Breakdown of penicillin by resistant bacteria elucidated

March 27, 2000

Almost as soon as penicillin was discovered, more than 70 years ago, certain bacteria had learned how to resist this common antibiotic. These resistant bacteria make beta-lactamase, an enzyme that quickly breaks down penicillin. Now, seven decades later, scientists at the University of Chicago led by Marvin W. Makinen, Ph.D., professor of biochemistry & molecular biology, have discovered exactly how b-lactamases deactivate penicillin.

Their findings, published in the March 28 issue of the journal Proceedings of the National Academy of Sciences, could lead to improved antibiotic design.

"While we cannot predict how these results may lead to improved antibiotics, the chemical principles governing the reactivity of penicillin that we have found are fundamental for designing compounds of pharmacologic importance," says Makinen.

Penicillin-resistant organisms are currently among the most important sources of hospital-acquired infections. Some bacteria have acquired the genetic blueprints for producing a very effective zinc-containing b-lactamase enzyme that is being encountered with increasing frequency in hospitals and in the community.

Makinen and colleagues used analysis of electrostatic forces between individual atoms of the penicillin and b-lactamase enzyme and computational simulation of their interactions. They concluded that b-lactamase attacks penicillin in a way different than previously thought. An intact penicillin molecule contains a characteristic segment known as the b-lactam ring. Destruction of one crucial bond in the ring causes the penicillin to become deactivated. But instead of the b-lactamase breaking the bond by attacking a key carbon atom that forms part of the bond, b-lactamase destroys the bond by first adding a single proton to it to destabilize it and make it easier to break.

"Knowing more accurately the chemical and physical basis of the interaction of penicillin and b-lacatamses will help in structure-based drug design," Makinen says.

University of Chicago Medical Center

Related Bacteria Articles from Brightsurf:

Siblings can also differ from one another in bacteria
A research team from the University of Tübingen and the German Center for Infection Research (DZIF) is investigating how pathogens influence the immune response of their host with genetic variation.

How bacteria fertilize soya
Soya and clover have their very own fertiliser factories in their roots, where bacteria manufacture ammonium, which is crucial for plant growth.

Bacteria might help other bacteria to tolerate antibiotics better
A new paper by the Dynamical Systems Biology lab at UPF shows that the response by bacteria to antibiotics may depend on other species of bacteria they live with, in such a way that some bacteria may make others more tolerant to antibiotics.

Two-faced bacteria
The gut microbiome, which is a collection of numerous beneficial bacteria species, is key to our overall well-being and good health.

Microcensus in bacteria
Bacillus subtilis can determine proportions of different groups within a mixed population.

Right beneath the skin we all have the same bacteria
In the dermis skin layer, the same bacteria are found across age and gender.

Bacteria must be 'stressed out' to divide
Bacterial cell division is controlled by both enzymatic activity and mechanical forces, which work together to control its timing and location, a new study from EPFL finds.

How bees live with bacteria
More than 90 percent of all bee species are not organized in colonies, but fight their way through life alone.

The bacteria building your baby
Australian researchers have laid to rest a longstanding controversy: is the womb sterile?

Hopping bacteria
Scientists have long known that key models of bacterial movement in real-world conditions are flawed.

Read More: Bacteria News and Bacteria Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to