Streptococcus penicillin-binding protein

In contrast to macrolides, the targets of (3-lactams, the penicillin binding proteins (PBPs) require several mutations in order to become resistant while simultaneously maintaining their viable function as cell wall transpeptidases/transglycosidases. Thus, in order to achieve clinically relevant resistance Streptococcus pneumoniae uses a unique strategy to rapidly accumulate several point mutations. Due to its natural competence for transformation during respiratory tract... 

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Changes in the nature or expression of penicillin-binding proteins (PBPs) render them insensitive to /3-lactam antibiotics although they can still be involved in peptidoglycan synthesis. Laboratory mutants of E. coli which are not killed by the mecillinam ester (33) have been described in these there is a reduced affinity of PBP2 for the antibiotic [165], More serious is the occurrence of this mechanism, involving PBP2b, in clinical isolates of Streptococcus pneumoniae [6]. 

Some streptococci have developed a different mechanism of acquired resistance to penicillin drugs. These bacteria have altered transpeptidases (also known as penicillin-binding proteins) that no longer bind penicillin, and thus peptidoglycan synthesis is not disrupted. This mechanism of resistance is found in Streptococcus pneumoniae. Estimates of penicillin-resistant S. pneumoniae in the United States range from 25% to 66%, including strains recovered from ocular and periocular infections. Many isolates of penicillin-resistant S.pneumoniae also are resistant to the cephalosporins, macrolides, and the older fluoroquinolones. Use of alternative antibiotics such as vancomycin is necessary for infections caused by penicillin-resistant isolates. 

In addition to S. pneumoniae, the viridans group of streptococci is also developing resistance to penicillin through the same mechanism, altered penicillin-binding proteins. In contrast, resistance has not developed in Streptococcus pyogenes, and both penicillins G and V are antibiotics of choice for systemic infections caused by this organism. 

Answer A- Microbial resistance to fluoroquinolones is increasing, and some strains of Streptococcus pneumoniae are now resistant to ciprofloxacin. The mechanism can involve changes in the structure of topoisomerase IV, one of the targets of fluoroquinolones, which inhibit nucleic acid synthesis. Pneumococcal resistance to penicillins is also increasing via changes in penicillin-binding proteins (PBPs). The other mechanisms listed underlie microbial resistance to other antibiotics as follows sulfonamides (choice B), macrolides (choice C), extended-spectrum penicillins (choice D), and beta-lactams (choice E). 

Miguet, L., Tervosen, A., Gerards, T., Pasha, F.A., Luxen, A., Disteche-Nguyen, M., and Thomas, A. (2009) Discovery of new inhibitors of resistant streptococcus pneumoniae penicillin binding protein (PBP) 2x by structure-based virtual screening. Journal of Medicinal Chemistry, 52, 5926-5936. 

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