Manganese transport by Streptococcus sanguinis in acidic conditions and its impact on growth in vitro and in vivo

• Published in: Molecular microbiology 2022-02, Vol.117 (2), p.375-393
• Main Authors: Puccio, Tanya, An, Seon‐Sook, Schultz, Alexander C., Lizarraga, Claudia A., Bryant, Ashley S., Culp, David J., Burne, Robert A., Kitten, Todd
• Format: Article
• Language: English
• Subjects: carbon catabolite repression; Catabolite repression; Deletion mutant; Dental caries; Endocarditis; Etiology; Heterogeneity; Manganese; Mutants; NRAMP protein; Streptococcus infections; Streptococcus sanguinis; Transcriptomics; Virulence; ZIP‐family protein
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1111/mmi.14854

Streptococcus sanguinis is an oral commensal and an etiological agent of infective endocarditis. Previous studies have identified the SsaACB manganese transporter as essential for endocarditis virulence; however, the significance of SsaACB in the oral environment has never been examined. Here we report that a ΔssaACB deletion mutant of strain SK36 exhibits reduced growth and manganese uptake under acidic conditions. Further studies revealed that these deficits resulted from the decreased activity of TmpA, shown in the accompanying paper to function as a ZIP‐family manganese transporter. Transcriptomic analysis of fermentor‐grown cultures of SK36 WT and ΔssaACB strains identified pH‐dependent changes related to carbon catabolite repression in both strains, though their magnitude was generally greater in the mutant. In strain VMC66, which possesses a MntH transporter, loss of SsaACB did not significantly alter growth or cellular manganese levels under the same conditions. Interestingly, there were only modest differences between SK36 and its ΔssaACB mutant in competition with Streptococcus mutans in vitro and in a murine oral colonization model. Our results suggest that the heterogeneity of the oral environment may provide a rationale for the variety of manganese transporters found in S. sanguinis. Streptococcus sanguinis is an oral bacterium that competes with Streptococcus mutans, a causative agent of dental caries. We report that growth of S. sanguinis SK36 in acidic media leads to decreased manganese levels and changes in carbon catabolite repression. A knockout mutant of the primary manganese transporter grows poorly in acidic media but shows similar colonization and competition with S. mutans in vivo when compared with wild type.