Antibiotics from nematodes

July 16, 2018 0 By CH Unnikrishnan

Derived from soil dwelling worms, odilorhabdins hold promise for treating drug-resistant infections

Scientists have created a new class of antibiotics based on a mechanism employed by nematode worms to survive the onslaught of invading microbes.
Besides the unconventional origin, what makes this new antibiotic truly unique is its distinct modality of action, according to the joint team of researchers that discovered and developed the drugs. The team comprised researchers from the University of Illinois, Chicago, and Nosopharm, an upstart biotechnology company based in France.

The researchers believe that the new group of drugs, called odilorhabdins (ODLs), could effectively deal with rising antibiotic resistance associated with commonly prescribed drugs. ODLs are produced by symbiotic bacteria found in soil-dwelling nematode worms that colonize insects for food.
The conclusion is based on a study of 80 cultured strains of the bacteria for antimicrobial activity. After isolating the active compounds, they produced more potent derivatives from the chemical structures.

In line with many clinically useful antibiotics, ODLs also target the ribosome, wrote the team of researchers explaining the mechanism of action in the study published in the journal Molecular Cell.

However, the uniqueness of ODLs, as mentioned earlier, is that they bind to a place on the ribosome that has never been used by other known antibiotics. They also found that when bound to this protein making molecular machine within a cell, the antibiotic disrupts the ribosome’s ability to interpret and translate genetic code.

“When ODLs are introduced to the bacterial cells, they impact the reading ability of the ribosome and cause the ribosome to make mistakes when it creates new proteins,” stated UIC’s Alexander Mankin , one of the corresponding authors on the study. “This miscoding corrupts the cell with flawed proteins and causes the bacterial cell to die.”

Since bactericidal antibiotics are rare, the fact that ODLs bind to a site on the ribosome not exploited by any known antibiotic lends it a potential edge in treating infections that are unresponsive to other antibiotics.

In France, the Nosopharm researchers tested the ODL compounds against bacterial pathogens, including many known to develop resistance.
“We found that the ODL compounds cured mice infected with several pathogenic bacteria and demonstrated activity against both Gram-negative and Gram-positive pathogens, notably including carbapenem-resistant Enterobacteriaceae,” said co-corresponding author Maxime Gualtieri, co-founder and chief scientific officer of Nosopharm.

Carbapenem-resistant Enterobacteriaceae, or CRE, which are implicated in bloodstream and surgical site infections, have high levels of resistance to antibiotics.

Discovery of ODLs comes at a time when a wide range of innovators are looking for novel methods to combat drug resistance, one of the biggest threats to global health at present.