Resistance to lincosamides

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. 

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. 

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... 

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. 

The spread of multiple drug resistance has serious implications because of its persistence. Plasmid-mediated resistance to lincosamides and macrolides is the result of methylation of the shared receptor site on the 50S subunit of the bacterial ribosome. Plasmid transferable resistance has recently been reported for fluoroquinolones (Martinez-Martinez et ah, 1998). 

Macrolides inhibit growth of bacteria by inhibiting protein synthesis on ribosomes (17,415,416). Bacterial resistance to macrolides is often accompanied by cross-resistance to lincosamide and streptogramin B antibiotics (MLS-resistance), which can be either inducible or constitutive (417). 14-Membered macrolides generally induce resistance to themselves, whereas 16-membered macrolides do not consequendy, one advantage of the latter is their activity against bacteria which are inducibly resistant to erythromycin. Both 14- and 16-membered macrolides lack activity against constitutively resistant strains (387,388). 

Brisson-Noel, A., and Courvalin, P. (1986). Nucleotide sequence of gene linA encoding resistance to lincosamide in Streptococcus haemolyticus. Gene 43, 247-253. 

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

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... 

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. 

Most of the data on rokitamycin have been published in Japanese and Italian journals. As a propionyl ester of leucomycin, rokitamycin has an antimicrobial spectrum similar to that of erythromycin, it is especially potent against L. pneumophila, M. pneumoniae, and Chlamydia. Like other 16-membered macrolides, it is active against bacteria that are inducibly resistant to erythromycin but inactive against strains that are constitutively resistant to macrolide-lincosamide-streptogramin B antibiotics. 

In recent years, new resistance phenotypes (macrolide and streptogramin B antibiotics [MS] or partial macrolide and streptogramin B antibiotics [PMS], and macrolide antibiotics [M]) have been observed in elinical isolates of staphylococci and streptococci. Ross et al. [61, 125, 193] and Goldman and Capobianco [126] reported that MS-resistant strains of Staphylococcus epidermidis were resistant to 14- or 15-membered-ring macrolides and streptogramin B, but were susceptible to 16-membered-ring macrolide and lincosamide antibiotics. 

The molecular biological mode of action of macrolide antibiotics and the biochemical and genetic mechanism of resistance to macrolide, lincosamide, and type B streptogramin antibiotics were reviewed in this chapter. 

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