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Moraxella catarrhalis is generally associated with upper respiratory tract infections in children and lower respiratory tract infections in adults. However, little is known regarding the population biology of isolates infecting these two age groups. To address this, a population-screening strategy was employed to investigate 195 worldwide M. catarrhalis isolates cultured from children (<5 years of age) and adults (>20 years of age) presenting with respiratory disease in the years 2001-2002. Parameters compared included: genotype analysis; autoagglutination/biofilm-forming ability; serum resistance; uspA1, uspA2, uspA2H, hag and mcaP incidence; copB/LOS/ompCD/16S rRNA types; and UspA1/Hag expression. A significant difference in biofilm formation (P=0.002), but not in autoagglutination or serum resistance, was observed, as well as significant differences in the incidence of uspA2- and uspA2H-positive isolates, and the distribution of lipooligosaccharide (LOS) types (P<0.0001 and P=0.01, respectively). Further, a significant decrease in the incidence of Hag expression (for isolates possessing the hag gene) was observed in adult isolates (P=0.001). Both uspA2H and LOS type B were associated with 16S rRNA type 1 isolates only, and two surrogate markers (copB and ompCD PCR RFLP types) for the two major M. catarrhalis 16S rRNA genetic lineages were identified. In conclusion, there are significant differences in phenotype and gene incidence between M. catarrhalis isolates from children and adults presenting with respiratory disease, possibly as a result of immune evasion in the adult age group. Our results should also be useful in the choice of effective vaccine candidates against M. catarrhalis.