期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 61, 期 17, 页码 2200-2223出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-004-4060-9
关键词
beta-lactam; beta-lactamase; penicillin-binding protein; efflux; impermeability
beta-lactams have a long history in the treatment of infectious diseases, though their use has been and continues to be confounded by the development of resistance in target organisms. beta-lactamases, particularly in Gram-negative pathogens, are a major determinant of this resistance, although alterations in the beta-lactam targets, the penicillin-binding proteins (PBPs), are also important, especially in Gram-positive pathogens. Mechanisms for the efflux and/or exclusion of these agents also contribute, though often in conjunction these other two. Approaches for overcoming these resistance mechanisms include the development of novel beta-lactamase-stable beta-lactams, P-lactamase inhibitors to be employed with existing beta-lactams, beta-lactam compounds that bind strongly to low-affinity PBPs and agents that potentiate the activity of existing beta-lactams against low-affinity PBP-producing organisms.
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