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Characterization of the mutS-proximal region of the Salmonella typhimurium SPI-1 identifies a group of pathogenicity island-associated genes.

The virulence properties of Salmonella enterica are largely encoded within a set of horizontally acquired gene blocks termed pathogenicity islands. One such pathogenicity island, SPI-1, located at centisome 63 of the Salmonella chromosome between the mutS and fhlA genes, encodes a type III protein secretion system and an iron uptake system. We have characterized the mutS-proximal border of this pathogenicity island and have identified two sets of genes, pigAB and pigCD. All four genes have homologs of unknown function in several bacteria that share the ability to establish an intimate association with higher eukaryotic hosts. The expression of at least two of these genes, pigA and pigB, is controlled by SprA, a transcription factor encoded within SPI-1 that controls the expression of genes associated with the type III secretion system of this island. In addition, we found that homologs of the pig genes are also found at different locations of the S. enterica chromosome in association with segments of DNA that exhibit features of pathogenicity islands. The presence of several apparently functional copies of these genes argues for an important role in the biology of this bacterial pathogen. Furthermore, they constitute a valuable tool to identify potential pathogenicity islands.

Animals↗

Sulfated polysaccharide-directed recruitment of mammalian host proteins: a novel strategy in microbial pathogenesis.

Fundamental to the virulence of microbial pathogens is their capacity for adaptation and survival within variable, and often hostile, environments encountered in the host. We describe a novel, extragenomic mechanism of surface modulation which may amplify the adaptive and pathogenic potential of numerous bacterial species, including Staphylococcus, Yersinia, and pathogenic Neisseria species, as well as Helicobacter pylori and Streptococcus pyogenes. The mechanism involves specific bacterial recruitment of heparin, glycosaminoglycans, or related sulfated polysaccharides, which in turn serve as universal binding sites for a diverse array of mammalian heparin binding proteins, including adhesive glycoproteins (vitronectin and fibronectin), inflammatory (MCP-3, PF-4, and MIP-1alpha) and immunomodulatory (gamma interferon) intermediates, and fibroblast growth factor. This strategy impacts key aspects of microbial pathogenicity as exemplified by increased bacterial invasion of epithelial cells and inhibition of chemokine-induced chemotaxis. Our findings illustrate a previously unrecognized form of parasitism that complements classical virulence strategies encoded within the microbial genome.

Animals↗

The conservative physiology of the immune system.

Current immunological opinion disdains the necessity to define global interconnections between lymphocytes and regards natural autoantibodies and autoreactive T cells as intrinsically pathogenic. Immunological theories address the recognition of foreignness by independent clones of lymphocytes, not the relations among lymphocytes or between lymphocytes and the organism. However, although extremely variable in cellular/molecular composition, the immune system preserves as invariant a set of essential relations among its components and constantly enacts contacts with the organism of which it is a component. These invariant relations are reflected, for example, in the life-long stability of profiles of reactivity of immunoglobulins formed by normal organisms (natural antibodies). Oral contacts with dietary proteins and the intestinal microbiota also result in steady states that lack the progressive quality of secondary-type reactivity. Autoreactivity (natural autoantibody and autoreactive T cell formation) is also stable and lacks the progressive quality of clonal expansion. Specific immune responses, currently regarded as the fundament of the operation of the immune system, may actually result from transient interruptions in this stable connectivity among lymphocytes. More permanent deficits in interconnectivity result in oligoclonal expansions of T lymphocytes, as seen in Omenn's syndrome and in the experimental transplantation of a suboptimal diversity of syngeneic T cells to immunodeficient hosts, which also have pathogenic consequences. Contrary to theories that forbid autoreactivity as potentially pathogenic, the physiology of the immune system is conservative and autoreactive. Pathology derives from failures of these conservative mechanisms.

Animals↗

The bacterial flora of the nasopharynx, with special reference to middle ear pathogens. A quantitative study in twenty children.

Quantification of middle ear pathogens (S. pneumoniae, H. influenzae and B. catarrhalis) and potential pathogens (S. aureus and coagulase-negative staphylococci) adhering to the posterior wall of the nasopharynx was performed in 20 patients of whom 5 were suffering from secretory otitis media (SOM), 5 from recurrent attacks of acute otitis media (rAOM), 5 from attacks of upper respiratory infection (URI) and 5 from blocked nose (BN). While the patients were under general anesthesia a glass cylinder (diameter 1.3 cm) was pressed against the posterior wall of the nasopharynx and swabs were taken from the mucosa delineated by the glass tube. Quantification of the bacteria was performed using blood and chocolate agar plates. Total bacterial counts ranged between 2.6 x 10(4)CFU/cm2 and 4.0 x 10(8)CFU/cm2. In the rAOM group, 4 out of 5 children had bacterial counts in the nasopharynx which constituted of 95% pathogens. Coagulase-negative staphylococci never exceeded 1.9 x 10(5)CFU/cm2.

Acute Disease↗

[Fabry's disease associated with rheumatoid arthritis. Multisystemic crossroads].

Fabry's disease is a rare congenic disorder of glycosphingolipid catabolism resulting from deficient activity of the alpha galactosidasa. Is an X-linked disorder and in hemizygous males the activity of this enzyme is very low, resulting in severe manifestations. Fabry disease is confirmed by the lack alfa-galactosidase in serum. In the literature have been reported a few cases of coexistent Fabry's disease and connective disorders, but there is not cases of rheumatoid arthritis coexistent. This report describes a case of a female with Fabry's disease who vas subsequently diagnosed with rheumatoid arthritis. The suspect diagnosis was very important because the two disorders are multisystem and new symptoms could be attributed to Fabry's disease. The accumulation of lipids may results in numerous pathogenic autoantibodies, which could make immunocomplex. This is the potential pathogenic mechanisms explaining the association between Fabry's disease and autoimmune diseases.

Arthritis, Rheumatoid↗

[Characterization of the biological properties of enterococci of different origin].

The species composition of enterococci isolated from different ecological niches in newborn infants was determined. Pathogenicity and persistence markers were unified into a single complex which integrally determined the pathogenic potential of enterococci. The mathematical model suitable for differentiation pathogenic and nonpatogenic enterococci was developed.

Digestive System↗

Understanding mucosal responsiveness: lessons from enteric bacterial pathogens.

Mucosal immune responses must discriminate between commensal flora within the lumen and potential pathogens. These responses are highly adapted to induce protection without excessive inflammation. The balances that regulate mucosal immune and inflammatory responses have to be understood if effective mucosal immunity is to be induced through local immunization. This review will summarize some of the lessons learnt from studies of antigens derived from enteric bacterial pathogens and discuss how the gastrointestinal epithelia can 'fight back' when it encounters pathogens.

Animals↗

The incidence of conditionally pathogenic mycobacteria in the northern Moravia region in 1978-1987.

The incidence of potential pathogenic mycobacteria (PPM) has been studied in the Northern Moravia since 1970. The present paper follows up a previous communication summing up the finding for the period 1970-1977 during which were isolated from 713 persons. In 1978-1987, 4,658 strains were isolated from 1,917 persons. The species most frequently isolated was M. gordonae. A significant increase was observed in the incidence of mycobacterioses due to M. kansasii, namely from 2.90/100,000 in 1970 to 17.70/100,000 in 1987 in the Karvina district, the centre of endemic area. PPM was isolated from 321 water samples.

Bacteriological Techniques↗

Die-off of enteric bacterial pathogens during mesophilic anaerobic digestion.

Conventionally treated sewage sludge may contain high concentrations of potentially pathogenic microorganisms and additional treatment is required to minimise the risks to health if it is to be recycled to agricultural land. Mesophilic anaerobic digestion (MAD) is the most widely used process in the UK for stabilising sludge prior to agricultural recycling, but little is known about the fate of a number of enteric pathogens as the sludge passes through the treatment processes. The aim of this study was to determine the efficiency of MAD in removing the bacterial enteric pathogens, Salmonella senftenberg, Listeria monocytogenes and Campylobacter jejuni which were added as a spike to the digester feedstock, together with the die-off of indigenous Escherichia coli already present in the sludge. The primary sludge digestion stage of MAD was found to achieve a log removal of 1.66 for E. coli, 2.23 for L. monocytogenes and 2.23 for S. senftenberg. However, the extent of die-off was a function of the numbers of pathogens in the feed and as these increased the log removal also increased. The numbers of C. jejuni were not affected by primary sludge digestion. Additional die-off was provided by secondary sludge digestion with log removals of 1.70 for E. coli, 2.10 for S. senftenberg and 0.36 for C. jejuni.

Agriculture↗

Is antibiotic therapy justified in the treatment of human chronic inflammatory periodontal disease?

New insight into the possible involvement of specific bacteria in the etiology of periodontal disease has stimulated interest in antibiotic therapy. However, current knowledge does not allow the designation of one or more pathogens in periodontal diseases. Some bacteria are considered suspected periodontal pathogens due to their predominance in the pocket and their potential pathogenicity, yet they all appear to be indigenous bacteria. For this reason, one can question the rationale for the use of antibiotics in the treatment of periodontal disease since the theoretical basis for their application seems small. Several reports of clinical trials in which antibiotics were administered as an adjunct to scaling and rootplaning in adult periodontitis conclude with encouraging statements concerning bacterial inhibition and the cure of inflammatory periodontal disease. However, the data are conflicting and mostly negative. Antibiotic treatment in combination with scaling and rootplaning in juvenile periodontitis and refractory adult periodontitis has shown some benefit, but the clinical trials were not sufficiently controlled to permit conclusions. So far, antibiotics have been applied as a last resort in order to supplement the non-specific approach of mechanical root debridement, but it can be doubted whether this approach offers any benefit in the long run.

Anti-Bacterial Agents↗

A passive transfer model of the organ-specific autoimmune disease, bullous pemphigoid, using antibodies generated against the hemidesmosomal antigen, BP180.

Subepidermal blistering associated with the human skin diseases bullous pemphigoid and herpes gestationis has been thought to be an IgG autoantibody-mediated process; however, previous attempts to demonstrate the pathogenicity of patient autoantibodies have been unsuccessful. An immunodominant and potentially pathogenic epitope associated with these blistering diseases has recently been mapped to the extracellular domain of a human epidermal antigen, BP180. Patient autoantibodies that react with this well-defined antigenic site failed to crossreact with the murine form of this autoantigen and thus could not be assayed for pathogenicity in a conventional passive transfer mouse model. As an alternative, rabbit polyclonal antibodies were generated against a segment of the murine BP180 protein homologous with the human BP180 autoantibody-reactive site and were passively transferred into neonatal BALB/c mice. The injected animals developed a subepidermal blistering disease that closely mimicked bullous pemphigoid and herpes gestationis at the clinical, histological, and immunological levels. Autoantibodies that recognize the human BP180 ectodomain are therefore likely to play an initiatory role in the pathogenesis of bullous pemphigoid and herpes gestationis.

Amino Acid Sequence↗

Antimicrobial agents in elective surgery: prophylaxis or "early therapy"?

A lack of a clear distinction between antimicrobial prophylaxis and therapy still exists in the surgical setting. Major concerns are: 1) Which surgical procedures are eligible for antimicrobial prophylaxis? 2) Which kind of antimicrobial agent should be used for surgical prophylaxis? 3) What is the optimal timing for administering antimicrobial prophylaxis and how long should administration be continued? In this paper we assess the rationales leading to the following answers: 1) Only clean-contaminated and prosthetic clean operations should be eligible for antimicrobial prophylaxis, whereas contaminated or dirty operations should be eligible for "early therapy". 2) First- or second-generation cephalosporins or aminopenicillin/beta-lactamase inhibitors are optimal choices for surgical prophylaxis, depending on location of the surgical wound. 3) The highest licensed dosage of the chosen antimicrobial agent should be administered at induction of anesthesia and redosing should be considered when the intervention lasts more than 2 antibiotic half-lives. This allows maintenance of optimal drug exposure against the potential pathogens in plasma and in the extracellular environment of the potentially contaminated tissues for the entire procedure and for some hours after wound closure. Post-surgical doses are not recommended in most cases whereas ultra-short prophylaxis is preferred.

Anti-Bacterial Agents↗

Characterization of Haemophilus influenzae isolates from the respiratory tract of patients with primary antibody deficiencies: evidence for persistent colonizations.

A total of 117 consecutive patients with primary antibody deficiencies were followed for up to 5 years with regard to acute respiratory tract infections. Nontypeable Haemophilus influenzae (NTHI) was the sole pathogen in 61% (202/330) of the samples from which a potential pathogen was recovered. Common variable immunodeficiency (CVI) was the most prevalent condition (27/39 patients) in the group where H. influenzae was isolated. In patients where H. influenzae was not found only 9/78 patients had CVI. 49 of these 78 patients had isolated IgG3 or IgA deficiency. Both of these entities seemed to be associated with a lower prevalence of NTHI infections. 13 of 18 patients with at least 2 isolates of NTHI were colonized with the same strain from 3 to 43 months as shown by total genomic DNA-fingerprinting. Recurrent symptomatic infections occurred in these patients despite substitution therapy with gammaglobulins and repeated antibiotic treatments. All but 2 of the 224 H. influenzae isolates were beta-lactamase negative and sensitive to ampicillin. The use of 10 lipopolysaccharide-specific monoclonal antibodies in a whole cell ELISA showed that the LPS-epitopes on the 224 H. influenzae isolates from the hypogammaglobulinemic group were very similar to 499 NTHI isolates from immunocompetent patients with respiratory infections. One may therefore conclude that i) patients with CVI, were prone to be permanently colonized with NTHI, and ii) the colonizing bacteria were ordinary strains showing the same LPS-phenotypes as those strains that cause acute respiratory tract infections in immunocompetent individuals.

Adolescent↗

Infectious myositis. A tropical disease steals out of its zone.

Infectious myositis is an acute infection of skeletal muscle that is increasing in prevalence with the increased incidence of HIV disease. Typical presentation is asymmetric swelling of an isolated muscle, with exquisite pain and fever. Results of laboratory studies are usually nonspecific, but magnetic resonance imaging of the affected area suggests the diagnosis. Muscle biopsy and direct identification of the pathogen on tissue culture are required, because the list of potential pathogens is long. With prompt treatment, most patients achieve complete resolution and return to their preinfection level of health.

Adult↗

Giardiasis and other intestinal parasitic infections in a Manitoba residential school for the mentally retarded.

A case of severely symptomatic giardiasis in a school for the mentally retarded prompted an epidemiologic survey of the institution. The rate of parasitic infection in the children were just under 50%. Multiple infections were common and one child harboured five different protozoa. The yield included known pathogens (Giardia lamblia, Metorchis conjunctus and Diphyllobothrium sp.), protozoa of potential pathogenicity (Dientamoeba fragilis) and other protozoa, the significance of which has yet to be determined. The prevalence of G. lamblia in the index ward was significantly higher than in a control ward matched for age and mobility of the children. The epidemiologic data suggested person-to-person transmission of G. lamblia within the institution. Recommendations for the control of protozoal intestinal infections in custodial institutions are presented.

Child↗

Pathogenic intestinal parasites and bacterial agents in solid wastes.

OBJECTIVE: To determine the profile of potentially pathogenic enteric parasites and bacterial agents in municipal refuse dumps in Ibadan, Nigeria. DESIGN: A cross-sectional survey. SETTING: Five major market places refuse dumps in Ibadan municipality, Nigeria. METHODS: The major market places in Ibadan city were randomly selected by lottery method. The refuse sludge were sampled and examined parasitologically and bacteriologically using the methods as described. Data analysis was done by using chi-square test where applicable. RESULTS: Cases of multiple intestinal parasites and bacterial agents were commonly encountered in the sludge refuse samples. The commonly found parasitic agents were of both human and veterinary importance. These include Ascaris Lumbricoides (9.3 egp), Entamoeba histolytica (8.07 cyst per gram), Hookworm/strongyle (6.27 egp) and Ascaris suum (1.07 egp). Others were Ascaris vitolorum (1.09 epg), Strongyloides papillosu (0.52 larvae per gram.), Schistosoma suis (0.31 epg) Dicrocoelium dendriticum (0.9 egp). The most commonly found bacterial agents were Klebsiella species, Escherichia Coli, Proteus species, streptococci, and other gram-positive organisms. Climatic conditions affected the distribution of both parasites and bacterial agents in the sludge (P<0.001). More intestinal parasites 2423 (53.4%) and bacterial agents 2150 (27.2%) were encountered at mean air temperature 26.1 +/- 0.6, mean relative humidity of 72 +/- 3.5%. The degree of contamination by market locations varies significantly (P<0.001). CONCLUSION: A high degree of contamination of solid waste dumpsites with bacterial and parasitic agents was observed in the present study. As a result of the public health importance of the organisms isolated it is opined that well planned waste management and health education programs will go a long way to reduce the potential epidemic risks posed by such sites in Ibadan, Nigeria.

Animals↗

Mediation of pathogen resistance by exudation of antimicrobials from roots.

Most plant species are resistant to most potential pathogens. It is not known why most plant-microbe interactions do not lead to disease, although recent work indicates that this basic disease resistance is multi-factorial. Here we show that the exudation of root-derived antimicrobial metabolites by Arabidopsis thaliana confers tissue-specific resistance to a wide range of bacterial pathogens. However, a Pseudomonas syringae strain that is both at least partly resistant to these compounds and capable of blocking their synthesis/exudation is able to infect the roots and cause disease. We also show that the ability of this P. syringae strain to block antimicrobial exudation is dependent on the type III secretory system.

Anti-Infective Agents↗

Role of contact lens wear, bacterial flora, and mannose-induced pathogenic protease in the pathogenesis of amoebic keratitis.

The ocular surface is continuously exposed to potential pathogens, including free-living amoebae. Acanthamoeba species are among the most ubiquitous amoebae, yet Acanthamoeba keratitis is remarkably rare. The pathogenesis of Acanthamoeba keratitis is a complex, sequential process. Here we show that Acanthamoeba keratitis is profoundly affected by mannosylated proteins on the ocular surface, which stimulate the amoebae to elaborate a 133-kDa pathogenic protease. The mannose-induced protease (MIP133) mediates apoptosis of the corneal epithelium, facilitates corneal invasion, and degrades the corneal stroma. We show that contact lens wear upregulates mannosylated proteins on the corneal epithelium, stimulates MIP133 secretion, and exacerbates corneal disease. Corynebacterium xerosis, a constituent of the ocular flora, contains large amounts of mannose and is associated with Acanthamoeba keratitis. The present results show that amoebae exposed to C. xerosis produce increased amounts of MIP133 and more severe corneal disease. Oral immunization with MIP133 mitigates Acanthamoeba keratitis and demonstrates the feasibility of antidisease vaccines for pathogens that resist immune elimination.

Acanthamoeba Keratitis↗