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Streptococcus equi is the causative agent of strangles, a prevalent and highly contagious disease of horses. Despite the animal suffering and economic burden associated with strangles, little is known about the molecular basis ofS. equi virulence. Here we have investigated the contributions of a specific lipoprotein and the general lipoprotein processing pathway to the abilities ofS. equi to colonize equine epithelial tissues in vitro and to cause disease in both a mouse model and the natural host in vivo. Colonization of air interface organ cultures after they were inoculated with a mutant strain deficient in the maturase lipoprotein (ΔprtM 138 - 213 , with a deletion of nucleotides 138 to 213) was significantly less than that for cultures infected with wild-typeS. equi strain 4047 or a mutant strain that was unable to lipidate preprolipoproteins (Δlgt 190 - 685 ). Moreover, mucus production was significantly greater in both wild-type-infected and Δlgt 190 - 685 -infected organ cultures. Both mutants were significantly attenuated compared with the wild-type strain in a mouse model of strangles, although 2 of 30 mice infected with the Δlgt 190 - 685 mutant did still exhibit signs of disease. In contrast, only the ΔprtM 138 - 213 mutant was significantly attenuated in a pony infection study, with 0 of 5 infected ponies exhibiting pathological signs of strangles compared with 4 of 4 infected with the wild-type and 3 of 5 infected with the Δlgt 190 - 685 mutant. We believe that this is the first study to evaluate the contribution of lipoproteins to the virulence of a gram-positive pathogen in its natural host. These data suggest that the PrtM lipoprotein is a potential vaccine candidate, and further investigation of its activity and its substrate(s) are warranted.

infection and immunity

Mutation of the Maturase Lipoprotein Attenuates the Virulence of <i>Streptococcus equi</i> to a Greater Extent than Does Loss of General Lipoprotein Lipidation

Mutation of the Maturase Lipoprotein Attenuates the Virulence of Streptococcus equi to a Greater Extent than Does Loss of General Lipoprotein Lipidation