15 research outputs found

    Molecular characterization and antimicrobial susceptibilities of Clostridium difficile clinical isolates from Victoria, Australia

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    Some Australian strain types of Clostridium difficile appear unique, highlighting the global diversity of this bacterium. We examined recent and historic local isolates, finding predominantly toxinotype 0 strains, but also toxinotypes V and VIII. All isolates tested were susceptible to vancomycin and metronidazole, while moxifloxacin resistance was only detected in recent strains

    Disseminated tuberculosis, CMV viraemia & haemophagocytic-lymphohistiocystosis syndrome in an adult patient with anti- IFNγ autoantibodies – case report and brief review

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    We report a case of an adult female with disseminated tuberculosis, cytomegalovirus viraemia and haemophagocytic-lymphohistiocystosis syndrome associated with neutralizing anti- interferon gamma (IFNγ) autoantibodies demonstrated by absent IFNγ stimulated STAT1 phosphorylation in the presence of patient sera. A brief review of immunodeficiency caused by anti-IFNγ autoantibodies is also described

    The anti-sigma factor TcdC modulates hypervirulence in an epidemic BI/NAP1/027 clinical isolate of Clostridium difficile

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    Nosocomial infections are increasingly being recognised as a major patient safety issue. The modern hospital environment and associated health care practices have provided a niche for the rapid evolution of microbial pathogens that are well adapted to surviving and proliferating in this setting, after which they can infect susceptible patients. This is clearly the case for bacterial pathogens such as Methicillin Resistant Staphylococcus aureus (MRSA) and Vancomycin Resistant Enterococcus (VRE) species, both of which have acquired resistance to antimicrobial agents as well as enhanced survival and virulence properties that present serious therapeutic dilemmas for treating physicians. It has recently become apparent that the spore-forming bacterium Clostridium difficile also falls within this category. Since 2000, there has been a striking increase in C. difficile nosocomial infections worldwide, predominantly due to the emergence of epidemic or hypervirulent isolates that appear to possess extended antibiotic resistance and virulence properties. Various hypotheses have been proposed for the emergence of these strains, and for their persistence and increased virulence, but supportive experimental data are lacking. Here we describe a genetic approach using isogenic strains to identify a factor linked to the development of hypervirulence in C. difficile. This study provides evidence that a naturally occurring mutation in a negative regulator of toxin production, the anti-sigma factor TcdC, is an important factor in the development of hypervirulence in epidemic C. difficile isolates, presumably because the mutation leads to significantly increased toxin production, a contentious hypothesis until now. These results have important implications for C. difficile pathogenesis and virulence since they suggest that strains carrying a similar mutation have the inherent potential to develop a hypervirulent phenotype

    Emergence of a ribotype 244 strain of clostridium difficile associated with severe disease and related to the epidemic ribotype 027 strain

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    Background. We identified 12 patients with Clostridium difficile infection between July 2011 and March 2012 from whom an unusual C. difficile strain was isolated. This strain had a single-nucleotide deletion of the tcdC gene at position 117 and binary toxin genes, which are characteristic of the hypervirulent ribotype (RT) 027 strain.Methods. A retrospective cohort study of 12 patients infected with C. difficile RT244 and 24 patients infected with non-RT244/non-RT027 strains matched for place of diagnosis and time of collection of specimen was performed. We performed whole-genome sequencing to understand the relationship of the RT244 strain to other C. difficile strains and further understand its virulence potential.Results. Clostridium difficile RT244 was associated with more severe disease and a higher mortality rate. Phylogenomic analysis using core genome single-nucleotide polymorphisms showed that RT244 is in the same genetic clade (clade 2) as RT027 but is distinct from all RT027 strains. The pathogenicity locus of the RT244 strain encodes a variant toxin B, and this was confirmed by demonstration of Clostridium sordellii-like cytopathic effect on Vero cells. Toxin B production in culture supernatants was lower than that seen with a RT027 strain.Conclusions. Our findings demonstrate the pathogenic potential of this RT244 C. difficile strain and emphasize the importance of ongoing surveillance for emergent strains

    The light climate of Loch Leven, a shallow Scottish lake, in relation to primary production of phytoplankton

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    Seasonal changes in incident irradiance and underwater light penetration at Loch Leven from 1968 to 1971 are discussed in relation to the photosynthetic behaviour and crop density of phytoplankton. Light extinction was highest in the blue and lowest in the orange spectral regions, a pattern typical of other turbid waters. Euphotic depth varied between 1·2 and 7·4 m and was on average c. three times the Secchi disc transparency. Underwater light extinction depended chiefly on phytoplankton crop density (estimated as chlorophyll a). Despite the shallowness and wind-exposed situation of the loch there was no evidence of appreciable light extinction due to sediment disturbance. Possible causes of variability in the relationship between the minimum vertical extinction coefficient (k min) and the concentration of chlorophyll a are discussed. The value of ks, the increment in kmin per unit increment in algal concentration, was estimated from field data as 0·0086 In units per mg chl a/m2 and from laboratory spectroradiometer data as 0·0079 In units per mg chl a/m2. These ks values imply theoretical upper limits for the amount of chlorophyll a in the euphotic zone (Σn max) of 430 and 468 mg chl a/m2, respectively. Observed euphotic chlorophyll a contents (Σn) were sometimes close to these upper limits. Typical photosynthesis/depth profiles are described. Profile area is shown to be related to the logarithm of the ratio between surface-penetrating irradiance (Io') and the irradiance (Ik) defining the onset of light-saturation of photosynthesis. Standardized profiles, plotted on a common scale of 'optical depth', are used to illustrate the relatively minor influence of variations in Io' and Ik on hourly rates of photosynthesis per unit area. The saturation parameter (Ik) generally increased as photosynthetic capacity (Pmax) increased; the temperature-dependence of Ik is explained by the temperature-dependence of the enzyme-controlled (dark) reactions of photosynthesis, which control Pmax. A spring peak in the ratio between surface penetrating irradiance (Io') and Ik is interpreted as a result of a lag in the seasonal increase in water temperature with increase in surface irradiance. The gradient (K') of the linear light-limited region of the photosynthesis-irradiance curve showed little variation and had an average value of 0·31 mg O2/mg chl a.h per 1 W/m2 (PAR). Interactions between mixed depth, underwater light extinction and phytoplankton productivity are discussed; comparisons are made with other shallow, optically deep lakes
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