Saturday, June 8, 2013

Human Alpha-Lactalbumin Made Lethal to Tumour (HAMLET) Can Help to Overcome Bacterial Resistant & Kill Tumour Cells

On June 6th 2013, I came across an article in the Sun that a Texas-based-firm Lollyphile has brought out a new range of sweet treats having breast milk flavour.

The candies were developed in line of the flavor of breast milk samples taken from four new mums; four of the sweets may cost around £6.


This reminded me of the benefits of actual breast milk and I am inspired to recapitulate the benefits once again.
Breast milk has several protective effects, not only during the new born period, but also, it protects through out the childhood. Apart from protecting the child from various infections and tumors (particularly the Lymphomas); it reduces the chances of getting allergic diseases in future and improves intelligence.
Recently, an article was published in the prestigious Magazine the PLOS One, which re-discovers the bacteria and tumour killing property of a compound formed from different ingredients in the breast milk.
This property is only seen in human breast milk, not in milk of other animals like goat or donkey.
It is HAMLET, the acronym for Human Alpha-Lactalbumin Made Lethal to Tumor. This reminds us of the Hamlet; the classic tragedy by William Shakespeare; probably first played on 26 July 1602.
Our HAMLET is also, somewhat like Hamlet of the classic, kills the treacherous bacteria and tumors.
Sara Linse, Department of Biophysical Chemistry, Lund University came up with the acronym HAMLET for Human Alpha-lactalbumin Made LEthal to Tumor cells.
She along with her co-researchers found out the way to change the configuration of alpha-lactalbumin and stabilized that with fatty acids, so that, it becomes lethal to tumor cells and bacteria.
All the ingredients like alpha-lactalbumin, fatty acid (Oleic acid) are naturally present in the breast milk; and the conducive environment is provided in stomach of baby in presence of low acidity.
This compound also likened to the Hydra of the ancient Greek mythology that has so many heads, in a way that HAMLET attacks its target in a multi-pronged manner.
HAMLET carries out independent attacks on many distinct cell organelles, including mitochondria, proteasomes, cell nucleus, and interferes with cell processes such as macroautophagy.
It has been shown that HAMLET binds to the cell surface and rapidly invades cells; which is more pronounced in tumor cells that take up far more protein than healthy and differentiated cells.
The preferential entry may be due the oleic acid in the HAMLET complex that interacts with phosphatidylserine and o-glycosylated mucin on the plasma membrane, both of which are over expressed on the plasma membrane of tumor cells.
Adjuvant Property to Antibiotics:
In one study, it was stated that about 19.000 Americans die each year due to staphylococcal infection, resistant to many antibiotics including methicillin.
HAMLET alone has well documented antibacterial properties against the gram-positive bacterium Streptococcus pneumoniae, as well as against strains of H. influenzae and some strains of M. catarrhalis in vitro, but fails to kill most other bacterial species. But, when used at sub lethal concentrations potentiate the effect of common antibiotics, seen in a study.
It acted as an effective antimicrobial adjuvant with the ability to increase the efficacy of a broad range of commonly used antibiotics including methicillin, vancomycin, erythromycin, and gentamicin to the degree that drug-resistant S. aureus could again become sensitive to these antibiotics; as well as for eradication of biofilms and nasopharyngeal colonization in vivo.
Treatment of MRSA (Methicillin Resistant Staphylococcal Aureus) infections depends upon the pattern of the organism, but normally entails the use of drugs such as vancomycin, linezolid, daptomycin, clindamycin, and mupirocin.
The mechanisms of resistance, among many, may be due to the ability of bacteria to produce biofilms that protects those from the attack of antibiotics; or, may be due to the ability to pump out antibiotics from inside of the cells, what is called as Efflux Pump.
Although the daptomycin/oxacillin synergy is comparable to the potentiation effect of HAMLET on methicillin, HAMLET has a much stronger potentiation effect in eradicating biofilms, even at relatively low concentrations (6–30 μM, which amounts to 100–500 µg/ml. These concentrations are well within the physiological range found in human milk (2,000 µg/ml).
In vivo treatment is primarily based on the use of vancomycin with linezolid and clindamycin as main adjunctive therapies, and daptomycin is the antibiotic of choice in cases of vancomycin insensitivity; but both in vitro assays and in vivo treatment show that antibiotic combination treatment of MRSA invariably result in increased resistance of the agents used, producing increasingly multi-drug resistant strains, which continuously escalate the problems with MRSA treatment.
The adjuvant activity of HAMLET has three benefits in this regard.
First, it could significantly decrease nasopharyngeal colonization with MRSA with just one administration of methicillin in the presence of HAMLET for 12 hours.
Researchers have seen that HAMLET can make methicillin and maybe other, currently unusable, antibiotics useful for treatment of mucosal surfaces; and have the potential to offer a return to these safer agents for topical use.
Second part of the mechanism for the increased adaptation of MRSA, HAMLET have a major advantage in this regard, as it dissipates the proton motive force as effectively as CCCP but shows no toxicity to healthy human cells or to the S. aureus cells.
The third benefit of HAMLET's dual and potentially parallel actions on the bacterial membrane function is its ability to inhibit MRSA resistance-development after exposure to increasing methicillin concentrations.
These adjuvant properties of HAMLET are not limited to staphylococci as all bacterial species tested, including gram-positive and gram-negative species Streptococcus pneumoniae, Moraxella catarrhalis, and Acinetobacter baumanni, are similarly sensitive to the potentiating effects of HAMLET.
Its safety, efficacy, specificity, quick onset of action, and low risk for resistance may allow to hard-to-treat bacterial infections to be successfully controlled and potentially ‘resuscitating’ old or discarded antibiotics.
Or, may be, some other molecule be developed keeping in view of the mechanism of action of HAMLET to be used as killer of cancers and bacterial resistance to antibiotics.
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