Zinc import mediated by AdcABC is critical for colonization of the dental biofilm by Streptococcus mutans in an animal model

• Main Authors: Abranches, J. (Author), Ganguly, T. (Author), Kajfasz, J.K (Author), Lemos, J.A (Author), Peterson, A.M (Author)
• Format: Article
• Language: English
• Published: John Wiley and Sons Inc 2021
• Subjects: ABC transporter; adenosine triphosphatase; animal; animal experiment; animal model; Animals; antibody dependent cellular cytotoxicity; Article; bacterial colonization; bacterial endocarditis; bacterial genome; bacterial growth; bacterial strain; bacterial virulence; bacterium culture; biofilm; Biofilms; chelating agent; controlled study; dental caries; Dental Caries; gene inactivation; genetics; iron; manganese; metal; metal binding; metal homeostasis; Models, Animal; mouth infection; nonhuman; nutritional immunity; permease; peroxide; rat; Rats; Streptococcus mutans; sucrose; tooth flora; zinc; Zinc; zinc binding protein
• Online Access: View Fulltext in Publisher

 Trace metals are essential to all domains of life but toxic when found at high concentrations. Although the importance of iron in host–pathogen interactions is firmly established, contemporary studies indicate that other trace metals, including manganese and zinc, are also critical to the infectious process. In this study, we sought to identify and characterize the zinc uptake system(s) of Streptococcus mutans, a keystone pathogen in dental caries and a causative agent of bacterial endocarditis. Different than other pathogenic bacteria, including several streptococci, that encode multiple zinc import systems, bioinformatic analysis indicated that the S. mutans core genome encodes a single, highly conserved, zinc importer commonly known as AdcABC. Inactivation of the genes coding for the metal-binding AdcA (ΔadcA) or both AdcC ATPase and AdcB permease (ΔadcCB) severely impaired the ability of S. mutans to grow under zinc-depleted conditions. Intracellular metal quantifications revealed that both mutants accumulated less zinc when grown in the presence of a subinhibitory concentration of a zinc-specific chelator. Notably, the ΔadcCB strain displayed a severe colonization defect in a rat oral infection model. Both Δadc strains were hypersensitive to high concentrations of manganese, showed reduced peroxide tolerance, and formed less biofilm in sucrose-containing media when cultivated in the presence of the lowest amount of zinc that support their growth, but not when zinc was supplied in excess. Collectively, this study identifies AdcABC as the major high affinity zinc importer of S. mutans and provides preliminary evidence that zinc is a growth-limiting factor within the dental biofilm. © 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd