Manganese Uptake, Mediated by SloABC and MntH, Is Essential for the Fitness of Streptococcus mutans.

Early epidemiological studies implicated manganese (Mn) as a possible caries-promoting agent, while laboratory studies have indicated that manganese stimulates the expression of virulence-related factors in the dental pathogen To better understand the importance of manganese homeostasis to pathophysiology, we first used RNA sequencing to obtain the global transcriptional profile of UA159 grown under Mn-restricted conditions. Among the most highly expressed genes were those of the entire operon, encoding a dual iron/manganese transporter, and an uncharacterized gene, here , that codes for a protein bearing strong similarity to Nramp-type transporters. While inactivation of , which encodes the lipoprotein receptor of the SloABC system, or of alone had no major consequence for the overall fitness of , simultaneous inactivation of and (Δ Δ) impaired growth and survival under Mn-restricted conditions, including in human saliva or in the presence of calprotectin. Further, disruption of Mn transport resulted in diminished stress tolerance and reduced biofilm formation in the presence of sucrose. These phenotypes were markedly improved when cells were provided with excess Mn. Metal quantifications revealed that the single mutant strains contained intracellular levels of Mn similar to those seen with the parent strain, whereas Mn was nearly undetectable in the Δ Δ strain. Collectively, these results reveal that SloABC and MntH work independently and cooperatively to promote cell growth under Mn-restricted conditions and that maintenance of Mn homeostasis is essential for the expression of major virulence attributes in As transition biometals such as manganese (Mn) are essential for all forms of life, the ability to scavenge biometals in the metal-restricted host environment is an important trait of successful cariogenic pathobionts. Here, we showed that the caries pathogen utilizes two Mn transport systems, namely, SloABC and MntH, to acquire Mn from the environment and that the ability to maintain the cellular levels of Mn is important for the manifestation of characteristics that associate with dental caries. Our results indicate that the development of strategies to deprive of Mn hold promise in the combat against this important bacterial pathogen.