The bacterium Aggregatibacter actinomycetemcomitans is a common commensal of the human oral cavity and the putative causative agent of the disease localized aggressive periodontitis. A. actinomycetemcomitans is a slow-growing bacterium that possesses limited metabolic machinery for carbon utilization. This likely impacts its ability to colonize the oral cavity, where growth and community composition is mediated by carbon availability. We present evidence that in the presence of the in vivo relevant carbon substrates glucose, fructose, and lactate A. actinomycetemcomitans preferentially metabolizes lactate. This preference for lactate exists despite the fact that A. actinomycetemcomitans grows faster and obtains higher cell yields during growth with carbohydrates. The preference for lactate is mediated by a novel exclusion mechanism in which metabolism of lactate inhibits carbohydrate uptake. Coculture studies reveal that A. actinomycetemcomitans utilizes lactate produced by the oral bacterium Streptococcus gordonii, suggesting the potential for cross-feeding in the oral cavity.Aggregatibacter (Actinobacillus) actinomycetemcomitans is a nonmotile, facultative anaerobic gram-negative bacterium found in the mammalian oral cavity (27). A. actinomycetemcomitans is the putative causative agent of localized aggressive periodontitis, a disease characterized by tissue destruction and tooth loss (38,49). Within the oral cavity, A. actinomycetemcomitans resides in the gingival crevice, the area around the tooth bounded by the tooth surface on one side and the epithelium lining the gingiva on the other. The gingival crevice contains a robust microbial population that is consistently bathed in crevicular fluid, which differentiates it from the tooth surface, which is immersed in saliva. Crevicular fluid is a plasma exudate that passes through the gingiva and flows along the teeth (20) and contains a number of potential carbon sources including sugars, small acids, and amino acids (6,11,20,48). A. actinomycetemcomitans primarily resides in the "moderate" pockets (4 to 6 mm in depth) in the gingival crevice instead of the deeper portions (9). Moderate pockets differ from deeper subgingival pockets by containing oxygen (19), and controlled studies in the laboratory indicate that A. actinomycetemcomitans exhibits enhanced growth in the presence of oxygen (32). Although the importance of A. actinomycetemcomitans as a common commensal and a potential pathogen has been appreciated for some time, virtually nothing is known about the growth and physiology of this bacterium.The mammalian oral cavity is a diverse environment that contains an estimated 500 bacterial species (17). Although the microbiology of the oral cavity has been the subject of study for many years, surprisingly little is known about the basic nutritional preference of oral bacteria. Compared to many common bacteria within the oral cavity, such as the streptococci, A. actinomycetemcomitans grows slowly and possesses the enzymatic capabilities to utilize only a small ...