The Next Generation of Potential Remedies Against Microbes

By on
The Next Generation of Potential Remedies Against Microbes Like Phages

Our recent antimicrobial series discussed concerns that the currently available antibiotic, antifungal, antiparasitic and antiviral drugs are losing efficacy due to the efficient ability of bacteria, fungi, parasites and viruses to mutate. So, there is urgency in seeking alternatives, which researchers are now actively pursuing.

Think about it: something in nature must be keeping these microbes in check. Otherwise, they would rule the world. As we pointed out in our antifungal resistance article, bacteria and fungi are fighting within our bodies for space.

Indeed, many of antimicrobial medications are derived from another microbe. Possibly the best known example is penicillin. Penicillium spp. mold naturally produces the antibiotic penicillin.

Of course, the number of antibiotic-resistant strains of organisms has increased to penicillin and to many antimicrobial agents – no matter if they are synthetic or naturally derived.

The Traditional Path Can Be Innovative

Some researchers are continuing down the traditional antimicrobial medication path. But, even though the path may be traditional, the researchers are still being innovative. They are trying to think of other ways and use of existing and new microbial materials to create new antimicrobials. For instance, a team at Yale University found that neomycin (a common antibiotic) decreased the herpes virus, level and symptoms in infected mice. They observed greater expression of genes that are stimulated by the body’s interferons, proteins that block viral replication.

A group of Israeli scientists has developed a gel made from the bacterium, Bacillus subtilis, to fight skin fungal infections so that they do not penetrate the inner dermis layer of the skin.

A team from Rockefeller University discovered a new class of broad-spectrum antibiotics they are calling malacidins. They say this class kills several superbugs that are resistant to other antibiotics, and thus far, have been unable to induce drug-resistance to this class, although they admit that it could still happen.

Biswajit Roy’s article in Antiviral Chemistry & Chemotherapy proposed exploration into fungal metabolites as a potential source for antiviral medications:

“Fungal metabolites with great diversity and preapproved biocompatibility can be a potential source for new antiviral drug leads. Considering a very small fraction of fungal species has been discovered and only a few percent of these extracts are tested for various viral diseases.

Though there are many fungal metabolite drugs being used for many other diseases, so far no antiviral drug has been discovered from fungal metabolites.”

Extremophiles

Extremophiles live in extreme conditions such as hot springs and salt lakes. They are members of the Archaea kingdom.

Out of a concern of drug-resistant microbes, the United States Department of Defense is funding research into whether or not extremophiles could be viable antimicrobial sources against bioweapons like anthrax, rabbit fever, or even yellow fever. 

Phage Therapy

The biggest scientific buzz these days surrounds phage therapy.

Bacteriophages – more commonly known as phages – are viruses that infect and kill bacteria.

Phages were actually discovered in the early 20th century and were distributed to treat bacterial conditions. However, due to poor handling and poorly controlled trials, they fell out of favor after antibiotics were discovered in the 1940’s. With the advent of antibiotic resistance, researchers have started exploring phage therapy once again.

Unlike antibiotics – which usually cover a broad spectrum of bacterial infections – phages are very specific. They only infect one type or a few types of bacteria. Luckily, there are thousands of them. So, antibiotic resistance is very low due to this specificity.

Phage specificity and the limited research done to date have their drawbacks. Currently, medical professionals often resort to taking a swab of the patient’s bacteria, nurturing it in a petri dish, and then testing which phages are able to kill it. Sadly, in some cases, the proper phage to fight an antibiotic-resistant bacteria is found too late to save a patient.

On the other hand, the collateral damage to other bacteria or human cells is minimal and the risk of resistance to phages by bacteria is low. It is low because phages are bountiful in nature. So, if resistance occurs to one phage, a new phage could be found.

Another plus is that phages are not antibiotic resistant because they use mechanisms that differ from those of antibiotics. So, specific antibiotic resistance mechanisms usually do not translate into mechanisms of phage resistance.

Phage therapy is currently dispensed on a compassionate basis that needs approval by the U.S. Food and Drug Administration (FDA). For each case, scientists have to prove that all standard treatment options have failed and explain why phage therapy is a necessity. Thankfully, FDA approval can be obtained within hours in emergencies.

References

Coker, James A. “Extremophiles and biotechnology: current uses and prospects.” F1000Research vol. 5 F1000 Faculty Rev-396. 24 Mar. 2016, doi:10.12688/f1000research.7432.1, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806705.

Hover, Bradley, et al. “Culture-Independent Discovery of the Malacidins as Calcium-Dependent Antibiotics with Activity against Multidrug-Resistant Gram-Positive Pathogens.” Nature Microbiology, vol. 3, 12 Feb. 2018, pp. 415–422, https://www.nature.com/articles/s41564-018-0110-1.

Loc-Carrillo, Catherine, and Stephen T Abedon. “Pros and cons of phage therapy.” Bacteriophage vol. 1,2 (2011): 111-114. doi:10.4161/bact.1.2.14590, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278648/.

Lufton, Maayan, et al. “Living Bacteria in Thermoresponsive Gel for Treating Fungal Infections.” Advanced Functional Materials, vol. 28, no. 40, 4 Oct. 2018, doi:10.1002/adfm.201801581, https://onlinelibrary.wiley.com/doi/full/10.1002/adfm.201801581.

“Phage 101.” University of California San Diego School of Medicine Center for Innovative Phage Applications and Therapeutics, http://medschool.ucsd.edu/som/medicine/divisions/idgph/research/center-innovative-phage-applications-and-therapeutics/research/Pages/default.aspx.

Pires, Diana, et al. “Phage Therapy: a Step Forward in the Treatment of Pseudomonas Aeruginosa Infections.” Journal of Virology, vol. 89, no. 15, Aug. 2015, pp. 7449–7456., doi:10.1128/JVI.00385-15, https://jvi.asm.org/content/89/15/7449.

Roy, Biswajit G. “Potential of small-molecule fungal metabolites in antiviral chemotherapy.” Antiviral Chemistry & Chemotherapy vol. 25,2 (2017): 20-52. doi:10.1177/2040206617705500, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890529.  

“Topical Antibiotic Triggers Unexpected Antiviral Response.” ScienceDaily, ScienceDaily, 9 Apr. 2018, http://www.sciencedaily.com/releases/2018/04/180409112602.htm.

Share this message: