Innovative Strategies for Fighting Antimicrobial Resistance

“Microorganisms are among man’s best friends and worst enemies,” wrote the authors of a Frontiers in Veterinary Science review paper on antimicrobial resistance (AMR). Antimicrobials were developed to combat the “enemy” side of microorganisms’ activities; yet, as Sir Alexander Fleming warned in his Nobel Prize speech in 1945, bacteria could develop resistance to antimicrobials.

The Problem

Antimicrobial misuse, such as nontherapeutic administration of antimicrobials in food animals, has contributed significantly to AMR development. This resistance has serious consequences, including reduced efficacy of current antibiotics and increased cost and complexity of treating infections.

Given that developing new antibiotics has lost favor within the pharmaceutical industry, the authors outlined several alternative strategies for combating AMR, primarily from the perspective of dairy animals.

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Potential Solutions

Vaccines

Vaccine administration in food animals improves food production, reduces infection rates, and can decrease the incidence of foodborne disease in humans. Recombinant veterinary vaccines have been explored to address AMR. These vaccines, categorized as DNA or RNA vaccines, subunit recombinant vaccines, or vectored vaccines, eliminate the need for attenuated infectious agents in vaccines and allow for targeted immune responses. Further research is needed to determine recombinant vaccine biology.

To ensure that vaccines remain effective against AMR, vaccine development would need to remain dynamic to capture evolving strains of bacteria that “escape” vaccine-induced immunity, the authors noted.

Phytocompounds

Phytocompounds with broad-spectrum antimicrobial activity present another alternative to conventional antibiotics. This activity occurs through numerous mechanisms, including B- and T-cell proliferation and free radical suppression.

Previous studies have reported antimicrobial activity of many phytocompounds. For example, plant extracts from turmeric rhizomes and Morinda citrifolia (commonly known as noni) have antimicrobial properties. Other compounds reportedly have in vitro antibacterial activity against such multidrug-resistant bacteria as methicillin-resistant Staphylococcus aureus.

More research is needed to further characterize phytocompounds (safety, stability, pharmacokinetics, etc) and determine standardized doses for use in dairy animals.

Probiotics, Prebiotics, and Synbiotics

Probiotics are growth promoters and help maintain a balanced intestinal flora. Prebiotics, such as polysaccharides, are nondigestible food additives that selectively promote intestinal bacterial proliferation and demonstrate antimicrobial activity. Synbiotics combine probiotics and prebiotics. Because numerous factors (eg, age, diet, stressors, dose) can influence the effectiveness of prebiotics, postbiotics, and synbiotics, further research is needed before these products can be used as alernatives to antimicrobials.

Antimicrobial Peptides

Antimicrobial peptides (AMPs), known as host defense peptides, have strong broad-spectrum antimicrobial activity against bacteria and fungi. Synthesized either ribosomally (bacteriocins) or nonribosomally (eg, bacitracin), AMPs are amphipathic and can thus insert themselves into and disrupt the bacterial phospholipid bilayer. Importantly, AMPs are not susceptible to the resistance mechanisms that render conventional antibiotics ineffective.

Several AMPs has been investigated. For example, AMP Esc-1a has shown potent antimicrobial activity against Streptococcus agalactiae, which causes bovine mastitis.

Currently, clinical application of AMPs in dairy animals remains limited for several reasons, including high production cost, safety concerns, and protease-induced hydrolysis in the digestive tract.

Moving Forward

The authors highlighted many other solutions, including immunostimulants and cytokines. Combining these innovative solutions with judicious antimicrobial usage could have a significant and positive impact in the fight against AMR, the authors noted. Also, improving food animal hygiene and strictly enforcing antimicrobial usage laws are needed.

In summary, the authors concluded that “control of AMR should be taken as a ‘global priority’ before it becomes too grim.”

Dr. Pendergrass received her Doctor of Veterinary Medicine degree from the Virginia-Maryland College of Veterinary Medicine. Following veterinary school, she completed a postdoctoral fellowship at Emory University’s Yerkes National Primate Research Center. Dr. Pendergrass is the founder and owner of JPen Communications, a medical communications company.