RESUMO
The balancing act between microbes and their host in commensal and disease states needs to be deciphered in order to fully treat and combat infectious diseases. The elucidation of microbial genome dynamics in each instance is therefore required. In this context, the major bacterial meningitis pathogens are Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae. In prokaryotic CNS pathogenesis both the intact organism as well as its released components can elicit disease, often resulting in neurological sequelae, neurodegeneration or fatal outcome. The study of microbial virulence in CNS disease is expected to generate findings that yield new information on the general mechanisms of brain edema and excitatory neuronal disturbances due to meningitis, with significant potential for discoveries that can directly influence and inspire new strategies for prevention and treatment of this serious disease.
Assuntos
Abscesso Encefálico/genética , Encefalite/genética , Genoma Bacteriano/genética , Meningites Bacterianas/genética , Animais , Abscesso Encefálico/metabolismo , Abscesso Encefálico/fisiopatologia , Reparo do DNA/genética , Encefalite/metabolismo , Encefalite/fisiopatologia , Regulação Bacteriana da Expressão Gênica/genética , Humanos , Imunidade Inata/genética , Meningites Bacterianas/metabolismo , Meningites Bacterianas/fisiopatologia , Mutação/genética , Recombinação Genética/genéticaRESUMO
Genome alterations due to horizontal gene transfer and stress constantly generate strain on the gene pool of Neisseria meningitidis, the causative agent of meningococcal (MC) disease. The DNA glycosylase MutY of the base excision repair pathway is involved in the protection against oxidative stress. MC MutY expressed in Escherichia coli exhibited base excision activity towards DNA substrates containing A:7,8-dihydro-8-oxo-2'-deoxyguanosine and A:C mismatches. Expression in E. coli fully suppressed the elevated spontaneous mutation rate found in the E. coli mutY mutant. An assessment of MutY activity in lysates of neisserial wild-type and mutY mutant strains showed that both MC and gonococcal (GC) MutY is expressed and active in vivo. Strikingly, MC and GC mutY mutants exhibited 60- to 140-fold and 20-fold increases in mutation rates, respectively, compared to the wild-type strains. Moreover, the differences in transitions and transversions in rpoB conferring rifampin resistance observed with the wild type and mutants demonstrated that the neisserial MutY enzyme works in preventing GC-->AT transversions. These findings are important in the context of models linking mutator phenotypes of disease isolates to microbial fitness.
Assuntos
Pareamento Incorreto de Bases/genética , DNA Glicosilases/metabolismo , Guanina/metabolismo , Neisseria/enzimologia , DNA Glicosilases/genética , DNA Glicosilases/fisiologia , Análise Mutacional de DNA , Reparo do DNA , Guanina/análogos & derivados , Neisseria/genética , Neisseria/metabolismo , Proteínas Recombinantes de Fusão/isolamento & purificaçãoRESUMO
The complete genome sequence of Geobacter sulfurreducens, a delta-proteobacterium, reveals unsuspected capabilities, including evidence of aerobic metabolism, one-carbon and complex carbon metabolism, motility, and chemotactic behavior. These characteristics, coupled with the possession of many two-component sensors and many c-type cytochromes, reveal an ability to create alternative, redundant, electron transport networks and offer insights into the process of metal ion reduction in subsurface environments. As well as playing roles in the global cycling of metals and carbon, this organism clearly has the potential for use in bioremediation of radioactive metals and in the generation of electricity.