Colonization of healthy children by Moraxella catarrhalis is characterized by genotype heterogeneity, virulence gene diversity and co-colonization with Haemophilus influenzae

Abstract

The colonization dynamics ofMoraxella catarrhaliswere studied in a population comprising 1079 healthy children living in Rotterdam, The Netherlands (the Generation R Focus cohort). A total of 2751 nasal swabs were obtained during four clinic visits timed to take place at 1.5, 6, 14 and 24 months of age, yielding a total of 709M. catarrhalisand 621Haemophilus influenzaeisolates. Between January 2004 and December 2006, approximate but regular 6-monthly cycles of colonization were observed, with peak colonization incidences occurring in the autumn/winter forM. catarrhalis, and winter/spring forH. influenzae. Co-colonization was significantly more likely than single-species colonization with eitherM. catarrhalisorH. influenzae, with genotypic analysis revealing no clonality for co-colonizing or single colonizers of either bacterial species. This finding is especially relevant considering the recent discovery of the importance ofH. influenzae–M. catarrhalisquorum sensing in biofilm formation and host clearance. Bacterial genotype heterogeneity was maintained over the 3-year period of the study, even within this relatively localized geographical region, and there was no association of genotypes with either season or year of isolation. Furthermore, chronological and genotypic diversity in three immunologically importantM. catarrhalisvirulence genes (uspA1,uspA2andhag/mid) was also observed. This study indicates that genotypic variation is a key factor contributing to the success ofM. catarrhaliscolonization of healthy children in the first years of life. Furthermore, variation in immunologically relevant virulence genes within colonizing populations, and even within genotypically identicalM. catarrhalisisolates, may be a result of immune evasion by this pathogen. Finally, the factors facilitatingM. catarrhalisandH. influenzaeco-colonization need to be further investigated.