New Study finds innovative Peptide-Hydrogel restores the effectiveness of antibiotics against drug-resistant bacteria
Swedish med-tech firm Amferia announced findings that antibiotic-resistant bacteria can regain its sensitivity to antibiotics when combined with the company’s peptide-hydrogel. Results of a collaboration between Chalmers University of Technology and Amferia show that antibiotics can have a 64 times higher bactericidal effect when used together with Amferia’s proprietary material, whose antibacterial properties are also greatly enhanced by this combination.
The bacteria-killing material is a proprietary hydrogel, which can be adapted to many medical applications. Photo: Saba Atefyekta
“These findings resonate with Amferia’s vision of utilizing antimicrobial peptides to their fullest potential,” says Anand Kumar Rajasekharan, CEO of Amferia AB.
The research also suggests Amferia has developed a promising strategy for fighting drug resistant biomaterial-associated infections and for reversing antimicrobial resistance.
An innovation in stability
Amferia’s innovative material consists of a specially designed hydrogel embedded with antimicrobial peptides, a type of molecule that forms the building block of proteins.
Peptides have long been known to possess potent antimicrobial properties, destroying bacteria by disrupting the integrity of cell membranes rather than by chemical processes. Until recently, the problem with applying peptides to medical needs like wound care has been their fragility. Peptides are easily destroyed by naturally occurring enzymes and salts in the body. Amferia’s innovation is a hydrogel material that protects the peptides without compromising their bacteria-destroying structures.
In order for this material to be used clinically--in combination with standard treatments like antibiotics, for example—researchers had to ensure that the hydrogel does not negatively affect the antibiotic's effectiveness when used simultaneously.
The new findings demonstrate the peptide-hydrogel’s substantial potential for applications in various medical devices and infection treatments.
Resistant bacteria becomes sensitive
The study produced surprisingly positive results: when applied in concert with Amferia hydrogel, the effectiveness of antibiotics tested was elevated significantly. Drug synergism is defined as the combined effect of different drugs, where the resulting effect is greater than the sum of their individual effects. Chalmers researchers discovered exactly that synergism when using the peptide material and antibiotics together against certain antibiotic-resistant bacteria. This had not been shown before.
The peptide material was evaluated in combination with two different antibiotics, oxacillin and vancomycin. The bacteria involved in the trials were two types of staphylococci (S. aureus), one of which is resistant to multiple antibiotics.
The most powerful effect in the study was measured against the multi-resistant S. aureus. When the Amferia hydrogel was combined with oxacillin, an antibiotic to which S. aureus had developed a resistance, the combination of hydrogel and oxacillin lowered the effective concentration of oxacillin 64-fold compared to when the antibiotic was used alone. At concentrations below the level where bacteria are classified as resistant, oxacillin regained its effectiveness against the bacteria.
For vancomycin, the effective concentration was also lowered when the drug was combined with the hydrogel, although in this case, while the two bactericidal effects added to each other, they did not achieve a synergistic amplification.
“When particles of the hydrogel came into close contact with the bacteria, they weakened and became more susceptible to the antibiotic treatment. In some cases, the antibiotic became effective again against bacteria that were previously resistant,” says Annija Stepulane, PhD student in applied chemistry at Chalmers and first author of the scientific article.
Stable and active treatment over time
Researchers have tried using antimicrobial peptides alongside antibiotics before, but only in solution. In that form, the peptides became sensitive and stopped working when they contacted body fluids, such as blood. When peptides are embedded in the hydrogel, however, they become much more stable and remain active far longer.
The Chalmers team has previously measured active bactericidal properties of the hydrogel lasting several days, compared with only a few hours for peptides in solution. They see many advantages of the hydrogel material.
“The new peptide-based material can be inserted locally, i.e. on a limited part of the body so that the whole body is not affected. The material is non-toxic and produces no unwanted side effects,” says Martin Andersson, research leader and professor of applied chemistry at Chalmers.
Peptide hydrogels reduce infections and the risk of complications
The hydrogel, which can also be formulated as particles in a spray, can increase the safety and effectiveness of an antibiotic regimen for patients. This has clinical potential in the in the treatment of wounds.
“You often don't know if the bacteria that caused a wound infection is resistant to a certain antibiotic when you start treatment,” says Andersson. “If the peptide material is used on the wound at the same time, the probability that the type of antibiotic will work against the bacteria increases. Then you can cure the infection without having to use additional types of antibiotics.”
Researchers also see advantages in using it as a standard treatment to prevent wound infections. The material could be used in patch form to care for wounds following surgery, for instance—the potential for which is already being explored in veterinary care in various countries.
These findings underscore the importance of developing antimicrobial biomaterials for future medical devices to fight bacterial infections and to reverse antimicrobial resistance.
“This can be particularly interesting in areas with a high prevalence of resistant infections, such as certain parts of Africa and Asia, where extra care should be taken with wounds,” says Andersson.
More about: The research results and the peptide material
Antimicrobial peptides occur naturally in the human body. Their bactericidal function has been understood for some time: peptides’ positive charge interact with negative charges in bacterial cell membranes, compromising the membranes and destroying those cells.
A bacterial cell (left) is attacked simultaneously from two fronts. Partly by antibiotics, partly by a bactericidal peptide-based material. The positively charged peptide damages the structure of the bacteria's negatively charged cell membrane. Now a study from Chalmers shows a synergistic effect of this combination that is significantly greater than the sum of the separate effects of the antibiotic and the material. Illustration: Annija Stepulane, Chalmers University of Technology
Synergistic effects between peptides and antibiotics have previously been demonstrated, as well, but only with free peptides in solution—a formulation not efficacious for in clinical use because free peptides break down quickly in the presence of body fluids. The Chalmers research is the first to show efficacy when the peptides are bound to a material that stabilizes them enough for clinical applications.
Chalmers researchers have previously shown that 99.99 percent of skin bacteria are killed by the Amferia hydrogel and that the material’s germ-killing ability is active for more than two days. This means the hydrogel can be used in products such as wound care materials or in surface coatings on medical technology products, like implants, that are introduced into the body.
More about: Research and product development
The Chalmers work on peptide antibacterial material is carried out in close collaboration with Amferia, a spin-off company intended to develop healthcare products based on research results.
This fall, a peptide hydrogel wound dressing intended for veterinary use will be launched in eight different European countries. A proposal for a human wound dressing has been submitted to U.S. regulators. Amferia hopes the hydrogel will be available for use there within a year.
The article “Antibacterial efficacy of antimicrobial peptide-functionalized hydrogel particles combined with vancomycin and oxacillin antibiotics” has been published in the International Journal of Pharmaceutics. The study was conducted by Annija Stepulane (Chalmers), Anand Kumar Rajasekharan (Amferia) and Martin Andersson (Chalmers and Amferia).
Read press release from Chalmers University
Previous press releases about the research:
Read more about the research:
Martin Andersson was recently awarded the Chalmers Impact Award 2024:
Previous press releases:
New spray fights infections and antibiotic resistance
New material to treat wounds can protect against resistant bacteria
For more information, contact:
Anand Kumar Rajasekharan, CEO, Amferia AB, 07 62 98 21 38, anandk@amferia.com
Martin Andersson, professor, institutionen för kemi och kemiteknik, Chalmers, 031 772 29 66, martin.andersson@chalmers
