Combating Bacteria: A New Approach to Multi-Drug Resistance

BY YUSHA SHUN

Over the last decade, antibiotic-resistant bacteria have proliferated; according to the CDC, at least 90,000 deaths a year in the U.S. are due to bacterial infections, with a majority of these infections being resistant to some antibiotic. Alarmingly, hospitals and other health-care facilities have been the epicenter for the outbreak of drug-resistant bugs, simply because these places allow for bacteria to enter the bloodstream and open wounds most quickly. Bacterial infections caused by multidrug-resistant (MDR) bacteria are a serious threat to public health because of their virulence and resilience to many forms of treatment.

There are two major types of MDR bacteria — gram-positive and gram-negative, distinguished by how these bacteria stain on a Gram test. Although gram-positive MDR bacteria such as the well-known methicillin-resistant Staphylococcus aureus (MRSA) are still a major threat, there have been many developments of new antibiotics that should work effectively again them (at least for the time being). However, gram-negative MDR bacteria are much more concerning; these bacteria have an additional outer membrane that has effectively halted progress in drug development that can kill them. For this reason, there is currently a lack of drug candidates for this type of bacteria, posing a huge threat to global health.

Last month, though, in a study published in Nature Microbiology, researchers have described a new tool that has great potential in tackling these MDR gram-negative bacteria. They describe a new class of antimicrobial agents called structurally nanoengineered antimicrobial peptide polymers (SNAPPs); these so-called SNAPPs are engineered by a special type of peptide synthesis process. Two SNAPPs, S16 and S32, mimic naturally occurring anti-microbial peptides and have shown great results when tested against a range of MDR bacteria.

Specifically, researchers incubated SNAPPs with bacteria in a lab setting, and S16 and S32 were equally effective against strains of MDR gram-negative species, as drug resistance was not detected even after 600 generations of bacterial growth. They made sure that these peptides were not harmful to mammals by mixing the SNAPPs with human red blood cells and consequently observed no undesired interactions. The researchers also tested S16 and S32 in mouse models infected with MDR A. baumanii: treatment with S16 enabled survival of all mice for 24 hours, while 50% of the control mice died.

The scientists also ran experiments to determine what exactly in these SNAPPs can cause the death of MDR-resistant gram-negative bacteria. They found that the polymer peptide disrupts the outer membrane of these MDR bacteria because it can cross the membrane and the layers below that, leading to unregulated movement of ions across the membrane. SNAPPs can also cause the bacterial cell to spontaneously lyse (high concentrations) or cause the cell to follow programmed death (low concentrations).

This new research is crucial in facing this new global threat of multi-drug resistant gram-negative bacteria. For the first time, a suitable class of drug candidates that can not only destroy these bacteria but are also compatible with the mammalian body has been proposed. These SNAPPs may be the key to eliminating these unwanted pests that are resistant to any conventional method of antibiotic treatment. Hopefully, SNAPP-based drugs will be quickly developed and undergo clinical trials in the near future.

 

References:

http://www.nature.com/nrd/journal/v15/n11/full/nrd.2016.224.html

 

http://aac.asm.org/content/52/3/813.full

 

http://www.nature.com/articles/nmicrobiol2016162

 

http://science.sciencemag.org/content/sci/321/5887/356.full.pdf

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