Immune stealth-driven O2 serotype prevalence and potential for therapeutic antibodies against multidrug resistant Klebsiella pneumoniae. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Pennini, Meghan; Marco, Anna; Pelletier, Mark; Bonnell, Jessica; Cvitkovic, Romana; Beltramello, Martina; Cameroni, Elisabetta; Bianchi, Siro; Zatta, Fabrizia; Zhao, Wei; Xiao, Xiaodong; Camara, Maria; DiGiandomenico, Antonio; Semenova, Elena; Lanzavecchia, Antonio; Warrener, Paul; Suzich, JoAnn; Wang, Qun; Corti, Davide; Stover, C.
• Is Part Of: Nature communications. Volume 8:Issue 1(2017)
• Page Start: 1
• Page End: 12
• Publication Date: 2017-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-017-02223-7
• Languages: English
• ISSNs: 2041-1723

Abstract

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 ofKlebsiella 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 resistantK. pneumoniae infections, and underscore the effect humoral immunity has on evolving drug resistance. Therapeutics to combat multidrug-resistant bacteria such asKlebsiella pneumonia e are needed. Here the authors show immune evasion drives lipopolysaccharide O2 serotype expansion in multidrug-resistant isolates, and anti-O-antigen human monoclonal antibodies synergize with antibiotics to protect mice from infection.