TroA of Streptococcus suis is required for manganese acquisition and full virulence

Streptococcus suis causes infections in pigs and occasionally in humans resulting in 23 manifestations as meningitis, sepsis, arthritis and septic shock. For survival within the 24 host, S. suis requires numerous nutrients including trace metals. Little is known about 25 the specific proteins involved in metal scavenging in S. suis. In this study we evaluated 26 the role of the putative high affinity metal binding lipoprotein TroA in metal acquisition 27 and virulence. A mutant strain deficient in the expression of TroA (¿troA mutant) was 28 constructed. Growth of the ¿troA mutant in Todd-Hewitt broth was similar to wild type 29 growth, however growth of the ¿troA mutant in cation-deprived Todd-Hewitt broth and 30 in porcine serum was strongly reduced compared to growth of wild type bacteria. 31 Supplementing the media with extra manganese but not with magnesium, zinc, copper, 32 nickel or iron restored growth to wild type levels, indicating that TroA is specifically 33 required for growth in environments low in manganese. The ¿troA mutant also showed 34 increased susceptibility to H2O2, suggesting TroA is involved in counteracting oxidative 35 stress. Furthermore, the expression of the troA gene was subject to environmental 36 regulation at the transcript level. In a murine S. suis infection model the ¿troA mutant 37 displayed a non-virulent phenotype. These data indicate that S. suis TroA is involved in 38 manganese acquisition and required for full virulence in mice.