Researchers from the University of Bern in Switzerland have developed new compounds to aid in the treatment of bacterial infections. These compounds act to accumulate and neutralize specific toxin proteins formed by pathogenic bacteria.
Certain pathogenic bacteria, those that cause disease, create body-damaging toxins, which target our cell membranes.
Membranes define the boundary of a cell. A cell’s membrane separates the outside environment from its inside, and regulates in and out traffic. Membranes are composed of different fat molecules, known as lipids, which confer a dynamic and fluid shape to the cell.
Some toxins have the ability to poke holes in these membranes. This results in the leaking of cellular components, disrupting the balance of charged particles, and potentially leading to cell death.
Two of the most common bacteria that produce pore-forming toxins are Staphylococcus aureus, a common cause of Staph infections, and Streptococcus pneumoniae, a major cause of bacterial pneumonia.
Different toxins made by these pathogenic bacteria tend to target different lipids that are exclusively found in animal cell membranes. One example of these lipids is cholesterol.
The Switzerland team, led by Eduard Babiychuk and Annette Draeger, has created special liposomes composed of lipids that are similar to those that make up human cell membranes.
Liposomes are non-toxic in humans, and are typically used in medicine to deliver molecules, like drugs or nutrients, to specific cells in the body.
These engineered liposomes act as look-alike decoys for pore-forming bacterial toxins, attracting them away from their target cells. The liposomes effectively compete with the host cell membranes in the binding of these toxins.
The team has shown that the lipid composition of these liposomes can be tailored to make them more attractive to specific toxins.
The liposomes were shown to protect human cells that were treated with pore-forming toxins in test tubes. The team was able to demonstrate that the liposomes can be used to protect against active infections.
Mice were injected with lethal doses of either S. aureus or S. pneumoniae, and were either treated with specific liposomes or nothing. The mice that were left untreated died within a few days, while the liposome-treated mice survived if the intervention occurred within 10 hours after the initial infection.
Liposome treatment also protected mice from developing pneumonia in mice nasally infected with S. pneumoniae.
The distraction that the liposomes create allows the host’s immune system to do its job and clear the bacterial infection. The immune response would not be as effective in the absence of the liposomes, since immune cells are a common target of these pore-forming toxins.
The liposomes do not directly kill the pathogenic bacteria, which is very important. When conventional antibiotics are used, they can cause some complications. If a bacterium dies from antibiotic action, it releases all of its formed toxins at once, resulting in sudden host damage.
As well, antibiotic treatment has the possibility of naturally selecting for resistance. A simple way of picturing this is if you treated 100 bacterial cells with a particular antibiotic. Of those 100, 99 are susceptible to the antibiotic and die, but one is immune and lives on. That one particular bacterium can multiply and result in a new population of cells that are all resistant to that particular antibiotic.
Since this treatment does not target or kill particular bacterial cells, resistance is unlikely to develop. These toxins are not essential for bacterial life; they just contribute to a more effective infection. The research team suggests that the combination of liposomes and antibiotics may be a sound treatment of infections by pore-forming toxin-producing bacteria.
Antibiotic resistant bacterial strains are becoming a major concern in the modern world. Alternative treatments for bacterial infections,such as these liposomes, may be our answer to combatting antibiotic resistance in the future.
