RESUMEN
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.
Asunto(s)
Anticuerpos Antibacterianos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Infecciones por Klebsiella/terapia , Klebsiella pneumoniae/fisiología , Antígenos O/inmunología , Animales , Antibacterianos/uso terapéutico , Anticuerpos Antibacterianos/inmunología , Anticuerpos Monoclonales/inmunología , Línea Celular , Modelos Animales de Enfermedad , Farmacorresistencia Bacteriana Múltiple/genética , Farmacorresistencia Bacteriana Múltiple/inmunología , Humanos , Inmunidad Humoral , Factores Inmunológicos/uso terapéutico , Inmunoterapia/métodos , Infecciones por Klebsiella/inmunología , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/mortalidad , Klebsiella pneumoniae/efectos de los fármacos , Meropenem , Ratones , Ratones Endogámicos C57BL , Pruebas de Sensibilidad Microbiana , Serogrupo , Tasa de Supervivencia , Tienamicinas/uso terapéuticoRESUMEN
Distinct roadblocks prevent translating basic findings in viral pathogenesis into therapies and implementing potential solutions in the clinic. An ongoing partnership between the Volkswagen Foundation and Nature Medicine resulted in an interactive meeting in 2012, as part of the "Herrenhausen Symposia" series. Current challenges for various fields of viral research were recognized and discussed with a goal in mind--to identify solutions and propose an agenda to address the translational barriers. Here, some of the researchers who participated at the meeting provide a concise outlook at the most pressing unmet research and clinical needs, identifying these key obstacles is a necessary step towards the prevention and cure of human viral diseases.