" This pathogen is responsible for a large number of diseases ranging from skin conditions and wound infections , pneumonia and septicemia up that can lead to death. MRSA -related infections are among the most important of multiresistant pathogens due to the high mortality due annually. According to data collected in the United States, staph causes more than 80,000 infections each year , of which more than 11,000 end with the death of the patient, " says researcher John Beautiful CSIC , Institute of Physical Chemistry Rocasolano .
According to this study , the key MRSA resistance to beta-lactam antibiotics (such as penicillin derivatives ) protein PBP2a , which is involved in the biosynthesis of bacterial cell wall of the pathogen. In susceptible bacteria to these antibiotics proteins responsible for the construction of the wall are being blocked by the agents and stop reproducing . However, in the case of Staphylococcus aureus, PBP2a is insensitive to this blocking and allows the pathogen to its cell cycle continue even in the presence of antibiotics.
The mechanism that allows PBP2a resist most antibiotics is related to an allosteric site , ie , a site distant to the active site of the enzyme but capable of controlling its activation. X -ray crystallography researchers have determined the three dimensional structure in complex with ceftaroline PBP2a , one of the few antibiotics that are effective against MRSA today .
"This structure has revealed that the binding of the allosteric site ceftaroline produces a series of changes in the activated protein and leave sensitive to inactivation by the antibiotic. It's like a switch that activates the enzyme : conventional antibiotics can not turn that switch , so they are safe for the pathogen . This paper describes how this power and opens a new avenue for the development of new antibiotics , "says Fair.
A global health problem
Antimicrobial resistance represents one of the most serious health worldwide today. "The lack of efficacy of antibiotics incapacitates our way to fight infectious diseases and to address common complications in patients undergoing chemotherapy for cancer treatment , dialysis and surgery, especially in those organs for transplant which the ability to treat these secondary infections is vital, " CSIC researcher highlights .
The study was published in the journal Proceedings of the National Academy of Sciences (PNAS).
Lisandro H. Oteroa, Alzoray Rojas-Altuvea, Leticia I. Llarrull, Cesar Carrasco-López, Malika Kumarasiri, Elena Lastochkin, Jennifer Fishovitz, Matthew Dawley, Dusan Hesek, Mijoon Lee, Jarrod W. Johnson, Jed F. Fisher, Mayland Chang, Shahriar Mobashery, Juan A. Hermoso. How allosteric control of Staphylococcus aureus penicillin binding protein 2a enables methicillin resistance and physiological function. PNAS. DOI: 10.1073/pnas.1300118110