Comparative Genomics of @entity4195 M1 isolates differing in virulence and propensity to cause @entity281 in XXXX .

@entity1 @entity462 @entity19 @entity4195 @entity281 @entity9829
UNASSIGNED: @entity4195 serotype M1 is a frequent cause of severe @entity281 in @entity1 . Some M1 isolates are pathogenic in @entity19 and used in studies on @entity281 pathogenesis. We observed marked differences in @entity19 @entity281 caused by M1 strain SF370, 5448, 5448AP or @entity9829 which prompted us to sequence the whole genome of isolates 5448 and @entity9829 for comparative analysis. Strain 5448 is known to acquire inactivating mutations in the CovRS two-component system during @entity19 @entity281 , producing hypervirulent progeny such as 5448AP. Isolates @entity9829 and 5448AP, more than 5448, caused disseminating @entity281 that became systemic and lethal. SF370 was not pathogenic. Phages caused gross genetic differences and increased the gene content of @entity9829 by 8% as compared to 5448 and SF370. Each of six examined M1 genomes contained two CRISPR-Cas systems. Phage insertion destroyed a type II CRISPR-Cas system in @entity9829 and other strains of serotypes M1, M3, M6 and M24, but not in M1 strains 5448, SF370, MGAS5005, A20 or M1 476. A resulting impaired defence against invading genetic elements could have led to the wealth of phages in @entity9829 . @entity9829 lacks genetic features of the MGAS5005-like clonal complex including the streptodornase that drives selection for hypervirulent clones with inactivated CovRS system. Still, inactivating mutations in covS were a common genetic feature of @entity9829 and the MGAS5005-like isolate 5448AP. Abolished expression of the @entity462 proteinase SpeB, due to CovRS inactivation could be a common cause for hypervirulence of the two isolates. Moreover, an additional protein H-coding gene and a mutation in the regulator gene rofA distinguished @entity9829 form other M1 isolates. In conclusion, hypervirulence of @entity4195 M1 in @entity19 is not limited to the MGAS5005-like genotype.
