Novel Probiotic-Antibiotic Combination Eradicates Drug-Resistant Bacteria

A team of researchers from Massachusetts Institute of Technology has developed a novel approach for eradicating methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa from wounds, using a combination of antibiotics and alginate-encapsulated probiotics. The team’s work appears in the journal Advanced Materials.

Li et al devised a way to encapsulate probiotics so that they can be delivered along with antibiotics to kill multiple strains of bacteria. Image credit: Ryan Allen.

Li et al devised a way to encapsulate probiotics so that they can be delivered along with antibiotics to kill multiple strains of bacteria. Image credit: Ryan Allen.

The human body contains trillions of bacterial cells, many of which are beneficial.

In some cases, these bacteria help fend off infection by secreting antimicrobial peptides and other compounds that kill pathogenic strains of bacteria. Others outcompete harmful strains by taking up nutrients and other critical resources.

Scientists have previously tested the idea of applying probiotics to chronic wounds, and they’ve had some success in studies of patients with burns.

However, the probiotic strains usually can’t combat all of the bacteria that would be found in an infected wound.

Combining these strains with traditional antibiotics would help to kill more of the pathogenic bacteria, but the antibiotic would likely also kill off the probiotic bacteria.

MIT scientist Ana Jaklenec and colleagues devised a way to get around this problem by encapsulating the probiotic bacteria so that they would not be affected by the antibiotic.

The researchers chose alginate in part because it is already used in dressings for chronic wounds, where it helps to absorb secretions and keep the wound dry.

Additionally, they also found that alginate is a component of the biofilms that clusters of bacteria form to protect themselves from antibiotics.

“There are so many bacteria now that are resistant to antibiotics, which is a serious problem for human health,” Dr. Jaklenec said.

“We think one way to treat them is by encapsulating a live probiotic and letting it do its job.”

“We looked into the molecular components of biofilms and we found that for Pseudomonas infection, alginate is very important for its resistance against antibiotics,” added MIT researcher Zhihao Li.

“However, so far no one has used this ability to protect good bacteria from antibiotics.”

For the study, the team chose to encapsulate a type of commercially available probiotic known as Bio-K+, which consists of three strains of Lactobacillus bacteria. These strains are known to kill MRSA.

The exact mechanism by which they do this is not known, but one possibility is that the pathogens are susceptible to lactic acid produced by the probiotics.

Another possibility is that the probiotics secrete antimicrobial peptides or other proteins that kill the pathogens or disrupt their ability to form biofilms.

The study authors delivered the encapsulated probiotics along with an antibiotic called tobramycin, which they chose among other tested antibiotics because it effectively kills Pseudomonas aeruginosa, another strain commonly found in wound infections.

When MRSA and Pseudomonas aeruginosa growing in a lab dish were exposed to the combination of encapsulated Bio-K+ and tobramycin, all of the pathogenic bacteria were wiped out.

“It was quite a drastic effect. It completely eradicated the bacteria,” Dr. Jaklenec said.

When the scientists tried the same experiment with non-encapsulated probiotics, the probiotics were killed by the antibiotics, allowing the MRSA bacteria to survive.

“When we just used one component, either antibiotics or probiotics, they couldn’t eradicate all the pathogens,” Dr. Li said.

“That’s something which can be very important in clinical settings where you have wounds with different bacteria, and antibiotics are not enough to kill all the bacteria.”

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Zhihao Li et al. Biofilm-Inspired Encapsulation of Probiotics for the Treatment of Complex Infections. Advanced Materials, published online October 17, 2018; doi: 10.1002/adma.201803925

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