Moraxella catarrhalis outer membrane vesicles carry beta-lactamase and promote survival of Streptococcus pneumoniae and Haemophilus influenzae by inactivating amoxicillin.
Författare
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.
Publiceringsår
2011
Språk
Engelska
Sidor
3845-3853
Publikation/Tidskrift/Serie
Antimicrobial Agents and Chemotherapy
Volym
55
Fulltext
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Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
American Society for Microbiology
Ämne
- Microbiology in the medical area
Status
Published
Forskningsgrupp
- Clinical Microbiology, Malmö
ISBN/ISSN/Övrigt
- ISSN: 1098-6596