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Intracranial Subarachnoidal Route of Infection for Investigating Roles of Streptococcus suis Biofilms in Meningitis in a Mouse Infection Model
Published on: July 1, 2018
TroA of Streptococcus suis is required for manganese acquisition and full virulence
Paul J Wichgers Schreur1, Johanna M J Rebel, Mari A Smits
1Central Veterinary Institute, Wageningen UR, Edelhertweg 15, 8219 PH Lelystad, Netherlands. paul.wichgersschreur@wur.nl
Abstract:
Streptococcus suis causes infections in pigs and occasionally in humans, resulting in manifestations as meningitis, sepsis, arthritis, and septic shock. For survival within the host, S. suis requires numerous nutrients including trace metals. Little is known about the specific proteins involved in metal scavenging in S. suis. In this study we evaluated the role of the putative high-affinity metal binding lipoprotein TroA in metal acquisition and virulence. A mutant strain deficient in the expression of TroA (ΔtroA mutant) was constructed. Growth of the ΔtroA mutant in Todd-Hewitt broth was similar to wild-type growth; however, growth of the ΔtroA mutant in cation-deprived Todd-Hewitt broth and in porcine serum was strongly reduced compared to growth of wild-type bacteria. Supplementing the medium with extra manganese but not with magnesium, zinc, copper, nickel, or iron restored growth to wild-type levels, indicating that TroA is specifically required for growth in environments low in manganese. The ΔtroA mutant also showed increased susceptibility to H2O2, suggesting that TroA is involved in counteracting oxidative stress. Furthermore, the expression of the troA gene was subject to environmental regulation at the transcript level. In a murine S. suis infection model, the ΔtroA mutant displayed a nonvirulent phenotype. These data indicate that S. suis TroA is involved in manganese acquisition and is required for full virulence in mice.
Insights
Streptococcus suis utilizes TroA for manganese acquisition, crucial for its survival and virulence. Deleting TroA impairs bacterial growth in low-manganese environments and reduces infection severity in mice.
Area of Science:
- Bacteriology
- Molecular Biology
- Infectious Diseases
Background:
- Streptococcus suis is a significant pathogen causing severe infections in pigs and humans.
- Nutrient acquisition, particularly trace metals, is vital for S. suis survival within the host.
- The specific mechanisms and proteins involved in metal scavenging by S. suis remain largely uncharacterized.
Purpose of the Study:
- To investigate the function of the putative high-affinity metal binding lipoprotein TroA in S. suis.
- To determine TroA's role in metal acquisition, host-pathogen interactions, and virulence.
Main Methods:
- Construction and characterization of a S. suis mutant strain deficient in TroA expression (ΔtroA).
- Growth assays in various media, including cation-deprived broth and porcine serum.
- Assessment of oxidative stress resistance and gene expression analysis.
- Evaluation of virulence in a murine infection model.
Main Results:
- The ΔtroA mutant exhibited significantly reduced growth in manganese-limited conditions and porcine serum.
- Supplementation with manganese, but not other tested metals, restored growth of the ΔtroA mutant.
- The mutant showed increased susceptibility to hydrogen peroxide (H2O2), indicating a role in oxidative stress defense.
- The ΔtroA mutant displayed a nonvirulent phenotype in a murine infection model.
Conclusions:
- TroA is essential for manganese acquisition in S. suis.
- TroA plays a critical role in combating oxidative stress.
- TroA is indispensable for the full virulence of S. suis in a mouse model, highlighting its importance as a potential therapeutic target.
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