Index

A23187 ionophore specific for divalent ions

52 preferential binding of Ca2+ 52-3 structure 52

Acceptor in peptidoglycan biosynthesis 23

Acceptor site in protein biosynthesis 79 Acetylation

of aminoglycosides 144-5 of chloramphenicol 140-4

Acquired Immune Deficiency Syndrome current epidemic 2 drugs for 67-9, 98-9

Acridines binding to DNA 71-3 inhibition of nucleic acid synthesis by

71 medical history 71 vital staining 71

Acriflavine 3 Activation of aminoacids 78-9

inhibition by amino acid analogues and antibiotics 82-3

Activation of antimicrobial compounds by metabolism 5-6

Active transport of antimicrobial agents 109

Acyclovir activation by thymidylate kinase 67 antiviral action 67 selectivity for viral enzyme 67

Adenosine triphosphatase inhibition by A23187 53 in membrane 46 inhibition by chlorhexidine 46

Adenosine triphosphate inhibition of synthesis by antimicro­

bial agents 11 role in drug efflux 151

Adenylylation of aminoglycosides 144 Affinity for drugs, diminished in resist­

ance 6 AIDS see Acquired Immune Deficiency

Syndrome D-alanine

antagonism of antibacterial action of cycloserine 28

liberation in cross-linking of peptido­glycan 23

release in peptidoglycan cross-linking inhibited by penicillin 33

D-alanine antagonism of antibacterial action of

cycloserine 28 liberation in cross-linking of peptido­

glycan 23 release in peptidoglycan cross-linking

inhibited by penicillin 33 D-alanyl-D-alanine ligase

inhibition by cycloserine 28 in peptidoglycan biosynthesis 20

D-alanine carboxypeptidases in bacterial wall 25 inhibition by 13-lactams 34-6 in membrane preparations 34

Alanine perm eases in accumulation of D-cycloserine

Alanine racemase function 20 inhibition by cycloserine 113

Alcohols as antiseptics 45 Allylamine antifungals

clinical use 59 inhibition of fungal squalene epoxi­

dase 59 Amantadine

antiviral action 99-100 interaction with M 2Protein 99-100

structure 100 Amikacin 86 p-Aminobenzoic acid

as a bacterial growth factor 63 competitive antagonism of

sulphonamide action 63 part of the structure of folic acid 63

7-Aminocephalosporanic acid 32 Aminoglycoside antibiotics

acetylation 144-5 action on protein synthesis 84-7 adenylylation 144-5 interaction with 16S rRNA 85 killing action of 86 phosphorylation 144-5 resistance 144-5, 147-8 uptake by bacteria 116-17 see also Gentamicin; Kanamycin A;

Neomycin C; Spectinomycin; Streptomycin

6-Aminopenicillanic acid 30 Amoxycillin 30-1 Amphotericin B

action on cell membranes 55-6

effect as an antifungal agent 55 structure 55 toxicity 55

Ampicillin antibacterial spectrum 30 structure 3 1

Antibacterial action information from auxotrophic bacte­

ria 11 reversal by biologically important

compounds 11 Antibiotics

discovery 7-8 semi -synthetic 8

Antifungal agents 8, 55-9, 65-6, 98 Antigenic groups in Gram-negative wall

19 Antimicrobial action

at molecular level 12 determination of mechanism 10-12 evidence from effect on uptake of

nutrients 11 relationship to chemical structure

11 selectivity towards micro-organisms

13 Antimicrobial agents

distinction between primary and sec-ondary effects 10

early remedies 2-4 metabolism in the body 5, 13 pharmacological biochemistry 13 selectivity through concentration in

the microbial cell 13 social and economic importance 1-2 structural analogies with biologically

important molecules 11 Antiprotozoal drugs 5-6, 101-6 Antisepsis 2-3 Antiseptics

bacteriostatic action at low concen-trations 44

causing leakage of constituents 44 factors in bactericidal action 44 need for bactericidal action 44 penetration into bacterial cells 44 uptake by bacterial cytoplasmic mem-

brane 44 see also Antisepsis

Ara A see Arabinosyl adenine Arabinogalactan in cell walls of

mycobacteria 37

Index

Arabinosyl adenine antiviral action 68 inhibition of DNA synthesis 68 structure 67

Arsenicals 4, 104-5 Arsenious oxide as trypanocide 4 Artemether 102 Artemisinin

antimalarial action 102 interaction with haem 102-3 structure 102

Asepsis 3 Atebrin see Mepacrine Atovaquone

antimalarial action 103 inhibition of mitochondria 103-4 specificity of action 104 structure 103

Atoxyl efficacy against trypanosomes 4 structure 5

Auxotrophic bacteria, use in determin­ing site of antibacterial action 11

Azidothymidine antiviral action 69 biochemical mechanism of action

68-9 structure 67

Azole antifungals clinical use 57 inhibition of C-14 demethylase 57-8 structure 58

AZT see Azidothymidine

Bacitracin binding to polyprenylpyrophosphates

27 structure 27 topical application 27

Bacterial cell wall permeability function 109-11 protective function 15-16

Bacteriostatic and bactericidal action compared 5

Benzyl penicillin structure 31 susceptibility to b-lactamase 137

Biocides 43 Bone marrow toxic effects of chloram­

phenicol on 90, 95 Borrelidin 83 Bronopol45

Calcium binding to A23187 53 significance in Gram-negative bacteri­

al wall 18 Carboxypeptidases

active centre 36 extracellular 34 from streptomycetes 34 reaction intermediates 35-6 role in peptidoglycan synthesis 25

160

CAT see Chloramphenicol acetyl trans-ferase

Cationic antiseptics 45-6 Cefotaxime 31, 32 Cefotetan

antibacterial spectrum 32 structure 31

Cefuroxime stability to 13-lactamases 32 structure 31

Cephalexin stability to 13-lactamases 32 structure 31

Cephaloridine 31, 32 Cephalosporanoic acid 133-4 Cephalosporin C

biogenesis 32 structure 31

Cephamycin C 31, 32 Cetrimide

chain length and antiseptic action 45 structure 46

Chain, Ernst Boris 7 Chelation of cations

by tetracyclines 88-9, 113 by quinolones 115

Chemotherapy early history 3-6 its debt to Ehrlich 4-5

Chitin synthase inhibition by polyoxins and

nikkomycins 39-40 isoenzymes 39

Chitin biosynthesis 39 role in fungal cell walls 39

Chloramphenicol binding to ribosomes 90-1 clinical use 89, 90 effect on bone marrow 89, 90, 95 effect on yeast cells 95 inhibition of peptide bond formation

90 inhibition of puromycin reaction 90 resistance 140-4

Chloramphenicol acetyl transferase catabolite repression of 143-4 catalytic mechanism 140-1 induction mechanism 142-4 structure 141 types 141

Chlorhexidine antiseptic action 46 'blistering' of cell wall 46 physical properties 45 precipitation of bacterial nucleic acid

and protein 46 structure 46

Chloroplasts and inhibitors of 70S ribo­somes 95

Chloroquine inhibition of haemozoin formation

102

interaction with DNA 71-3 resistance 153-4 structure 71 uptake into malarial parasite 117

Cilastatin inhibitor of renal dehydropeptidase 32 structure 33

Cinchona bark as source of quinine 2 Clavulanic acid

inhibitor of 13-lactamase 30, 138 structure 33

Clindamycin action on ribosomes 92 antibacterial spectrum 92 structure 92

Cloxacillin resistance to 13-lactamase 30, 137 structure 31

Coccidiosis and drug treatment 52 Codon misreadings induction by amino­

glycosides 84-5, 86 Concentration of antimicrobial agents in

microbial cells 113-7 Conjugation

bacterial 123, 125-9 transfer of drug-resistance by 128-9

Conjugative trans po sons 125-6 Cotrimoxazole

double block of tetrahydrofolate biosynthesis 64

rei stance 149 Coumarin antibacterials 75-6 Cross-linking of peptidoglycan 23-5 Cycloguanil 63 Cycloheximide

action on ribosomes 94 action on translocation 94-5 antimicrobial action 94 structure 94

Cycloserine active uptake by bacteria 28, 113 antagonism of antibacterial effect by

D-alanine 28 inhibition of alanine racemase and D­

alanyl-D-alanine synthetase 28 significance of rigid structure 28 structure 27

Cyclothialidines inhibition of bacterial DNA gyrase

75-6 structure 75

Cytochrome P450 interaction with azole antifungals 57-8

Cytoplasmic membranes interaction with polypeptide antibi­

otics 46-9 interaction with synthetic antiseptics

45-6,47 permeability barrier to antimicrobial

agents 107-9

Dapsone see 4,4' -diaminodiphenyl-sul­phone

3,4-Dehydroproline incorporation into abnormal proteins 83

3-Deoxy-D-manno-octulosonic acid binding of Ca2+ and Mg2+ 18 component of lipopolysaccaride core

18 4,4' -Diaminodiphenylsulphone

biochemical action 63 structure 62 use in leprosy 62-3

Diaminopimelic acid in peptidoglycan 24

Di-deoxyinosine in the treatment of AIDS 69

Diffusion facilitated 109 passive 107-9

Difluoromethylornithine see eflornithine Dihydrofolate reductase inhibitors

biochemical effects 63-5 resistance to 148-9 specificity towards different organ­

isms 64 Dihydrofolate reductase

differences between bacterial and mammalian enzymes 64

drug-resistant forms 148-9 Dihydropteroate synthase

inhibition by sulphonamides 63 role in folic acid biosynthesis 63 sulphonamide-resistant form 148-9

Dihydropteroic acid biosynthesis inhib­ited by sulphonamides 63

Disinfectants chemically reactive 44 early history 3 modern uses 43 need for bactericidal action 43

DNA circular 73, 74 effects of intercalating drugs on phys­

ical properties 72 polymerases 66-8

DNA gyrase inhibition by cyclothialidines 75-6 inhibition by quinolones 74-5 inhibition by coumarins 75-6 role in supercoiling 73-4

DNA synthesis inhibition by inhibitors of nucleotide biosynthe­

sis 62-6 by inhibitors of polymerization 66-8

Donor site in protein biosynthesis 79 Doxycycline 88 Drug efflux

in resistant bacteria 151 in resistant fungal cells 153 in resistant tumour cells 151

Drug efflux pumps 151 see also Multidrug efflux systems

Drug-resistance biochemical mechanisms 133-57 genetic basis 119-31

Echinocandin B effect on glucan biosynthesis 39-40 structure 40

Eflornithine inhibition of ornithine decarboxylase

105-6 permease-mediated entry into cells

117 specific antitrypanosomal action

105-6 structure 105

Ehrlich, Paul 4-6 Emetine 2 Energy metabolism inhibition by

anti protozoal agents 103-5 4-Epitetracycline 89 Ergosterol

biosynthesis inhibition 56-9 target for polyenes 55-6

Erythromycin antibacterial action 91 effect of pH on antibacterial activity

of 109 effect on eukaryotic cells 95 inhibition of translocation 92 interaction with 23S rRNA 91 resistance 91, 146-7 structure 91

Ethambutol activity against mycobacteria 38 inhibition of arabinosyl transferase III

38 structure 38

Ethanol disinfectant action 45 effects on membranes 45

Ethidium action on trypanosoma I DNA 73 intercalation with DNA 72 structure 71

Ethionine incorporation into abnormal proteins 83

N-ethylglycine 83 Ethylene oxide 44 Ethylenediaminetetraacetic acid, disrup-

tion of Gram-negative outer enve­lope 110

Eukaryotic cells, effects of inhibitors of protein synthesis on 95

Exit domain of ribosomes 78

Facilitated diffusion of antimicrobial agents 109

Fenarimol 58 Ferrimycin AI

structure 116 transport 115-6

Ferrioxamine B structure 116 transport 116

Fick's law of diffusion 108 Filamentous forms of E. coli caused by

/3-lactams 34-5

Index

Filipin 56 Fleming, Alexander 7 Florey, Howard Walter 7 5 -Fluorocytosine

antifungal action 65-6 facilitated transport into fungal cells

66, 117 metabolism of 66 resistance 117 structure 66

Fluoroquinolones see Quinolone antibacterials

Folic acid biosynthesis 63-4 inhibition of biosynthesis 63-4 structure 64

Folic acid analogues impermeability to bacterial cells 63 toxicity 63

Footprinting application to antibiotic­ribosome interactions 85-6

N-formylmethionyl tRNAFroie in pro­tein biosynthesis 79, 89-91

Fosfomycin inhibition of MurA 27 inhibition of peptidoglycan synthesis

27-8 structure 27

Fungal cell walls inhibition of biosynthesis 39-41 structure 38-9

Fungal hyphae affected by griseofulvin 98

Furanomycin 83 Fusidic acid

clinical use 93 inhibition of translocation 94 resistance of Gram-negative bacteria

93 structure 94

Ganciclovir antiviral action 67-8 structure 67

Gene cassettes, role in bacterial drug resistance 124

Genomics, importance in antimicrobial drug research 12

Gentamicin C" biochemical action 86-7 structure 84

Global regulators of expression of drug resistance genes 131

Glucan in fungal cell walls 38 inhibition of biosynthesis 39-40

L-a-Glycerophosphate permease trans­ports fosfomycin 113

Glycine-specific transfer RNA in pepti­doglycan biosynthesis 21

Glycopeptide see Peptidoglycan GR122222X see Cyclothialidines

161

Index

Gramicidin A biochemical action 53 effect on membrane conductivity 53 pore formation in membranes 53 structure 54

Gramicidin D inhibits Plasmodium falci­parum 53-5

Gramicidin S antibacterial action 46-8 conformation in solution 49 structural requirements for activity

49 structure 48

Gram-negative bacteria, intrinsic resist­ance to certain antibacterial agents 109-11

Gram-negative bacterial walls chemical composition 17-19 linkage of lipoprotein and peptido­

glycan 19 Gram-positive bacteria

osmotic pressure 16 cell wall 16-17

Griseofulvin antifungal activity 98 inhibition of microtubule formation

98 structure 98

Guanine nucleotides, inhibition of biosynthesis by ribavirin 66

Halogens as biocides 44 Halophilic bacteria, resistance to antibi­

otics affecting peptidoglycan syn­thesis 26

Hansch equation application to antibac­terial agents 108

Haptophore 5 Herpes treatment with nucleoside ana­

logues 67-8 Hexose-6-phosphate permeases in accu­

mulation of fosfomycin 113 HIV protease

as a target in AIDS therapy 98-9 involvement in viral replication 98-9 inhibitors 98-9

HIV see Human Immunodeficiency Virus

Human Immunodeficiency Virus mutations in 120-2 resistance to reverse transcriprtase

inhibitors 149-50 treatment with inhibitors of HIV pro­

tease 98-9 treatment with inhibitors of reverse

transcriptase 68-9 Hydrogen peroxide 44 Hydroxynaphthoquinones as antiproto­

zoals 103 Hypochlorite 44

Imipenem, N-formimidoyl derivative of thienamycin 32

162

Immunological control of infectious dis­ease 2, 156

IMP-dehydrogenase inhibition by rib­avirin 66

Indinavir combination therapy for AIDS 98 inhibition of HIV protease 98-9 structure 100

Indolmycin 83 Influenza A2 prophylaxis and therapy

with amantadine 99 Initiation of protein biosynthesis 79 Integrons

role in bacterial drug resistance 124 structure 124

Intercalation of DNA by planar mole­cules 71-3

Interferon antiviral action 100 biological activities 100 gene family 101 receptor 101 mechanism of antiviral action 101

5 -Iododeoxyuridine interference with DNA synthesis and

function 68 structure 67 use in herpes infections 68

Ionization of antibacterial agents, effect on penetration into bacterial cells 108-9

Ionophoric antibiotics anti protozoal activity 53-4 effects on calcium transport 52-3 effects on potassium transport 50-3 promotion of potassium flux in artifi-

cial membranes 53 relative affinities for sodium and

potassium 50-2 I pecacuanha root 2 Iron-chelating antibiotics 115-16 Iron-chelating growth factors 115-16 Isoniazid

activation by catalase-peroxidase 37-8 inhibition of InhA 37 resistance in mycobacteria 38 structure 38

Isoprenyl phosphate (Css ) see Undecaprenyl phosphate

Isopropanol, effects on membranes 45

Kanamycin A N-acetylation 145 biochemical action 86-7 structure 84

KDO see 3-Deoxy-D-manno-octuloson­ic acid

Ketoconazole clinical use 58 effect on chitin synthesis 58 inhibition of C-14 sterol demethyla-

tion 57-8 structure 58

toxicity 57

13-Lactamases catalytic mechanisms 136-7 chemical approaches to the problem

of 137 Gram-negative 135 Gram-positive 134-5 inhibitors of 13 8-9 metallo-enzymes 13 7 regulation of 134-5 relationship to carboxypeptidases and

transpeptidases 136-7 serine active centre 136, 13 9-40 classification schemes 139-40

Lamivudine resistance in AIDS patients 120

Leprosy treatment with 4,4' -diamin­odiphenylsulphone

Lincomycin antimicrobial effects 92 binding to ribosomes 92 structure 92

Lipid A component of lipopolysaccha­ride 18-19

Lipopolysaccharide of Gram-negative cells and permeability of outer enve­lope to antibacterial agents 109-10

Lipoprotein in Gram-negative bacteria 18-19 structure 19

Lister, Joseph 3 L-phase enhanced sensitivity to antibac­

terial agents 11 0

Macrotetrolides, structure of potassium complex 51

Magnesium displaced from cytoplasmic mem­

brane by polymyxin 48 release from mitochondria by

A2318753 significance in Gram-negative bacteri­

al wall 18 tetracycline and 88-9, 113

Malaria drug resistance 153-4 treatment 101-4

Mapharsen metabolite of salvarsan 5-6 structure 5

Mecillinam effect on bacterial morphology 34-5 structure 31

Mefloquine mode of action 102 resistance 154 structure 102

Melarsoprol inhibition of glycolysis in try­

panosomes 104-5 interaction with trypanothione 105 structure 105

Mepacrine antimalarial agent 6 structure 7

Mercuric chloride as antiseptic 3 failure as systemic antibacterial 3-4

Meso-2,6-diaminopimelic acid in pepti­doglycan 24

Messenger RNA, translational attenua­tion in induction of drug resistance 143, 147, 152

Metabolism in activation of antimicro­bial compounds 5,12

Methicillin resistance 146 stability to p-Iactamase 30, 137 structure 31

Methotrexate cytotoxic action 63 structure 65

Methylene blue 4 N-methyl transferases

in resistance to macro Ii des 146-7 induction mechanism 147

Metronidazole activity due to reduction product

97-8 antimicrobial spectrum 97 structure 97

Miconazole antifungal effects 58 structure 58

Microbial resistance recognition by Ehrlich 6 genetics 119-31 biochemical mechanisms 133-57

Minocycline penetration into bacteria 113

Misreading of genetic code, induction by aminoglycosides 85-6

Mitochondrial ribosomes 77, 95 MLS antibiotics 91-3 Mode of action of antimicrobial agents

methods of study 10-11 Monensin

coccidiostat 52 preferential binding to sodium 52 structure 52 used to improve food conversion in

ruminants 52 Monobactams 32-3 Morpholine antifungals, inhibition of

sterol biosynthesis 58-9 Mosaic genes

origins 123 role in drug resistance 122-3

Mucopeptide see Peptidoglycan Multidrug efflux systems 11-12, 151 Mupirocin

antibacterial spectrum 83 inhibition of bacterial isoleucyl tRNA

synthestase 83 structure 83

Murein see Peptidoglycan Mutations

drug-resistance and 120-2 types of 120

Mycobacterial infections treatment of 37-8,69,83 lipids in cell wall 37

Mycolic acid linkage to peptidoglycan in mycobacteria 25

Mycoplasmas outside usual Gram stain classifica­

tion 16 resistance to antibiotics affecting pep­

tidoglycan synthesis 26 sensitivity to polyene antibiotics and

sterol content of membrane 55

Naftifine antifungal action 59 inhibition of squalene epoxidase 59 selectivity for the fungal enzyme 59 structure 59

Nalidixic acid clinical use 74 inhibitor of DNA gyrase 74-5 resistance 75, 111, 147 structure 59

Neomycin B biochemical action 86-7 structure 84

Nevirapine inhibition of reverse transcriptase 69 resistance 69, 150 structure 69

Nikkomycin Z inhibition of fungal chitin biosynthe­

sis 39 structure 40

Nitrofurantoin clinical uses 95 inhibition of inducible enzyme syn­

thesis 95 structure 95

Nonactin 50-1 Norfloxacin

inhibition of DNA gyrase 74-5 structure 74

Novobiocin clinical use 76 inhibition of DNA supercoiling 75-6 structure 75

Nucleic acid polymerases as targets for drug action 61

Nucleic acid disturbance of template function of

71-3 inhibitors of biosynthesis of 61-76

Nucleotides, inhibition of biosynthesis 61-6

Nystatin clinical use 55 disruption of membrane integrity 55 interaction with sterols 55

Index

structure 55

Octapeptins 47 Outer envelope of Gram-negative bacte­

ria as permeability barrier 109-11 Outer membrane of Gram-negative bac-

teria anchorage to peptidoglycan layer 19 asymmetry 18 phospholipid composition 18 porins 11 0-11 selective permeability 109-11

Oxytetracycline 88 Ozone 44

Pasteur, Louis 3 Penicillin binding proteins

differing functions 34-5 interaction with p-lactams 25, 33-5 mosaic genes for, 122-3, 146

Penicillin G inactivation by acid 29 Penicillin V stability to acid 29 Penicillin

accumulation of nucleotides in Staphylococcus aureus 32-3

antibacterial action 29 derivatives stable to penicillinases 30 discovery 7-8 inhibition of peptidoglycan cross­

linking 33 isolation and purification 8 precursors in fermentation medium

29 resistance 122, 133-40, 145-6 rigid structure 36-7 structural resemblance to D-alanyl-D­

alanine end group 36-7 Penicillinase see p-lactamases Penicillium notatum, source of penicillin

7-8 Pentaglycine group in peptidoglycan

biosynthesis 21, 23 Penta-N-benzyl polymyxin preferential

activity against Gram-positive bac­teria 47

Peptide bond formation inhibited by chloramphenicol 90-1

Peptide chain termination and release 81

Peptidoglycan biosynthesis amidation of carboxyl group of D-

glutamic acid 20 cross-linking 23, 25 inhibition by antibiotics 26-37 transpeptidation in cross-linking

process 23 uncross-linked linear polymer in bac­

teria treated with penicillin 33 Peptidoglycan

catabolism during cell growth 135 cross-linking pattern 23 differences between bacterial strains

23

163

Index

Peptidoglycan continued elasticity 16 function 16 fragment in induction of Gram-nega­

tive [3-lactamase 135 hydrolysis products linkage with lipoprotein in

Escherichia coli wall 25 linkage with teichoic acid in

Staphylococcus aureus 25 structure and biosynthesis 19-26

Peptidyl transferase inhibition by antibiotics 89-91 in peptide bond formation 78 role of 23S rRNA 78

Periplasmic space 17, 112, 115, 144-5 Permeability of cytoplasmic membrane

caused by antiseptics 45 Permeability of microbial cells to drugs

107-18 Phage transduction of drug resistance

129-30 Pharmacological biochemistry of antimi-

crobial agents 13 Phenanthridines, veterinary use 71 Phenols as antiseptics 45 Phenoxy acetic acid as penicillin V pre­

cursor 29 Phenoxymethylpenicillin 29 Phenylacetic acid as penicillin G precur­

sor 29 Phosphatidylethanolamine in Gram-neg­

ative outer membrane 18 Phosphatidylglycerol in Gram-negative

outer membrane 18 Phospholipids in Gram-negative walls Phosphonomycin see Fosfomycin Phosphorylation of aminoglycosides

144-5 Plasmids in drug resistance 126-9 Polyene antibiotics

action on fungal infections 55 basis of selectivity 55 effects on permeability of fungal

membranes 56 structures 55 toxicity 55

Polymyxin binding to bacteria 47-8 clinical application 47 effects on permeability of cytoplasmic

membrane 47 nature of binding to cytoplasmic

membrane 48 structure 48

Polyoxins competition with UDP-N-acetylglu-

cosamine 39 entry into fungal cells 39 inhibition of chitin synthesis 39 structure 40

164

Polypeptide antibiotics 46-50 Pores of outer membrane of Gram-nega­

tive bacteria 18-19, 11 0-11 Porins

permeability characteristics 19, 110 role in drug penetration 111 structure 19, 110

Potassium ions leakage caused by chlorhexidine 46 leakage caused by polymyxin 48 preferential binding to certain

ionophoric antibiotics 49-53 promotion of flux through artificial

membranes by ionophoric antibiotics 49-53

Pradimicin A complex with mannan 40 structure 41

Proflavine disinfectant action 71 intercalation with DNA 71-3 structure 71

Proguanil activation by host metabolism 63 resistance 149 structure 65

Prontosil rubrum antibacterial activity 6, 62 structure 62

Protein binding effects on activity of antimicrobial

agents 13 promotion of suramin uptake by try­

panosomal cells 104 Protein biosynthesis

inhibition 77-96 stages in 78-81

Proton motive force, energy source for drug transport across membranes 109, 151

Protoplasts, absorption of antiseptics 44 Protozoal diseases, chemotherapy

101-6 Pseudomonic acid see mupirocin Puromycin

effects on protein biosynthesis 81 fragment reaction 81-2 structural analogues 82 structural resemblance to amino acyl

tRNA 81 structure 82

Pyrimethamine affinity for dihydrofolate reductase

from malarial parasite 64 structure 65

Pyrophosphatase inhibition by baci­tracin 27

Qinghaosu see artemisinin Quinacrine see mepacrine Quinine 2

Quinolone antibacterials inhibition of DNA gyrase 74-5 resistance 147 uptake by bacteria 115

Receptors for drugs, Ehrlich's theory 5 Recombination in

conjugative transposons 125 integrons 124-5 mosaic genes 122-3 transposons 124

Release factors, role in peptide chain termination 81

Replica plating technique 120, 121 Resistance genes, origins of 122-3 Resistance

approaches to the control of 155-6 biochemical mechanisms 133-57 genetic basis 119-13 1

Reverse transcriptase inhibition by AZT 88-9 inhibition by di-deoxyinosine 69 inhibition by nevirapine 69, 150 mutations in 149-50

Ribavirin antiviral effects 66 inhibition of IMP dehydrogenase 66 structure 67

Ribosome cycle 80 proteins 77 RNA 77,78 role in peptide bond synthesis 78-9 target for for antibiotics 78 types 77 structure 77-8 subunits 77-8

Rifampicin clinical use 69 inhibition of bacterial RNA poly­

merase 69-70 resistance to 70, 148 structure 70

Rifampin see rifampicin Rifamycins see rifampicin Ritonavir

inhibition of HIV protease 98-9 in combination therapy for AIDS 98 resistance to 150 structure 100

RNA biosynthesis effects of inhibition on protein

biosynthesis 61 inhibition by rifamycins 69,70 inhibition by streptolydigin 70 inhibition by streptovaricins 69

RNA polymerase inhibition by antibiotics 69-71 subunit structure 69

R-plasmids classification 126

mechanism of transfer 128 relationship to F-factors 126 role in spread of drug-resistance

128-9 structure 126-7

Salvarsan efficacy against syphilis 4 metabolism to mapharsen 5-6 structure 5

Screening in the search for antimicrobial drugs 5

Sedimentation coefficient of DNA, effect of intercalating dyes 72

Selectivity in antimicrobial action 13 Septum formation, effect of penicillins

34 Sex pili role in bacterial conjugation

127-8 Sideramines, role in iron uptake by bac­

teria 116 Sideromycins, uptake by bacterial cells

116 Sleeping sickness

atoxyl treatment 4 eflornithine treatment 105 melarsoprol treatment 104-5 see also Trypanosomiasis

Spectinomycin biochemical action 87 structure 84

Spheroplasts, absorption of antiseptics 44

Sterilants 43 Sterol biosynthesis inhibition

by allylamines 59 by azoles 57-8 by morpholines 58-9 by tolnaftate 59

Sterols in fungal membrane, binding of polyene antibiotics 55-6

Streptogramins inhibition of protein biosynthesis 92 synergism between Types A and B 92 see also Virginiamycins

Streptolydigin inhibitor of bacterial RNA poly­

merase 70-1 structure 71

Streptomycin adenylylation of 144-5 antibacterial action 83 bactericidal action 84 binding to ribosomes 85 clinical use 83 discovery 83 effect on Chlamydomonas 95 effect on Euglena 95 effects on protein biosynthesis 84-5 induction of codon misreading 85 mode of entry into bacterial cells

116-17

phosphorylation 144-5 resistance 85, 144-5, 147-8 site of ribosomal action 85-6 structure 84 toxicity 83-4

Streptovaricins inhibitors of bacterial RNA poly­

merase 69, 70 structure 70

Sulfazecin 32, 33 Sulphamethoxazole

combination with trimethoprim 64 structure 62

Sulphanilamide biochemical action 63 metabolic product from Prontosil

rubrum 62 structure 62

Sulphonamides antibacterial activity 62 competition with p-aminobenzoate

63 favourable factors in their practical

success 63 inhibition of synthesis of dihy­

dropteroic acid 63 resistance to 148-9

Suramin inhibition of trypanosomal enzymes

104 structure 7 uptake into trypanosomes 104

Syphilis treatment by salvarsan 4

Teichoic acid labile linkage to peptidoglycan 25 possible function 6 possible influence on drug penetra­

tion 110 structure 16

Teichoplanin 28, 29 Teichuronic acid 16 Terbinafine

antifungal use 59 inhibition of squalene epoxidation in

fungi 59 structure 59

Termination in protein biosynthesis 81 Terminator codons 81 Tetracyclines

active uptake by bacterial cells 87, 113-15

antimicrobial actions 87 binding to ribosomes 87-8 chelating activity 88-9 efflux systems 111-12, 151-2 inhibition of amino acyl tRNA-ribo-

some interaction 87 mechanism of resistance to 151-3 ribosomal resistance 152-3 ribosomal site of action 87 selectivity of antibacterial action 87

Index

structure-activity relationships 88-9 structures 88

Tetrahydrofolate biosynthesis 63 double blockage of synthesis 64-5 importance in nucleotide synthesis 65

Thienamycin antibacterial action 32 resistance to 13-lactamase 32 structure 33

Thiol groups possible involvement in antimicrobial action of arsenicals 105

Thymidine kinase activation of acyclovir 67 activation of azidothymidine 68

Thymidylate synthase, inhibition by 5-fluorodeoxyuridine 66

Timentin 30 Tolnaftate

clinical use 59 inhibition of squalene epoxidation 59 structure 59

Topoisomerases catenation of chromosomes 73 DNA gyrase 73 inhibitors 73-6 supercoiling of DNA 73 types of 74-5

Toxophore 5 Transduction

generalized 129 possible contribution to spread of

drug-resistance 13 0 specialized 13 0

Transfer RNA binding to ribosomes 79 conversion to aminoacyl transfer (t)

RNA 78-9 translocation in protein biosynthesis

79-80 Transformation

contribution to the spread of drug­resistance 13 0-1

mechanism of 130 Transglycolase

component of penicillin-binding pro­teins 33-4

inhibition by vancomycin 29 role in peptidoglycan biosynthesis 21

Translational domain on ribosomes 78 Translocation

inhibition by cycloheximide 94 inhibition by erythromycin 91 inhibition by fusidic acid 91 in protein biosynthesis 81

Transpeptidase inhibition by 13-lactams 35-6 in peptidoglycan cross-linking 23

Transposons in drug-resistance 124-5 insertion mechanism 124

165

Index

Transposons continued structure 125 see also Conjugative transposons

Tridemorph 59 Trimethoprim

resistance 148 selective inhibition of bacterial dihy­

drofolate reductase 64 structure 65

Trypan red antitrypanosomal action 4 resistance in trypanosomes 6

Trypanosomes kinetoplast DNA and intercalating

molecules 73 glycolytic metabolism in 104-5 polyamines synthesis in 105 redox balance in 105

Trypanosomiasis current treatments 104-6 early treatments 4 forms of 104

Trypanothione role in redox control in try­

panosomes 105 interaction with melarsoprol 105

Tuberculosis

166

treatment with synthetic compounds 7,37-8

treatment with antibiotics 69, 83 Tyrocidin A

action on membranes 46, 48-9 structure 48

UDP-N-acetylmuramic acid biosynthesis 20

UDP-N-acetylmuramyl pentapeptide accumulation in antibiotic-treated

bacteria 27, 33 synthesis 20

Undecaprenyl phosphate in peptidogly-can biosynthesis 21

Undecaprenyl pyrophosphatase 23, 27 Uptake of antimicrobial drugs 107-18 Uridine nucleotides of N-acetyl muram-

ic acid accumulation caused by inhibitors of

peptidoglycan biosynthesis 27, 33

biosynthesis 20

Valinomycin mechanism of potassium complex

formation 49-50

mobile carrier of ions 50 structure 49-50 turnover number 50

Vancomycin antibacterial activity 28 binding to D-alanyl-D-alanine group

28-9 dimerization 29 inhibition of transglycolase 29 resistance 154-5 structure 27

Variable surface glycoprotein in try­panosomes 106

Vidarabine see Arabinosyl adenine Virginiamicins

inhibition of protein biosynthesis 92 structures 93 synergism between 92

Virus chemotherapy 66-9,98-101 Vital stains 4, 71

Waksman, Selman 8

Xenobiotic acetyl transferases, possible role in drug resistance 144