Immune stealth-driven O2 serotype prevalence and potential for therapeutic antibodies against multidrug resistant Klebsiella pneumoniae View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Meghan E. Pennini, Anna De Marco, Mark Pelletier, Jessica Bonnell, Romana Cvitkovic, Martina Beltramello, Elisabetta Cameroni, Siro Bianchi, Fabrizia Zatta, Wei Zhao, Xiaodong Xiao, Maria M. Camara, Antonio DiGiandomenico, Elena Semenova, Antonio Lanzavecchia, Paul Warrener, JoAnn Suzich, Qun Wang, Davide Corti, C. Kendall Stover

ABSTRACT

Emerging multidrug-resistant bacteria are a challenge for modern medicine, but how these pathogens are so successful is not fully understood. Robust antibacterial vaccines have prevented and reduced resistance suggesting a pivotal role for immunity in deterring antibiotic resistance. Here, we show the increased prevalence of Klebsiella pneumoniae lipopolysaccharide O2 serotype strains in all major drug resistance groups correlating with a paucity of anti-O2 antibodies in human B cell repertoires. We identify human monoclonal antibodies to O-antigens that are highly protective in mouse models of infection, even against heavily encapsulated strains. These antibodies, including a rare anti-O2 specific antibody, synergistically protect against drug-resistant strains in adjunctive therapy with meropenem, a standard-of-care antibiotic, confirming the importance of immune assistance in antibiotic therapy. These findings support an antibody-based immunotherapeutic strategy even for highly resistant K. pneumoniae infections, and underscore the effect humoral immunity has on evolving drug resistance. More... »

PAGES

1991

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-017-02223-7

DOI

http://dx.doi.org/10.1038/s41467-017-02223-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1093156839

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29222409


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