RESUMO
Expression of the extensive arsenal of virulence factors by Streptococcus pyogenes is controlled by many regulators, of which CovRS is one of the best characterized and can influence â¼15â% of the genome. Animal models have established that mutants of covRS arise spontaneously in vivo resulting in highly invasive organisms. We analysed a pharyngeal and a blood isolate of S. pyogenes recovered from the same individual 13 days apart. The two isolates varied in many phenotypic properties including SpeB production, which were reflected in transcriptomic analyses. PFGE, multilocus sequence typing and partial sequencing of some key genes failed to show any differences except for an 11 bp insert in the covS gene in the blood isolate which caused a premature termination of transcription. Complementation of a fully functional covS gene into the blood isolate resulted in high expression of CovS and expression of speB. These results, showing a pharyngeal and a blood isolate from a single individual differing by a simple insertion, provide evidence for the model that regulatory gene mutations allow S. pyogenes to invade different niches in the body.
Assuntos
Proteínas de Bactérias/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Streptococcus pyogenes/genética , Fatores de Virulência/genética , Sequência de Bases , Sangue/microbiologia , Criança , DNA Bacteriano/genética , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Teste de Complementação Genética , Histidina Quinase , Humanos , Masculino , Dados de Sequência Molecular , Tipagem de Sequências Multilocus , Mutagênese Insercional , Análise de Sequência com Séries de Oligonucleotídeos , Faringe/microbiologia , Fenótipo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Streptococcus pyogenes/classificação , Streptococcus pyogenes/isolamento & purificação , Streptococcus pyogenes/patogenicidadeRESUMO
OBJECTIVE: To examine the genotypic and phenotypic characteristics of a Micronesian kindred with autosomal dominant precocious osteoarthritis (OA). METHODS: We reviewed records and radiographs of 3 index patients and their parents, administered questionnaires to 16 additional kindred members, performed whole-genome scans of 24 family members, and sequenced relevant genes from 16 family members. RESULTS: The kindred displayed early onset OA, enlarged epiphyses, platyspondyly, and brachydactyly with dysplastic findings consistent with mild spondyloepiphyseal dysplasia. Genetic analysis revealed an arginine to cysteine substitution at position 75 of the collagen 2A1 gene, a mutation that has been described in 4 other geographically distinct families. The major phenotypic differences among the families were in height (ranging from short to tall) and hearing loss noted in 3 of the 5 families. CONCLUSION: The presence of the COL2A1 Arg75Cys mutation in 5 geographically distinct areas helps to confirm a potential mutational hotspot. The diverse phenotypic spectrum suggests that modifier genes and environmental factors play a role in the expression of this mutation.