Complement factor H allotype 402H is associated with increased C3b opsonization and phagocytosis of Streptococcus pyogenes.

The main virulence factor of group A streptococcus (GAS), M protein, binds plasma complement regulators factor H (FH) and FH-like protein 1 (FHL-1) leading to decreased opsonization. The M protein binding site on FH is within domain 7 in which also the age-related macular degeneration (AMD)-associated polymorphism Y402H is located. We studied if FH allotypes 402H and 402Y have different binding affinities to GAS. Plasma-derived FH allotype 402H and its recombinant fragment FH5-7(402H) showed decreased binding to several GAS strains. Growth of GAS in human blood taken from FH(402H) homozygous individuals was decreased when compared with blood taken from FH(402Y) homozygous individuals. The effect of the allotype 402H can be explained by combining the previous M protein mutagenesis data and the recently published crystal structure of FH6-8. In conclusion the data indicate that the AMD-associated allotype 402H leads to diminished binding of FH to GAS and increased opsonophagocytosis of the bacteria in blood. These results suggest that the homozygous presence of the allele 402H could be associated with decreased risk for severe GAS infections offering an explanation for the high frequency of the allele despite its association with visual impairment.

Tetracycline resistance in group a streptococci: emergence on a global scale and influence on multiple-drug resistance.

A global sample of group A streptococci (GAS) revealed > or =80 separate acquisitions of tetracycline resistance. Of 244 clones, 38 and 25% displayed resistance to tetracycline and erythromycin, respectively; a relatively high proportion (15%) were resistant to both classes of drugs. tet(M) displayed a highly significant association with erm(B).

Evolution and global dissemination of macrolide-resistant group A streptococci.

Macrolide-resistant group A streptococci (MRGAS) have been recovered from many countries worldwide. However, the strain typing information that is available has been insufficient for estimating the total number of macrolide-resistant clones, their geographic distributions, and their evolutionary relationships. In this study, sequence-based strain typing was used to characterize 212 MRGAS isolates from 34 countries. Evaluation of clonal complexes, emm type, and resistance gene content [erm(A), erm(B), mef(A), and undefined] indicate that macrolide resistance was acquired by GAS organisms via > or independent genetic events. In contrast to other collections of mostly susceptible GAS, genetic diversification of MRGAS clones has occurred primarily by mutation rather than by recombination. Twenty-two MRGAS clonal complexes were recovered from more than one continent; intercontinental strains represent nearly 80% of the MRGAS isolates under study. The findings suggest that horizontal transfer of macrolide resistance genes to numerous genetic backgrounds and global dissemination of resistant clones and their descendants are both major components of the present-day macrolide resistance problem found within this species.

M protein gene (emm type) analysis of group A beta-hemolytic streptococci from Ethiopia reveals unique patterns.

The genetic diversity of group A streptococcal (GAS) isolates obtained in 1990 from Ethiopian children with various streptococcal diseases was studied by using emm gene sequence analysis. A total of 217 GAS isolates were included: 155 and 62 isolates from throat and skin, respectively. A total of 78 different emm/st types were detected among the 217 isolates. Of these, 166 (76.5%) belonged to 52 validated reference emm types, 26 (11.9%) belonged to 16 already recognized sequence types (st types) and 25 (11.5%) belonged to 10 undocumented new sequence types. Resistance to tetracycline (148 of 217) was not correlated to emm type. Isolation rate of the classical rheumatogenic and nephritogenic strains was low from cases of acute rheumatic fever (ARF) and acute glomerulonephritis (AGN), respectively. Instead, the recently discovered st types were overrepresented among isolates from patients with ARF (3 of 7) and AGN (9 of 16) (P < 0.01) compared to isolates from subjects with tonsillitis and from healthy carriers (10 of 57 and 16 of 90, respectively). In contrast to rheumatogenic strains from the temperate regions, more than half of the isolates from ARF (four of seven) carried the genetic marker for skin preference, emm pattern D, although most of them (six of seven) were isolated from throat. Of 57 tonsillitis-associated isolates, 16 (28%) belonged to emm pattern D compared to <1% in temperate regions. As in other reports emm patterns A to C were strongly associated with throat, whereas emm pattern D did not correlate to skin. This first large-scale emm typing report from Africa has demonstrated a heterogeneous GAS population and contrasting nature of GAS epidemiology in the region.