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

Schaar, Viveka LU ; Nordström, Therése LU ; Mörgelin, Matthias LU and Riesbeck, Kristian LU (2011) In Antimicrobial Agents and Chemotherapy 55. p.3845-3853
Abstract
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... (More)
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. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Antimicrobial Agents and Chemotherapy
volume
55
pages
3845 - 3853
publisher
American Society for Microbiology
external identifiers
  • wos:000292733800026
  • pmid:21576428
  • scopus:79960339316
ISSN
1098-6596
DOI
10.1128/AAC.01772-10
language
English
LU publication?
yes
id
bb908e72-4b04-4d95-838c-544da68b7878 (old id 1972518)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21576428?dopt=Abstract
date added to LUP
2011-06-07 20:07:32
date last changed
2017-11-12 03:42:57
@article{bb908e72-4b04-4d95-838c-544da68b7878,
  abstract     = {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.},
  author       = {Schaar, Viveka and Nordström, Therése and Mörgelin, Matthias and Riesbeck, Kristian},
  issn         = {1098-6596},
  language     = {eng},
  pages        = {3845--3853},
  publisher    = {American Society for Microbiology},
  series       = {Antimicrobial Agents and Chemotherapy},
  title        = {Moraxella catarrhalis outer membrane vesicles carry beta-lactamase and promote survival of Streptococcus pneumoniae and Haemophilus influenzae by inactivating amoxicillin.},
  url          = {http://dx.doi.org/10.1128/AAC.01772-10},
  volume       = {55},
  year         = {2011},
}