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

Nat Commun. 2017 Dec 8;8(1):1991. doi: 10.1038/s41467-017-02223-7.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / therapeutic use
  • Antibodies, Bacterial / immunology
  • Antibodies, Bacterial / therapeutic use*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Cell Line
  • Disease Models, Animal
  • Drug Resistance, Multiple, Bacterial / genetics
  • Drug Resistance, Multiple, Bacterial / immunology
  • Humans
  • Immunity, Humoral
  • Immunologic Factors / therapeutic use
  • Immunotherapy / methods
  • Klebsiella Infections / immunology
  • Klebsiella Infections / microbiology
  • Klebsiella Infections / mortality
  • Klebsiella Infections / therapy*
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / physiology*
  • Meropenem
  • Mice
  • Mice, Inbred C57BL
  • Microbial Sensitivity Tests
  • O Antigens / immunology*
  • Serogroup
  • Survival Rate
  • Thienamycins / therapeutic use


  • Anti-Bacterial Agents
  • Antibodies, Bacterial
  • Antibodies, Monoclonal
  • Immunologic Factors
  • O Antigens
  • Thienamycins
  • Meropenem