Efflux, antibiotic inactivation

Fig. 9.1 Schematic representation of possible mechanisms of resistance in Gram-negative and Gram-positive bacteria. 1, antibiotic-inactivating enzymes 2, antibiotic efflux proteins 3, alteration or duplication of intracellular targets 4, alteration of the cell membrane reducing antibiotic uptake 5, alterations in porins or lipopolysaccharide reducing antibiotic uptake or binding.

Drug resistance may be mediated by a variety of mechanisms, such as lack of or an alteration in a target site, lowered penetrability of the drug due to decreased permeability, or increased efflux or presence of antibiotic-inactivating enzymes (Table 28.1). 

Mechanism or resistance (1) Antibiotic inactivation (2) Efflux Does not occur Occurs by membrane transporters... 

Antibiotic resistance can be the result of several molecular mechanisms (Table 1). Some of the most important of these mechanisms include enzyme-catalyzed antibiotic inactivation or modification, altered transport such as efflux, and others such as metabolic bypass and sequestration. Each of these mechanisms requires the synthesis of associated proteins to mediate resistance. These are often highly specialized and efficient, and frequently the corresponding genes can be acquired on mobile... 

Mechanisms (1) Alteration of biocide (enzymatic inactivation) (2) Impaired uptake (3) Efflux Chromosomally mediated, but not usually relevant Applies to several biocides Not known Plasmid/Tn-mediated e.g. mercurials Less important Cationic biocides and antibiotic-resistant staphylococci... 

A number of microorganisms have evolved mechanisms to overcome the inhibitory actions of the p-lactam antibiotics. There are four major mechanisms of resistance inactivation of the p-lactam ring, alteration of PBPs, reduction of antibiotic access to PBPs, and elaboration of antibiotic efflux mechanisms. Bacterial resistance may arise from one or more than one of these mechanisms. 

Bacterial resistance to antibiotics usually results from modification of a target site, enzymatic inactivation, or reduced uptake into or increased efflux from bacterial cells. 

Plasmid- or transposon-encoded resistance to antibiotics in bacteria involves drug inactivation, target site changes, decreased antibiotic accumulation as a result of impaired uptake or enhanced efflux and duplication of the target site [6] (Table 4.11). Table 4.12 provides examples of the occurrence of transposons in bacteria and of the types of resistance encoded [6],... 

Within these two broad types of resistance, several biochemical mechanisms are known, including reduced uptake, enzymatic inactivation, target site modification and enhanced efflux. The last mentioned is assuming greater importance as additional studies are undertaken. A direct link between antibiotic and biocide resistance remains to be established. 

The resistance mechanisms are divided into three major groups (1) target modification, (2) decreased macrolide accumulation due to enhanced drug efflux, and (3) inactivation of the antibiotics. 

Resistance is widespread and often is indncible. The three main resistance mechanisms are (1) decreased accumulation of tetracycline (decreased antibiotic influx or acquisition of an energy-dependent efflux pathway) (2) production of a ribosomal protein that displaces tetracycline from its target, a protection that also may occur by mutation and (3) enzymatic inactivation of tetracyclines. Cross-resistance amongst tetracyclines depends on which mechanism is operative. Tetracycline resistance due to a ribosomal protection mechanism produces cross-resistance to doxycycUne and minocycline because the target site protected is the same for all tetracyclines. 

The mechanisms of microbial resistance to antibiotics are generally due to alterations of the antibiotic s target site, enzymatic inactivation of the antibiotic, cell impermeability, reduced cellular uptake, or increased efflux of antibiotic from cells [218]. The occurrence of these mechanisms in macrolide-resistant organisms has been reviewed [219-221]. The most widespread mechanism is modification of the macrolide s ribosomal... 

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