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Could Immunotherapy Provide An Effective Solution To Antibiotic-Resistant Infections?

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Antibiotic resistance may be one of the “biggest threats to global health”, but researchers at Lehigh University in Pennsylvania might just have a solution: use the body's natural defense mechanisms to track down and destroy any harmful antibiotic-resistant bacteria lurking in the system. Their paper is published in the journal Cell Chemical Biology.

Antibiotic resistance is a naturally occurring process whereby bacteria evolve, either through mutation or horizontal gene transfer, to survive the drugs that are intended to kill them. We cannot stop it from happening, but we can affect the rate at which it occurs. And so far, it seems, we have done our best to speed up the process, either by prescribing unnecessary prescriptions, intensifying farming methods, or (and to a lesser extent) surfing. (For more information on antibiotic resistance, click here.)

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This creates a major dilemma. Bacteria are building up resistance to life-saving antibiotics faster than we can come up with new ones, and with no new drug on the horizon, we may be heading for what some medical experts are calling an "antibiotic apocalypse". 

So the researchers at Lehigh have turned to a process called immunotherapy. This is a process that uses drugs to trigger a response from the body's own immune system. Marcos Pires, an associate professor in the university’s Department of Chemistry, was inspired by the success of trials using immunotherapy to treat cancer (so far, only in mice). If it can kill cancer cells, might it also be used to treat deadly bacteria cells?

Gram-negative bacteria are some of the hardiest and deadliest bacteria out there – and among the toughest to destroy. The pneumonia-causing Pseudomonas aeruginosa and foodborne E. coli are two examples. To target gram-negative bacteria, the researchers created an "immunobiotic" made from an antibiotic called polymyxin B, currently used as a last-resort drug. The immunobiotic works by binding to specific molecules found on the surface of bacteria cells but, importantly, not on human cells. This acts as a siren call, attracting antibodies and white blood cells, which together destroy the deadly bacteria. 

Because immunobiotics target the immune system and not the bacteria directly, they may be more resistant to antibiotic resistance, Tim McHugh, a professor and director of the UCL Centre for Clinical Microbiology, told The Guardian.

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The team tested the efficiency of their new drug on various bacteria listed as high-priority by the World Health Organization (WHO), including Pseudomonas aeruginosa. Nematode worms infected with the bacteria were administered the drug – and it seems to have worked. The immunobiotic killed the deadly bacteria, effectively treating the worms.

When tested on bacteria that had developed a resistance to the antibiotic, the drug was once again successful, suggesting immunobiotics have the power to "re-sensitize" bacteria to the antibiotic. If this is confirmed in later trials, it may mean that antibiotics no longer believed effective because of antibiotic resistance may still be used in treatment as an immunobiotic.

“With this one-two punch against these difficult-to-kill bacteria, we believe there is great potential for in vivo testing to evaluate them further,” Pires said in a statement. It's very early stages but could be one to watch. 

Watch antibiotic resistance in action below:

Technion-Israel Institute of Technology/Havard Medical School/YouTube


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