title: Antibacterial Antifolates: From Development through Resistance to the Next Generation.
abstract: The folate cycle is one of the key metabolic pathways used by bacteria to synthesize vital building blocks required for proliferation. Therapeutic agents targeting enzymes in this cycle, such as trimethoprim and sulfamethoxazole, are among some of the most important and continually used antibacterials to treat both Gram-positive and Gram-negative pathogens. As with all antibacterial agents, the emergence of resistance threatens the continued clinical use of these life-saving drugs. In this article, we describe and analyze resistance mechanisms that have been clinically observed and review newer generations of preclinical compounds designed to overcome the molecular basis of the resistance.
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut 06269.
authors.forename: Alexavier
authors.initials: A
authors.lastname: Estrada
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut 06269.
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Wright
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut 06269.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Anderson
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy; D006801:Humans; D013420:Sulfamethoxazole / Q000494:pharmacology; D014296:Trimethoprim Resistance
chemical_list: D000900:Anti-Bacterial Agents; D005493:Folic Acid Antagonists; D013420:Sulfamethoxazole