Bacteria preventing human infections

Table 27.4 gives the amino acid composition of human lysozyme, also called a-lactalbumin. Lysozyme hydrolyzes the cell walls of gram-positive bacteria and provides a natural defense against bacterial infection. It is present, for instance, in the eye and helps to prevent eye infections. Lysozyme contains 120 amino acids. 

Table 5. Parenterally administered antimicrobial agents which can be used alone or combined to provide effective coverage of the mixed aerobic-anaerobic infections arising from human colonic bacteria for patients requiring preventive therapy...

Approximately 19 million pounds of antibiotics are used each year in U.S. cattle, hogs, poultry, and other food animals this is over 40% of the antibiotics sold in the U.S. (17). The routine use of antibiotics on farms to accelerate growth and prevent diseases has been speculated to have created strains of disease-causing bacteria that are resistant to antibiotics, which in turn infect more human beings every year (18). Because of the widespread use of antibiotics in livestock production, it would not be surprising to see antibiotic contamination of the aquatic environments situated near animal feedlots and confinements. The presence of antibiotics in water resources is suspected to contribute to the proliferation of resistant microorganisms, ft is not clear how much of these chemicals finds its way into the surface water near livestock operations. 

All of these compounds are inhibitors of dihydrofolate reductase in bacteria, plasmodia, and humans. Fortunately, they have a significantly high affinity for bacterial and protozoan dihydrofolate reductases. Pyrimethamine, for example, inhibits parasite dihydrofolate reductase at levels several hundred times lower than required to inhibit dihydrofolate reductase in humans. This is the basis of their selective toxicity. The selective toxicity can be increased upon supplying additional folic acid to the host organism, which the parasite cannot use. In fact, diaminopyrimidines (trimetoprim, pyrimethamine) were initially suggested as medicinal and preventative drugs against malarial infections. It was shown that all powerful inhibitors of dihydrofolate reductase can remove the malarial parasite with relatively minor consequences in the host. 

Figure 1.1. Opposite) Sulpha drugs and their mode of action. The first sulpha drug to be used medically was the red dye prontosil rubrum (a). In the early 1930s, experiments illustrated that the administration of this dye to mice infected with haemolytic streptococci prevented the death of the mice. This drug, while effective in vivo, was devoid of in vitro antibacterial activity. It was first used clinically in 1935 under the name Streptozon. It was subsequently shown that prontosil rubrum was enzymatically reduced by the liver, forming sulphanilamide, the actual active antimicrobial agent (b). Sulphanilamide induces its effect by acting as an anti-metabolite with respect to /iflra-aminobenzoic acid (PABA) (c). PABA is an essential component of tetrahydrofolic acid (THF) (d). THF serves as an essential co-factor for several cellular enzymes. Sulphanilamide (at sufficiently high concentrations) inhibits manufacture of THF by competing with PABA. This effectively inhibits essential THF-dependent enzyme reactions within the cell. Unlike humans, who can derive folates from their diets, most bacteria must synthesize it de novo, as they cannot absorb it intact from their surroundings...

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. 

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