Bicarbonate Alters Bacterial Susceptibility to Antibiotics by Targeting the Proton Motive Force

• DOI: 10.1021/acsinfecdis.7b00194
• Publication Date: 2017-12-21T12:44:00Z
• Authors: Maya A. Farha; Shawn French; Jonathan M. Stokes; Eric D. Brown
• Keywords: Bicarbonate

The antibacterial properties of sodium bicarbonate have been known for years, yet the molecular understanding its mechanism action is still lacking. Utilizing chemical–chemical combinations, we first explored effect on activity conventional antibiotics to infer mechanism. Remarkably, 8 classes differed in presence this ubiquitous buffer. These interactions and a study revealed that, at physiological concentrations, selective dissipater pH gradient proton motive force across cytoplasmic membrane both Gram-negative Gram-positive bacteria. Further, while components that make up innate immunity extensively studied, link bicarbonate, dominant buffer extracellular fluid, has never made. Here, also effects immunity. Although immune response buffering system distinct functions body, posit there interplay between these, as antimicrobial several were enhanced by concentration bicarbonate. Our findings implicate an overlooked potentiator host defense against pathogens. Overall, unique far-reaching predictable antibiotics. We conclude remarkable power antibiotic adjuvant suggest great potential exploit discovery development new drugs leveraging testing paradigms better reflect