules that bind tightly to the enzyme active site and prevent catalytic function essentially disarming the pathogen. This method requires a high-resolution structure to serve as the model for small molecule inhibitor development, which illuminates the path to drug development. This alternative strategy to antibiotic therapy represents a paradigm shift that may circumvent multi-drug resistance in the offending microbe through anti-virulence therapy. In this report, the rationale for the anti-virulence structural approach will be discussed along with recent efforts to apply this method to treat honey bee diseases using natural products.

scholarly journals Virulence Factor Genes Incidence among Enterococci from Sewage Sludge in Eastern Slovakia following Safety Aspect

2019 ◽  
Vol 2019 ◽  
pp. 1-5
Author(s):  
Andrea Lauková ◽  
Viola Strompfová ◽  
Jana Ščerbová ◽  
Monika Pogány Simonová
Keyword(s):  
Species Identification ◽  
Virulence Factors ◽  
Virulence Factor ◽  
Pathogenic Bacteria ◽  
Health Hazard ◽  
Potential Health ◽  
Safety Aspect ◽  
Potential Health Hazard ◽  
Genus Identification ◽  
Virulence Factor Genes

The sewage sludges represent a potential health hazard because of the quantity of different microbiota detected in sewages. Among microbiota detected in sewages, also belong representatives of the phylum Firmicutes. In the past, environmental enterococci in addition to coliforms were widely used as indicators of faecal contamination. Regarding the enterococcal strains as potential pathogenic bacteria, their pathogenicity is mainly caused by production of virulence factors. Therefore, the aim of the study was to analyse incidence of virulence factors in enterococci from cows' dung water. Species identification of 24 enterococci using MALDI-TOF MS system allotted 23 strains to the species Enterococcus faecium with highly probable species identification and E. faecalis EEV20 with a score value meaning secure genus identification/probable species identification. Enterococci were absent of cytolysin A gene, hyaluronidase gene, and element IS gene. It can be concluded that they are not invasive which is very important from safety aspect. The most frequently detected gene was adhesin E. faecium (efaAfm, in 22 E. faecium strains and in one E. faecalis). Adhesin efaAfs gene was detected in E. faecalis EEV20 and in two E. faecium. GelE gene was present in three strains. E. faecium EF/EC31 was absent of virulence factor genes.

scholarly journals Structure of the Potential Virulence Factor from Francisella tularensis Shows Unexpected Presence of the SHS2 Motif and Similarity to Other Bacterial Virulence Factors

2022 ◽  
Author(s):  
Janette Chammas ◽  
Mallika Iyer ◽  
George Minasov ◽  
Ludmilla Shuvalova ◽  
Wayne Anderson ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Francisella Tularensis ◽  
Virulence Factor ◽  
Pathogenic Bacteria ◽  
Large Family ◽  
Structural Motif ◽  
Dimensional Structure ◽  
Human Pathogens ◽  
Recognition Sequence ◽  
Potential Virulence Factor

Pathogenic bacteria attack their host by secreting virulence factors that in various ways interrupt host defenses and damage their cells. Functions of many virulence factors, even from well-studied pathogens, are still unknown. Francisella tularensis is a class A pathogen and a causative agent of tularemia, a disease that is lethal without proper treatment. Here we report the three-dimensional structure and preliminary analysis of the potential virulence factor identified by the transcriptomic analysis of the F. tularensis disease models that is encoded by the FTT_1539 gene. The structure of the FTT_1539 protein contains two sets of three stranded antiparallel beta sheets, with a helix placed between the first and the second beta strand in each sheet. This structural motif, previously seen in virulence factors from other pathogens, was named the SHS2 motif and identified to play a role in protein-protein interactions and small molecule recognition. Sequence and structure analysis identified FTT_1539 as a member of a large family of secreted proteins from a broad range of pathogenic bacteria, such as Helicobacter pylori and Mycobacterium tuberculosis. While the specific function of the proteins from this class is still unknown, their similarity to the H. pylori Tip-α protein that induces TNF-a and other chemokines through NF-kB activation suggests the existence of a common pathogen-host interference mechanism shared by multiple human pathogens.

Virulence factors associated with organisms causing asymptomatic bacteriuria in pregnant females attending a tertiary care hospital

2017 ◽  
Vol 6 (05) ◽  
pp. 5373
Author(s):  
Prabha Ponnusamy* ◽  
Radhika Katragadda ◽  
Thyagarajan Ravinder
Keyword(s):  
Virulence Factors ◽  
Host Defense ◽  
Virulence Factor ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Asymptomatic Bacteriuria ◽  
Phenotypic Expression ◽  
Care Hospital ◽  
Cross Sectional ◽  
Pregnant Females

Asymptomatic bacteriuria (ASB), most common during pregnancy is endangering as it may lead to maternal and fetal complications. Various organisms causing ASB combats the host defense mechanisms through virulence factors exhibited by them. In order to understand the pathogenesis and sequelae of infections, virulence factors like hemolysin production, gelatinase production, haemagglutination, biofilm production and many more should be identified. Hence, we aimed at studying the distribution of virulence factors among each organism causing asymptomatic bacteriuria in pregnant females attending a tertiary care hospital. Materials and Methods: This cross-sectional study was conducted in Department of Microbiology over a period of one year and six months (January 2014 to June 2015) at a tertiary care teaching hospital. A total of 1000 urine samples were included in study taken from pregnant women with asymptomatic bacteriuria. Isolation, identification of organisms was done according to standard microbiological techniques and virulence factors for individual organisms by phenotypic method were tested. Results: Out of 1000 samples screened for ASB, organisms were isolated in following frequency distribution: Escherichia coli, the commonest 54/118 (45.76%), Klebsiella pneumoniae 21/118 (17.80%), Staphylococcus aureus 19/118 (16.10%), Staphylococcus saprophyticus 10/118 (8.45%), Enterococcus faecalis 9/118 (7.63%), Pseudomonas aeruginosa 3/118 (2.54%) and Proteus mirabilis 2/118 (1.69%). Virulence factors for individual organisms and biofilm detection for all organisms were done. Conclusion: Multifactorial mechanisms determine the pathogenicity of an organism and it needs to be explored by analyzing each virulence factor and mechanism of invasion in combating the host defense systems. Hence analyzing the phenotypic expression of each virulence factor helps in better understanding about the complications of ASB.

scholarly journals The severity of glomerular endothelial cell injury is associated with infiltrating macrophage heterogeneity in endocapillary proliferative glomerulonephritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Momoko Arai ◽  
Akiko Mii ◽  
Tetsuya Kashiwagi ◽  
Akira Shimizu ◽  
Yukinao Sakai
Keyword(s):  
Endothelial Cell ◽  
Cell Injury ◽  
Cell Damage ◽  
Computer Assisted ◽  
Endothelial Cell Injury ◽  
Glomerular Capillary ◽  
Luminal Area ◽  
Endocapillary Proliferative Glomerulonephritis ◽  
Cell Phenotypes ◽  
Schonlein Purpura

AbstractEndocapillary proliferation occurs in various types of glomerulonephritis (GN), with varying prognoses. We examined 42 renal biopsy samples representing endocapillary proliferative lesions from post-streptococcal acute GN (PSAGN), Henoch–Schönlein purpura nephritis (HSPN), and lupus nephritis (LN). In PSAGN, the glomerular capillary network was maintained, although severe lesions displayed dots or short, curved lines, indicating CD34-positive capillaries and suggesting capillary obstruction. Conversely, patients with LN and HSPN displayed obstruction of CD34-positive capillaries with dissociation from the glomerular basement membrane even in mild lesions. According to computer-assisted morphologic analysis, the cell density did not differ between the diseases. However, in PSAGN, the number of capillary loops was significantly increased, with a larger glomerular capillary luminal area than in the other groups. In addition, the number and frequency of CD163-positive cells (M2 macrophages) tended to be higher in PSAGN, while there were no significant differences in the number of CD68-positive (total) macrophages. These results indicate that in PSAGN, endothelial cell damage is less severe, and angiogenesis may be promoted. The severity of endothelial cell injury in each disease may be associated with differences in infiltrating inflammatory cell phenotypes.

scholarly journals Potential Role of Phospholipases in Virulence and Fungal Pathogenesis

2000 ◽  
Vol 13 (1) ◽  
pp. 122-143 ◽  
Author(s):  
Mahmoud A. Ghannoum
Keyword(s):  
Virulence Factor ◽  
Cell Damage ◽  
Pathogenic Fungi ◽  
Microbial Pathogens ◽  
Immunogold Electron Microscopy ◽  
Lytic Enzymes ◽  
Fungal Virulence ◽  
Phospholipase B ◽  
Genes Encoding

SUMMARY Microbial pathogens use a number of genetic strategies to invade the host and cause infection. These common themes are found throughout microbial systems. Secretion of enzymes, such as phospholipase, has been proposed as one of these themes that are used by bacteria, parasites, and pathogenic fungi. The role of extracellular phospholipase as a potential virulence factor in pathogenic fungi, including Candida albicans, Cryptococcus neoformans, and Aspergillus, has gained credence recently. In this review, data implicating phospholipase as a virulence factor in C. albicans, Candida glabrata, C. neoformans, and A. fumigatus are presented. A detailed description of the molecular and biochemical approaches used to more definitively delineate the role of phospholipase in the virulence of C. albicans is also covered. These approaches resulted in cloning of three genes encoding candidal phospholipases (caPLP1, caPLB2, and PLD). By using targeted gene disruption, C. albicans null mutants that failed to secrete phospholipase B, encoded by caPLB1, were constructed. When these isogenic strain pairs were tested in two clinically relevant murine models of candidiasis, deletion of caPLB1 was shown to lead to attenuation of candidal virulence. Importantly, immunogold electron microscopy studies showed that C. albicans secretes this enzyme during the infectious process. These data indicate that phospholipase B is essential for candidal virulence. Although the mechanism(s) through which phospholipase modulates fungal virulence is still under investigations, early data suggest that direct host cell damage and lysis are the main mechanisms contributing to fungal virulence. Since the importance of phospholipases in fungal virulence is already known, the next challenge will be to utilize these lytic enzymes as therapeutic and diagnostic targets.

Effect of oxidative stress on cellular functions and cytosolic free calcium of rat pancreatic acinar cells

1997 ◽  
Vol 272 (6) ◽  
pp. G1489-G1498 ◽  
Author(s):  
H. Klonowski-Stumpe ◽  
R. Schreiber ◽  
M. Grolik ◽  
H. U. Schulz ◽  
D. Haussinger ◽  
...  
Keyword(s):  
Cell Injury ◽  
Cell Damage ◽  
Acinar Cells ◽  
Pancreatic Acinar Cell ◽  
Pancreatic Acinar Cells ◽  
Free Calcium ◽  
Cellular Functions ◽  
Cytosolic Free Calcium ◽  
Catalyzed Oxidation ◽  
Sustained Increase

The present study evaluates the effect of free radicals generated by xanthine oxidase-catalyzed oxidation of hypoxanthine on cellular function of isolated rat pancreatic acinar cells. The results show that a rapid and sustained increase in intracellular Ca2+ concentration ([Ca2+]i) preceded all other morphological and functional alterations investigated. Radical-induced [Ca2+]i increase was largely inhibited by 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester, which prevents Ca2+ release from intracellular stores, but not by Ca2(+)-depleted medium. Radicals released Ca2+ from thapsigargin-insensitive, ryanodine-sensitive intracellular stores, whereas the secretagogue caerulein at physiological concentrations mainly released Ca2+ from thapsigargin-sensitive stores. In contrast to effects of the secretagogue, radical-induced Ca2+ changes did not cause luminal protein secretion but cell death. In single-cell measurements, both secretagogue and radicals induced oscillations of [Ca2+]i. Radical-induced oscillations had a lower frequency but similar amplitude when compared with caerulein-induced oscillations. 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid and ryanodine, which prevented the radical-induced Ca2+ increase without altering the generation of radicals, markedly reduced the radical-induced cell damage. These results suggest that the Ca2+ increase mediates the radical-induced cell injury. The studies also indicate that not only the extent and duration but also the origin of [Ca2+]i release as well as the frequency of Ca2+ oscillations may determine whether a pancreatic acinar cell will secrete or die.

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