A naturally occurring single amino acid replacement in multiple gene regulator of group A Streptococcus significantly increases virulence.

Single-nucleotide polymorphisms (SNPs) are the most common source of genetic variation within a species; however, few investigations demonstrate how naturally occurring SNPs may increase strain virulence. We recently used group A Streptococcus as a model pathogen to study bacteria strain genotype-patient disease phenotype relationships. Whole-genome sequencing of approximately 800 serotype M59 group A Streptococcus strains, recovered during an outbreak of severe invasive infections across North America, identified a disproportionate number of SNPs in the gene encoding multiple gene regulator of group A Streptococcus (mga). Herein, we report results of studies designed to test the hypothesis that the most commonly occurring SNP, encoding a replacement of arginine for histidine at codon 201 of Mga (H201R), significantly increases virulence. Whole transcriptome analysis revealed that the H201R replacement significantly increased expression of mga and 54 other genes, including many proven virulence factors. Compared to the wild-type strain, a H201R isogenic mutant strain caused significantly larger skin lesions in mice. Serial quantitative bacterial culture and noninvasive magnetic resonance imaging also demonstrated that the isogenic H201R strain was significantly more virulent in a nonhuman primate model of joint infection. These findings show that the H201R replacement in Mga increases the virulence of M59 group A Streptococcus and provide new insight to how a naturally occurring SNP in bacteria contributes to human disease phenotypes.

The current state of poststreptococcal glomerulonephritis.

Poststreptococcal glomerulonephritis is one of the oldest recognized renal diseases. In the past three decades, significant changes have occurred in its epidemiology, in new insight gained in the nephritogenic characteristics of streptococcal antigens, and in the natural history of the disease. The disease is now rare in industrialized nations, but in the underprivileged world, the burden of poststreptococcal glomerulonephritis ranges between 9.5 and 28.5 new cases per 100,000 individuals per year. Prophylactic antibiotic treatment is advisable in epidemic conditions and to household contacts of index cases in communities where the prevalence of the disease is high. The long-term prognosis is variable; in general, prognosis is excellent in children but significantly worse when it occurs in elderly individuals and in populations that present other risk factors of chronic kidney disease. Contemporary large-scale research strategies such as genome-wide sequencing may uncover new information about pathogenic factors contributing to disease.

Molecular epidemiology of Haemophilus influenzae type B isolates from Uruguay

A informaçäo disponível sobre a epidemiologia molecular e as interrelaçöes genéticas dos Haemophilus influenzae serotipo b (Hib) recuperados de pacientes que vivem na América do Sul é escassa. Quarenta e três cepas isoladas de pacientes com doença invasiva no Uruguai entre 1987 e 1992 foram caracterizadas por genótipo enzimático multilocus e por subtipo de proteína de membrana externa (outer membrana protein: OMP). As análises de OMP identificaram 3 dos subtipos conhecidos, incluindo 3L (70 por cento), 2L (18 por cento) e 18L(2 por cento). Também se encontrou dois padröes, näo descritos anteriormente, relacionados à famílias dos subtipos L e U, cada um representando 5 por cento dos organismos. Quatro tipos electroforéticos de enzimas multilocus foram identificados, incluindo ET 12,5 (67,3 por cento), 12,8 (23,3 por cento), 12,7 (4,7 por cento), e um ET 12.5/3L foi responsável por 63 por cento de todos os isolamentos, e causou 83 por cento dos casos de meningite mas somente 55 por cento dos episódios de pneumonia e septicemia. Em geral, a frequência da ocorrência de subclones Hib no Uruguai foi igual à registrada em vários países da Europa