Researchers in the United States have created a new class of antibiotics that can kill even the most resistant chemical bacteria, in what they describe as a “potential landmark.”
If marketed, hospital patients infected with ultra-powerful and highly advanced “super-bugs” could take intravenous drugs – called dual-acting immuno-antibiotics (DAIAs) – to eliminate a bacterial infection.
DAIA addresses the huge ongoing problem of antimicrobial resistance (AMR) – when bacteria and other microbes adapt and evolve in response to modern chemicals designed to kill them, becoming ultra-powerful “superbugs”.
DAIA works by targeting a metabolic pathway of bacteria that most need to survive and thrive.
At the same time, DAIA also stimulates an immune response in humans, making us less susceptible to superbugs in the first place.
In laboratory tests, DAIA has been shown to be effective against bacteria, including E. coli, a common source of infection that is becoming increasingly resistant to antibiotics.
DAIA even targets pan-resistant bacteria – bacteria resistant to any antibiotic drug on the market.
Scroll down for the video
Drugs – called DAIA – have been described as a “potential benchmark” in the war on antimicrobial resistance (AMR).
“We have taken a creative, two-way strategy to develop new molecules that can kill difficult-to-treat infections while improving the natural host’s immune response,” said study author Farokh Dotiwala of the Wistar Institute, an independent nonprofit institution. -profit in Pennsylvania, USA.
“We reasoned that capitalizing on the immune system to simultaneously attack bacteria on two different fronts makes it difficult for them to develop resistance.
“We believe that this innovative DAIA strategy can be a potential benchmark in the global fight against AMR, creating a synergy between the ability to kill antibiotics directly and the natural strength of the immune system.”
An entire science industry is now dedicated to addressing the serious problem of antimicrobial resistance (AMR) and the resulting superbugs.
The World Health Organization (WHO) estimates that these giants will kill 10 million people each year by 2050 – patients dying from harmless infections – and will impose a cumulative $ 100 trillion burden on the global economy.
Pathogens such as bacteria and fungi can evolve to become super resistant to our chemical treatments. WHO estimates superbugs will kill 10 million people each year by 2050, with patients dying from harmless infections
The WHO said AMR was one of the world’s top 10 threats to public health against humanity, while one expert called the threat of AMR as severe as terrorism.
“RAM” includes antibiotic resistance (ABR) – a term specific to bacteria that are resistant to drugs that kill them (antibiotics).
To make matters worse, the list of bacteria that become resistant to treatment is growing.
According to the Wistar Institute, few new drugs are underway, creating an “urgent need” for new classes of antibiotics to prevent public health crises.
Existing antibiotics target essential bacterial functions, including nucleic acid and protein synthesis, cell membrane construction, and metabolic pathways.
However, bacteria can gain resistance from antibiotics through their natural ability to evolve and move in the fight for survival.
Specifically, bacteria move against any specific bacterial target against which the antibiotic is directed, effectively inactivating the antibiotic in the process.
Fluorescence microscopy staining showing the effects of DAIA treatment on bacterial viability. E.coli bacteria were treated with isopropanol (a bactericidal chemical compound), a carrier molecule (without killing action) and increasing concentrations of the active drug DAIA and stained with propidium iodide (PI, red), which stains dead cells and SYTO 9 (green), which stains only living cells
Wistar Institute researchers have focused on a metabolic pathway that is essential for most bacteria but absent in humans, making it an ideal target for the development of antibiotics.
This pathway, called methyl-D-erythritol phosphate (MEP) or non-mevalonate pathway, is responsible for the biosynthesis of isoprenoises – molecules needed for cell survival in most disease-causing bacteria.
The lab targeted the IspH enzyme, an enzyme essential in isoprenoid biosynthesis, as a way to block this pathway and kill microbes.
Given the broad presence of IspH in the bacterial world, this approach probably targets a wide range of bacteria, the researchers say.
They then used computer modeling to examine several million commercially available compounds for their ability to bind to the enzyme.
They selected the strongest who inhibited IspH function as starting points for drug discovery.
Since previously available IspH inhibitors could not penetrate the bacterial cell wall, the researchers identified and synthesized new molecules of IspH inhibitors that managed to penetrate inside the bacteria.
The team demonstrated that IspH inhibitors stimulated the immune system with stronger bacterial killing activity than the best current antibiotics in the class.
“Immune activation is the second line of attack of the DAIA strategy,” said study author Kumar Singh, also at the Wistar Institute.
They tested the clinical isolates of antibiotic-resistant bacteria, including a wide range of pathogenic gram-negative and gram-positive bacteria, “in vitro” (in a glass Petri dish).
The researchers said: “In pre-clinical models of gram-negative bacterial infection, the bactericide [bacteria-killing] the effects of IspH inhibitors outweighed the performance of traditional antibiotics.
All compounds tested were found to be non-toxic to human cells.
The promising study was published in Nature.