Distribution of macrolide, lincosamide, streptogramin, ketolide and oxazolidinone (MLSKO) resistance genes in Gram-negative bacteria.
A number of different mechanisms of macrolide resistance have been described in Gram-negative bacteria. These include 16 acquired genes (esterases, phosphorylases, rRNA methylases, and effluxes) and include those thought to be unique to Gram-negative bacteria (both esterases and two of the phosphorylases) and those shared with Gram-positive bacteria (one phosphorylase) and those primarily of Gram-positive origin (rRNA methylases and efflux genes). In addition, mutations, which modify the 23S rRNA, ribosomal proteins L4 and/or L22, and/or changes in expression of innate efflux systems which occur by missense, deletion and/or insertion events have been described in five Gram-negative groups, while an innate transferase conferring resistance to streptogramin A has been identified in a sixth genus. However, the amount of information on both acquisition and mutations leading to macrolide, lincosamides, streptogramins, ketolides and oxazolidinones (MLSKO) resistance is limited. As a consequence this review likely underestimates the true distribution of acquired genes and mutations in Gram-negative bacteria. As use of these drugs increases, it is likely that interaction between members of the MLSKO antibiotic family and Gram-negative bacteria will continue to change resistance to these antibiotics; by mutations of existing genes as well as by acquisition and perhaps mutations of acquired resistant genes in these organisms and more work needs to be done to get a clearer picture of what is in the Gram-negative population now, such that changes can be monitored.
Roberts
Marilyn C
MC
Department of Pathobiology, Box 357238, School of Public Health and Community Medicine, University of Washington, Seattle WA, 98195, USA. marilynr@u.washington.edu
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000235:genetics*; D055231:Lincosamides; D018942:Macrolides / Q000494:pharmacology*; D009154:Mutation / Q000235:genetics / Q000502:physiology; D023303:Oxazolidinones / Q000494:pharmacology*; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics; D025361:Streptogramins / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D055231:Lincosamides; D018942:Macrolides; D023303:Oxazolidinones; D012335:RNA, Ribosomal; D025361:Streptogramins