Vitamin B3 confers resistance to sulfa drugs in Saccharomyces cerevisiae

Sulfa drugs are ubiquitous antibiotics used to treat bacterial infections and diseases caused by eukaryotes, such as Pneumocystis carinii, the leading cause of pneumonia (PCP) in HIV patients. A daily regimen of sulfonamides and multivitamins including vitamin B3 is also recommended for persons with HIV. We show that exogenous vitamin B3 (nicotinate) confers resistance to sulfa drugs in Saccharomyces cerevisiae, a model for P. carinii. We propose a model of metabolic rerouting in which increased nicotinate leads to increased intracellular concentration of p-aminobenzoate, thus leading to sulfonamide resistance.     

Dermatomycoses Caused by Nattrassia Mangiferae in São Paulo,Brazil

Nattrassia mangiferae formerly known as Hendersonula toruloidea,is a phaeoid coelomycete described by Nattrass in 1933. We report five casesof N. mangiferae infections in São Paulo, Brazil. This fungus wasisolated from interdigital lesions on the feet in one patient, toenails in threecases and fingernails in the other one. The infections were initially consideredto be caused by a dermatophyte. Although there are only a few cases describedin the medical literature, the five cases reported suggest that N. mangiferaeshould be taken into consideration in the differential diagnosis of tinea pedisinfections.     

Inhibition of catalase by aminotriazole <Emphasis Type="Italic">in vivo</Emphasis> results in reduction of glucose-6-phosphate dehydrogenase activity in <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis> cells

The inhibitor of catalase 3-amino-1,2,4-triazole (AMT) was used to study the physiological role of catalase in the yeast Saccharomyces cerevisiae under starvation. It was shown that AMT at the concentration of 10 mM did not affect the growth of the yeast. In vivo and in vitro the degree of catalase inhibition by AMT was concentration- and time-dependent. Peroxisomal catalase in bakers' yeast was more sensitive to AMT than the cytosolic one. In vivo inhibition of catalase by AMT in S. cerevisiae caused a simultaneous decrease in glucose-6-phosphate dehydrogenase activity and an increase in glutathione reductase activity. At the same time, the level of protein carbonyls, a marker of oxidative modification, was not affected. Possible mechanisms compensating the negative effects caused by AMT inhibition of catalase are discussed.     

Saccharomyces cerevisiae infections in man

Saccharomyces cerevisiae is a yeast commonly used to make food products such as bread, beer and wine, or ingested whole as a 'health' food. We report five cases of infections involving S. cerevisiae, including one in which S. cerevisiae alone was implicated, and review the literature on its pathogenicity.     

Onychomycosis Caused by Fusarium Solani and Fusarium Oxysporum In São Paulo,Brazil

Fusarium species are common soil saprophytes and plant pathogens that have been frequently reported as etiologic agents of opportunistic infections in humans. We report eight cases of onychomycosis caused by Fusarium solani (4) and Fusarium oxysporum (4) in São Paulo, Brazil. These species were isolated from toenails in all cases. The infections were initially considered to be caused by dermatophytes. The clinical appearance of the affected toenails was leukonychia or distal subungual hyperkeratosis with yellowish brown coloration. The eight cases reported here suggest that Fusarium spp. should be taken into consideration in the differential diagnosis of tinea unguium.     

Fingerprinting of yeasts at the strain level by differential sensitivity responses to a panel of selected killer toxins

We used differential sensitivities to a panel of twenty-five cell-free crude killer toxins to fingerprint forty-four Saccharomyces cerevisiae strains of different origin and all taxonomically certified by nDNA-nDNA reassociation. Cluster analysis of numerical data obtained by different growth inhibition areas observed in Petri dishes allowed the complete and reproducible discrimination of all S. cerevisiae strains.     

Extensive dermatophytoses caused by Trichophyton mentagrophytes and Microsporum canis in a patient with AIDS

Retrospective studies have shown the occurrence of episodes of deep or superficial fungal infections in 58 to 81% of HIV/AIDS patients as a result of impairment of cell immunity. We describe a case of disseminated cutaneous dermatophytoses caused by Trichophyton mentagrophytes and Microsporum canis in a patients with AIDS. Diagnostic and therapeutic problems in relation to this unsual presentation are emphasized as well as the importance of an early mycologic diagnosis to prescribe antifungal therapy.     

噬菌体治疗肺炎克雷伯菌感染的研究进展

随着细菌的进化以及部分抗生素的滥用，耐药细菌的感染已成为21世纪主要的公共卫生挑战之一。其中，耐药肺炎克雷伯菌(Klebsiella pneumoniae)问题尤为突出。噬菌体在治疗耐药细菌感染引起的疾病方面展现出一定的潜力及独特优势，但目前噬菌体治疗尚缺乏统一的临床指导规范。虽然临床上有少数将噬菌体用于治疗肺炎克雷伯菌感染的成功案例，但多数情况下是采用噬菌体配合抗生素疗法，噬菌体在其中的作用仍不明确。本文综合评述国内外研究数据，回顾与噬菌体治疗肺炎克雷伯菌感染相关的数个重点问题，包括噬菌体的特性以及影响其疗效的因素，旨在为肺炎克雷伯菌和其他耐药细菌的噬菌体治疗提供参考。     

Comparative study of the activity and kinetic properties of malate dehydrogenase and pyruvate decarboxylase from Candida albicans, Malassezia pachydermatis, and Saccharomyces cerevisiae

Candida albicans and Malassezia pachydermatis cause human and animal infections of the skin and internal organs. We compare the properties of two enzymes, pyruvate decarboxylase (PDC) and malate dehydrogenase (MDH), from these species and from Saccharomyces cerevisiae cultivated under aerobic and anaerobic conditions to find differences between the enzymes that adapt pathogens for virulence and help us in searching for new antifungal agents. Malassezia pachydermatis did not show any growth under anaerobic conditions, as opposed to C. albicans and S. cerevisiae. Under aerobic conditions, C. albicans showed the highest growth rate. Malassezia pachydermatis, contrary to the others, did not show any PDC activity, simultaneously showing the highest MDH activity under aerobic conditions and a Km value for oxaloacetate lower than S. cerevisiae. Candida albicans and S. cerevisiae showed a strong decrease in MDH activity under anaerobic conditions. Candida albicans shows four different isoforms of MDH, while M. pachydermatis and S. cerevisiae are characterized by two and three isoforms. Candida albicans shows about a twofold lower activity of PDC but, simultaneously, almost a threefold lower Km value for pyruvate in comparison with S. cerevisiae. The PDC apoform share under aerobic conditions in C. albicans was 47%, while in S. cerevisiae was only 26%; under anaerobic conditions, the PDC apoform decreased to 12% and 8%, respectively. The properties of enzymes from C. albicans show its high metabolic flexibility (contrary to M. pachydermatis) and cause easy switching between fermentative and oxidative metabolism. This feature allows C. albicans to cause both surface and deep infections. We take into consideration the use of thiamin antimetabolites as antifungal factors that can affect both oxidative and fermentative metabolism.     

Use of live Saccharomyces cerevisiae cells as a biological response modifier in experimental infections

Abstract A short-term oral administration of live Saccharomyces cerevisiae cells, strain Sillix Hansen DSM 1883, resulted in enhanced resistance of mice toward infections with K. pneumoniae, S. pneumoniae and S. pyogenes A produced by intranasal inoculation. Yeast pre-treatment also increased the efficacy of antibiotic therapy in bacterial infections and of antiviral drugs in viral infections. Yeast treatment of animals stimulated phagocytosis, activated the complement system and induced interferon which are likely to represent the main mechanisms of action whereby pretreatment of mice with live S. cerevisiae cells increases resistance to infection. It is concluded that preventive administration of live Saccharomyces cerevisiae cells should be used for increasing resistance to bacterial infections, in particular of the respiratory tract, or to viral infections, as well as an adjunct to antibiotic and antiviral drug therapy.     

Use of live Saccharomyces cerevisiae cells as a biological response modifier in experimental infections

A short-term oral administration of live Saccharomyces cerevisiae cells, strain Sillix Hansen DSM 1883, resulted in enhanced resistance of mice toward infections with K. pneumoniae. S. pneumoniae and S. pyogenes A produced by intranasal inoculation. Yeast pre-treatment also increased the efficacy of antibiotic therapy in bacterial infections and of antiviral drugs in viral infections. Yeast treatment of animals stimulated phagocytosis, activated the complement system and induced interferon which are likely to represent the main mechanisms of action whereby pretreatment of mice with live S. cerevisiae cells increases resistance to infection. It is concluded that preventive administration of live Saccharomyces cerevisiae cells should be used for increasing resistance to bacterial infections, in particular of the respiratory tract, or to viral infections, as well as an adjunct to antibiotic and antiviral drug therapy.     

Analysis of yeast populations during alcoholic fermentation: a six year follow-up study

Wine yeasts were isolated from fermenting Garnatxa and Xarel.lo musts fermented in a newly built and operated winery between 1995 and 2000. The species of non-Saccharomyces yeasts and the Saccharomyces cerevisiae strains were identified by ribosomal DNA and mitochondrial DNA RFLP analysis respectively. Non-Saccharomyces yeasts, particularly Hanseniaspora uvarum and Candida stellata, dominated the first stages of fermentation. However Saccharomyces cerevisiae was present at the beginning of the fermentation and was the main yeast in the musts in one vintage (1999). In all the cases, S. cerevisiae took over the process in the middle and final stages of fermentation. The analysis of the S. cerevisiae strains showed that indigenous strains competed with commercial strains inoculated in other fermentation tanks of the cellar. The continuous use of commercial yeasts reduced the diversity and importance of the indigenous S. cerevisiae strains.     

Manipulation of intracellular magnesium levels in Saccharomyces cerevisiae with deletion of magnesium transporters

Magnesium is an important divalent ion for organisms. There have been a number of studies in vitro suggesting that magnesium affects enzyme activity. Surprisingly, there have been few studies to determine the cellular mechanism for magnesium regulation. We wished to determine if magnesium levels could be regulated in vivo. It is known that Saccharomyces cerevisiae has two magnesium transporters (ALR1 and ALR2) across the plasma membrane. We created S. cerevisiae strains with deletion of one (alr1 or alr2) or both (alr1 alr2) transporters. The deletion of ALR1 resulted in a decrease in intracellular magnesium levels. An increase from 5 to 100 mM in the exogenous magnesium level increased the intracellular levels of magnesium in the alr1 and alr1 alr2 strains, whereas the expression of magnesium transporters from S. cerevisiae or Arabidopsis thaliana led to a change of the intracellular levels of magnesium in those strains. The deletion of magnesium transporters in A. cerevisiae and overexpression of magnesium transporters from A. thaliana also affected the intracellular concentrations of a range of metal ions, which suggests that cells use non-specific transporters to help regulate metal homeostasis.     

葡萄球菌致病毒力因子酚溶性调节蛋白的研究进展

葡萄球菌是临床常见的革兰氏阳性致病菌,包括表皮葡萄球菌和金黄色葡萄球菌等.随着耐药葡萄球菌的出现,尤其是多药耐药葡萄球菌的传播和蔓延,其感染性疾病的发病率和死亡率逐年升高.葡萄球菌的高致病性与其表达大量毒力因子密切相关.酚溶性调节蛋白(phenol-soluble modulin,PSM)是一组具有广泛溶细胞活性的两亲...     

Over-expression of Saccharomyces cerevisiae hsp90 enhances the virulence of this yeast in mice

Abstract Saccharomyces cerevisiae , a yeast of low pathogenic potential, is a rare but well-documented cause of invasive infections in humans. The yeast Candida albicans is a much commoner cause of significant and life-threatening infections. In such infections the heat shock protein hsp90 is an immunodominant antigen associated with protective humoral immunity. In this study it was shown that over-expression of S. cerevisiae hsp90, the amino acid sequence of which shows 84% identity to C. albicans hsp90, significantly increased the virulence of a laboratory strain of S. cerevisiae in mice, both in terms of colony counts in the kidney, liver and spleen, and in terms of mortality. This is the first direct evidence that hsp90 is a virulence factor.     

A case of recurrent episodes of Candida parapsilosis fungemia

Candida species is the fourth most commonly isolated organism in blood stream infections in the hospital setting. Patients with candidemia frequently succumb to this infection. For those that survive an initial candidemia, an increasing number of cases of breakthrough or recurrent candidemias have been reported in the literature. We report three episodes of C. parapsilosis fungemia in a cancer patient. Molecular testing was performed and confirmed that all these episodes occurring within an eight-month period were caused by the same organism. The incidence of recurrent candidemia is likely to increase in the near future. Studies and therapeutic interventions for patients at risk for recurrent candidemias are warranted.     

Microsatellite analysis of genetic diversity among clinical and nonclinical Saccharomyces cerevisiae isolates suggests heterozygote advantage in clinical environments

The genetic structure of a global sample of 170 clinical and nonclinical Saccharomyces cerevisiae isolates was analysed using 12 microsatellite markers. High levels of genetic diversity were revealed both among the clinical and among the nonclinical S. cerevisiae isolates without significant differentiation between these two groups of isolates, rendering a single origin of pathogenic isolates unlikely. This suggests that S. cerevisiae is a true opportunistic pathogen, with a diversity of unrelated genetic backgrounds able to cause infections in humans, and that the ability of S. cerevisiae isolates to cause infections is likely due to a combination of their phenotypic plasticity and the immune system status of the exposed individuals. As was previously reported for bread, beer and wine strains and for environmental S. cerevisiae isolates, the microsatellite genotypes indicated ploidy level variation, from possibly haploid up to tetraploid, among clinical S. cerevisiae isolates. However, rather than haploid, sporulation proficiency and spore viability data indicated that most S. cerevisiae isolates that were mono-allelic at all examined microsatellite loci were likely homothallic and self-diploidized. Interestingly, the proportion of heterozygous clinical isolates was found to be significantly higher than the proportion of heterozygous nonclinical isolates, suggesting a selective advantage of heterozygous S. cerevisiae yeasts in clinical environments.     

Genome-wide association analysis of clinical vs. nonclinical origin provides insights into Saccharomyces cerevisiae pathogenesis

Because domesticated Saccharomyces cerevisiae strains have been used to produce fermented food and beverages for centuries without apparent health implications, S. cerevisiae has always been considered a Generally Recognized As Safe (GRAS) microorganism. However, the number of reported mucosal and systemic S. cerevisiae infections in the human population has increased and fatal infections have occurred even in relatively healthy individuals. In order to gain insight into the pathogenesis of S. cerevisiae and improve our understanding of the emergence of fungal pathogens, we performed a population-based genome-wide environmental association analysis of clinical vs. nonclinical origin in S. cerevisiae. Using tiling array-based, high-density genotypes of 44 clinical and 44 nonclinical S. cerevisiae strains from diverse geographical origins and source substrates, we identified several genetic loci associated with clinical background in S. cerevisiae. Associated polymorphisms within the coding sequences of VRP1, KIC1, SBE22 and PDR5, and the 5' upstream region of YGR146C indicate the importance of pseudohyphal formation, robust cell wall maintenance and cellular detoxification for S. cerevisiae pathogenesis, and constitute good candidates for follow-up verification of virulence and virulence-related factors underlying the pathogenicity of S. cerevisiae.