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Pseudomonas aeruginosa for the evaluation of swimming pool chlorination and algicides.

Concentrations of ammonia and the chlorine stabilizer, cyanuric acid, which could be expected in swimming pools decreased the rate of kill by chlorine of the potential pathogen, Pseudomonas aeruginosa. The effect of cyanuric acid increased as the concentration of chlorine decreased, a fact of significance from a public health view. Quaternary ammonium algcides had little effect on the kill rate of chlorine, but an organic mercury algicide had a synergistic effect with chlorine when the chlorine activity was stressed by the addition of ammonia or the use of 100 times the normal concentration of bacteria. The effect of natural waters, rain, beaches, and swimming pools on the kill rate by 0.5 mg of chlorine per liter indicated that a treatment time of 1 hr or more was required to kill 99.9% of 10(6)Pseudomonas cells per ml. The synergism of chlorine and the organic mercury algicide was also demonstrated with these waters and with sewage treatment plant effluents. The necessity of developing and using laboratory tests which simulate conditions in swimming pools with heavy loads of swimmers, as opposed to tests in chlorine demand-free conditions, is discussed. Samples taken from well-supervised swimming pools when the swimmer load had been especially high required treatment times of 1 to 3 hr to obtain 99.9% kills of the potential pathogen, P. aeruginosa, with 0.5 mg of chlorine per liter.

Ammonia↗

Antiphospholipid syndrome and the idiotypic network.

To study whether monoclonal anticardiolipin antibodies (aCL), derived from patients with antiphospholipid syndrome (APS), have similar pathogenic potential, we have employed an experimental model of antiphospholipid syndrome. Monoclonal aCL were produced by the combined method of EBV transformation and somatic cell hybridization of lymphocytes, derived from patients with APS. The monoclonal aCL were used to immunize mice at the footpads and the mice were followed for serological and clinical manifestations of APS. The monoclonal antibody EY2C9, was found to bind weakly to cardiolipin and other phospholipids (i.e. phosphatidyl-serine, phosphatidyl-ethanolamine and phosphatidyl-inositol). The antibody TM1B9, although derived from a patient with SLE and with secondary APS, did not react with phospholipids. Immunization of naive BALB/c mice with EY2C9 was followed by production of sustained high titers of antiphospholipid antibodies associated with prolonged activated partial thromboplastin time (APTT) (46.8 +/- 5.0 s vs. 22.4 +/- 1.7 s, in the non-immunized mice). Mice immunized with TM1B9 had a more moderate titer of antiphospholipid antibodies and did not show prolonged APTT. The pregnant mice, that were immunized with EY2C9, had increased fetal resorption rate (the equivalent of fetal loss in the human) of 36.8 +/- 10% (vs. 2 +/- 4% in mice immunized with TM1B9). Our results confirm that monoclonal aCL, derived from a patient with APS, can have a pathogenic potential, dysregulating the idiotypic network and leading to the development of characteristic signs of APS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Regulatory CD8+ T cells fine-tune the myelin basic protein-reactive T cell receptor V beta repertoire during experimental autoimmune encephalomyelitis.

A significant number of self-reactive T cell clones escape thymic negative selection and are released into the periphery, where some are potentially pathogenic. The clonal expansion of self-reactive T cells is known to be limited during initial antigen encounter by apoptotic or anergic mechanisms, regulatory CD4+ T cells, and cytokines. Here we report that superimposed on these mechanisms, during the evolution of autoimmunity in experimental autoimmune encephalomyelitis (EAE), CD8+ T cells are induced, which fine-tune the peripheral self-reactive T cell receptor (TCR) repertoire. We assayed the myelin basic protein-reactive TCR repertoire in naive, EAE-recovered mice as well as EAE-recovered mice depleted of CD8+ T cells by TCRV beta surface expression, complementarity-determining region 3 length distribution, and complementarity-determining region 3 sequencing analysis. In EAE-recovered mice, certain myelin basic protein-reactive CD4+V beta 8.2+ clones are significantly decreased and this decrease is not observed if CD8+ T cells were depleted from these mice. The clones that persist in CD8+ T cell-intact mice are highly diverse in contrast to the clones expanded in CD8+ T cell-depleted mice, which are dominated by the significant outgrowth of a few clones. Importantly, the T cell clones that expand in the absence of CD8+ T cell control are enriched in potentially pathogenic self-reactive T cell clones capable of inducing EAE in vivo.

Adoptive Transfer↗

[Microbiological quality of human milk from a Brazilian milk bank].

OBJECTIVE: The objectives of the present study were to determine the prevalence of potentially pathogenic microorganisms that indicate the hygienic and sanitary conditions of human milk samples collected at a Human Milk Bank. METHODS: Three hundred and thirty eight (338) samples of human milk collected from a milk bank in a maternity in the municipality of Goiânia, in the state of Goias, Brazil were submitted to microbiological analysis. The latter were plated on McConkey agar according to the type of bacteria. Among the total number of samples collected, 194 consisted of raw milk and the remaining 144 were pasteurized milk. RESULTS: The presence of Staphylococcus spp., Streptococcus spp., yeasts and molds, and Enterobacteriaceae was verified in the raw milk samples. Staphylococcus aureus were isolated in 10 (5.2%) samples, Staphylococcus epidermidis in 28 (14.4%) samples, Streptococcus spp. in three (1.6%) samples, yeasts and molds in 43 (22.2%) and Enterobacteriaceae in 49 (25.3%) samples. In a hundred and forty four (144) samples which underwent thermal treatment Staphylococcus aureus was detected in five (3.5%) samples, Staphylococcus epidermidis in 15 (10.4%), Staphylococcus lugdenensis in two (1.4%), Streptococcus spp. in four (2.8%), yeasts and molds in 37 (25.7%), and Enterobacteriaceae in nine (6.3%). CONCLUSIONS: Analysis indicated a high degree of contamination in raw human milk, and as for the pasteurized milk, despite elimination of the great majority of potentially pathogenic microorganisms, the percentage of yeasts and molds was higher than in raw milk, demonstrating that a lower degree of initial contamination would be necessary for pasteurization to be an efficient means of microbiological control.

Brazil↗

Control of bacterial pneumonia during mechanical ventilation.

Pneumonia complicates the course of 50% of patients on mechanical ventilation, requiring three or more days of mechanical ventilation and potentially increasing the relative risk of mortality by 20-40%. The predominant potentially pathogenic micro-organisms are Streptococcus pneumoniae, Staphylococcus aureus (sensitive to methicillin in the previously healthy host), Pseudomonas aeruginosa (aerobic gram-negative bacilli), and methicillin-resistant Staphylococcus aureus in the host with underlying disease. Approximately 85% of pneumonias are endogenous, caused by bacteria present in the patient's oropharyngeal flora. Bacteria present on admission cause primary endogenous pneumonia (55%), whereas bacteria acquired in the unit lead to supercarriage or secondary carriage and subsequently secondary endogenous pneumonia (30%). The remaining 15% are exogenous, ie the bacteria causing pneumonia are not carried by the patient. The diagnosis is usually based on clinical, radiological, and microbiological criteria, using the non-invasive method of tracheal aspirate, which yields >/=10(5) micro-organisms. Seven randomized trials have evaluated three non-antibiotic prophylactic maneuvers: hygiene (1 trial), subglottic drainage (4 trials), and semirecumbent position (2 trials). The impact on pneumonia was mixed, whereas mortality was unchanged. Selective digestive decontamination, using parenteral and enteral antimicrobials to control the three types of pneumonia, has been evaluated in 54 trials and showed an absolute mortality reduction of 8%. The therapy of pneumonia relies on six basic principles: (a) surveillance and diagnostic cultures to identify micro-organisms; (b) immediate and adequate antibiotic treatment to sterilize the lower airways, (c) the source of potential pathogens requires elimination for recovery of the original infection and prevention of relapses and/or superinfections; (d) aerosolized antimicrobials; (e) removal or replacement of the endotracheal tube; and (f) surveillance samples are indispensable to monitor efficacy of treatment. The aim of our review was to evaluate up to date facts regarding control of bacterial pneumonias during mechanical ventilation in intensive care unit settings.

Amphotericin B↗

Equine alopecia areata autoantibodies target multiple hair follicle antigens and may alter hair growth. A preliminary study.

Several cases of an alopecia areata (AA)-like disease have been reported in mammalian species. How similar this disorder(s) is to human AA is unclear. We have previously shown that human AA is associated with antibodies to hair follicle (HF)-specific antigens and that similar antibody reactivities also occur in the C3H/HeJ "AA" murine model and in dogs with spontaneously occurring AA. The current preliminary study was conducted to determine whether a horse with AA-like hair loss contained circulating antibodies to HE The pathogenic potential of these antibodies was examined by passive transfer into anagen skin of C57BL/ 10 black mice. Indirect immunofluorescence analysis indicated that the equine "AA" serum reacted intensely with the inner root sheath, outer root sheath and pre-cortex of equine HF Immunoblot examination revealed antibodies to a 200-220 kDa doublet and to antigens of 40-60 kDa. Notably, this serum, but not control serum, contained antibodies that selectively immunoprecipitated trichohyalin from HF protein extracts. IgG fractions of serum obtained from an "AA" horse and from a normal control horse were injected into anagen murine skin. Histologically, normal hair regrowth was observed in mice injected with normal equine IgG. By contrast, hair did not re-grow in an area around the injection site of AA-treated mice even 13 weeks after first injection. This skin contained telogen follicles, most often without associated shafts, despite the presence of anagen HF in the remaining dorsum skin. While this study is preliminary, it demonstrates for the first time that antibodies to HF antigens are a feature of AA-like hair loss in horses. Some reactivities (e.g. against trichohyalin) were similar to those previously observed in "AA" dogs. Further, we provide in this pilot study preliminary evidence that such antibodies may disrupt hair re-growth when passively transferred into mice, supporting the view that anti-HF antibodies in AA may have pathogenic potential.

Alopecia↗

Respiratory microbiology patterns within the first 24 h of ARDS diagnosis: influence on outcome.

BACKGROUND: Airway colonization and infection are frequent complications during the course of ARDS. The impact on outcomes of microbiological patterns recovered within the first 24 h after diagnosis has not been evaluated. OBJECTIVES: To describe the incidence and patterns of bronchial colonization and lung infection within the first 24 h of ARDS diagnosis and to evaluate the influence on ICU outcomes. METHODS: Prospective study of ARDS patients evaluated within 24 h of diagnosis. Patients were studied with tracheobronchial aspirate and right and left bronchoscopic protected specimen brush. All samples were cultured quantitatively. RESULTS: Fifty-five consecutive patients were included. Twelve patients (22%) were clinically suspected of having nosocomial pneumonia (NP), which was confirmed microbiologically in 7 patients, a frequency of 13%. In those patients without suspected pneumonia, we also found potentially pathogenic microorganisms (PPMs) and potentially drug-resistant microorganisms (PDRMs) in 36% and 31%, respectively. Mortality was not significantly higher in those patients with recovery of a PPM (87% vs 73%, p = 0.31), PDRM (89% vs 74%, p = 0.18), or with NP (79% vs 85%, p = 1.0). CONCLUSION: There is a strikingly high rate of PPM recovery in early ARDS. However, neither isolation of pathogenic microorganisms nor the confirmation of NP could be associated with an increased mortality.

APACHE↗

The stethoscope. A potential source of nosocomial infection?

BACKGROUND: Stethoscope diaphragms have been shown to harbor potentially pathogenic bacteria. OBJECTIVES: To assess bacterial contamination on the diaphragm and under the plastic rim that secures the diaphragm of stethoscopes of physicians, nurses, medical students, and house staff in an intensive care unit and a general medical ward of a large university hospital. Also to compare the effectiveness of various cleaning agents and assess the transmissibility of bacteria from contaminated stethoscopes to human skin. METHODS: Aerobic and anaerobic bacterial cultures were performed on 40 randomly selected stethoscopes. We compared the effects of isopropyl alcohol, sodium hypochlorite (bleach), and benzalkonium chloride swabs, as well as soap and water, on reducing bacterial contamination on the stethoscope diaphragm and under the rim. The transmissibility of Micrococcus luteus inoculated onto a stethoscope diaphragm to clean human skin was also determined. RESULTS: Eleven genera and species of bacteria were isolated, with coagulase-negative staphylococcus present on 100% of stethoscopes and Staphylococcus aureus on 38%. Clostridium difficile was not isolated. The mean (+/-SE) number of total colony-forming units was 158 +/- 33 per diaphragm and 289 +/- 54 per rim. Physicians' stethoscope diaphragms had significantly more colony-forming units of coagulase-negative staphylococci than those of nurses: 163 +/- 44 vs 50 +/- 12, respectively (P = .02). The most effective cleaning agent was isopropyl alcohol after cleaning the diaphragm surface, the stethoscope diaphragms contained 0.2 +/- 0.2 colony-forming units and the rims contained 2.2 +/- 1.5 colony-forming units (P = .01). In addition, M luteus was transferred from inoculated stethoscopes to human skin. CONCLUSIONS: Most stethoscopes harbor potential pathogens but are not a source of C difficile. Physicians' stethoscopes generally had a higher bacterial load than nurses' stethoscopes. Isopropyl alcohol is an effective cleaning agent when applied to the stethoscope diaphragm. Stethoscopes transfer M luteus to human skin, making it likely that other bacteria can be transferred as well.

Cross Infection↗

Distribution of HPV16 and 18 intratypic variants in normal cytology, intraepithelial lesions, and cervical cancer in a Mexican population.

OBJECTIVE: Several intratype variants of HPV16 and 18 have been identified. These variants are associated with populations from different geographic regions, and show a differential distribution among the severity of the cervical lesion, most likely due to different pathogenic potential. The objective of this study was to investigate the variant distribution of HPV16 and 18 in a Mexican population and its association with the severity of the cervical lesion and the histological lineage of cervical cancer. METHODS: HPV types 16 and 18 detection was performed in 412 samples of preinvasive and invasive specimens from patients attending a Primary Health-Care Center, an Early Cervical Lesion Clinic, or a Cancer Center. Distribution of HPV variants was correlated with the cytological findings and tumor cell types using contingency tables. Statistical difference was tested with the Fisher's Exact Test or its Fisher-Freeman-Halton extension for RXC tables. Alpha value was set at the P < 0.05. RESULTS: Among the 277 women included in this study without cancer, 63.5% (176 cases) had a normal cytology; from the remaining 101 women, 53.5% were LSIL (54 cases), and 46.5% HSIL (47 cases). From a total of 135 invasive carcinomas, 78.5% were squamous (106 cases); 6.6% adenocarcinoma (9 cases); 9.6% adenosquamous (ADSC) (13 cases); and 5.1% were undifferentiated carcinoma (7 cases). HPV16 E and AA-a were evenly distributed among preinvasive and invasive lesions. However, the isolate AA-c was exclusively found in cervical cancer. HPV18 Var-1(E) was almost exclusively found in invasive lesions, while the HPV18 Var-2(Af) predominated in normal or preinvasive lesions. In invasive cancer, this variant was found only in squamous tumors. CONCLUSIONS: The differential distribution of HPV16 and 18 variants in cervical lesions we found further supports experimental data on the different pathogenic potential of HPV16 and 18 variants for cervical cancer development.

Cervix Uteri↗

[Routine throat swabs in artificially ventilated patients: meaningful bacteriologic monitoring or a needless procedure?].

UNLABELLED: Organisms colonizing the oropharynx of patients in the intensive care unit (ICU) play an important role in the development of nosocomial infection. Thus, routine throat swab specimens of ICU patients are recommended to screen for potential pathogens [20]. This investigation was designed to clarify the value of throat swabs taken in addition to tracheal aspirates, urine cultures, and wound swabs with regard to antibiotic therapy in patients with pneumonia and other infections. MATERIALS AND METHODS. A total 627 intubated patients were examined in a surgical ICU during a 12 month period. Pharyngeal swabs, tracheal aspirates, urine cultures, and-if necessary-swabs from wounds and drains were taken immediately after admission to the ICU and routinely thereafter three times each week. DEFINITIONS: Early onset pneumonia: pneumonia occurring within 4 days; late onset pneumonia: pneumonia occurring after the 4th day. Intra-abdominal infection: diffuse or localized peritonitis or abdominal abscess. Wound infection: soft-tissue or bone infection. Corresponding organisms: the same species of bacteria with the same sensitivity pattern (Table 1). RESULTS. Sixty-eight of the patients developed pneumonia. 37 had early onset pneumonia. In 22 of these patients, throat and tracheal specimens had been obtained 2-3 days before the pneumonia was diagnosed. In these specimens, the causative organisms for the subsequent pneumonia were isolated in the throat in 60% of cases and in tracheal secretions in 40% (Table 3). In 35 patients with late onset pneumonia, the causative bacteria were found in 66% of the cases in the throat swabs obtained 2-3 days before the diagnosis was made, in tracheal aspirates in 74% (Table 4). Throat swabs obtained at admission to the ICU from already infected patients or from patients who developed an infection were significantly more colonized with potentially pathogenic micro-organisms (Fig. 1). In 4 patients with early onset pneumonia the results of the throat swab cultures influenced antibiotic therapy, but none of the throat culture results influenced the therapy of the patients with late onset pneumonia or other infections (intra-abdominal infection, wound infection, urinary tract infection). CONCLUSIONS. The throat swab taken at admission may indicate patients at risk for infection. However, throat cultures taken routinely thereafter, parallel with tracheal aspirate cultures, do not provide additional information that is diagnostically or therapeutically helpful. Therefore, throat swab cultures are not necessary for routine bacteriological monitoring. For the prevention of colonization by local administration of antimicrobial agents, regular throat cultures are mandatory.

Adolescent↗

The prpR1 and prR2 arginine-specific protease genes of Porphyromonas gingivalis W50 produce five biochemically distinct enzymes.

The arginine-specific protease activity of Porphyromonas gingivalis is considered to be an important factor in the pathogenic potential of this organism in destructive periodontal disease. Multiple forms of closely related Arg-x proteases are present in the culture supernatants of P. gingivalis W50. RI is a heterodimer (alpha/beta) in which the catalytic alpha chain is associated with a second beta chain which functions as a haemagglutinin. RIA is a single-chain enzyme (alpha) and RIB is a highly post-translationally lipid-modified enzyme (LPS-alpha) with reduced solubility compared to the other two forms. The N-terminal sequence of the alpha chain of all three forms is identical, suggesting that all these enzymes may arise by differential processing of the prpR1 (protease polyprotein for RI). In the present study we constructed a prpR1- strain of P. gingivalis W50 by insertional gene inactivation and characterized the residual extracellular Arg-x protease activity of the resulting mutant. Loss of prpR1 expression led to the abolition of RI, RIA and RIB but the total Arg-x activity in the supernatant of this strain was reduced by only c. 66%. The remaining activity was composed of two novel forms of Arg-x protease (RIIA and RIIB) which appeared to be structurally and kinetically almost identical to RIA and RIB, respectively, except for two amino acid differences in the N-terminus at position 8 (Q-->E) and position 17 (A-->P) and with respect to their stability to high pH. Confirmation that RIIA and RIIB are the products of a homologous locus (prR2) was obtained by cloning and sequencing the prR2 which showed the predicted substitutions in the deduced translation. These data indicate that RI, RIA and RIB are produced by prpR1 expression and a maturation pathway which can give rise to a dimer and an unmodified- or LPS-modified catalytic monomer. Furthermore, RIIA and RIIB, the products of prR2, are exported into the culture supernatant in the absence of prpR1 expression and these forms may also contribute to the pathogenic potential of this organism in destructive disease.

Adhesins, Bacterial↗

Evidence that caterpillar labial saliva suppresses infectivity of potential bacterial pathogens.

Salivary enzyme, glucose oxidase (GOX) from the caterpillar Helicoverpa zea, catalyzes the conversion of glucose to gluconic acid and hydrogen peroxide. Because hydrogen peroxide has well-known antimicrobial properties, we examined whether caterpillar labial saliva could reduce the infectivity of bacterial pathogens. We examined the effects of caterpillar saliva on the growth of two bacteria species Serratia marcescens and Pseudomonas aeruginosa. Wells formed in LB agar contained a solution of salivary gland extract (Sx) and glucose, GOX and glucose, Sx only, GOX only, or glucose only. After 18 h of incubation, the diameter of cleared bacteria was measured. Wells treated with only GOX, Sx, or glucose showed no measurable area of clearing, while wells treated with GOX with glucose or Sx with glucose had considerable clearing. To determine if saliva could provide protection to caterpillars in vivo, a surgery was performed on caterpillars that prevented the secretion of labial saliva. Caterpillars were fed a diet containing either no added bacteria or treated with high levels of S. marcescens or P. aeruginosa. Caterpillars that could not secrete saliva had significantly higher levels of mortality when feeding on diet treated with either bacterium than caterpillars that could secrete saliva when feeding on equal levels of bacteria-treated diet. Our evidence demonstrates for the first time that insect saliva in situ can provide protection against bacterial pathogens and that the salivary enzyme GOX appears to provide the antimicrobial properties.

Animals↗

Epidemic potential and pathogenicity in outbreaks of infection with EMRSA and EMREC.

Multiply antibiotic-resistant Staphylococcus aureus and Escherichia coli have both caused outbreaks in London in recent years, and for this reason have been referred to as E(epidemic)MRSA and EMREC respectively. In each case it has been questioned whether either organism has properties other than antibiotic resistance that distinguish them from other strains. Evidence is adduced to suggest that EMRSA has properties that enable it to spread particularly well, and that EMREC is particularly virulent. Both were introduced into our environment by chance, and were helped by their antibiotic resistance to become involved in a train of events--different in each case--that culminated in severe infection in a small number of patients, and thus to further investigation. The organisms involved in such outbreaks are worthy of investigation and control, if only because of the difficulty of treating clinical infections when they develop.

Cross Infection↗

Enhanced HIF-1&#x3b1; cooperation by a human ROR&#x3b3;t mutant potentiates Th17 pathogenicity.

T helper 17 (Th17) cells are pivotal in mucosal defense and autoimmune pathology, with their function governed by the transcription factor retinoic acid receptor-related orphan receptor gamma t (ROR&#x3b3;t). Although genome-wide association studies link RORC variants to inflammatory diseases, their functional consequences remain poorly understood. We identify a pathogenic ROR&#x3b3;t mutation N277D (mouse homolog N275D) that amplifies Th17 pathogenicity through cooperation with hypoxia-inducible factor HIF-1&#x3b1;. This mutation enhances IFN-&#x3b3; and other Th1-type cytokine production by Th17 cells, exacerbating colitis without disrupting T cell development or homeostasis. Integrated transcriptomic and metabolomic profiling reveals activation of glycolytic and hypoxia-associated pathways, consistent with increased ROR&#x3b3;tN275D recruitment by HIF-1&#x3b1; to the Pdk1 locus. Notably, silencing Pdk1 normalizes the excessive IFN-&#x3b3; production in ROR&#x3b3;tN275D Th17 cells. Together, these findings define a regulatory axis linking ROR&#x3b3;t and HIF-1&#x3b1; that coordinates transcriptional and metabolic programs in pathogenic Th17 cells, providing a framework for dissecting the functional impact of autoimmune risk variants.

CP: immunology↗

Occurrence of potential bacterial pathogens in coastal areas of the Adriatic Sea.

A monitoring program was carried out in bathing waters along the sea-coast of the Adriatic Sea. The investigation was aimed at obtaining a quali-quantitative picture of microorganisms of anthropic origin and of a more strictly autochthonous origin and at verifying the existence of possible reciprocal correlations and combinations of relationship between them. Results showed that the concentrations of indicators of faecal contamination, whether within or over the values established by legislation, are not always related to the presence and density of microorganisms of environmental origin but the regression models used can help to describe how these latter microorganisms can be in relation to levels of the other parameters. The difficulty is evident of the predictability of health effects swimming-associated; for this reason more complex models that are currently used should be taken into account for minimising the risk for bathers.

Enterobacteriaceae↗

Sulfate-reducing bacteria in relation with other potential periodontal pathogens.

BACKGROUND, AIMS: Oral sulfate-reducing bacteria are involved in several clinical categories of periodontitis. The aim of this cross-sectional study was to compare the presence of sulfate-reducing bacteria (SRB) with other putative pathogens including spirochetes, Actinobacillus actinomycetemcomitans, Bacteroides forsythus, Porphyromonas gingivalis, and Treponema denticola in periodontal lesions. METHOD: Periodontal SRB were detected by enrichment culture and compared with a microscopic spirochete count (n=168). Species-specific oligonucleotide probes directed against the 16S rRNA were employed to determine the presence of A. actinomycetemcomitans, P. gingivalis, B. forsythus, and T. denticola (n=55). RESULTS: A significant positive correlation was observed between the presence of SRB and the proportions of spirochetes in subgingival plaque, although the 2 bacterial groups also occurred separately. SRB tended to be negatively correlated with the presence of A. actinomycetemcomitans. In contrast, all pockets with SRB harbored either T. denticola, or both T. denticola and B. forsythus (12/14) before therapy. Interestingly, the combination of SRB with P. gingivalis occurred in 32% of the periodontal pockets before treatment. After initial periodontal therapy, the prevalence of this combination was reduced to 2% of the sites, and to 25% of the sites in recall patients. CONCLUSION: The presence of SRB was positively correlated with T. denticola, B. forsythus, and P. gingivalis in periodontal lesions. These suspected pathogens form a complex strongly associated with destructive periodontitis.

Adult↗

Histoplasma capsulatum alpha-(1,3)-glucan blocks innate immune recognition by the beta-glucan receptor.

Successful infection by fungal pathogens depends on subversion of host immune mechanisms that detect conserved cell wall components such as beta-glucans. A less common polysaccharide, alpha-(1,3)-glucan, is a cell wall constituent of most fungal respiratory pathogens and has been correlated with pathogenicity or linked directly to virulence. However, the precise mechanism by which alpha-(1,3)-glucan promotes fungal virulence is unknown. Here, we show that alpha-(1,3)-glucan is present in the outermost layer of the Histoplasma capsulatum yeast cell wall and contributes to pathogenesis by concealing immunostimulatory beta-glucans from detection by host phagocytic cells. Production of proinflammatory TNFalpha by phagocytes was suppressed either by the presence of the alpha-(1,3)-glucan layer on yeast cells or by RNA interference based depletion of the host beta-glucan receptor dectin-1. Thus, we have functionally defined key molecular components influencing the initial host-pathogen interaction in histoplasmosis and have revealed an important mechanism by which H. capsulatum thwarts the host immune system. Furthermore, we propose that the degree of this evasion contributes to the difference in pathogenic potential between dimorphic fungal pathogens and opportunistic fungi.

Animals↗