Lincosamide resistance

Practically all anaerobic Gram-negative bacteria are resistant to lincosamides. Resistance to lincosamides can occur because of the inability of drugs to permeate through the cellular membrane of bacteria, or because of changes in the ribosomal-binding regions. 

Karlsson M, Fellstrom C, Heldtander MU, Johansson KE, Franklin A. Genetic basis of macrolide and lincosamide resistance in Brachyspira (Serpulina) hyodysenteriae. FEMS Microbiol Lett 1999 172(2) 255-60. 

Calcutt, M. J., and Cundliffe, E. (1990). Cloning of a lincosamide resistance determinant from Streptomyces caelestis, the producer of celesticetin and characterization of the resistance mechanism. J. Bacteriol. 172,4710-4714. 

Leclercq R, Courvalin P (1991) Bacterial resistance to macrolide, lincosamide, and streptogramin antibiotics by target modification. Antimicrob Agents Chemother 35 1267-1272... 

Nucleotidylation - the addition of adenylate-residues by Lnu enzymes - can also be the cause of resistance to lincosamide antibiotics in staphylococci and enterococci. A plasmid encoded ADP-ribosylating transferase (Arr-2) that leads to rifampicin resistance has been detected in various Enterobacteriaceae as well as in Pseudomonas aeruginosa. 

Macrolide, lincosamide and streptogramin B resistance (MLSb phenotype) can be linked to specific nucleotide changes within the 23 S rRNA of the large ribosomal subunit, mainly at position A2058 or neighbouring bases (E. coli numbering). This is the... 

Roberts MC, Sutcliffe J, Courvalin P et al (1999) Nomenclature for macrolide and macrolide-lincosamide-streptogramin B resistance determinats. Antimicrob Agents Chemother 43 2823-2830... 

A gene designated msrA has been identified in Staph, aureus which confers resistance to macrolides and streptogramins but not to lincosamides. Its function is unknown but the DNA sequence is homologous to genes coding for known efflux proteins. 

Horinouchi, S. and Weisblum, B. (1982) Nucleotide sequence and functional map of pE194, a plasmid that specifies inducible resistance to macrolide, lincosamide, and streptogramin type B antibodies. Journal of... 

Linalool, 3 231, 232, 233 24 477, 495, 496, 500-503, 546 acid treatment of, 24 502 epoxidation of, 24 502 main producers of, 24 501 Linalool oxide, 24 502 Linalyl, 24 479 Linalyl acetate, 24 501 Linalyl alcohol, 24 500 Linalyl esters, 3 231 Linalyl oxide, 24 503 Lincomycin, registered for use in aquaculture in Japan, 3 221t Lincosamide, bacterial resistance mechanisms, 3 32t Lindane, 13 145-147... 

Pharmacology Lincomycin and clindamycin, known collectively as lincosamides, bind exclusively to the 50 S subunit of bacterial ribosomes and suppress protein synthesis. Cross-resistance has been demonstrated between these 2 agents. Clindamycin is preferred because it is better absorbed and more potent. Pharmacokinetics Administration with food markedly impairs lincomycin (but not clindamycin) oral absorption. 

Roberts M.C., J. Sutcliffe, P. CourvaUn, L.B. Jesen, J. Rood, and H. Seppala (1999). Nomenclature for macroUde and macroUde-lincosamide-streptogramin B resistance determinants. Antimicrobial Agents and Chemotherapy 43 2823-2830. 

Macrolides inhibit growth of bacteria by inhibiting protein synthesis on ribosomes. Bacterial resistance to macrolides is often accompanied by cross-resistance to lincosamide and sireptogramin B antibiotics (MLS-resistance), which can be either inducible or constitutive. 14-Membered... 

Currently, one structure of a Irncosamide antibiotic bound to the ribosome is available for analysis [4]. like the macrolide antibiotics, drndamycin binds near the hydrophobic crevice at the entrance to the peptide exit turmel. As with the macrolide carbomycin A, dindamycin interacts not only with the hydrophobic crevice at the entrance to the peptide exit turmd, but also with the active site hydrophobic crevice. The nudeotides that surroimd the clindamydn binding site were previously implicated in binding of lincosamides based on nucleotide protection studies and on the analysis of mutations conferred by resistance (Fig. 4.4). 

Stockman BJ, Leclercq R. A new resistance gene, linB, conferring resistance to lincosamides by nucleotidylation in Enterococcus faecium HM1025. Antimicrob. Agents Chemother. 1999 43(4) 925-929. 70. 

Superinfection with resistant strains of Pseudomonas, Proteus, or staphylococci has been observed with lincosamides. Suppression of Bacteroides in the intestinal flora may be related to the prohferation of C. difficile, which is important in causing pseudomembranous colitis. Excessive growth of Candida on the skin occurred when lincomycin was applied topically (6). 

The erythromycin ribosomal methylase (erm) genes encode 23S ribosomal RNA methylases. This modification results in reduced binding of aU known macrolides, lincosamides, and streptogramin B to the ribosome (MLS resistance). Novel triazine-containing methyltransferase inhibitors that may reverse erm-mediated resistance are under development (46). 

Lina G, Quaglia A, Reverdy ME, Leclercq R, Vandenesch F, Etienne J. Distribution of genes encoding resistance to macrolides, lincosamides, and streptogramins among staphylococci. Antimicrob Agents Chemother 1999 43(5) 1062-6. 

The MLS (macrolides, lincosamides, streptogramins) group of antibiotics all inhibit protein synthesis by binding to the 50S ribosomal subunit. Resistance mechanisms specific to individual members occur but resistance to all may be conferred by a single mechanism that involves 23S rRNA. However, it is claimed that the quinupristin-dalfopristin combination does not demonstrate cross-resistance to other antibiotics within the MLS group or to other antibiotics. 

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