The pathogens Streptococcus pyogenes and Moraxella catarrhalis colonize overlapping regions of the human nasopharynx. We have found that M. catarrhalis can dramatically increase S. pyogenes adherence to human epithelial cells and that species-specific coaggregation of these bacteria correlates with this enhanced adherence.In most environments, the interaction of individual microbes with other microbial species can have a profound effect on the colonization, persistence, and survival of the microorganisms. The importance of polymicrobial interactions has also been documented in human and animal diseases (5). In the case of periodontal disease, the binding or coaggregation of Porphyromonas gingivalis to Streptococcus gordonii enhances the colonization of the tooth surface by P. gingivalis (19). This coaggregation is complex and is mediated by at least two adhesinreceptor pairs (9,19). Although much is known about polymicrobial interactions in the human colon and oral cavity, little work has been done investigating polymicrobial interactions among bacteria that colonize or infect the human nasopharynx.As a model for possible polymicrobial interactions in the human nasopharynx, we investigated interactions between Streptococcus pyogenes and Moraxella catarrhalis for several reasons. First, S. pyogenes and M. catarrhalis are human-specific pathogens that colonize the nasopharynx, causing a variety of diseases (4,7,8,13,17,21,23,28,33). Their carriage rates among asymptomatic individuals can be very high, and the adherence of both organisms to epithelial cells is critical for their pathogenesis and they adhere to the same human epithelial cell lines (11,15,16,22,31).M. catarrhalis increases S. pyogenes adherence to human epithelial cells. To assess whether S. pyogenes (strain 1881, serotype M1) (Table 1) and M. catarrhalis (strain 035E) interact, we measured their adherence to A549 (lung) and Chang (conjunctival) human epithelial cells alone or in combination with a quantitative adherence assay that we previously described (18). The presence of S. pyogenes had a small (less-than-threefold) negative influence on the binding of M. catarrhalis to both cell lines. However, M. catarrhalis substantially increased S. pyogenes adherence to Chang cells (22-fold) and to A549 cells (15-fold) (Fig. 1A and B). In contrast, a nonadherent Escherichia coli strain had no effect on S. pyogenes adherence. M. catarrhalis had a modest effect (threefold) on the adherence of the closely related species S. agalactiae. In addition, we observed that the adherence of two other gram-positive cocci (S. aureus and S. pneumoniae) was not significantly affected by M. catarrhalis (Fig. 1C). Thus, the dramatic effect of M. catarrhalis on S. pyogenes adherence is not shared by other grampositive human pathogens.Microscopic examination of M. catarrhalis and S. pyogenes bound to human cells suggested that the bacteria were colocalized on the eukaryotic cell surface (data not shown). We therefore hypothesized that M. catarrhalis was acting as an adapter, ...