Facoltà di scienze biomediche

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

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

In: Nature communications, 2017, vol. 8, p. 1991

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... More

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    Summary
    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.