North Carolina
State University
chemists have created a compound that makes existing antibiotics 16 times more
effective against recently discovered antibiotic-resistant superbugs.
These so-called superbugs are actually bacterial strains that produce an
enzyme known as New Delhi
metallo-?-lactamase (NDM-1). Bacteria that produce this enzyme are practically
impervious to antibiotics because NDM-1renders certain antibiotics unable to
bind with their bacterial targets. Since NDM-1 is found in Gram-negative bacteria
like K. pneumoniae, which causes pneumonia, urinary tract, and other
common hospital-acquired infections, it is of particular concern.
“To begin with, there are fewer antibiotic options for treating infections
caused by Gram-negative bacteria than for those caused by Gram-positive
bacteria,” says Roberta Worthington, PhD, NC State research assistant professor
of chemistry. “Gram-negative bacteria with the NDM-1 enzyme effectively
neutralize the few weapons we have in our arsenal, making them especially
difficult, if not impossible, to treat with existing antibiotic therapy.”
Previously, NC State chemist Christian Melander, PhD, had found that a
compound derived from a class of molecules known as 2-aminoimidazoles “recharged” existing antibiotics, making them effective against Gram-positive
antibiotic-resistant bacteria like the Staphylococcus strain MRSA. So
Melander, Worthington
and graduate students Cynthia Bunders and Catherine Reed set to work on a
variety of the compound that might prove similarly effective against their
Gram-negative brethren.
In a paper published in ACS Medicinal
Chemistry Letters, Worthington
and Melander describe a compound that, when used in conjunction with the
antibiotic imipenem, increased the antibiotic’s effectiveness against the
antibiotic-resistant K. pneumoniae 16-fold. The researchers believe
that these early results are very promising for future treatments.
“We’ve demonstrated that we have the ability to take out the scariest
superbug out there,” Melander says. “Hopefully further research will allow us
to make the compound even more effective, and make these infections little more
than a nuisance.”
