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Moraxella catarrhalis outer membrane vesicles carry beta-lactamase and promote survival of Streptococcus pneumoniae and Haemophilus influenzae by inactivating amoxicillin.

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Author

Summary, in English

Moraxella catarrhalis is a common pathogen found in children with upper respiratory tract infections, and in patients with chronic obstructive pulmonary disease during exacerbations. The bacterial species is often isolated together with Streptococcus pneumoniae and Haemophilus influenzae. Outer membrane vesicles (OMV) are released by M. catarrhalis and contain phospholipids, adhesins, and immunomodulatory compounds such as lipooligosaccharide. We have recently shown that M. catarrhalis OMV exist in patients upon nasopharyngeal colonization. As virtually all M. catarrhalis are β-lactamase positive, the goal of this study was to investigate whether M. catarrhalis OMV carry β-lactamase, and to analyze if OMV consequently can prevent amoxicillin-induced killing. Recombinant RH4 β-lactamase was produced and antibodies were raised in rabbits. Transmission electron microscopy, flow cytometry and Western blots verified that OMV carried β-lactamase. Moreover, enzyme assays revealed that M. catarrhalis OMV contained active β-lactamase. OMV (25 μg/ml) incubated with amoxicillin for 1 hr completely hydrolyzed amoxicillin at concentrations up to 2.5 μg/ml. In functional experiments, pre-incubation of amoxicillin (10xMIC) with M. catarrhalis OMV fully rescued amoxicillin-susceptible M. catarrhalis, S. pneumoniae and type b or non-typeable H. influenzae from β-lactam-induced killing. Our results suggest that the presence of amoxicillin-resistant M. catarrhalis originating from β-lactamase-containing OMV may pave the way for respiratory pathogens that by definition are susceptible to β-lactam antibiotics.

Publishing year

2011

Language

English

Pages

3845-3853

Publication/Series

Antimicrobial Agents and Chemotherapy

Volume

55

Document type

Journal article

Publisher

American Society for Microbiology

Topic

  • Microbiology in the medical area

Status

Published

Research group

  • Clinical Microbiology, Malmö

ISBN/ISSN/Other

  • ISSN: 1098-6596