﻿CHEMOTHERAPEUTIC 
  AGENTS 
  — 
  WEINTRAUB 
  551 
  

  

  peptides 
  constructed 
  in 
  a 
  fashion 
  somewhat 
  similar 
  to 
  the 
  common 
  

   proteins 
  but 
  differing 
  from 
  these 
  in 
  a 
  number 
  of 
  important 
  details. 
  

   The 
  precise 
  empirical 
  formulas 
  are 
  not 
  yet 
  known; 
  gramicidin 
  ap- 
  

   pears 
  to 
  be 
  approximately 
  C 
  7 
  4H 
  106 
  N 
  15 
  Oi3, 
  while 
  tyrocidine 
  may 
  be 
  

   C 
  l26 
  H 
  166 
  N 
  2 
  6026 
  or 
  possibly 
  a 
  unit 
  one-half 
  this 
  size. 
  

  

  Although 
  both 
  gramicidin 
  and 
  tyrocidine 
  possess 
  antibacterial 
  

   activity, 
  and 
  despite 
  their 
  chemical 
  similarity, 
  their 
  biological 
  proper- 
  

   ties 
  are 
  quite 
  different. 
  The 
  action 
  of 
  gramicidin 
  is 
  primarily 
  bac- 
  

   teriostatic; 
  the 
  great 
  majority 
  of 
  Gram-positive 
  species 
  tested 
  are 
  

   highly 
  susceptible, 
  whereas 
  the 
  Gram-negative 
  bacilli 
  are 
  entirely 
  in- 
  

   sensitive. 
  Tyrocidine, 
  on 
  the 
  contrary, 
  exerts 
  a 
  marked 
  bactericidal 
  

   effect 
  upon 
  both 
  Gram-negative 
  and 
  Gram-positive 
  organisms. 
  

  

  Tyrocidine 
  causes 
  the 
  lysis 
  of 
  a 
  number 
  of 
  bacterial 
  species, 
  whereas 
  

   gramicidin 
  has 
  no 
  such 
  effect. 
  It 
  appears 
  likely, 
  however, 
  that 
  the 
  

   dissolution 
  is 
  not 
  a 
  direct 
  result 
  of 
  the 
  action 
  of 
  tyrocidine 
  but 
  rather 
  

   is 
  a 
  secondary 
  self-digestion 
  brought 
  about 
  by 
  the 
  bacterial 
  enzymes 
  

   after 
  the 
  cells 
  have 
  been 
  killed 
  by 
  the 
  bactericidal 
  agent. 
  Gramicidin, 
  

   on 
  the 
  other 
  hand, 
  does 
  not 
  occasion 
  the 
  lysis 
  of 
  even 
  the 
  most 
  sus- 
  

   ceptible 
  bacteria. 
  

  

  Both 
  agents 
  cause 
  the 
  dissolution 
  of 
  red 
  blood 
  cells, 
  but 
  the 
  

   mechanism 
  of 
  the 
  action 
  is 
  quite 
  different 
  for 
  the 
  two 
  substances. 
  

   The 
  hemolytic 
  effect 
  of 
  gramicidin 
  becomes 
  apparent 
  only 
  after 
  several 
  

   hours, 
  although 
  it 
  may 
  be 
  elicited 
  by 
  very 
  small 
  amounts 
  of 
  the 
  

   agent. 
  The 
  action 
  is 
  completely 
  inhibited 
  by 
  the 
  presence 
  of 
  glucose 
  

   or 
  certain 
  other 
  carbohydrates. 
  Tyrocidine, 
  contrariwise, 
  produces 
  

   immediate 
  hemolysis 
  irrespective 
  of 
  the 
  presence 
  of 
  glucose 
  ; 
  its 
  action, 
  

   however, 
  is 
  inhibited 
  by 
  blood 
  serum 
  to 
  a 
  much 
  greater 
  degree 
  than 
  

   is 
  that 
  of 
  gramicidin. 
  The 
  hemolytic 
  activity 
  of 
  gramicidin 
  and 
  

   tyrocidine 
  seems 
  to 
  be 
  influenced 
  by 
  factors 
  which 
  are 
  not 
  yet 
  entirely 
  

   appreciated, 
  as 
  conflicting 
  results 
  have 
  been 
  obtained 
  by 
  different 
  

   workers. 
  

  

  The 
  mechanism 
  of 
  the 
  action 
  of 
  gramicidin 
  and 
  tyrocidine 
  on 
  cells 
  

   has 
  been 
  studied 
  to 
  a 
  greater 
  extent 
  than 
  that 
  of 
  most 
  of 
  the 
  other 
  

   natural 
  antimicrobial 
  substances. 
  Tyrocidine 
  acts 
  much 
  like 
  a 
  gen- 
  

   eral 
  protoplasmic 
  poison. 
  It 
  induces 
  an 
  immediate 
  and 
  irreversible 
  

   cessation 
  of 
  metabolic 
  activity 
  which, 
  in 
  many 
  cases, 
  is 
  followed 
  by 
  

   cellular 
  disintegration. 
  Its 
  action 
  in 
  these 
  respects 
  resembles 
  closely 
  

   that 
  of 
  certain 
  detergents, 
  as 
  do 
  also 
  its 
  behavior 
  as 
  a 
  protein 
  pre- 
  

   cipitant 
  and 
  its 
  surface 
  activity. 
  

  

  While 
  gramicidin 
  has 
  many 
  of 
  the 
  physical 
  and 
  biological 
  proper- 
  

   ties 
  of 
  detergents, 
  there 
  is 
  considerable 
  evidence 
  that 
  its 
  antibacterial 
  

   activity 
  is 
  not 
  due 
  to 
  these 
  characteristics 
  alone, 
  although 
  its 
  tendency 
  

   to 
  concentrate 
  at 
  the 
  bacterial 
  surface 
  well 
  might 
  enhance 
  the 
  action 
  

   due 
  to 
  other 
  properties. 
  The 
  effects 
  produced 
  by 
  gramicidin 
  are 
  

  

  