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Re-sensitizing Bacteria to Antibiotics
Antibiotic resistant bacteria are on the rise across the country. Many types of bacteria have become resistant to first line treatments due to misuse and overuse of antibiotics. This resistance occurs from natural selection. If a full course of the prescribed antibiotic is not taken, bacteria that have some natural resistance will survive and multiple, increasing the number of resistant bacteria. These resistant bacteria would then be unresponsive to future antibiotic treatments. The spread of antibiotic resistant bacteria is of great concern in many areas of the healthcare field. Methicillin-resistant Staphylococcus aureus (MRSA) is on the rise in hospitals, and represents a major nosocomial infection. Other resistant bacteria are on the rise worldwide, including various forms of Mycobacterium tuberculosis (mTB), the causative agent of tuberculosis (TB). Some strains, termed multi drug-resistant TB are resistant to first line antibiotics. Other strains, termed extremely drug-resistant TB are also resistant to second line antibiotics. Recently, strains of mTB have been identified that are resistant to all available antibiotics. This is representative of the major problems of antibiotic resistance worldwide.

Finding ways to combat antibiotic resistant strains of bacteria has been difficult. In a hospital setting, it can be very difficult to completely sterilize instruments. Movement of patients, visitors, and personnel can cause spreading of antibiotic resistant bacteria throughout the hospital. The problem of resistant bacteria is becoming a major source of spending for health care, as the number one complication patients can have in a hospital is infection. Very few new antibiotics have been discovered in recent years to replace those that have become ineffective. Many of the second line therapies used in resistant bacteria have unpleasant side effects, or require extensive therapy, making compliance difficult. The rise of antibacterial hand soaps, household cleansers, and other items has increased the number of bacteria being exposed to these drugs, also potentially increasing resistance.

Rather than focusing on new methods to kill drug resistant bacteria, researchers at the University of Buffalo are looking for adjunct therapy that can help current antibiotics function more effectively, even in drug resistant strains of bacteria. The researchers found that a protein-lipid complex in human breast milk, termed HAMLET (human alpha-lactalbumin made lethal to tumor cells) was able to sensitize MRSA to methicillin. Other antibiotic resistant bacteria were also made sensitive to various antibiotics, including vancomycin, erythromycin, and gentamycin. These studies were performed in an animal model, and were the first such studies to show an effective in vivo therapy to help antibiotics function properly against drug resistant strains of bacteria. This demonstration is important, as bacteria may react differently to therapy when treated in vitro as opposed to in vivo.

HAMLET was first produced in the 1990s by combing protein and lipid components from human breast milk. The protein-lipid complex was found to help destroy tumor cells by compromising the membrane of the mitochondria, the organelle responsible for providing energy to the cell. When the mitochondrial membrane is compromised, a pathway for cell death is initiated, thereby killing the tumor cell. HAMLET was later shown to kill Steptococcus pneumoniae bacteria via a similar mechanism of membrane disruption. The group then went on to determine if HAMLET could effectively weaken drug resistant strains of bacteria to a point where antibiotics could be used to fight the bacteria. In the research referenced above, HAMLET was able to not only prevent growth of antibiotic resistant strains of bacteria, but to effectively allow the bacteria to be killed by the antibiotics.

While finding ways to make first line antibiotic therapies effective against drug resistant strains of bacteria has major implications for the healthcare field, researchers warn that HAMLET is not a perfect solution. In order to treat systemic infections, high concentrations of HAMLET would be required, and this might be difficult to produce. However, for open wounds, a topical application of antibiotics and HAMLET could be effective at preventing or treating infections. In addition, even if HAMLET itself is not an appropriate solution for helping re-sensitize bacteria systemically, the research shows another potential mechanism to help fight antibiotic resistant strains of bacteria. Finding an adjunct therapy to assist the antibiotic could assist in destroying antibiotic resistant bacteria, thus preventing the spread of these lethal microbes.

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