Chapter 11. New Approaches and Agents to Overcome Bacterial Resistance
Annual Reports in Medicinal Chemistry, ISSN: 0065-7743, Vol: 32, Issue: C, Page: 111-120
1997
- 15Citations
- 7Captures
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Article Description
This chapter discusses the challenges posed by anti-bacterial resistance (AR) in four sections, covering the magnitude and scope of AR and the problem organisms, the mechanistic aspects of AR, new bacterial targets and the methods for screening and synthesis, and a review of the selected anti-bacterials reported to offer some solution or promise toward overcoming AR. Anti-bacterial resistance is a serious health and worldwide problem with catastrophic potential. Several overviews on the general mechanisms, by which bacteria acquire resistance, have appeared and the modes of quinolone resistance in particular have been described in the chapter. Gyrase and topoisomerase IV are the quinolone targets in bacteria. All high level quinolone resistance in gram-negatives, methicillin resistant S. aureus (MRSA), S. pneumoniae, and Enterococci, have been shown to be associated with double mutations in gyrase at the Ser 83 and the amino acid (AA) at 87 (E. coli numbering). Porin and efflux mutations play minor roles in high level resistance. Mechanisms of tetracycline resistance involve efflux and ribosomal protection. The glycylglycines are the first tetracylines to overcome this resistance. The mechanism of vancomycin resistance has been described in this chapter. Enterococci with the vanB phenotype are resistant to vancomycin but not teicoplanin. This resistant phenotype has been shown to originate with the two component signaling proteins vanS and vanR that activate the gene cascade, leading to vancomycin resistance (VRE). In the vanB phenotype, the histidine kinase fails to recognize teicoplanin. Aminoglycoside (AG) resistance arises from acetylation, adenylation, or phosphorylation by AG modifying enzymes. To defeat MRSA, MecA (the modified penicillin binding protein), and several essential auxiliary gene products for cell wall synthesis are suggested as targets. Such genes have been identified by a novel selection technique.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0065774308614694; http://dx.doi.org/10.1016/s0065-7743(08)61469-4; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=77956746097&origin=inward; https://linkinghub.elsevier.com/retrieve/pii/S0065774308614694; http://linkinghub.elsevier.com/retrieve/pii/S0065774308614694; http://dx.doi.org/10.1016/s0065-7743%2808%2961469-4; https://dx.doi.org/10.1016/s0065-7743%2808%2961469-4
Elsevier BV
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