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 of Moraxella catarrhalis were 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 709 M. catarrhalis and 621 Haemophilus influenzae isolates. 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 for M. catarrhalis, and winter/spring for H. influenzae. Co-colonization was significantly more likely than single-species colonization with either M. catarrhalis or H. 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 of H. influenzae-M. catarrhalis quorum 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 important M. catarrhalis virulence genes (uspA1, uspA2 and hag/mid ) was also observed. This study indicates that genotypic variation is a key factor contributing to the success of M. catarrhalis colonization of healthy children in the first years of life. Furthermore, variation in immunologically relevant virulence genes within colonizing populations, and even within genotypically identical M. catarrhalis isolates, may be a result of immune evasion by this pathogen. Finally, the factors facilitating M. catarrhalis and H. influenzae co-colonization need to be further investigated. INTRODUCTIONMoraxella catarrhalis is part of the normal bacterial flora in the nasopharynx of children, although over the past two decades, it has emerged as a significant bacterial pathogen and not simply a commensal colonizer (Verduin et al., 2002). Studies have shown that the bacterium rapidly colonizes the nasopharynx soon after birth and that the carriage rate of M. catarrhalis in healthy children varies between 7 and 36 % (Verhaegh et al., 2010). However, in children with upper respiratory tract infections (URTI), including acute otitis media (AOM), the carriage rate increases to approximately 50 % (Berner et al., 1996;Konno et al., 2006;Pettigrew et al., 2008). Otitis media itself is a particularly important URTI during early Abbreviations: AOM, acute otitis media; CEACAM, carcinoembryonic antigen-related cell adhesion molecule; LOS, lipooligosaccharide; MLST, multilocus sequence typing; OMP, outer-membrane protein; OR, odds ratio; OMV, outer-membrane vesicle; URTI, upper respiratory tract infection. childhood and the primary reason for children to visit a physician (Freid et al., 1998;Plasschaert et al., 2006). Furt...

Microbiological Features of Upper Respiratory Tract Infections in Bulgarian Children for the Period 1998-2014

“…From the results it is noteworthy that in contrast to the infectious process of some other body systems, the URTI, particularly rhinosinusitis, ethmoiditis, rhinopharyngitis and adenoiditis most often (in more than 70% of cases) were with polymicrobial etiology. Similar results have also been reported in our earlier studies as well as other authors (3,4,13,14).…”

“…A little known fact is that the most common microbial combination of causative agents, actually are exactly those two microorganisms in association, not only for epiglottitis but also for other URTI as adenoiditis and rhinopharyngitis in children, that have been confirmed by other authors through the last years (14).…”

Effect of Pneumococcal Vaccination on Nasopharyngeal Carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus in Fijian Children

“…Other researchers have reported similar associations between S. pneumoniae and H. influenzae (10,12,14), S. pneumoniae and M. catarrhalis (10,12), and M. catarrhalis and H. influenzae (10,37) in children of a comparable age. Pettigrew et al (20) found negative associations between S. pneumoniae and H. influenzae and between M. catarrhalis and H. influenzae in children with upper respiratory infections, suggesting that the presence of an active infection may influence colonization dynamics.…”

Temporal development of the humoral immune response to surface antigens of Moraxella catarrhalis in young infants

“…This respectively. The colonization status was determined using standard M. catarrhalis culture and detection techniques [1].…”

“…Studies have shown that the bacterium colonizes the nasopharynx soon after birth and that the carriage rate of M. catarrhalis in healthy children may differ per geographical region, season and year of isolation [1]. For example, in a German study (November 1991 to April 1992), 9% of children attending day-care centers ranging in age from 4 months to 3 years old were colonized with M. catarrhalis [2].…”