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Breast milk protein complex helps reverse antibiotic resistance

A healthy Streptococcus pneumoniae bacterial cell (upper left) next to a bacterial cell destroyed and lysed by the human milk protein complex HAMLET (lower right). Image: Laura R. Marks


Published May 2, 2013

“HAMLET has the potential minimize the concentrations of antibiotics we need to use to fight infections, and enable us to use well-established antibiotics against resistant strains again.”
Anders Hakansson, Assistant Professor
Department of Microbiology and Immunology

A protein complex found in human breast milk can help reverse the antibiotic resistance of bacterial species that cause dangerous pneumonia and staph infections, according to new UB research.

In petri dish and animal experiments, the protein complex—called Human Alpha-lactalbumin Made Lethal to Tumor Cells (HAMLET)—increased bacteria’s sensitivity to multiple classes of antibiotics, such as penicillin and erythromycin.

The effect was so pronounced that bacteria including penicillin-resistant Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA) regained sensitivity to the antibiotics they previously were able to beat, says researchers Anders Hakansson, Laura Marks and Hazeline Hakansson, all in UB’s Department of Microbiology and Immunology.

HAMLET’s effects against S. pneumoniae were published in the journal PLOS ONE in August 2012 with Marks, Anders Hakansson and UB PhD student Emily Clementi as authors. HAMLET’s effects on S. aureus appeared in PLOS ONE on May 1.

“HAMLET has the potential minimize the concentrations of antibiotics we need to use to fight infections, and enable us to use well-established antibiotics against resistant strains again,” says Anders Hakansson, lead researcher and UB assistant professor of microbiology and immunology who has long been interested in the protective effect of breast-feeding against infections.

The findings hold great promise in an era when hospitals are struggling to contain drug-resistant “superbugs” like MRSA, the culprit behind lethal hospital-acquired staph infections.

Bacteria seem to have difficulty developing resistance to HAMLET, dying in huge numbers even after being exposed to HAMLET for many generations.

Marks, an MD/PhD student in the School of Medicine and Biomedical Sciences’ Medical Scientist Training Program, described another of HAMLET’s benefits: “Unlike synthetic drugs, HAMLET is a naturally occurring human milk protein-lipid complex, and so is not associated with the types of toxic side effects that we so frequently see with the high-powered antibiotics needed to kill drug-resistant organisms.”

The idea to test HAMLET in combination with other antibiotics was inspired, in part, by a presentation Marks saw on using drug cocktails to treat HIV.

“What really hit home for me in this lecture was the idea of using drug combinations where each drug had a different mechanism that could enhance the action of the other drug as an appealing way to optimize therapy for resistant organisms,” she says. “I was immediately curious to see if using HAMLET together with existing therapies could result in synergistic interactions.”

UB’s Office of Science, Technology Transfer and Economic Outreach (STOR) has filed a provisional patent application detailing HAMLET’s antibiotic capabilities, and Anders and Hazeline Hakansson have founded a company called Evincor to further develop HAMLET.

“The pharmaceutical industry is currently reluctant to develop antibiotics because they are only used for a short time and they will be used infrequently initially and only when nothing else works,” Hazeline Hakansson says. “HAMLET, on the other hand, is more of an adjuvant and can be used widely in combination with common antibiotics; it already has a huge potential market that is only going to increase the next couple of years as antibiotic resistance increases.

“Some people estimate that it’s only a question of time before we run out of antibiotics to combat bacteria,” she continues. “HAMLET is promising because we haven’t been able to make bacteria resistant to it and it kills bacteria via a mechanism that is clearly different from that of commonly prescribed antibiotics.”

The Hakanssons, a husband-and-wife team, say the next step is to test HAMLET on additional strains of S. pneumoniae and S. aureus—including those currently infecting patients—and to expand the in-vivo infection models used for testing to provide a proof of principle.