Imagine a future where common infections and small wounds, such as a simple cut, could kill you. It is actually something that is far from being an apocalyptic fantasy written by Hollywood screenwriters, since it is a very real possibility for the 21st century according to a report written by the World Health Organization (WHO) in 2014. This report argues that antibiotic resistance, the fact that bacteria and other microbes are less and less sensitive to antimicrobial drugs, begins to be a major global threat.
WHO recently published a continuation of the report, where it presented 13 “priority bacteria,” including the MRSA. According to the report, we have to prioritize these bacteria in research because they cause the most diseases and deaths.
What is being done about it?
In fact, the pharmaceutical industry has been uncovering a new relevant class of antibiotics since 1987 and has little incentive to spend hundreds of millions of dollars on the development of new drugs. This is because any new medication that is developed is not going to be used until any other drug can treat a specific infection. In addition, most infections are not chronic in nature and their treatment only lasts ten days or less, which dramatically reduces drug sales and investment recovery.
Finally, once the new drug is being used, experience tells us that bacteria will inevitably become rapidly resistant to the drug, making the antibiotic become unusable. All this drastically limits market options and the profitability of new antibiotics.
But there is hope. Over the past decade, academic research, agreements with industry and other associations have begun to innovate with new ideas. To develop new antibiotics, these have to be directed to the parts of the bacteria that have difficulties to mutate, as is the case of the membrane. It is an approach with a lot of potential, but has not yet had any successful cases.
That said, there are other methods for you to succeed. Bacteria adapt to antibiotics in different ways until they become resistant by efflux pumps in their membranes that repel antibiotics so that the drug cannot reach its goal. Bacteria produce enzymes that directly inactivate or destroy antibiotics and they usually adapt with mutations or changing the antibiotic's objective so that it cannot have an effect and kill the bacteria. Therefore, new therapeutic strategies should not be based on finding new goals, but they have to make bacteria more sensitive to the antibiotics we already have. Attacking the bombs and bacteria enzymes directly is one way to get it.
The important role of breast milk
But there are also other methods and This is where breast milk and one of its components serves as a relevant example. Several years ago, we identified a special compound in breast milk based on proteins and fats that we call HAMLET: lethal human alpha-lactalbumin for tumor cells. We discovered that the compound HAMLET It could kill cancer cells without having any effect on nearby healthy cells. HAMLET managed to destroy the cancer cells in part by entering the cells and destroying the function of the mitochondria, the "energy center" of all cells, which means cell death. HAMLET could not access healthy cells, which means they were "insensitive" to this compound.
Interestingly, a long time ago in evolution, it is believed that mitochondria were a type of bacteria that formed as a symbiotic relationship with another type of bacteria. For this reason we decided to test the potential effects of HAMLET on bacteria and, indeed, HAMLET killed some types of bacteria, but the effect was not universal. Many of the most important types of bacteria were not affected and survived.
To kill bacteria, HAMLET adheres to the bacterial membrane. The first thing you get is to stop pumping hydrogen in the membrane, so that the concentration of hydrogen (pH) on each side of the membrane is the same. The change in pH allows calcium to enter the interior of the cell, something necessary for bacteria to die.
However, since then we have realized that the bacteria that survive are also affected. In fact, we discovered that HAMLET can affect membranes, allowing hydrogen and calcium ions to be introduced even in resistant bacteria. This caused the bacteria that were resistant to antibiotics to become vulnerable, reversing their resistance.
In fact, HAMLET was so effective that it got the MRSA bacteria back to be sensitive to the antibiotic methicillin. We were not only able to demonstrate that methicillin could end MRSA in a test tube, but also that it could eradicate the infection in mice, something that is a great advance. This demonstrates the great potential of these types of strategies to prolong the usefulness of the antibiotic arsenal that we already have and which is made up of safe and evaluated medications.
One of the biggest advantages of this approach is that bacteria do not usually become resistant to HAMLET-like substances, unlike what happens with new antibiotics. This is because they do not actually kill the bacteria themselves, but reduce the evolutionary pressure on the bacteria to mutate and survive. We are currently developing these findings in the hope that they will provide a new strategy in treatments to combat antibiotic resistance.
We still have a way to go: It is necessary to perform the usual tests (determine the efficacy and safety of the compound) before you can start doing clinical trials. What we are doing now are preparatory studies and we have many reasons to be optimistic about the future.
Author: Anders P Håkansson, Professor of Infectious Medicine at Lund University
This article has originally been published in The Conversation. You can read the original article here.
Photos | iStockphoto and Pixabay On Babies and more | A protein present in breast milk could kill drug-resistant bacteria
