Accumulation, macrolide, decreased

The decreased accumulation of macrolide antibiotics in resistant gram-positive bacteria is discussed in detail in Section III. 

In contrast, in S. aureus carrying the erm gene responsible for ML8 resistance—the so-called A ,/V -dimethylation of a specific adenine residue in 23rRNA, drag accumulation is easily decreased to about one-tenth of that in susceptible cells when they are washed five times with chilled salt solution. That is why a macrolide antibiotic present in their cells can hardly bind to their 508 ribosomes even at the highest permissible concentration of the drag [6, 54]. 

Macrolide Resistance Due to Decreased Accumulation (Enhanced Efflux) in Staphylococci and Streptococci... 

Two types of resistance, M type and MS or PMS type, due to decreased macrolide accumulation, have been recognized in clinical isolates of staphylocoeci and streptococci (Table III). 

Proteins MefA, MefE, and MreA are thought to be driven by PMF, because decreased macrolide accumulation by their mediating was increased to the same accumulation level as that in susceptible streptococci in the presence of some uncouplers, such as carbonylcyanide-m-chlorophenylhydrazone (CCCP), 2,4-dinitrophenol (DNP), and arsenate. 

Enzymatic mechanisms that inactivate macrolides appear to be rare among clinical isolates compared with mechanisms of phenotypically decreased macrolide accumulation due to either a target site alteration (i.e., ribosome modification) or enhanced macrolide efflux. 

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. 

The phenotypically decreased accumulation of macrolide antibiotics is usually observed in not only MLS-resistant but also PMS-resistant S. aureus, and probably in other clinical isolates. 

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