Could a Substance Derived from Broccoli Play a Role in Reducing AMR?
Methicillin-Resistant Staphylococcus aureus (MRSA), a notorious bacteria resistant to many antibiotics.

Researchers worldwide are searching for ways to reduce dependence on antibiotics to preserve these life-saving medicines in the face of the rise in antibiotic-resistant bacteria.

Drug resistance is currently implicated in 700,000 deaths each year, and the World Health Organization (WHO) raised the red flag last month over the lack of new antibacterial treatments being developed to address the mounting threat of AMR.

A new study conducted at Israel’s Ben-Gurion University and published recently in the peer-reviewed journal Pharmaceutics, showed that a substance found in broccoli called 3,3′-diindolylmethane (DIM) can reduce resistance to certain antibiotics.

The study was led by Prof Ariel Kushmaro and Dr Karina Golberg of BGU’s Avram and Stella Goldstein-Goren Department of Biotechnology Engineering.

What is DIM?

DIM is a natural substance that is already used in high doses in the treatment of some cancers. The new study found that DIM in low concentration can disrupt “quorum communication” among bacteria and prevent them from doing human harm.

Quorum communication allows bacteria to share information about cell density and adjust their gene expression accordingly, forming bacterial biofilms that protect bacteria from being eradicated by antibiotics.

“Drug-resistant biofilm-forming bacteria are known to pose an even greater threat once they have already infected and damaged healthy tissue, therefore the addition of an anti-biofilm compound to traditional antibiotic treatments may improve treatment outcomes,” the researchers wrote in their paper.

DIM could help, they showed.

Pharmaceutics 14 00967 g001
Figure 1. Prevention of the formation of biofilm by A. baumannii (A) and P. aeruginosa PA01 (B) in a flow system during 48 h of incubation with continuous supplementation of 50 μM DIM. Biofilms were stained with the live/dead bacterial viability kit. Quantification of live, dead, and total bio-volumes (μm3/μm2) based on image analysis and data from the IMARIS software together with % biofilm inhibition. Images were acquired from three different areas in each treatment, three independent repetitions. Asterisks indicate significant differences compared to control (independent samples t-test; *** p < 0.001).

The research findings show that the biofilm formation of two of the most prioritized bacterial pathogens, Acinetobacter baumannii and Pseudomonas aeruginosa, was inhibited by 65% and 70% respectively.

When tested in combination with the antibiotic Tobramycin, it was found that the DIM improved its ability to work and helped eliminate the bacterial resistance to it, suggesting that DIM may play a role in salvaging antibiotic potency. Specifically, combining the antibiotic with DIM enabled a 94% inhibition of P. aeruginosa biofilm.

Finally, the study also showed that DIM has an anti-inflammatory effect.

Effective on wounds

In a separate experiment, the scientists used DIM on infected wounds in an animal model and found that the wounds healed faster and more effectively than with antibiotics.

“When you are using antibiotics, your aim is to kill the bacteria,” Kushmaro told Health Policy Watch. “When we are using other materials, like DIM, we are only blocking the communication… If you are using antibiotics you will eventually have resistance. If you use materials that are just jamming communication, then you are more likely to have less resistance to this material.”

He said that what is also important is that DIM is already a known material that has passed all the necessary clinical safety trials in human beings, so developing it as a treatment or a food additive will be faster than other drugs or materials.

“Drug repurposing, involving the identification of new applications of an approved medication beyond the scope of its original specification, is gaining considerable attention in recent years,” the researchers wrote in their paper.

For animals first

Further development and commercialization of the technology is being done by a startup company, LifeMatters. Kushmaro said the business model is to get DIM approved first as a food additive and treatment in the agriculture arena, such as an additive to chicken, goat and cow feed, which could improve animal health. Only afterwards would they work towards approval for use in humans.

Presently, animals are the largest consumers of antimicrobial drugs – and thus the leading factor driving antimicrobial resistance, Health Policy Watch reported in May.

Kushmaro believes DIM could be approved for animal use within the next five years, and human use in the next 10 to 15.

“Today, after many years of research, we are confident that in the future DIM and other microbial communication disruptors will completely replace antibiotics,” Kushmaro said. “Our findings show promise for other avenues of research in addition to known classes of antibiotics.”

Image Credits: NIAID.

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