Antimicrob Agents Chemother. 2019 Feb ;63(2). Epub 2019 Jan 29. PMID: 30420480
A Protein Complex from Human Milk Enhances the Activity of Antibiotics and Drugs against.
, the causative agent of human tuberculosis (TB), has surpassed HIV/AIDS as the leading cause of death from a single infectious agent. The increasing occurrence of drug-resistant strains has become a major challenge for health care systems and, in some cases, has rendered TB untreatable. However, the development of new TB drugs has been plagued with high failure rates and costs. Alternative strategies to increase the efficacy of current TB treatment regimens include host-directed therapies or agents that makemore susceptible to existing TB drugs. In this study, we show that HAMLET, anα-lactalbumin-oleic acid complex derived from human milk, has bactericidal activity againstHAMLET consists of a micellar oleic acid core surrounded by a shell of partially denaturedα-lactalbumin molecules and unloads oleic acid into cells upon contact with lipid membranes. At sublethal concentrations, HAMLET potentiated a remarkably broad array of TB drugs and antibiotics againstFor example, the minimal inhibitory concentrations of rifampin, bedaquiline, delamanid, and clarithromycin were decreased by 8- to 16-fold. HAMLET also killedand enhanced the efficacy of TB drugs inside macrophages, a natural habitat ofPrevious studies showed that HAMLET is stable after oral delivery in mice and nontoxic in humans and that it is possible to package hydrophobic compounds in the oleic acid core of HAMLET to increase their solubility and metabolic stability. The potential of HAMLET and other liprotides as drug delivery and sensitization agents in TB chemotherapy is discussed here.