dc.contributor.author | Meikle, Virginia | |
dc.contributor.author | Mossberg, Ann-Kristin | |
dc.contributor.author | Mitra, Avishek | |
dc.contributor.author | Hakansson, Anders P. | |
dc.contributor.author | Niederweis, Michael | |
dc.date.accessioned | 2023-02-16T16:40:22Z | |
dc.date.available | 2023-02-16T16:40:22Z | |
dc.date.issued | 2019-02 | |
dc.identifier.citation | Meikle, V., Mossberg, A.-K., Mitra, A., Hakansson, A. P., Niederweis, M. (2019). A Protein Complex from Human Milk Enhances the Activity of Antibiotics and Drugs against Mycobacterium tuberculosis.. Antimicrobial Agents and Chemotherapy, 63(2), pp. e01846-e01818. https://doi.org/10.1128/aac.01846-18 | |
dc.identifier.issn | 0066-4804 | |
dc.identifier.uri | https://hdl.handle.net/11244/337039 | |
dc.description.abstract | Mycobacterium tuberculosis, 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 make M. tuberculosis more susceptible to existing TB drugs. In this study, we show that HAMLET, an α-lactalbumin-oleic acid complex derived from human milk, has bactericidal activity against M. tuberculosis HAMLET consists of a micellar oleic acid core surrounded by a shell of partially denatured α-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 against M. tuberculosis For example, the minimal inhibitory concentrations of rifampin, bedaquiline, delamanid, and clarithromycin were decreased by 8- to 16-fold. HAMLET also killed M. tuberculosis and enhanced the efficacy of TB drugs inside macrophages, a natural habitat of M. tuberculosis Previous 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. | |
dc.format | application/pdf | |
dc.language | eng | |
dc.publisher | American Society for Microbiology | |
dc.relation.ispartof | Antimicrobial Agents and Chemotherapy, 63 (2) | |
dc.relation.uri | https://www.ncbi.nlm.nih.gov/pubmed/30420480 | |
dc.relation.uri | http://dx.doi.org/10.1128/aac.01846-18 | |
dc.rights | This material has been previously published. In the Oklahoma State University Library's institutional repository this version is made available through the open access principles and the terms of agreement/consent between the author(s) and the publisher. The permission policy on the use, reproduction or distribution of the material falls under fair use for educational, scholarship, and research purposes. Contact Digital Resources and Discovery Services at lib-dls@okstate.edu or 405-744-9161 for further information. | |
dc.subject.mesh | Antitubercular Agents | |
dc.subject.mesh | Escherichia coli | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Lactalbumin | |
dc.subject.mesh | Microbial Sensitivity Tests | |
dc.subject.mesh | Milk, Human | |
dc.subject.mesh | Mycobacterium tuberculosis | |
dc.subject.mesh | Oleic Acids | |
dc.subject.mesh | Tuberculosis | |
dc.title | Protein complex from human milk enhances the activity of antibiotics and drugs against Mycobacterium tuberculosis. | |
dc.date.updated | 2023-02-15T23:00:06Z | |
dc.note | open access status: Green OA | |
dc.identifier.doi | 10.1128/aac.01846-18 | |
dc.description.department | Microbiology and Molecular Genetics | |
dc.type.genre | Article | |
dc.type.material | Text | |
dc.subject.keywords | Vaccine Related | |
dc.subject.keywords | HIV/AIDS | |
dc.subject.keywords | Biotechnology | |
dc.subject.keywords | Tuberculosis | |
dc.subject.keywords | Antimicrobial Resistance | |
dc.subject.keywords | Rare Diseases | |
dc.subject.keywords | Infectious Diseases | |
dc.subject.keywords | Orphan Drug | |
dc.subject.keywords | Pharmaceuticals | |
dc.subject.keywords | Development of treatments and therapeutic interventions | |
dc.subject.keywords | Infection | |
dc.subject.keywords | Good Health and Well Being | |
dc.subject.keywords | HAMLET | |
dc.subject.keywords | liprotides | |
dc.subject.keywords | macrophages | |
dc.subject.keywords | multidrug resistance | |
dc.subject.keywords | oleic acid | |
dc.subject.keywords | potentiation | |
dc.subject.keywords | sensitization | |
dc.subject.keywords | α-lactalbumin | |
dc.subject.keywords | Microbiology | |
dc.subject.keywords | Medical Microbiology | |
dc.subject.keywords | Pharmacology and Pharmaceutical Sciences | |
dc.relation.oaurl | https://pubmed.ncbi.nlm.nih.gov/30420480/ | |
dc.identifier.author | ORCID: 0000-0003-0243-2045 (Mitra, Avishek) | |
dc.identifier.essn | 1098-6596 | |