Comparative genomics of emerging pathogens in the Candida glabrata clade

BACKGROUND: Candida glabrata follows C. albicans as the second or third most prevalent cause of candidemia worldwide. These two pathogenic yeasts are distantly related, C. glabrata being part of the Nakaseomyces, a group more closely related to Saccharomyces cerevisiae. Although C. glabrata was thought to be the only pathogenic Nakaseomyces, two new pathogens have recently been described within this group: C. nivariensis and C. bracarensis. To gain insight into the genomic changes underlying the emergence of virulence, we sequenced the genomes of these two, and three other non-pathogenic Nakaseomyces, and compared them to other sequenced yeasts. RESULTS: Our results indicate that the two new pathogens are more closely related to the non-pathogenic N. delphensis than to C. glabrata. We uncover duplications and accelerated evolution that specifically affected genes in the lineage preceding the group containing N. delphensis and the three pathogens, which may provide clues to the higher propensity of this group to infect humans. Finally, the number of Epa-like adhesins is specifically enriched in the pathogens, particularly in C. glabrata. CONCLUSIONS: Remarkably, some features thought to be the result of adaptation of C. glabrata to a pathogenic lifestyle, are present throughout the Nakaseomyces, indicating these are rather ancient adaptations to other environments. Phylogeny suggests that human pathogenesis evolved several times, independently within the clade. The expansion of the EPA gene family in pathogens establishes an evolutionary link between adhesion and virulence phenotypes. Our analyses thus shed light onto the relationships between virulence and the recent genomic changes that occurred within the Nakaseomyces.

"In vitro" comparative experimental study of antimicrobial action of mouth washing products

Regular use of mouth rinses modifies the oral habitat, since bacterial populations are submitted to a high selective pressure during the treatment exercised by the active presence of the disinfectant. Mostly mouth rinses are based on the antibacterial effect of Chlorhexidine, Triclosan, essential oils and other antibacterials although other pharmaceutical characteristics can also affect their effectiveness. In this paper we compare"in vitro" the antibacterial effect of different oral rinsing solutions. Minimal Inhibitory Concentrations (MIC) and Minimal Bactericidal Concentrations (MBC) were determined as well as the kinetics of bacterial death in the presence of letal concentrations of the mouth rinses. MIC values expressed as Maximal Inhibitory Dilution (MID) of the mouth rinse ranged from 1 to 1/2048 depending on the microorganism and product, whereas Minimal Biocidal Concentration (MBC), expressed as Maximal Biocidal Dilution (MBD) ranged from 1 to 1/1024, being in general one dilution less than MIC. Maximal Biocidal Dilution is a good tool to measure the actual efficiency of mouth washing solutions. However, kinetics of death seems to be better in our work killing curves demonstrate that bacterial populations are mostly eliminated during the first minute after the contact of bacterial suspension and the mouth-washing solution. In all tested bacterial species mouth-washing solutions tested were able to reduce until suspension treated except 1 and 5

Saccharomyces cerevisiae as a model organism: a comparative study

Background: Model organisms are used for research because they provide a framework on which to develop and optimize methods that facilitate and standardize analysis. Such organisms should be representative of the living beings for which they are to serve as proxy. However, in practice, a model organism is often selected ad hoc, and without considering its representativeness, because a systematic and rational method to include this consideration in the selection process is still lacking. Methodology/Principal Findings: In this work we propose such a method and apply it in a pilot study of strengths and limitations of Saccharomyces cerevisiae as a model organism. The method relies on the functional classification of proteins into different biological pathways and processes and on full proteome comparisons between the putative model organism and other organisms for which we would like to extrapolate results. Here we compare S. cerevisiae to 704 other organisms from various phyla. For each organism, our results identify the pathways and processes for which S. cerevisiae is predicted to be a good model to extrapolate from. We find that animals in general and Homo sapiens in particular are some of the non-fungal organisms for which S. cerevisiae is likely to be a good model in which to study a significant fraction of common biological processes. We validate our approach by correctly predicting which organisms are phenotypically more distant from S. cerevisiae with respect to several different biological processes. Conclusions/Significance: The method we propose could be used to choose appropriate substitute model organisms for the study of biological processes in other species that are harder to study. For example, one could identify appropriate models to study either pathologies in humans or specific biological processes in species with a long development time, such as plants.

Mitochondrial DNA damage and animal longevity: insights from comparative studies

Chemical reactions in living cells are under strict enzyme control and conform to a tightly regulated metabolic program. However, uncontrolled and potentially deleterious endogenous reactions occur, even under physiological conditions. Aging, in this chemical context, could be viewed as an entropic process, the result of chemical side reactions that chronically and cumulatively degrade the function of biological systems. Mitochondria are a main source of reactive oxygen species (ROS) and chemical sidereactions in healthy aerobic tissues and are the only known extranuclear cellular organelles in animal cells that contain their own DNA (mtDNA). ROS can modify mtDNA directly at the sugar-phosphate backbone or at the bases, producing many different oxidatively modified purines and pyrimidines, as well as single and double strand breaks and DNA mutations. In this scenario, natural selection tends to decrease the mitochondrial ROS generation, the oxidative damage to mtDNA, and the mitochondrial mutation rate in long-lived species, in agreement with the mitochondrial oxidative stress theory of aging.

Comparative genomics of yeast species: new insights into their biology

The genomes of two hemiascomycetous yeasts (Saccharomyces cerevisiae and Candida albicans) and one archiascomycete (Schizosaccharomyces pombe) have been completely sequenced and the genes have been annotated. In addition, the genomes of 13 more Hemiascomycetes have been partially sequenced. The amount of data thus obtained provides information on the evolutionary relationships between yeast species. In addition, the differential genetic characteristics of the microorganisms explain a number of distinctive biological traits. Gene order conservation is observed between phylogenetically close species and is lost in distantly related species, probably due to rearrangements of short regions of DNA. However, gene function is much more conserved along evolution. Compared to S. cerevisiae and S. pombe, C. albicans has a larger number of specific genes, i.e., genes not found in other organisms, a fact that can account for the biological characteristics of this pathogenic dimorphic yeast which is able to colonize a large variety of environments.

A comparative study of silver amalgam and compomer as retrograde filling materials in periapical surgery

Objective: A comparative study is made of the histological effects of silver amalgam versus compomer (Dyract®) 90 days after placement as retrograde filling materials in experimental animals. Method: Six Beagle dogs were used, with total pulpectomy and orthograde material filling followed by periapical surgery of the 6 upper and 6 lower incisors (for a total of 72 teeth). Thirty-six teeth corresponded to the right side and were filled with the control material (silver amalgam), while the 36 teeth on the left side were filled with the compomer study material (Dyract®). After three months the animals were sacrificed and the histological study was carried out, with evaluation of bone formation, inflammation, and the tissue in contact with the filler material. The results obtained were subjected to a descriptive and comparative statistical analysis (chi-square test). Results: The samples retrogradely filled with compomer showed significantly greater percentage inflammation (76.19% versus 26.66% in the control group). On the other hand, a large proportion of samples with root cement growth were found in the compomer group. Filler material expulsion was also significantly more common when compomer was used. Conclusions: the comparative study of the histological findings showed greater inflammation but also greater root cement growth in the compomer group versus the controls

Family Size Evolution in Drosophila Chemosensory Gene Families: A Comparative Analysis with a Critical Appraisal of Methods

Gene turnover rates and the evolution of gene family sizes are important aspects of genome evolution. Here, we use curated sequence data of the major chemosensory gene families from Drosophila-the gustatory receptor, odorant receptor, ionotropic receptor, and odorant-binding protein families-to conduct a comparative analysis among families, exploring different methods to estimate gene birth and death rates, including an ad hoc simulation study. Remarkably, we found that the state-of-the-art methods may produce very different rate estimates, which may lead to disparate conclusions regarding the evolution of chemosensory gene family sizes in Drosophila. Among biological factors, we found that a peculiarity of D. sechellia's gene turnover rates was a major source of bias in global estimates, whereas gene conversion had negligible effects for the families analyzed herein. Turnover rates vary considerably among families, subfamilies, and ortholog groups although all analyzed families were quite dynamic in terms of gene turnover. Computer simulations showed that the methods that use ortholog group information appear to be the most accurate for the Drosophila chemosensory families. Most importantly, these results reveal the potential of rate heterogeneity among lineages to severely bias some turnover rate estimation methods and the need of further evaluating the performance of these methods in a more diverse sampling of gene families and phylogenetic contexts. Using branch-specific codon substitution models, we find further evidence of positive selection in recently duplicated genes, which attests to a nonneutral aspect of the gene birth-and-death process.