Aggregatibacter actinomycetemcomitanscolonization and persistence in a primate model

Abstract

Aggregatibacter actinomycetemcomitansis associated with aggressive periodontitis resulting in premature tooth loss in adolescents. Tooth adherence and biofilm persistence are prerequisites for survival in the oral domain. Here, using a rhesus monkey model, 16S rRNA sequencing, and weighted network analysis, we assessed colonization ofA. actinomycetemcomitansvariants and ascertained microbial interactions in biofilm communities. Variants inA. actinomycetemcomitansleukotoxin (ltx) were created, labeled, inoculated, and compared with their progenitor strain for in vivo colonization. Samples of tooth-related plaque were assessed for colonization at baseline and after debridement and inoculation of labeled strains. Null, minimal, and hyper-Ltx–producing strains were created and assessed for hydroxyapatite binding and biofilm formation in vitro. Ltx-hyperproducing strains colonized with greater prevalence and at higher levels than wild type orltxmutants (P= 0.05). Indigenous and inoculatedA. actinomycetemcomitansstrains that attached were associated with lactate-producing species (i.e., Leptotrichia, Abiotrophia, and Streptoccocci).A. actinomycetemcomitanswas found at 0.13% of the total flora at baseline and at 0.05% 4 wk after inoculation. In vivo data were supported by in vitro results. We conclude that hyper-Ltx production affords these strains with an attachment advantage providing a foothold for competition with members of the indigenous microbiota. Increased attachment can be linked toltxgene expression and up-regulation of adherence-associated genes. Growth of attachedA. actinomycetemcomitansin vivo was enhanced by lactate availability due to consorting species. These associations provideA. actinomycetemcomitanswith the constituents required for its colonization and survival in the complex and competitive oral environment.