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/genéticaAssuntos
Complexo Antígeno-Anticorpo/imunologia , Infecções Bacterianas/imunologia , Doenças do Complexo Imune , Fibrose Cística/complicações , Fibrose Cística/imunologia , Endocardite Bacteriana/imunologia , Humanos , Hanseníase/imunologia , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/imunologiaRESUMO
A 38-year-old woman had diffuse, nonnodular, lepromatous leprosy and Lucio's phenomenon. Most cases of Lucio's phenomenon have been reported to have a leukocytoclastic vasculitis as the underlying pathologic abnormality. In this patient, however, the histologic picture of an early lesion of Lucio's phenomenon showed a milk, mononuclear cell infiltration, endothelial swelling, vascular thrombosis, and ischemic necrosis. Lepra bacilli were abundant around nerves and blood vessels, and many were noted in vascular walls and endothelium. Our findings raise the possibility that some cases of Lucio's phenomenon may be caused by vascular damage due to direct invasion of Mycobacterium leprae and not necessarily by leukocytoclastic vasculitis.
Assuntos
Hanseníase/patologia , Pele/patologia , Adulto , Feminino , Humanos , Hanseníase/complicações , Infecções por Pseudomonas/complicações , Sepse/complicaçõesRESUMO
Heavy growth of Pseudomonas putrefaciens was isolated repeatedly in mixed culture with other Gram-negative rods from chronic ulcers on the extremities of an elderly patient with burnt-out leprosy. Treatment was with systemic cotrimoxazole, topical framycetin and general supportive therapy, and the ulcers gradually healed over a period of 4 weeks.