Mechanisms of Resistance

Bacteria can resist the effects of antimicrobials through a variety of mechanisms. In some cases this resistance is innate, but in many others it is acquired. Figure 21.14 depicts the most common mechanisms of acquired antimicrobial resistance.

Drug-Inactivating Enzymes

Some organisms produce enzymes that chemically modify a specific drug in such a way as to render it ineffective. Recall that bacteria that synthesize the enzyme penicillinase are resistant to the bactericidal effects of penicillin. As another example, the enzyme chloramphenicol acetyltransferase chemically alters the antibiotic chloramphenicol.

Alteration in the Target Molecule

An antimicrobial drug generally recognizes and binds to a specific target molecule in a bacterium, interfering with its function. Minor structural changes in the target, which result from mutation, can prevent the drug from binding. For example, alterations in the penicillin-binding proteins prevent b-lactam drugs from binding to them. Similarly, a change in the ribosomal RNA, the target for the macrolides, prevents those drugs from interfering with ribosome function.

Decreased Uptake of the Drug

The porin proteins in the outer membrane of Gram-negative bacteria selectively permit small hydrophobic molecules to enter a cell. Alterations in these proteins can therefore alter permeability and prevent certain drugs from entering the cell. By excluding entry of a drug, an organism avoids its effects. ■ porins, p. 59

Increased Elimination of the Drug

The systems that bacteria use to transport detrimental compounds out of a cell are called efflux pumps. Alterations that result in the increased expression of these pumps can increase the overall capacity of an organism to eliminate a drug, thus enabling the organism to resist higher concentrations of that drug. In addition, structural changes might influence the array of drugs that can be actively pumped out. Resistance that develops by this mechanism is particularly worrisome because it potentially enables an organism to become resistant to several drugs simultaneously. ■ efflux pumps, p. 56

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