RESUMO
In many human infections, hosts and pathogens coexist for years or decades. Important examples include HIV, herpes viruses, tuberculosis, leprosy, and malaria. With the exception of intensively studied viral infections such as HIV/AIDs, little is known about the extent to which the clonal expansion that occurs during long-term infection by pathogens involves important genetic adaptations. We report here a detailed, whole-genome analysis of one such infection, that of a cystic fibrosis (CF) patient by the opportunistic bacterial pathogen Pseudomonas aeruginosa. The bacteria underwent numerous genetic adaptations during 8 years of infection, as evidenced by a positive-selection signal across the genome and an overwhelming signal in specific genes, several of which are mutated during the course of most CF infections. Of particular interest is our finding that virulence factors that are required for the initiation of acute infections are often selected against during chronic infections. It is apparent that the genotypes of the P. aeruginosa strains present in advanced CF infections differ systematically from those of "wild-type" P. aeruginosa and that these differences may offer new opportunities for treatment of this chronic disease.
Assuntos
Adaptação Fisiológica/genética , Fibrose Cística/complicações , Fibrose Cística/microbiologia , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/fisiologia , Proteínas de Bactérias/genética , Doença Crônica , Fibrose Cística/patologia , Proteínas de Ligação a DNA/genética , Genoma Bacteriano/genética , Humanos , Dados de Sequência Molecular , Mutação/genética , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/isolamento & purificação , Seleção Genética , Fatores de Tempo , Transativadores/genéticaRESUMO
Saccharomyces boulardii (SB) (Saccharomces cerevisiae Hansen CBS 5926) is a yeast widely used in humans for the prevention and treatment of infectious enterocolitis. SB is said also to antagonize Candida albicans when given orally to living organisms. This double-blind trial was performed to determine the effect and tolerance of SB as an oral therapeutic in patients suffering from cystic fibrosis receiving long-term treatment with cephalosporins or cotrimoxazole, by examining C. albicans counts in the intestine. Extensive mycoserological examinations for drug safety evaluation were also performed. To be selected for the study patients had to present C. albicans in their intestinal flora. None of the patients enrolled exhibited clinical symptoms of candidosis. A daily dose of 750 mg (250 mg t.i.d.) of lyophilized SB given for 21 days did not affect the number of C. albicans commensals in those patients. However, the mycoserological data confirmed the safety of SB treatment with respect to a hypothetically possible SB fungaemia and a possible falsification of Candida serology.