Sunday, March 16, 2008

Penicillin is Back??

Last week we were treated to another demonstration of the general uselessness of university press offices and the hype that often times is associated with minor scientific discoveries. Much like the "could be", "might be" of global warming.

It seems that researchers at the University of Warwick together with collaborators at the Université Laval, Ste-Foy in Quebec, and The Rockefeller University in New York have managed to work out the enzymology of the MurM protein. Yawn............

The Mur pathway is essential for the synthesis of the bacterial cell wall and MurM is specifically involved with the production of dipeptide bridges within the peptidoglycan molecule, the major component of the wall. These cross-links give the structure increased mechanical strength. So now it looks like the entire Mur pathway is essentially characterized. End of story.

The real shocker in this article is the following statement: "The results will allow the Warwick team, and any interested pharmaceutical researchers, to target the MurM reaction in Streptococcus pneumoniae in a way which will lead to the development of drugs which will disrupt the resistance of Streptococcus pneumoniae to penicillin. The same research also offers exciting possibilities to disrupt the antibiotic resistance of MRSA which uses similarly constructed peptide bridges in the construction of the peptidoglycan component of its cell wall. Therefore, thanks to this research, even MRSA could now be opened up to treatment by penicillin."

What the article fails to point out is that penicillin resistance (and betalactam resistance in general) in MRSA does not involve the Mur pathway but an alternate penicillin-binding protein-2 (PBP2'). This alternate protein is encoded by the mecA gene which is transferred between staphylococci rather easily by phage, plasmid, etc. Once bacterial pick-up this gene, they are considered MRSA. This is the primary reason that up to 60% of Staphylococcus aureus strains are penicillin resistant leading to the designation of MRSA.

Unfortunately, there also are various other betalactam resistance mechanisms that are due to the production of "betalactamases"; secreted enzymes that degrade penicillins before they ever reach the cell. And to make matters worse, the Mur pathway has been the subject of many failed discovery projects by pharma companies. I doubt seriously that this one characterization of the MurM protein will suddenly lead to the discovery of new antibiotics. This pathway as a target class is DOA.

Taken together, it is unlikely that we will see a major resurgence in the use or clinical efficacy of penicillin in either streptococci or staphylococci.

One would expect a higher level of journalistic competence from university press offices.


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