BIOLOGY Volume 2 - A Guide to General Biology - 2004

15. HEALTH AND DISEASE

15.4. Disinfectants, Sterilization, and Antiseptics

15.4.3. Antibiotics

Antibiotics were originally defined as substances produced by microorganisms (mainly Bacteria, and more rarely Fungi) that are capable of killing or inhibiting the growth of other microorganisms (Section 12.10.2). Over time, The Scope of this definition has broadened. Antibiotics are now generally understood to include not only antimicrobial drugs but also their synthetic derivatives. Furthermore, it has been discovered that antimicrobial substances are also produced by plants and animals, including humans.

Antibiotics are classified as biocidal or biostatic. Biostatics, such as chloramphenicol, erythromycin, and Tetracyclines, inhibit microbial GROWTH AND REPRODUCTION without killing them. If such agents are removed from the environment, Microbial growth may resume. Biocides, such as streptomycin, Cephalosporins, Penicillins, and polymyxins, kill microorganisms. When the concentration of the substance decreases, its biocidal action may shift to a biostatic one. Depending on The Nature of their effect on bacteria, antibiotics are referred to as bactericidal or bacteriostatic, respectively.

In 1928, Sir Alexander Fleming noticed that a mold (a fungus of the genus Penicillium) contaminating an Agar plate cultured with Staphylococcus aureus inhibited the growth of this bacterium. Later, the antimicrobial substance produced by this fungus was isolated and named penicillin. The discovery of penicillin played a crucial role during World War II; thanks to this antibiotic, many soldiers were saved from wound infections (Section 12.11.1).

The first bactericidal drugs (not strictly antibiotics in the traditional sense) were synthesized even before the war. For instance, in 1935 German physicians discovered that a red dye called Prontosil cured Infections caused by hemolytic streptococci. The active component of this dye was named sulfanilamide. It belongs to the chemical group of sulfonamides, as do many subsequently synthesized antimicrobial substances with similar chemical structures (such as norsulfazol, sulfadimezin, etc.). They are used to treat streptococcal and certain Staphylococcal infections, meningitis, Pneumonia, Urinary Tract infections, and Sexually Transmitted Diseases, particularly Gonorrhea.

Sulfonamides are bacteriostatic agents. By their MECHANISM OF ACTION, they are Competitive Inhibitors of certain microbial Enzymes (see Section 4.4.1). When bacterial multiplication is halted by Chemotherapy, the body's own defense systems gradually destroy them. Bactericidal antibiotics, introduced after Fleming's discovery, act upon pathogenic microorganisms more strongly and rapidly. They are especially effective in infections of the Central Nervous system or joint cavities, i.e., in cases where the body's defense systems are virtually powerless.

Mechanism of Action of Antibiotics

Antibiotics affect microorganisms in various ways, but as a rule, they disrupt metabolic processes that occur in microbes while being absent in their hosts. For example, the enzyme complex responsible for Protein Synthesis in bacteria differs somewhat from the corresponding machinery in eukaryotes; There are also differences in The Structure of their Cell walls. It turns out that these very structures serve as the primary targets for antibiotic action. Table 15.11 provides relevant Examples.

Class="center">Table 15.11. Most common antibiotics

Broad-spectrum antibiotics are effective against many species of pathogenic microbes from various groups. For example, tetracyclines and chloramphenicol target almost all common Gram-positive and Gram-negative bacteria. Narrow-spectrum antibiotics are effective against only a specific group of microbes. For instance, penicillins are ineffective against most Gram-negative bacteria, including such an important pathogen as the CAUSATIVE AGENT OF tuberculosis.

Resistance

One of the most serious medical challenges is The Development of Antibiotic Resistance in pathogenic bacteria. The probability of strains emerging that are resistant to a particular drug correlates with the scale of its usage, as well as with patients' dietary regimens. It also depends on the Chemical Nature of the antibiotic.

Resistance mechanisms vary. For instance, a microbe may lack the metabolic pathway targeted by the antibiotic. Thus, Gram-negative bacteria exhibit natural resistance to penicillin because their cell wall synthesis does not involve the Chemical Reactions inhibited by this antibiotic. In other cases, resistance is due to the inability of the antibiotic to penetrate the microbial cell. For example, tetracycline resistance can arise from the synthesis of a protein that is integrated into the bacterial outer membrane and "pumps out" the antibiotic, preventing it from reaching a concentration that would disrupt metabolism.

Sometimes microorganisms contain enzymes that degrade antibiotics. The best-known example is penicillinases, which hydrolyze penicillins and cephalosporins. Consequently, such microorganisms will be resistant to these antibiotics. However, due to structural modifications, certain semi-synthetic penicillins are resistant to such Hydrolysis, making it possible to overcome this type of resistance.

Resistance to an antibiotic can also be caused by alterations in the Chemical Structure of the bacterial cell. For example, a substitution of a single amino acid in a bacterial ribosomal protein makes it impossible for the antibiotic to bind to the ribosome—a binding required to suppress bacterial PROTEIN SYNTHESIS AND thus destroy The Cell. Thus, such a minor change in the bacterium's chemical structure renders it invulnerable to the antibiotic.

From a genetic standpoint, an Organism can acquire resistance in two ways.

1. Mutation. Random, or spontaneous, Mutations are relatively rare; however, microbial populations of any species are so massive that the likelihood of at least a few resistant cells appearing is entirely realistic. The application of an antibiotic grants them a selective advantage over sensitive relatives, leading to the natural Selection of resistant clones and their transformation into the dominant form.

2. Transmission of resistance. Genes conferring resistance can be passed from one bacterium to another through various pathways. The most common mechanism is conjugation, a primitive form of sexual reproduction described in Section 2.3.3. Resistance genes are frequently located on Plasmids (small circular DNA fragments). They are capable of replication, and copies of them can be transferred during conjugation to sensitive bacteria, which subsequently become resistant to the given antibiotic. The exchange of Genetic information between microbes (even of different species) can lead to so-called multiple drug resistance, i.e., making a pathogen invulnerable to several drugs simultaneously. A major problem in many hospitals today is infections caused by multi-drug resistant strains of Staphylococcus aureus.

Antibiotics in Human Food

Antibiotics are widely used in agriculture. They are employed to treat mastitis in cows and other infections in livestock and crops, incorporated into the feed of young animals to stimulate growth, and added to feedstuffs as preservatives. As a result, trace amounts of antibiotics end up in human food and may pose a health hazard. This risk is associated with the direct Toxic effects of these drugs, allergic reactions to them, and the development of resistance in pathogens that infect humans. Infections caused by resistant microorganisms can no longer be successfully treated with conventional antibiotics.

In recent years, attempts have been made to monitor the presence of antibiotics in food products. According current regulations, at least 48 hours must elapse between the last administration of such drugs to livestock and their slaughter.