Bacterial Outer Membrane Vesicles. Mediators of virulence and antibiotic resistance.
Summary, in English
In our first study, we determined the protemoic composition of M. catarrhalis OMV, and found them to be composed of mainly outer membrane and periplasmic proteins. We also established that OMV bind to and activate respiratory epithelial cells and cause a pro-inflammatory response both in vitro and in vivo.
Considering that more than 97% of all M. catarrhalis strains are positive for β-lactamase, we determined in our second study that OMV from this pathogen contain β-lactamase. We further showed that OMV rescued other amoxicillin susceptible co-pathogens such as non-typeable H. influenzae (NTHi) and Streptococcus pneumoniae from killing. Thereafter, we established in our third study that serum from healthy adults contain anti-Moraxella β-lactamase antibodies. We showed that these antibodies bind to and neutralize β-lactamase in OMV to a certain degree, whereas OMV also act as protective vesicles, shielding the enzyme in the extracellular space.
Finally, in the last study we investigated the role of OMV in co-infections with other species dwelling in the respiratory tract. Previous studies have shown treatment failures of group A streptococci (GAS) in pharyngotonsillits even though the GAS are completely susceptible to β-lactams, and that NTHi and M. catarrhalis are often found associated with GAS during treatment failures. We found that OMV from β-lactamase positive NTHi and M. catarrhalis protect GAS from amoxicillin-induced killing, and we suggest OMV secretion to be a mechanism for bacteria in polymicrobial infections to interact and protect each other.
In summary, we determined that OMV secreted from Gram-negative bacteria of the upper respiratory tract are mediators of virulence and antibiotic resistance, interacting with host cells as well as other bacterial species found in polymicrobial infections.
Lund University Faculty of Medicine Doctoral Dissertation Series
Medical Microbiology, Lund University
- Microbiology in the medical area
- Antibiotic resistance
- Moraxella catarrhalis
- epithelial cells
- non-typeable Haemophilus influenzae
- outer membrane vesicles
- polymicrobial infections
- Clinical Microbiology, Malmö
- Institution of Laboratory Medicine, Medical Microbiolgy, Respiratory Pathogen Group
- Kristian Riesbeck
- Arne Forsgren
- ISSN: 1652-8220
- ISBN: 978-91-87449-83-3
18 October 2013
Main lecture hall, Pathology building, SUS Malmö
- Anders Håkansson (Assistant Professor)