title: Pharmacological Targeting of the Host-Pathogen Interaction: Alternatives to Classical Antibiotics to Combat Drug-Resistant Superbugs.
abstract: The rise of multidrug-resistant pathogens and the dearth of new antibiotic development place an existential strain on successful infectious disease therapy. Breakthrough strategies that go beyond classical antibiotic mechanisms are needed to combat this looming public health catastrophe. Reconceptualizing antibiotic therapy in the richer context of the host-pathogen interaction is required for innovative solutions. By defining specific virulence factors, the essence of a pathogen, and pharmacologically neutralizing their activities, one can block disease progression and sensitize microbes to immune clearance. Likewise, host-directed strategies to boost phagocyte bactericidal activity, enhance leukocyte recruitment, or reverse pathogen-induced immunosuppression seek to replicate the success of cancer immunotherapy in the field of infectious diseases. The answer to the threat of multidrug-resistant pathogens lies 'outside the box' of current antibiotic paradigms.
authors.affiliation: Department of Pediatrics, Division of Host-Microbe Systems and Therapeutics, University of California San Diego, La Jolla, CA 92093, USA; Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Munguia
authors.affiliation: Department of Pediatrics, Division of Host-Microbe Systems and Therapeutics, University of California San Diego, La Jolla, CA 92093, USA; Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA 92093, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA; Rady Children's Hospital, San Diego, CA 92123, USA. Electronic address: vnizet@ucsd.edu.
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001424:Bacterial Infections / Q000188:drug therapy*; D018432:Drug Resistance, Multiple; D054884:Host-Pathogen Interactions / Q000187:drug effects*; D006801:Humans
chemical_list: D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal
keywords: antibiotic resistance; bacterial infections; immunotherapy; macrophages; neutrophils; virulence factors