Rosario researchers participated in the development of a new class of antibiotics capable of attacking resistant Staphylococcus aureus (MRSA stands for ) , a bacterium that causes infections that do not respond to commonly used drugs such as penicillin. This class of compounds, called oxadiazoles , move on to the next phase of clinical experimentation , inhibits bacterial protein ( PBP2a ) responsible for constructing its cell wall , causing his death.
Dr. Sebastian Testero, a member of the Institute of Chemistry Rosario ( IQUIR , CONICET- UNR) and Service Discovery , Design and Pre – Clinical Drug Argentina ( SEDIPFAR ) , Development and Dr. Leticia Llarrull , from the Institute of Molecular Biology and Cellular Rosario ( IBR , CONICET- UNR ) and the Structural and Metabolomics Platform ( PLABEM ) Biology , remained four years at the University of Notre Dame, United States , participating in the multidisciplinary study that led to the discovery of the new antibiotic and whose results were recently published in the international Journal of the American Chemical Society ( J. Am Chem Soc 2014 , DOI: 10.1021/ja500053x ) .
Staphylococcus aureus causes mainly nosocomial infections, but has also managed to spread outside of hospitals. In Latin America, in 2008 , more than half of the strains of Staphylococcus aureus isolated were resistant to methicillin and also found some that were not affected by other drugs , less common , such as vancomycin and linezolid.
Dr. Testero says ” most type antibiotics penicillins to proteins of bacteria called PBPs necessary to build its cell wall structure essential for the viability of the organism attaches .” However, strains of Staphylococcus aureus have become resistant to methicillin have a protein called PBP2a , which fulfills the same function as all other PBPs -which does not bind penicillin allowing the microorganism to survive even in the presence of this drug .
To find a compound that can inhibit PBP2a , the research team used the available three-dimensional structure of the protein and by computational modeling performed a virtual screening of one million two hundred thousand known compounds and joined what was observed more effectively to its active site to lock . ” Compared to other PBPs proteins, which do respond to methicillin, PBP2a has closed its active site so the antibiotic should be able to open it to join him ,” says the doctor Llarrull .
Once scientists identified compounds, synthesized and tested in vitro effectiveness against MRSA. “We saw that one had an acceptable activity against bacteria , chemical modifications we made to optimize the interaction with the target until we found a compound that was really very good with which we continue the study in mice ,” explains Dr. Testero. Preclinical studies in rodents allowed to show that the compound is not toxic, showed that the half of the infected with lethal levels of mice surviving MRSA after the antibiotic will be supplied . The compound was patented and is expected to soon begin clinical trials in humans to take about ten years of study.
The doctor Llarrull that , locally, with Dr. Testero and CONICET fellows are studying other possible targets to attack MRSA. “We are trying to find compounds that block the system with which the bacterium detects the presence of antibiotics such as penicillin and to be delivered in conjunction with them ,” says Llarrull .
The researchers highlight the importance of finding new drugs given the speed with which microbes acquire resistance to existing and limited research in the area from the private sector. ” Between 1960 and 2000 no new antibiotic is not developed , only small changes to the same base structures were introduced ,” said guide base and concludes “we are in a race where bacteria acquire resistance faster than we can investigate . ”
by CCT Rosario
