New Class of Antibiotics: Hoping for a Great Future

Finding new types of antibiotic drugs could save human lives. It can also dramatically reduce health costs associated with the treatment of bacteria. Some bacterias are resistant to currently available drugs. Professor Chris McMaster is developing a new class of antibiotics. He wants to address the many difficulties associated with this particular research area. These include limited sales of these drugs and a greater focus on other pharmaceuticals.

Multi-drug resistant bacteria, widely known as superbugs, kill more than 700,000 people every year. More worryingly, though, this number is expected to grow to more than 10 million by 2050. This will have massive repercussions both in terms of the number of human lives lost and in terms of the global economy. This will lose some trillion dollars due to the disease and death of people infected with these bugs. Only a few scientists are developing new antibiotic medicines that might counteract these superbugs. But several problems are currently slowing down development.

The need for new antibiotics

New classes of antibiotics could save lives. They can totally eradicate bacteria that are immune to current drugs.

Antibiotics are a type of medication that kills or prevents microorganism development. They are usually used to treat or prevent various bacterial infections. These include pneumonia, tuberculosis, many sexually transmitted diseases (STDs).

Most of those antibiotics commonly established to treat these bacteria are based on late generations of existing antibiotics. However, resistance to these medications tends to develop quickly. It is because individual bacteria already have underlying mechanisms. By these mechanisms, they can have resistance to similar antibiotics. Professor Chris McMaster said, “Every single antibiotic currently in clinical trials, which there are less than 40, is a ‘me-too’ version of the current antibiotic versus a known target.

This highlights the need to create completely new classes of antibiotic medicines. They will treat infections caused by drug-resistant bacteria. To address this problem, Prof. Chris McMaster and his colleagues have developed a new class of antibiotics to treat infections better.

Why so few antibiotics in development?

Here are some of the reasons:

Scientific difficulties. The development of an antibiotic drug is extremely difficult. First, you need to get to the right position in the body at a high enough dose. The dose should not be toxic to the patient. It still needs to enter and stay in the bacterial cell, which has proved very problematic. Efforts to scan large existing small-molecule libraries have failed to identify new antibiotics.

Financial and regulatory hurdles. It is extremely difficult and often takes 10 years or longer to develop an antibiotic. Each new formulation has to undergo rigorous activity and patient safety monitoring. And only a minority can actually do so through the entire drug development process.

Lack of know-how. Many pharmaceutical companies abandoned their antibiotic research programs for some reason. They are: 

• Poor financial resources
• Technical difficulties in developing new antibiotics

This resulted in a lack of skills and specialized personnel in the field.

New class of antibiotics against a wide variety of bacteria 

Wistar Institute scientists have identified a new class of antibiotics. They precisely combine direct antibiotic killing of pan-drug-resistant bacterial infections. They do this with a simultaneous fast immune response to fight antimicrobial resistance (AMR).

The World Health Organisation (WHO) has declared AMR to be one of the top 10 global public health risks to humanity. It is projected that by 2050, antibiotic-resistant infections will take 10 million lives per year. It will also put a total burden of $100 trillion on the global economy. The list of bacteria resistant to medication with all antibiotic alternatives is growing. And few new medicines are in the pipeline. This creates an immediate need for new classes of antibiotics to prevent public health crises.

Established antibiotics target important bacterial functions. These include nucleic acid and protein synthesis, cell membrane building, and metabolic pathways. However, bacteria may develop drug resistance by mutating the bacterial target.

The team focused their experiments on a metabolic pathway that is important for most bacteria. But it is not present in humans. This makes it the perfect target for antibiotic development. “We are focusing on the pathway of methyl-d-erythritol phosphate (MEP) for isoprenoid biosynthesis. This is important for the survival of most Gram-negative bacteria and apicomplexans. But it is not present in humans and other metazoans,” the team wrote.

MEP—or non-mevalonate—the pathway is responsible for isoprenoid biosynthesis. These are molecules essential for cell survival in most pathogenic bacteria.

Researchers used computer simulation to screen many million commercially available compounds. They wanted to know their ability to bind to the enzyme. They chose the most potent inhibitors of IspH as the starting point for drug development. Previously available IspH inhibitors have not been able to penetrate the bacterial cell wall. And that is why Dotiwala has collaborated with Wistar’s medicinal chemist Joseph Salvino, PhD. Joseph Salvino is a professor at the Wistar Institute Cancer Center and co-senior author of the study. They were able to synthesize novel IspH inhibitor molecules that penetrated the bacteria.

The team found that IspH inhibitors activated the immune system. It had more potent bacterial killing activity. The versatility of current best-in-class antibiotics examined in vitro for clinical isolates of antibiotic-resistant bacteria includes a variety of pathogenic gram-negative and gram-positive bacteria.

As well as acting specifically on IspH, the substances also are non-toxic to human cells. ” Our DAIA prodrugs are permeable bacteria. And they are more potent against too many multidrug-resistant bacteria,” said the team.

The researchers also found out that the bacteria are unlikely to have developed resistance mechanisms to the mode of action of their DAIAs. “Unlike antibiotics derived from natural sources, no inhibitors of IspH have been found in microorganisms. So, it is less likely that resistance mechanisms have evolved directly against our medications,” they stated. ” The antimicrobial strategy that we are reporting are synergizing direct antibiotic action.” “We agree that this innovative DAIA solution could be a breakthrough. It may end the global war against AMR. So, it may provide a connection between the direct killing of antibiotics and the potential for AMR. It may also increase the natural strength of the immune system,” Dotiwala stated.