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PubMed1989

Potted plants in hospitals as reservoirs of pathogenic fungi.

The soils of five potted plants cultivated within a hospital were investigated for the presence of fungal opportunistic pathogens of humans. A total of 16 potentially pathogenic species were isolated, including Aspergillus fumigatus at up to 53.5 colony-forming units (CFU) per gram dry soil and Scedosporium apiospermum (Pseudallescheria boydii) at up to 97.0 CFU/g. Other common species included Phialophora verrucosa and Fusarium solani. Scedosporium inflatum, a recently described emerging pathogen, is reported for the first time from an environmental source. The results of this study, in combination with previous case reports linking mycoses to potted plants and available information on the establishment and dispersal of fungal opportunistic pathogens in indoor habitats, indicate that indoor plant soils constitute a serious mycotic hazard to the immunosuppressed patient.

Aspergillus↗

PubMed2006

Targeted inactivation of synaptic HRG4 (UNC119) causes dysfunction in the distal photoreceptor and slow retinal degeneration, revealing a new function.

HRG4 (UNC119) is a photoreceptor protein predominantly localized to the photoreceptor synapses and to the inner segments to a lesser degree. A heterozygous truncation mutation in HRG4 was found in a patient with late onset cone-rod dystrophy, and a transgenic (TG) mouse expressing the identical mutant protein developed late onset retinal degeneration, confirming the pathogenic potential of HRG4. Recently, the dominant negative pathogenic mechanism in the TG model was shown to involve increased affinity of the truncated mutant HRG4 for its target, ARL2, which leads to a delayed decrease in its downstream target, mitochondrial ANT1, mitochondrial stress, synaptic degeneration, trans-synaptic degeneration, and whole photoreceptor degeneration by apoptosis. In this study, the mouse HRG4 (MRG4) gene was cloned and targeted to construct a knock-out (KO) mouse model of HRG4 in order to study the effects of completely inactivating this protein. The KO model was examined by genomic Southern blotting, Western blotting, immunofluorescence, funduscopy, LM and EM histopathology, ERG, and TUNEL analyses. The KO model developed a slowly progressive retinal degeneration, characterized by mottling in the fundus, mild thinning of the photoreceptor layer, and increase in apoptosis as early as 6 months, dramatic acceleration at approximately 17 months, and virtual obliteration of the photoreceptors by 20 months. When compared to retinal degeneration in the TG model, significant differences existed in the KO consisting of more severe and early photoreceptor death without evidence of early synaptic and trans-synaptic degeneration as seen in the TG, confirmed by LM and EM histopathology, ERG, and Western blotting of synaptic proteins. The results indicated a dysfunction in the KO outside the synapses in the distal end of photoreceptors where MRG4 is also localized. Differences in the phenotypes of retinal degeneration in the KO and TG models reflect a dysfunction in the two opposite ends of photoreceptors, i.e., the distal inner/outer segments and proximal synapses, respectively, indicating a second function of MRG4 in the distal photoreceptor and dual functionality of MRG4. Thus, inactivation of MRG4 by gene targeting resulted in a retinal degeneration phenotype quite different from that previously seen in the TG, attesting to the multiplicity of MRG4 function, in addition to the importance of this protein for normal retinal function. These models will be useful in elucidating the functions of HRG4/MRG4 and the mechanism of slow retinal degeneration.

Adaptor Proteins, Signal Transducing↗

PubMed1996

Simian immunodeficiency virus variants: threat of new lentiviruses.

Infection in humans with the lentivirus HIV-1 typically results in the development of a chronic disease state characterized by the slow decline of CD4+ lymphocytes, the development of immunosuppression, and the development of opportunistic infections, ultimately leading to death. Although the average course of disease runs approximately 10 years, shorter and longer progression times have been noted. These alterations are presumed to be, at least partially, a factor of viral variation. The simian immunodeficiency viruses (SIVs) are the nonhuman primate counterparts to HIV. Several of these isolates, including SIV from sooty mangabey monkeys, induce a remarkably similar disease in Asian macaques. Recently, variants of SIV from sooty mangabey monkeys and SIV from African green monkeys have been described, which are increasingly more pathogenic. As in HIV-1 infections, this is probably due to genetic variation. On the basis of these findings, atypical viruses with tremendous pathogenic potential can arise from apathogenic or moderately pathogenic viruses.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Helicobacter pylori factors involved in the development of gastroduodenal mucosal damage and ulceration.

Many putative virulence determinants of Helicobacter pylori are believed to trigger and worsen the gastroduodenal mucosa damage observed in infected patients. H. pylori urease reacts with the gastric urea and generates ammonia; ammonia combines with water and yields ammonium hydroxide, which is cytotoxic. Ammonia may also inhibit cell proliferation and cause indirect mucosal injury by stimulating neutrophils. Phospholipases may damage the gastric mucosa by degrading phospholipids and generating precursors of ulcerogenic components. Other enzymes, such as protease, neuraminidase, fucosidase, and alcohol dehydrogenase, can contribute to damage of the gastric epithelium by destroying the integrity of mucus or by inducing lipid peroxidation. Infection by vacuolating cytotoxic (VacA+) H. pylori strains is considered to constitute increased risk for development of peptic ulcer and gastric cancer. Exploration of the vacA gene structure has shown the existence of strongly toxigenic strains, and has confirmed at the molecular level the increased ulcerogenic potential of VacA+ H. pylori strains. A pathogenicity island called cag has been recently described in Type 1 H. pylori strains (VacA+/CagA+).cag contains the cagA gene (whose expression is associated with toxigenicity) and many genes, some of which are highly homologous to virulence genes of other virulent bacteria, that account for the enhanced pathogenic potential of CagA+ organisms.

Animals↗

PubMedDate not supplied

Potential virulence factors of Ureaplasma urealyticum.

Our understanding of the pathogenic potential of Ureaplasma urealyticum awaits further characterization of the species. This review adds recently published findings to the previously established properties of this myocoplasma.

Humans↗

PubMed2000

Immunoglobulin isotype determines pathogenicity in antibody-mediated myocarditis in naïve mice.

Antimyosin reactivity is associated with cardiac damage in autoimmune myocarditis, an inflammatory heart disease characterized by a cellular infiltrate in the myocardium and myocyte necrosis. We are interested in the pathogenicity of antimyosin antibodies and their ability to cause autoimmune myocarditis. We have shown that antimyosin antibodies of the IgG isotype will induce disease in the DBA/2 mouse. In the present study, we show that IgM antimyosin antibodies do not induce myocarditis; however, these same antibodies become pathogenic when converted to the IgG isotype. Although IgM antibodies can penetrate the myocardium during cardiac inflammation, they are usually less able to leave the vascular compartment and penetrate cardiac tissue, thus accounting for their lack of pathogenicity. Thus, antimyosin B cells may be potentially pathogenic only after antigen activation and heavy chain class switching or under conditions that alter vascular permeability in the heart.

Animals↗

PubMed2003

Exposure to airborne Gram-negative bacteria, dust and endotoxin in paper factories.

Air samples for determination of the concentration of Gram-negative bacteria, dust and endotoxin were collected at 10 sites in 2 large pulp and paper mills (paper factories) located in northern Poland, of which one (plant "A") was an older type facility while the other (plant "B") was a modern, fully automated factory with an effective ventilatory system. In both factories paper was produced from wood chips derived mostly from Scots pine. The concentrations of Gram-negative bacteria in the air of examined factories were within a range of 11.0-310.0 cfu/m(3), being greatest in the old type factory "A" at the initial stages of production cycle comprising handling of chips and pulp production. The mean value for these sites (246.9 cfu/m(3)) was significantly greater (t-test, p < 0.01) compared to final stages of paper production in the same factory (mean 32.1 cfu/m(3)) and to corresponding stages of chip handling in the modern "B" factory (mean 94.4 cfu/m(3)). The values of the respirable fraction of airborne Gram-negative flora were at most sites within a range of 40.0-56.9%. The species of the family Enterobacteriaceacae, mostly belonging to the genera Enterobacter, Pantoea, Rahnella and Klebsiella, distinctly prevailed in the air of the examined factories. Altogether, 19 species or genera of Gram-negative bacteria were identified in the collected air samples, out of these 9 were reported as having allergenic, immunotoxic and/or infectious properties. The concentration of dust in the air of paper factories ranged from 0.13-3.9 mg/m(3) and never exceeded the safe level. The concentration of bacterial endotoxin in the air of paper factories varied within a fairly wide range of 0.0042-2.5 micro g/m(3). At 4 sites associated with initial chip handling and pulp production large concentrations of airborne endotoxin between 0.2-2.5 micro g/m(3) were found, significantly exceeding suggested safe levels. In conclusion, despite Gram-negative bacteria occur in the air of paper mills in relatively low concentrations which never exceeded the value of 1,000 cfu/m(3) proposed as safe level, they may exert adverse effects on exposed workers, as evidenced by high concentrations of airborne endotoxin and the presence of numerous potentially pathogenic species. Thus, these microorganisms pose a potential risk of respiratory disease for the workers of pulp and paper mills, in particular for those engaged in handling of wood chips and production of pulp.

Air Pollution, Indoor↗

PubMedDate not supplied

[Pathogenicity factors of mollicutes and pathogenesis of some human mycoplasmoses].

The data of pathogenicity factors of mollicutes and mechanisms of the effect of these microorganisms on the organisms they have infected and, first of all, on people occur in countless literary sources. Such data have been accumulated for above 100 year of mycoplasmology existence as science and remain unachievable for most interested specialists. An attempt has been made to generalize in maximum complete volume everything known about pathogenic potential of human and other mollicutes, their pathogenicity factors and mechanisms of their realization on the dramatic changes occurring in the affected organism under the effect of mycoplasmic infection.

Humans↗

PubMed2005

[Biological effects of space flight on several opportunistic pathogenic bacteria and biodestructive fungi].

OBJECTIVE: To investigate biological effects of space flight on several conditional pathogenic bacteria and biodestructive fungi. METHOD: Several potentially pathogenic or biodegrading microorganisms, including bacteria, actinomyces and fungi, were carried on-board spacecraft for 7 d. Some of the biological characteristics were studied by using general microbial test technology after recovery. RESULT: In space condition, survival and growth rate were promoted, and soluble pigments were produced, while morphological properties were changed differently. The antibiotic-sensitivity of certain strains decreased, while most of them showed no changes. CONCLUSION: The reproduction ability and growth rate of these microorganisms are promoted after being carried into space, and morphological differentiation increase. The resistance to antibiotics is stable.

Actinomyces↗

PubMed1997

[Animal husbandry and food handling today. Current food preservation has changed the intestinal flora].

In the modern world, as refrigerated storage has replaced lactic acid fermentation methods of food preservation, we no longer ingest large quantities of live lactobacilli with our food, but relatively large numbers of potentially pathogenic Gram-negative bacteria instead. In the brave new world, antibiotics are used as growth-promoting additives in animal feed in every country but Sweden. The antibiotics used in Europe at low dosages, and exempt from prescription requirements, include macrolides, streptogramins and nitro-imidazoles. There is reason to believe that avoparcin, recently banned in Europe as an antibiotic animal feed additive, has contributed to the occurrence of vancomycin-resistant enterococci in humans. Animal foodstuffs production in Europe and the USA is so intensive that it provides very favourable conditions for the spread of bacteria. Pig, cattle and poultry breeding in Europe are beset by formidable difficulties in the form of Salmonella infections, which constitute not only a hygiene but also a clinical problem. Sweden, the bravest of brave new worlds, faces an increase in the influx of domestic animals and foodstuffs from other countries, and in general less restrictive regulations concerning food production and animal husbandry, but reduced powers of control. Thus, we may expect problems both with pathogens (traditional ones such as Salmonella, and potential ones such as food-spoilage Gram-negative bacteria), and with antibiotic-resistant bacteria in our food-stuffs, to become greater.

Animal Husbandry↗

PubMed2006

Optimal site for throat culture: tonsillar surface versus posterior pharyngeal wall.

To determine the optimal site of throat culture for the detection of potential pathogens by comparing culture results from the tonsillar surface and the posterior pharyngeal wall in children selected for adenotonsillectomy and in children without upper respiratory disease. Cotton culture swabs were taken from the tonsillar surface and the posterior pharyngeal wall of 50 children selected for adenotonsillectomy for symptoms of recurrent tonsillitis and/or adenotonsillar hypertrophy and of 50 children without upper respiratory disease. Potential respiratory pathogens were identified. In the overall group (n = 100), positive culture results were found in 67 posterior pharyngeal wall samples and 47 tonsillar surface samples (P = 0.001). Haemophilus influenzae was the most frequently isolated micro-organism both in the posterior pharyngeal wall and the tonsillar surface samples; 55 and 35%, respectively (P = 0.001). Group A beta-haemolytic streptococci were found in the samples of the posterior pharyngeal wall and the tonsillar surface in 17 and 13%, respectively (P = 0.2). When dealing with patients with sore throat, sampling both tonsillar surfaces is enough for the detection of group A beta-haemolytic streptococci. When detection of other bacteria is also important, such as for research purposes, the posterior pharyngeal wall should be sampled as well.

Adenoidectomy↗

PubMedDate not supplied

[Pathogenic power of Salmonellae: virulence factors and study models].

Salmonellae are potentially pathogenic for humans as well as for numerous animal species. They possess numerous virulence factors, which allow them to adapt to various environmental conditions and to host response at each step of the pathogenic process. Key-steps such as the invasion of epithelial cells or survival within macrophages have been extensively studied. These studies have led to the discovery of an original protein secretion system and have demonstrated the existence of pathogenicity islands. This considerable progress is due to the development of numerous in vitro and in vivo models and of new identification strategies for the implicated genes. Recently, many original and elegant strategies have been recently proposed.

Animals↗

PubMed1995

Variation of multifunctional surface binding proteins--a virulence strategy for group A streptococci?

Variation in surface antigens has been well recognized as a mechanism by which pathogenic organisms can avoid elimination and remain as potential pathogens in immunocompetent individuals. A variety of viral and parasitic organisms elude the immune system by varying their surface antigenic structures. Other persistent human pathogens, for example group A streptococci, are associated with cyclic variation in the severity of infections without any major change in their surface antigenic structures. Recent analysis of group A streptococcal proteins, in particular surface M and M-like proteins, has documented the existence of an array of multifunctional surface proteins which have the ability to bind to a variety of normal human plasma proteins, extracellular matrix components and human cells. The ability to change the functional activities of these surface molecules by genetic recombination among members of a closely related M protein supergene family has now been reported. In this paper, the potential importance of generating functional heterogeneity in surface binding proteins of group A streptococcus is discussed. The role of these proteins in enabling an organism to sense its environment and express the appropriate virulence factors is proposed as an explanation for the periodic changes in the frequency and severity of invasive group A streptococcal infections that can occur in the absence of a toxic-shock-like syndrome.

Antigens, Bacterial↗

PubMed2002

Pathogen population genetics, evolutionary potential, and durable resistance.

We hypothesize that the evolutionary potential of a pathogen population is reflected in its population genetic structure. Pathogen populations with a high evolutionary potential are more likely to overcome genetic resistance than pathogen populations with a low evolutionary potential. We propose a flexible framework to predict the evolutionary potential of pathogen populations based on analysis of their genetic structure. According to this framework, pathogens that pose the greatest risk of breaking down resistance genes have a mixed reproduction system, a high potential for genotype flow, large effective population sizes, and high mutation rates. The lowest risk pathogens are those with strict asexual reproduction, low potential for gene flow, small effective population sizes, and low mutation rates. We present examples of high-risk and low-risk pathogens. We propose general guidelines for a rational approach to breed durable resistance according to the evolutionary potential of the pathogen.

Bacteria↗

PubMed2004

Systematic survey on the prevalence of genes coding for staphylococcal enterotoxins SElM, SElO, and SElN.

Staphylococcus aureus remains a leading cause of food-poisoning with substantial impact on public health. Using a multiplex polymerase chain reaction-DNA enzyme immunoassay (PCR-DEIA), we studied the presence of genes encoding staphylococcal enterotoxin-like (SEl) superantigens sem, sen, and seo, associated with the enterotoxin gene cluster (egc), in 429 clinical Staphylococcus aureus isolates. 294 (68.5%) isolates tested positive for at least one of the three SEl genes. In contrast to the fixed gene combination seg/sei also located on egc, a substantial number of isolates (n = 108) were found to bear only one or two of the genes encoding SElM, SElN, and SElO. Regarding the origin of the S. aureus isolates, a significant difference (P = 0.022) was found for the possession of seo (61.2% of blood isolates versus 42.9% of nasal strains). Also sem (not significantly) was found more common in blood isolates (52.1% versus 40.5%). The survey of the newly described SEl genes sem-seo supports the concept that most clinical S. aureus isolates harbor subsets of pyrogenic toxin superantigens. The potential contribution of seo and sem to the pathogenic potential of S. aureus has to be further evaluated.

Bacteremia↗

PubMed1993

Adult bacterial nasopharyngitis: a clinical entity?

OBJECTIVE: To investigate bacterial nasopharyngitis as a cause of adult upper respiratory infection. DESIGN: Prospective case series. SETTING: Walk-in medical clinic of a university hospital. PATIENTS: 507 patients with cold or flu symptoms, sore throat, or recent cough; 21 control subjects without symptoms of upper respiratory infection. MEASUREMENTS AND MAIN RESULTS: After thorough history and physical examination, the patients underwent nasopharyngeal aspiration and throat culture. Nasopharyngeal specimens were cultured for both bacteria and viruses; antigens for influenza, parainfluenza, and respiratory syncytial virus were sought by enzyme-linked immunosorbent assay (ELISA); serum antibodies to viral respiratory pathogens were determined. Group A beta-hemolytic streptococci grew from the throat specimens of 39 of the 507 patients (8%) or 38 of 334 patients (11%) who had clinical diagnoses of pharyngitis. Thirty-three cases of influenza A, 20 cases of influenza B, and seven cases of parainfluenza infections were diagnosed. Bacteria were cultured from the nasopharyngeal secretions of 284 patients (56%). In contrast to pharyngeal culture, commensal mixed flora were rarely found in nasopharyngeal culture. Nasopharyngeal culture of bacteria usually considered to be respiratory pathogens was significantly associated with the presence of leukocytes. Streptococcus pneumoniae (odds ratio 6.0, 95% confidence interval 2.6-14.2), Moraxella catarrhalis (odds ratio 12.9, 95% confidence interval 3.1-79.5), and Hemophilus influenzae (odds ratio 3.0, 95% confidence interval 1.2-7.4) were all associated with the presence of leukocytes. In contrast, nasopharyngeal culture of coagulase-negative staphylococci, mixed flora, and the documentation of a viral infection were not associated with the presence of leukocytes. For none of 21 control subjects were "pathogenic" bacteria found. CONCLUSIONS: These data suggest that potentially pathogenic bacteria may have a causal role in adult nasopharyngitis, although further data are needed to confirm this hypothesis.

Adolescent↗

PubMed2006

Microcracks in eggs.

An experimental program of mechanical testing has shown that microcracks initiate in hens' eggs at loads less than that necessary to cause total structural failure. In contact loading, computational modeling and numerical analysis show that very high stress levels develop on the inner surface of the eggshell as it conforms to a hard contact surface. This causes a series of microcracks to initiate at the inner surface of the shell and radiate out from the load site. A series of concentric circumferential microcracks also develop beneath the cuticle from the edge of the contact zone. Calculations relating to the eggshells' dynamic response indicate that microcracks have a little effect on the structural stiffness and resonant frequencies of the egg. As a result, microcracks are unlikely to be detected by online crack detection systems, which rely on mechanical excitation. Eggs in retail outlets are likely to contain microcracks as a result of insults experienced during the collection, grading, and packing processes. Because the eggshell forms the first line of defense against potentially pathogenic microorganisms entering the egg contents, microcracks could potentially compromise egg safety.

Animals↗

PubMed2006

Pathogen responses to host immunity: the impact of time delays and memory on the evolution of virulence.

Current analytical models of the mammalian immune system typically assume a specialist predator-prey relationship between invading pathogens and the active components of the immune response. However, in reality, the specific immune system is not immediately effective following invasion by a novel pathogen. First, there may be an explicit time delay between infection and immune initiation and, second, there may be a gradual build-up in immune efficacy (for instance, during the period of B-cell affinity maturation) during which the immune response develops, before reaching maximal specificity to the pathogen. Here, we use a novel theoretical approach to show that these processes, together with the presence of long-lived immune memory, decouple the immune response from current pathogen levels, greatly changing the dynamics of the pathogen-immune system interaction and the ability of the immune response to eliminate the pathogen. Furthermore, we use this model to show how distributed primary immune responses combine with immune memory to greatly affect the optimal virulence of the pathogen, potentially resulting in the evolution of highly virulent pathogens.

Animals↗