Feb
06
2021

Researchers Developed a New Antibiotic to Solve Antibiotic Resistance

In Philadelphia, PA Wistar Institute researchers developed a new antibiotic to solve antibiotic resistance. In the past 10 to 15 years antibiotic resistance has caused difficulties to cure infectious diseases. But Wistar Institute researchers were able to develop a new class of antibiotics that does not only kill bacteria, but also stimulates the immune system to fight the bacteria. The WHO has published a statement in July 2020 about the topic of antibiotic resistance.

This report points out that pneumonia, tuberculosis, blood poisoning, gonorrhoea, and foodborne diseases are becoming harder to treat because of multiple antibiotic resistant bacterial strains. Sometimes physicians find it impossible to successfully treat these conditions. The Wistar Institute research hopefully will have the solution to overcoming resistance to antibiotics. An overall description of what the Wistar Institute researchers did is summarized here.

Development of antimicrobials named dual-acting immuno-antibiotics

The researchers developed a new class of antibiotics that have a dual action of being immunostimulants and antibiotics (DAIA antibiotics). This makes it much more difficult for bacteria to develop resistance. Conventional antibiotics usually target functions of the bacteria that are essential. This involves the synthesis of nucleic acid and proteins. It also targets the building up of cell membranes and metabolic pathways in the bacterium. But bacteria can fight back by becoming drug resistant and mutating the bacterial target of the antibiotic. This renders the antibiotic powerless against the bacteria that researchers originally designed to eliminate.

The researchers argued that attacking bacteria on two different fronts makes it hard for them to develop resistant strains.

Interruption of essential metabolic pathway in most bacteria

The first the researchers focused on was a metabolic pathway that is essential for most bacteria, however it is absent in humans. This makes it an ideal target when you want to develop an antibiotic. The researchers chose to block an essential pathway in the pathogenic bacteria. More about this pathway is explained in this link. Isoprenoids are lipid compounds common in membranes of bacteria and vital for their survival. There is a key enzyme that is necessary to build up isoprenoids. It has the name IspH enzyme. The Wistar researchers concentrated on finding compounds that were able to inhibit the IspH enzyme. Most compounds they found were not able to penetrate the bacterial cell wall. However, they found compounds that penetrated the bacterial wall and inhibited the IspH enzyme. The researchers tested the new antibiotics against resistant gram-positive and gram-negative bacteria. They were superior to conventional antibiotics.

Immune activation of the novel antibiotics

The Wistar Institute researchers showed that the antibiotics that inhibit the IspH enzyme are also creating powerful antigens against which the immune system mounts a strong immune response. With the dual action of being immunostimulants and antibiotics the antimicrobial agents are much more powerful than any existing conventional broad-spectrum antibiotic. The researchers tested a number of new DAIA antibiotics and could demonstrate that they were non-toxic to human cells. They also tested them against a wide range of pathogenic gram-negative and gram-positive bacteria and found that they were very potent.

Farokh Dotiwala, M.B.B.S., Ph.D., assistant professor in the Vaccine & Immunotherapy Center and coauthor of the study said: “We believe this innovative DAIA strategy may represent a potential landmark in the world’s fight against AMR, creating a synergy between the direct killing ability of antibiotics and the natural power of the immune system.” AMR stands for antimicrobial resistance.

Researchers Developed a New Antibiotic to Solve Antibiotic Resistance

Researchers Developed a New Antibiotic to Solve Antibiotic Resistance

Conclusion

The emergence of more and more resistant bacterial strains makes it difficult and expensive to treat bacterial infections. But the Wistar Institute published a research paper that introduces us to a new class of antibiotics. They have a dual action of being immunostimulants and antibiotics (DAIA antibiotics). The antibiotic action is a novel approach in that a DAIA antibiotic blocks an essential pathway in the pathogenic bacteria. This coupled with a strong immune response from the body against the bacteria ensures that no resistance against the DAIA antibiotics can develop. Studies with human cell cultures showed that the DAIA antibiotics are well tolerated. Human studies about various diseases due to antibiotic resistance will follow. This new antibiotic class has great potential to treat resistant bacteria, which will mean much better survival rates for persons with serious infections.