Possible Substitute forBeta-lactam AntibioticsThrough the Explorationof Penicillin-bindingProteinsNicolle A. RosaMercadoRISE 2012UPR Cayey
Penicillin Binding Proteins Fig. 1: PBP• Group of proteins characterized structure by uniting to beta-lactam antibiotics• Give the antibiotic the ability of preventing the formation of the bacterial cell wall.• Speciﬁcally involved in the last stages of peptydoglycan synthesis.
Penicillin-bindingProteins1) 2) 3) Fig. 2: These images explain how PBPs work. http://www.youtube.com/ watch?v=qBdYnRhdWcQ
Beta-lactamAntibiotics• Characterized by a beta- lactam nucleus in their structure• Inhibit bacterial cell wall biosynthesis• Bacteria may become resistant to them by means of beta-lactamase Fig. 3: Beta-Lactam Ring
Beta-lactam Antibiotics http://www.youtube.com/ watch?v=qBdYnRhdWcQ Fig. 4: Explains how beta-lactam antibiotics work
Beta-lactamases • Enzymes that create a resistance to beta-lactam antibiotics • Breaks open the beta-lactam ring in these antibiotics, preventing them to stop penicillin-binding proteins from “sealing” the bacterial cell wall.
Hypothesis• Antibiotics that have a similar structure to beta-lactams might be used to substitute them in bacteria that have developed a resistance to beta-lactams. To do this, the antibiotic must be able to bind with a penicillin-binding protein so it can destroy the bacterial cell wall.
Methods• Compare different non beta-lactam antibiotic structures to beta-lacatam antibiotics.• Select ten of the non beta-lactam antibiotics and add them to a colony of Escherichia coli, a Gram-negative bacteria, and a colony of Streptococcus pneumoniae, a Gram-positive bacteria.• Choose the successful antibiotics to study their relation to PBPs
Expected Results • Find a non beta-lactam antibiotic that is able to effectively kill bacteria through PBPs
References • http://www.ncbi.nlm.nih.gov/pmc/articles/PMC192226/ • Basu J., Chattopadhyay R., Kundu M., and Chakrabarti P. (1992) Puriﬁcation and partial characterization of a penicillin binding protein from Mycobacterium smegmatis. American Society for Microbiology – Journal of Bacteriology. Vol 174, No 14 pp 4829–4832 • Basu J., Chattopadhyay R., Kundu M., and Chakrabarti P. (1992) Puriﬁcation and partial characterization of a penicillin binding protein from Mycobacterium smegmatis. American Society for Microbiology – Journal of Bacteriology. Vol. 174, No. 14 pp. 4829–4832