INSERTIONAL INACTIVATION OF A CHROMOSOMAL LOCUS THAT MODULATES EXPRESSION OF POTENTIAL VIRULENCE DETERMINANTS IN STAPHYLOCOCCUS-AUREUS

A single insertion of transposon Tn551 into a unique chromosomal locus of Staphylococcus aureus ISP479C has resulted in a pleiotropic effect on the expression of both extracellular and cell wall proteins. In pa rticular, the expression of cell wall protein A and clumping activity with fibrinogen were rendered undetectable in the mutant 1E3 compared with the parent. The secretion of alpha-hemolysin in mutant 1E3 was mo destly increased. Southern blot and phenotypic analyses indicated that this locus is distinct from ngr, xpr, and sar, three previously descr ibed global regulatory loci. Transduction experiments demonstrated tha t the genotype associated with mutant 1E3 could be transferred hack in to the parental strain ISP479C. The transductant 1E3-2 displayed a phe notypic profile similar to that of the original mutant. Northern (RNA) blot studies showed that this locus may be involved in modulating tar get genes at the mRNA level. In the rabbit endocarditis model, there w as a significant decrease in both the infectivity rate and intravegeta tion bacterial density with mutant 1E3 compared with the parent at an inoculum of 10(3) CFU. Since protein A and the fibrinogen-binding prot ein(s) are major surface proteins that may mediate bacterial adhesion to host tissues, this locus may be an important genetic element involv ed in the expression of virulence determinants in S. aureus.