Lincosamides

[4] Biosynthesis of lincosamides occurs through a biphasic pathway, in which propylproline and methylthiolincosamide are independently synthesized immediately before condensation of the two precursor molecules.

In a mechanism similar to macrolides and streptogramin B, lincosamides bind close to the peptidyl transferase center on the 23S portion of the 50S subunit of bacterial ribosomes.

Under the influence of high resolution X-ray, structures of clindamycin and ribosomal subunits from bacterium have previously revealed exclusive binding to the 23S segment of the peptidyl transferase cavity.

Soon after the emergence of clinical lincosamide use in 1953, strains of resistant staphylococci were isolated in several countries including France, Japan and the United States.

[13] Resistant strains were characterized by expression of methyltransferases which dimethylate residues within the 23S subunit of ribosomal RNA, preventing binding of macrolides, lincosamides and streptogramins B.

[15] Several strains of bacteria which are highly resistant to macrolide treatment have been isolated and found to possess mutations at the transferase binding pocket in the 23S ribosomal subunit.

Macrolide-resistant Streptococcus pneumoniae isolated from hospital patients in Eastern Europe and North America were found to contain mutations in either 23S or other ribosomal protein genes.

[16] Gram-negative bacteria harbor genes encoding for molecular pumps which can contribute to resistance of hydrophobic compounds like macrolides and lincosamides.

Clindamycin alone has been shown to be efficacious in the treatment of acne,[24] toxic shock syndrome[25] and malaria,[26] and to decrease the risk of premature births in women with bacterial vaginosis.

Pseudomembranous enterocolitis resulting from clindamycin-induced disruption of gastrointestinal flora can be a lethal adverse event observed in several species when used in the veterinary clinic, particularly in horses.

[30] The first lincosamide compound discovered was lincomycin, isolated from Streptomyces lincolnensis in a soil sample from Lincoln, Nebraska (hence the bacterial name).

Lincomycin
Clindamycin (note chlorine atom compared to lincomycin)
Chemical synthesis of lincomycin A. Propylproline and methylthio-lincosamide are joined via a condensation reaction. This reaction forms N -demethyllincomycin A, which is methylated via S -adenosylmethionine to form lincomycin A.
Clindamycin, a commonly used lincosamide, binds the 50s subunit and causes steric hindrance which inhibits the transfer of amino acids to the longer polypeptide chain. [ 12 ]
Example of drug efflux through a pump belonging to the resistance-nodulation-cell division superfamily, the type of pump primarily responsible for lincosamide efflux.
Endoscopic image of pseudomembranous enterocollitis within the intestinal tract. Disruption of gastrointestinal flora and subsequent observed pathology can result from clindamycin administration.