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

作者：Meghan E. Pennini, Anna De Marco, Mark R. Pelletier, Jessica C. Bonnell, Romana Cvitkovic, Martina Beltramello, Elisabetta Cameroni, Siro Bianchi, Fabrizia Zatta, Zhao Wei, Xiaodong Xiao, María M. Cámara, Antonio DiGiandomenico, Elena Aleksandrovna Semenova, Antonio Lanzavecchia, Paul Warrener, JoAnn Suzich, Qun Wang, Davide Corti, C. Kendall Stover · 发表于：Nature Communications · 年份：2017 · DOI：10.1038/s41467-017-02223-7 · 被引用次数：117 · 研究领域：Antibiotic Resistance in Bacteria、Escherichia coli research studies、Pneumonia and Respiratory Infections

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.