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Chapter 6 : Macrolide, Lincosamide, Streptogramin, Ketolide, and Oxazolidinone Resistance

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Macrolide, Lincosamide, Streptogramin, Ketolide, and Oxazolidinone Resistance, Page 1 of 2

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Abstract:

Macrolides, lincosamides, streptogramins, ketolides, and oxazolidinones (MLSKO), though chemically distinct, share overlapping binding sites on the 50S subunit of the ribosome. Bacteria acquire resistance to one or more of these antibiotics by the acquisition of a gene(s) or with certain mutations. The ketolides are macrolide derivatives that have recently become available for human therapy. The lincosamides are a distinct group of antibiotics that are structurally unrelated to macrolides. The streptogramin B component shares an overlapping ribosomal binding site, on the 50S ribosomal subunit, with the macrolides and lincosamides and is impacted by methylation at A2058 ( numbering). The MLSKO antibiotics inhibit protein synthesis by binding to the 50S ribosomal subunit and blocking peptide bond formation and/or translation. The binding of 14-, 15-, and 16-membered macrolides, clindamycin, and two ketolides has been described in this chapter. The genes are regulated at the translation step. These genes confer resistance to macrolides and lincosamides but not to streptogramin B. Mutations associated with resistance to macrolides, ketolides, streptogramins, or oxazolidinones have been described in the chapter. However, with the addition of the newer macrolides, streptogramins, ketolides, and oxazolidinones, use of this group of antibiotics has increased, and today they are important in the treatment of a variety of infectious diseases in both community and hospital environments. Ketolide resistance in streptococci and oxazolidinone resistance in gram-positive enterococci or staphylococci are surfacing with increased therapeutic use.

Citation: Roberts M, Sutcliffe J. 2005. Macrolide, Lincosamide, Streptogramin, Ketolide, and Oxazolidinone Resistance, p 66-84. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch6

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Mobile Genetic Elements
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Antibacterial Agents
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Major Facilitator Superfamily
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Amino Acid Addition
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Figure 1a

Structures of the various MLSKO antibiotics. (.)

Citation: Roberts M, Sutcliffe J. 2005. Macrolide, Lincosamide, Streptogramin, Ketolide, and Oxazolidinone Resistance, p 66-84. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch6
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Image of Figure 1b
Figure 1b

Structures of the various MLSKO antibiotics. (.)

Citation: Roberts M, Sutcliffe J. 2005. Macrolide, Lincosamide, Streptogramin, Ketolide, and Oxazolidinone Resistance, p 66-84. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch6
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Tables

Generic image for table
Table 1

Mechanism of resistance

http://faculty.washington.edu/marilynr.

See reference 27.

See reference 80a.

See reference 46a.

Citation: Roberts M, Sutcliffe J. 2005. Macrolide, Lincosamide, Streptogramin, Ketolide, and Oxazolidinone Resistance, p 66-84. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch6
Generic image for table
Table 2

Bacteria carrying specific resistance genes

The erm(B) gene is the only rRNA methylase screened for in enteric gram-negative bacteria. Thus the distribution of other erm genes in aerobic gram-negative genera is most likely underrepresented in the table.

http://faculty.washington.edu/marilynr. This website is updated yearly.

Macrolide-lincosamide-streptogramin B resistance.

Resistance to either lincomycin, oleandomycin, spriamycin, tylosin, or streptogramin A or both erythromycin and streptogramin B.

Reference 153, the msr(D) gene may not be functional.

Resistance to either lincomycin or erythromycin.

The (A) gene produces a truncated protein which is missing N-terminal amino acids and most likely is not functional.

Resistance to erythromycin.

Resistance to streptogramin B.

Resistance to either lincomycin or streptogramin A.

Resistance to macrolides.

Citation: Roberts M, Sutcliffe J. 2005. Macrolide, Lincosamide, Streptogramin, Ketolide, and Oxazolidinone Resistance, p 66-84. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch6
Generic image for table
Table 3

Species identified with 23S rRNA, L4, and/or L22 ribosomal protein mutations conferring resistance to MLSKO antibiotics

Data from references , and .

At either the A2058 or A2059 position with numbering

Citation: Roberts M, Sutcliffe J. 2005. Macrolide, Lincosamide, Streptogramin, Ketolide, and Oxazolidinone Resistance, p 66-84. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch6
Generic image for table
Table 4

MLSKO antibiotic resistance genes linked to other antibiotic resistance genes or elements

This table is meant to illustrate the diversity of the genes and elements that the MLS genes have been linked to ( ).

The (A) and the (D) genes appear to be together in all clinical isolates examined from any genera; however, when cloned separately into naive strains of both conferred macrolide resistance alone ( ).

Integron codes for an integrase (IntI) that mediates recombination between a recombination site (attI) and a target recombination sequence 59-base element.).

Required for high level erythromycin resistance in .

Citation: Roberts M, Sutcliffe J. 2005. Macrolide, Lincosamide, Streptogramin, Ketolide, and Oxazolidinone Resistance, p 66-84. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch6

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