Beta-lactamase: lessons in the art of survival.

1. A beta-lactamase molecule is a marvelous device enabling its marker to thrive in a hostile and potentially lethal environment. What is more, the protective effect is extended to otherwise vulnerable organisms, securing their survival in the sheltered neighborhood. Curiously, such environmental implications had no discernible impact on the strategy of antibacterial chemotherapy. Moreover, traditional diagnostic routines are largely responsible for the sheltered survival of susceptible pathogens. 2. For half a century, since their existence was discovered by Abraham and Chain, beta-lactamases have never ceased to amaze us with an ever-widening spectrum of structural and functional variants, appearing in increasingly rapid succession in an ever broader range of bacteria. Whereas the phenomenon itself was the predicted outcome of unguarded expansion of beta-lactam therapy, its scope is a testimony to the unique advantage of an otherwise irrelevant, and thus freely modifiable and transmissible, enzyme as a key to survival. 3. Perhaps the least expected lesson is to be had from the adaptive behaviour of the beta-lactamase molecule itself. Faced with virtually countless structural variations on the beta-lactam theme, nearly all created so as to frustrate its function, the beta-lactamase molecule proves to be so versatile in overcoming so many of its potential inhibitors that it makes us reflect on the evolutionary significance of coping and survival at the molecular level.