Penicillin, one of the scientific marvels of the 20th century, is currently losing a lot of battles it once won against bacterial infections. But scientists at the University of South Carolina have just reported a new approach to restoring its combat effectiveness, even against so-called “superbugs.â€
Bacteria have been chipping away at the power of the penicillin family of drugs since their first wide-scale use as antibiotics in the 1940s. For example, the staph infection, brought about by the bacterium Staphylococcus aureus, was once readily treated with penicillin and its molecular cousins.
But that bug has changed. In the 1960s, a new strain arrived, termed MRSA for methicillin- (or sometimes multidrug-) resistant S. aureus. It has become a serious public health problem because the earliest deployed antibiotics are often useless against the new strain, and its prevalence has only increased since it was first observed. MRSA (pronounced mer-suh) is sometimes called a superbug because of the difficulty physicians have in treating infected patients.
The S. aureus microbe has evolved the MRSA strain by developing a variety of defenses against antibiotics to which they’ve been exposed. One of those defenses effectively neutralizes penicillin’s greatest strength.
That strength is its molecular core, a cyclic four-membered amide ring termed a beta-lactam. It is a common structural element of the penicillins, their synthetic and semi-synthetic derivatives, and other related molecules that constitute the broad family of drugs called the beta-lactam antibiotics. Just a few examples (of dozens) include amoxicillin, ampicillin and cefazolin.
The beta-lactam structure in a molecule is something that many bacteria don’t like at all. It greatly hinders their ability to reproduce by cell division, and so chemists have for years spent time making molecules that all contain the beta-lactam structural motif, but differ in the surrounding molecular “shrubbery.†Physicians heavily use the many versions of beta-lactam antibiotics to fight bacterial infections, and many have been retired because they’re no longer effective against the defenses bacteria have evolved in response.
One of the most effective bacterial defenses is an enzyme called beta-lactamase, which chews up the beta-lactam structure. Some bacteria, such as MRSA, have developed the ability to biosynthesize and release beta-lactamase when needed. It’s a devastating defense because it’s so general, targeting the common structural motif in all of the many beta-lactam antibiotics.
But that also creates the opportunity for a general approach to solving the problem, which is what Carolina’s Chuanbing Tang and colleagues just reported in the Journal of the American Chemical Society.