Published May 13, 2013
UB researchers have found that a protein complex in human breast milk can force drug-resistant bacteria—even highly resistant superbugs—to respond to antibiotics again.
HAMLET (human alpha-lactalbumin made lethal to tumor cells) has shown the ability to selectively kill both tumor cells and bacteria.
Through petri dish and animal experiments, the UB team has shown that this natural protein-lipid complex increased bacteria's sensitivity to multiple classes of antibiotics, such as penicillin and erythromycin.
The UB research shows that HAMLET can help reverse the
antibiotic resistance of bacterial species that cause dangerous
pneumonia and staph infections,
including methicillin-resistant Staphylococcus aureus (MRSA),
the culprit behind lethal hospital-acquired staph infections.
Its powerful effect also works against Streptococcus pneumoniae, which is resistant to penicillin, and strains of bacteria resistant to vancomycin, known as the “antibiotic of last resort.”
While a graduate student in Sweden, Anders Hakansson, PhD, now assistant professor of microbiology and immunology, discovered that HAMLET induces apoptosis (cell death) in tumor cells without affecting healthy cells.
Long interested in the protective effect of breast-feeding
against infections, he is now leading the research demonstrating
the protein complex's ability to fight harmful bacteria.
His most recent study describing HAMLET’s effect on S.
aureus has been published in the journal PLOS ONE.
The study also involved his research partner and wife, Hazeline Hakansson, PhD, research assistant professor, and Laura Marks, PhD candidate, both in UB's Department of Microbiology and Immunology.
An earlier paper published in the same journal details HAMLET’s effects against S. pneumoniae. That study involved Anders Hakansson, Marks and Emily Clementi, PhD candidate.
Compared to traditional antibiotics, the protein complex has distinct advantages.
First, bacteria seem to have difficulty developing resistance to HAMLET, dying in huge numbers even after being exposed to HAMLET for many generations.
The protein complex also appears to be safe.
“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,” says Marks.
The researchers also have discovered that average antibiotics achieve super strength when combined with HAMLET. The synergistic effect makes bacteria more sensitive to the drugs.
“HAMLET has the potential to minimize the concentrations of antibiotics we need to use to fight infections, and enable us to use well-established antibiotics against resistant strains again,” said Anders Hakansson.
Used together, HAMLET and antibiotics eradicated streptococcal and staphylococcal biofilms in petri dishes and deep in the noses of mice. This held true for strains previously resistant to antibiotics.
In lab experiments, HAMLET lowered the dose of antibiotics needed to fight S. pneumoniae and S. aureus by as much as a factor of eight or more.
The ability to combine HAMLET with existing antibiotics makes the protein complex economically promising.
“The pharmaceutical industry is 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 in the next couple of years as antibiotic resistance increases.”
“HAMLET kills bacteria via a mechanism that is clearly different from that of commonly prescribed antibiotics,” Hazeline Hakansson says.
HAMLET appears to spark a chain of chemical reactions in the bacteria it kills through a process that mirrors what happens naturally when bacterial cells self-destruct for the greater good of a bacterial community.
This deadly process includes an influx of calcium and the activation of a serine/threonine kinase, and ends with cells rupturing.
In certain bacteria (including S. pneumoniae and S. aureus), HAMLET binds to and halts the activity of biological pumps and transporters that help regulate the flow of ions in and out of a cell.
HAMLET also binds to and blocks the activity of two enzymes needed for glycolysis, a process bacteria use to obtain energy.
The Hakanssons founded a company called Evincor to further develop HAMLET. In addition, a provisional patent application detailing HAMLET’s antibiotic capabilities has been filed by UB’s Office of Science, Technology Transfer and Economic Outreach.
The Hakanssons now plan to test HAMLET on additional strains of S. pneumoniae and S. aureus — including those currently infecting patients.
They also plan to expand the in-vivo infection models used for testing to provide a proof of principle.