﻿566 
  ANNUAL 
  REPORT 
  SMITHSONIAN 
  INSTITUTION, 
  1943 
  

  

  or 
  vitamins, 
  for 
  various 
  bacteria 
  is 
  p-aminobenzoic 
  acid 
  which 
  must 
  

   be 
  available 
  if 
  these 
  organisms 
  are 
  to 
  multiply 
  in 
  the 
  infected 
  animal. 
  

   The 
  utilization 
  of 
  this 
  substance 
  is 
  effected 
  through 
  the 
  agency 
  of 
  

   certain 
  enzymes 
  of 
  the 
  bacterial 
  cell. 
  Now 
  it 
  has 
  long 
  been 
  known 
  

   that 
  compounds 
  structurally 
  similar 
  to 
  those 
  upon 
  which 
  the 
  enzyme 
  

   normally 
  acts 
  may, 
  if 
  furnished 
  together 
  with 
  the 
  natural 
  substrate, 
  

   compete 
  with 
  it 
  for 
  the 
  enzyme 
  and 
  so 
  prevent 
  or 
  retard 
  the 
  normal 
  

   interaction. 
  In 
  just 
  this 
  way 
  the 
  utilization 
  of 
  p-aminobenzoic 
  acid 
  

   is 
  prevented 
  by 
  the 
  presence 
  of 
  the 
  chemically 
  related 
  sulfanilamide. 
  

   This 
  mechanism 
  was 
  not 
  at 
  all 
  understood 
  at 
  the 
  time 
  of 
  the 
  intro- 
  

   duction 
  of 
  sulfanilamide, 
  of 
  course, 
  but 
  it 
  appears 
  now 
  that 
  a 
  similar 
  

   principle 
  may 
  obtain 
  in 
  the 
  action 
  of 
  many, 
  though 
  not 
  all, 
  other 
  

   antibacterial 
  agents. 
  This 
  has 
  been 
  indicated 
  above 
  in 
  the 
  discussion 
  

   of 
  gramicidin, 
  one 
  of 
  the 
  few 
  microbial 
  agents 
  of 
  which, 
  to 
  date, 
  

   the 
  mode 
  of 
  action 
  is 
  at 
  all 
  understood. 
  In 
  this 
  connection 
  it 
  may 
  

   be 
  significant 
  also 
  that 
  a-hydroxyphenazine, 
  one 
  of 
  the 
  antibacterial 
  

   substances 
  produced 
  by 
  Pseudomonas 
  aeruginosa, 
  bears 
  a 
  certain 
  

   structural 
  similarity 
  to 
  riboflavin, 
  or 
  vitamin 
  B 
  2 
  . 
  

  

  The 
  inhibitory 
  effect 
  of 
  notatin, 
  on 
  the 
  other 
  hand, 
  appears 
  to 
  be 
  

   of 
  a 
  quite 
  different 
  nature, 
  being 
  occasioned 
  by 
  the 
  toxicity 
  of 
  the 
  

   hydrogen 
  peroxide 
  which 
  it 
  produces. 
  

  

  An 
  interesting 
  phase 
  of 
  the 
  mechanism 
  of 
  action 
  is 
  the 
  high 
  degree 
  

   of 
  specificity 
  for 
  certain 
  micro-organisms 
  exhibited 
  by 
  many 
  of 
  the 
  

   agents. 
  In 
  a 
  number 
  of 
  cases 
  this 
  specificity 
  appears 
  to 
  parallel 
  

   closely 
  the 
  Gram-staining 
  reaction. 
  Better 
  understanding 
  of 
  the 
  

   factors 
  responsible 
  for 
  bacterial 
  differences 
  in 
  this 
  staining 
  technic 
  

   may 
  conceivably 
  aid 
  in 
  the 
  further 
  development 
  of 
  other 
  specific 
  

   chemical 
  inhibitors. 
  

  

  It 
  seems 
  axiomatic 
  now 
  that 
  a 
  practical 
  chemotherapeutic 
  agent 
  

   must 
  be 
  inhibitory 
  toward 
  the 
  pathogen, 
  not 
  merely 
  in 
  vitro 
  but 
  

   under 
  the 
  conditions 
  existing 
  in 
  the 
  diseased 
  host, 
  and 
  that 
  it 
  should 
  

   exert 
  a 
  minimal 
  deleterious 
  effect 
  on 
  the 
  latter. 
  There 
  are, 
  in 
  addi- 
  

   tion, 
  a 
  number 
  of 
  subsidiary 
  desiderata, 
  such 
  as 
  convenient 
  mode 
  of 
  

   administration, 
  stability 
  in 
  the 
  body 
  and 
  during 
  storage, 
  etc. 
  In 
  the 
  

   past 
  these 
  requirements 
  have 
  not 
  always 
  been 
  fully 
  appreciated. 
  

   Before 
  the 
  etiology 
  of 
  infectious 
  disease 
  was 
  understood, 
  the 
  search 
  

   for 
  chemical 
  specifics 
  was 
  of 
  necessity 
  a 
  trial 
  and 
  error 
  affair. 
  With 
  

   the 
  recognition 
  of 
  pathogenic 
  micro-organisms 
  came 
  the 
  idea 
  of 
  

   chemical 
  bullets 
  fatal 
  to 
  the 
  parasite 
  but 
  not 
  the 
  host. 
  Knowledge 
  

   of 
  the 
  chemical 
  structure 
  of 
  such 
  bullets 
  furnished 
  guiding 
  principles, 
  

   according 
  to 
  which 
  better 
  ammunition 
  could 
  be 
  molded. 
  Increased 
  

   knowledge 
  of 
  the 
  precise 
  means 
  by 
  which 
  inhibition 
  of 
  bacterial 
  

   activities 
  can 
  be 
  effected 
  and 
  of 
  bacterial 
  physiology 
  in 
  general 
  may 
  

   be 
  expected 
  to 
  lead 
  to 
  a 
  new 
  phase 
  in 
  the 
  development 
  of 
  chemo- 
  

  

  