Researchers at the Univeristy of Notre Dame, Spain have recently published a study which explains the mechanism of regulation of the critical cell wall cross linking step in the Methicillin Resistant Staphylococcus aureus.
Proceedings of the National Academy of Sciences, the journal which published the results of this study performed by Mayland Chang and Shahriar Mobashery along with their team, has revealed the basis of how the MRSA has evolved into such a dreaded pathogen over the past 50 years when it rapidly spread all over the world. It is noteworthy that the modern strains of MRSA are resistant to antibiotics in a broader sense, including the popularly uses beta-lactams.
In the study, it has been reported that an allosteric portion was discovered in the X-ray structure of the penicillin binding protein 2a of the MRSA bacterium. The penicillin binding protein is the enzyme involved in the cross linking step.
Chang, Mobashery and Juan Hermoso have documented at the CSIC, the Spanish Research Council, that conformational changes are set due to a trigger from an allosteric fragment in the cell wall at a distance of 6 nm. These changes ultimately lead to the opening of the closed active site that enables the catalysis of the physiological function of the enzyme.
The researchers also found that Ceftaroline, a new beta lactam antibiotic which has been approved by the FDA recently, can also bind to the allosteric site and initiate the same response. This is followed by the interaction of another molecule of the antibiotic with the active site of the enzyme which inhibits its function and leads to the death of the bacterial cell. The discovery of this mechanism of action of the new drug is a breakthrough and will help in designing new drugs to tackle the menace of MRSA.
A difficult hospital pathogen to control, MRSA has slowly entered the population in the past few decades, especially in places like nurseries, locker rooms and prisons. It is estimated that in the US almost 20,000 people of the 100,000 affected by this bacterium annually, eventually perish.