Purine and Pyrimidine Analogues and the Mucopeptide 

 Biosynthesis in Staphylococci 



H. J, Rogers and H. R. Perkins 



National Institute for Medical Research, 

 Mill Hill, London, England 



Both Gram positive and Gram negative micro-organisms are sur- 

 rounded by a rigid layer or cell wall. The outer surface of this material is 

 distinguished with some difficulty from capsular material; its inner 

 surface is applied closely to the "membrane" which, among many other 

 functions, controls the passage of smaller metabolites into and out of the 

 cell. If this rigid outer layer of insoluble material, the so-called cell wall, 

 be removed, the remainder of the cell will only remain whole, as a spherical 

 protoplast, providing high concentrations of material which cannot readily 

 penetrate the "membrane" are present in the external medium. If this 

 condition is not met the cell bursts because the internal concentration of 

 solutes in the cell produces an osmotic pressure equivalent to about twenty 

 atmospheres for cocci and about ten atmospheres for some rod forms, too 

 great a force for the weak membrane, unsupported by the cell wall, to 

 withstand. A large proportion of this insoluble cell wall material, in Gram 

 positive micro-organisms, consists of a limited number of amino acids, 

 usually two amino sugars and in some species a few hexoses. Such com- 

 plexes, we have suggested, should be called mucopeptides [i]. In the 

 staphylococci, these mucopeptides contain only alanine, lysine, glycine 

 and glutamic acid together with glucosamine and muramic acid (3-O- 

 carboxyethylglucosamine) ; most of each of the amino sugars exists as the 

 N-acetyl derivative ; some of the alanine and probably all the glutamic acid 

 are in the d configuration [2, 3]. Apart from mucopeptide the wall material 

 of staphylococci also contains 40-60",, of a teichoic acid [4, 5] consisting 

 of a polymer of ribitolphosphate with N-acetylglucosamine and D-alanine 

 attached. In some strains it has been suggested that this material may 

 account for up to 70-80*^ ,j of the weight of the isolated wall material [6]. 



The biosynthesis of mucopeptide is inhibited by penicillin, bacitracin 

 and oxamycin [7, 8, 9] but not by chloramphenicol [10, 8]. It seems prob- 

 able that the inhibition of this process represents a primary site of action 

 of the former group of antibiotics. During inhibition caused by penicillin 



