| DOI | Resolve DOI: https://doi.org/10.1128/AAC.02168-19 |
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| Author | Search for: Richard, Gabrielle1; Search for: Mackenzie, C. Roger1; Search for: Henry, Kevin A.1; Search for: Vinogradov, Evgeny1; Search for: Hall, J. Christopher; Search for: Hussack, Greg1 |
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| Affiliation | - National Research Council of Canada. Human Health Therapeutics
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| Format | Text, Article |
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| Subject | lipopolysaccharide; LPS; O-specific antigen; antibacterial antibodies; outer membrane disruption; atomic force microscopy; AFM |
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| Abstract | Pseudomonas aeruginosa is an opportunistic pathogen that is inherently resistant to many antibiotics and represents an increasing threat due to the emergence of drug-resistant strains. There is a pressing need to develop innovative antimicrobials against this pathogen. In this study, we identified the O-specific antigen (OSA) of P. aeruginosa serotype O6 as a novel target for therapeutic intervention. Binding of monoclonal antibodies and antigen-binding fragments therefrom to O6 OSA leads to rapid outer membrane destabilization and inhibition of cell growth. The antimicrobial effect correlated directly with antibody affinity. Antibody binding to the O antigen of a second lipopolysaccharide (LPS) type present in P. aeruginosa or to the LPS core did not affect cell viability. Atomic force microscopy showed that antibody binding to OSA resulted in early flagellum loss, formation of membrane blebs, and eventually complete outer membrane loss. We hypothesize that antibody binding to OSA disrupts a key interaction in the P. aeruginosa outer membrane. |
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| Publication date | 2020-02-03 |
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| Publisher | American Society for Microbiology |
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| In | |
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| Language | English |
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| Peer reviewed | Yes |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | 9fa419ce-10d2-4ec5-ac60-0b4d2f9e7e79 |
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| Record created | 2020-07-24 |
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| Record modified | 2021-09-17 |
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