10-1 Controling the growth of microbes

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The control of microbial growth is necessary in many practical situations, and some of the most important advances in medicine, agriculture and food science have been made by applications of microbiological knowledge. Control can be effected either by killing organisms or by inhibiting their growth. The killing of organisms can be brought about by use of heat, radiation and chemicals. Methods for inhibiting growth may involve drying (recall that all organisms require water for growth), low temperatures and chemicals. An antimicrobial agent is a chemical which kills or inhibits the growth of microorganisms. Such a substance may be either a synthetic chemical or a natural product.

Agents which kill organisms are called cidal agents, with a prefix indicating the kind of organisms killed. Thus, we have bactericidal and fungicidal agents. The cidal agents may be divided conveniently into two groups: antiseptics and disinfectants. An antiseptic is sufficiently harmless so that it can be applied to the skin or mucous membranes, although it is not necessarily safe enough to be taken internally. A disinfectant is an agent that kills microorganisms (but not necessarily their spores) and is distinguishable from an antiseptic by the fact that it is not safe for application to living tissue. Disinfectants are restricted to inanimate objects such as tables, floors and dishes.

Chemicals which do not kill but only inhibit growth are called static agents, and they may be bacteriostatic and/or fungistatic. The distinction between cidal and static is somewhat arbitrary, since an agent that is cidal at high concentrations may be only static at low concentrations. To be effective, a static agent must be present continuously with the product, and if it is removed or its activity neutralized, the organisms present in the product will initiate growth. Static agents are often used as food preservatives, and since they must be present continuously to be effective, they remain in the food when eaten and hence must be nontoxic. Many drugs used in the treatment of microbial infections are static agents and must be kept present for a period of time long enough for body defenses to destroy the infecting agent. Such drugs obviously must be nontoxic to the body.

Thousands of antibiotics, another class of control compounds, have been discovered, but relatively few have become valuable in medicine. These few have found widespread and revolutionary use in the treatment of many infectious diseases. Many antibiotics commercially available come from various species of the genus Streptomyces. Examples include streptomycin, tetracycline, erythromycin and chloramphenicol. A few species of Bacillus produce antibiotics, e.g., polymyxin from B. polymyxa. The first commercially-available antibiotic, penicillin, comes from the mold, Penicillium chrysogenum. Much of the pioneering work concerning the production of this antibiotic was done by the late Dr. Kenneth Raper of this department.

Organisms sensitive (susceptible) to an antibiotic or similar compound are affected by the agent at a target site, a specific structure or essential biochemical reaction in the cell. As an example, you learned that Staphylococcus epidermidis is sensitive to streptomycin which inhibits cells at the ribosomes, stopping translation (protein synthesis). Mutant cells may arise in the population which have resistant ribosomes, and such a cell is then resistant to streptomycin. Indeed, many species of bacteria are naturally resistant to streptomycin and would never be affected by it. Target sites hit by other agents include cell membrane synthesis (polymyxin), cell wall synthesis (penicillin) and DNA replication (nalidixic acid). Sulfadiazine, like other sulfonamides, can substitute for a reactant in the synthesis of tetrahydrofolate, an essential biochemical process, and thus growth of the organism can be halted after several generations.

Gram-positive bacteria are usually more sensitive to antibiotics than are gram-negative bacteria, although, conversely, some antibiotics act only on gram-negative cells. An antibiotic which acts upon a wide variety of gram-positive and negative bacteria is called a broad-spectrum antibiotic. In general, such an antibiotic will find wider medical usage than one which is narrow-spectrum, although the latter may be quite valuable for the control of specific disease-causing organisms. The physician needs and utilizes a wide variety of antibiotics and must select carefully the one that is needed for a particular patient with a particular kind of infection.

Unfortunately, the use of some antibiotics has allowed for the enrichment of antibiotic-resistant mutant bacteria in the human population. An antibiotic must always be tested on the infectious agent in such a way that it can be found to be truly inhibitory at the target site of that organism. Any indication that resistant mutants will arise will necessitate the consideration of another antibiotic! The chapter on the control of microorganisms in the microbiology textbook has more information.

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