Bacteria, drug targets

Development of resistance to rifaximin is primarily due to a chromosomal one-step alteration in the drug target, DNA-dependent RNA polymerase. This differs from the plasmid-mediated resistance commonly acquired by bacteria to aminoglycoside antibiotics such as neomycin... 

Scientists have determined complete genomic sequences for a number of viruses, over fifteen bacteria, and laboratory yeast. Many pharmaceutical companies are interested in the sequence information from bacteria that cause disease, in the hopes that the information obtained will lead to new drug targets. 

In principle, other coenzyme biosynthetic pathways that occur in pathogenic bacteria but not in humans should qualify as anti-infective drug targets with a favorable toxicity profile. Novel anti-infective principles would be highly desirable in light of the rapid spread of resistant pathogens. 

Microorganisms responsible for infection (various bacteria, viruses, protozoan, etc.) often have carbohydrates different from those seen in humans. For this reason, it will be possible to prevent the onset of associated diseases by using drugs targeted at these particular carbohydrates [ 127]. This section will outline these drugs. 

As with bacteria, drug resistance in some parasites such as Plasmodium is a major problem and tends to appear where chemotherapy has been used extensively. This problem is exacerbated by the fact there are so few drugs available for the control of some parasites. Parasites utilize the same five basic resistance mechanisms that are displayed by bacteria 1) metabolic inactivation of the drug 2) use of efflux pumps 3) use of alternative metabolic pathways 4) alteration of the target 5) elevation of the amount of target enzyme. 

Perhaps the best characterized organic cofactor-dependent racemase is alanine racemase, which employs pyridoxal 5 -phosphate (PLP) (Table 7.1). o-alanine is necessary for the synthesis of the peptidoglycan layer of bacterial cell walls in Gram negative and positive bacteria [1]. Alanine racemase is thus a ubiquitous enzyme in bacteria and an excellent drug target [2]. Both its crystal structure and mechanism have been well investigated. PLP reacts with amino acids to produce... 

The monomeric protein is 38 kDa and contains one FAD. With the increased prevalence of antibiotic-resistant bacteria, MurB is a possible drug target due to its critical role in cell wall biosynthesis. MurB is an essential gene in both E. coli and Bacillus further validating it as a suitable drug target. 

Enzymes of the folate biosynthesis pathway are important drug targets for the treatment of infections with bacteria and of certain malignancies. In fact, sulfonamide (Figure 9) drugs that interfere with the formation of the THF precursor, dihydropteroate, were discovered and widely used therapeutically more that a decade prior to the structure elucidation of folic acid. ... 

Michl P, Gress TM (2004) Bacteria and bacterial toxins as therapeutic agents for solid tumors. Curr Cancer Drug Targets 4 689-702... 

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