FM AUGUST 2018 ISSUE1 - digital edition

drug resistance
Antibiotics from
nematodes
Derived from soil dwelling worms, odilorhabdins
hold promise for treating drug-resistant infections
S
cientists 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 carbapenemresistant
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 - FM
48 / FUTURE MEDICINE / AUGUST 2018