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Chapter 51 : In Pursuit of New Antibiotics
Author:
André Bryskier
Content Type: Reference
Publication Year:
2005
Category: Bacterial Pathogenesis
Book DOI:
10.1128/9781555815929
Chapter DOI:
10.1128/9781555815929.ch51
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Abstract:
Antibacterial agents were required to eradicate Helicobacter pylori, Clostridium difficile, and Legionella pneumophila microorganisms, and the objective has been achieved satisfactorily in the case of some bacterial species but not others, or intensive research has not yet resulted in one or more medications that fulfill the requirements, as for H. pylori. From 1980s to the 1990s, about two families of antibiotics resulting from the fermentation products of microorganisms were developed, such as mupirocin and monocyclic β-lactams from sulfazecin, giving rise to two medications, aztreonam and carumonam. More complex research has shown that the mechanisms of expulsion may differ in the same family of antibiotics. Bacteria need the iron which is found in the external environment for their physiology, and they use siderophores to obtain it. Some antibiotics, such as cephalosporins of the catechol type, use this route as a second mechanism of action. The adherence of bacteria can occur through pili for gram-negative bacilli or sortases for gram-positive bacilli. To enlarge the potential of virulence factor inhibitors, the central regulatory pathway was focused to avoid the narrow spectrum obtained with antipili, antitoxins. Anti-infective agents are not limited to antibacterial agents, and intensive research has been conducted on antifungal agents. There is an urgent need to find agents against Plasmodium falciparum, but also to increase the number of agents active against Leishmania donovani and Trypanosoma gambiense, to find drugs active against Chagas’ disease, and to produce new molecules against Giardia lamblia.
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
Figures
In Pursuit of New Antibiotics
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Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig01
Figure 1
Vancoresmycin
10.1128/9781555815929/f1243-01_thmb.gif
10.1128/9781555815929/f1243-01.gif
Figure 1
Vancoresmycin
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig02
Figure 2
Inhibitors of DHFR of M. avium and P. carinii
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10.1128/9781555815929/f1245-01.gif
Figure 2
Inhibitors of DHFR of M. avium and P. carinii
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig03
Figure 3
Benzoimidazole derivatives: site A inhibitors
10.1128/9781555815929/f1247-01_thmb.gif
10.1128/9781555815929/f1247-01.gif
Figure 3
Benzoimidazole derivatives: site A inhibitors
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig04
Figure 4
Phenylalanine tRNA transferase inhibitor
10.1128/9781555815929/f1247-02_thmb.gif
10.1128/9781555815929/f1247-02.gif
Figure 4
Phenylalanine tRNA transferase inhibitor
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig05
Figure 5
SB 219383, a tyrosyl-tRNA synthetase inhibitor
10.1128/9781555815929/f1247-03_thmb.gif
10.1128/9781555815929/f1247-03.gif
Figure 5
SB 219383, a tyrosyl-tRNA synthetase inhibitor
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig06
Figure 6
Kirromycin, an elongation factor inhibitor
10.1128/9781555815929/f1248-01_thmb.gif
10.1128/9781555815929/f1248-01.gif
Figure 6
Kirromycin, an elongation factor inhibitor
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig07
Figure 7
Structure of EF-Tu and EF-Ts inhibitors
10.1128/9781555815929/f1248-02_thmb.gif
10.1128/9781555815929/f1248-02.gif
Figure 7
Structure of EF-Tu and EF-Ts inhibitors
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig08
Figure 8
Polymerase III inhibitors
10.1128/9781555815929/f1249-01_thmb.gif
10.1128/9781555815929/f1249-01.gif
Figure 8
Polymerase III inhibitors
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig09
Figure 9
REP 6021
10.1128/9781555815929/f1249-02_thmb.gif
10.1128/9781555815929/f1249-02.gif
Figure 9
REP 6021
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig10
Figure 10
Formycins A and B
10.1128/9781555815929/f1250-01_thmb.gif
10.1128/9781555815929/f1250-01.gif
Figure 10
Formycins A and B
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig11
Figure 11
DNA gyrase inhibitors
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10.1128/9781555815929/f1250-02.gif
Figure 11
DNA gyrase inhibitors
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig12
Figure 12
Osmotransporter inhibitor
10.1128/9781555815929/f1250-03_thmb.gif
10.1128/9781555815929/f1250-03.gif
Figure 12
Osmotransporter inhibitor
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig13
Figure 13
Fatty acid biosynthesis inhibitors
10.1128/9781555815929/f1251-01_thmb.gif
10.1128/9781555815929/f1251-01.gif
Figure 13
Fatty acid biosynthesis inhibitors
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig14
Figure 14
AP-1401
10.1128/9781555815929/f1251-02_thmb.gif
10.1128/9781555815929/f1251-02.gif
Figure 14
AP-1401
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig15
Figure 15
Two-component system inhibitors
10.1128/9781555815929/f1252-01_thmb.gif
10.1128/9781555815929/f1252-01.gif
Figure 15
Two-component system inhibitors
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig16
Figure 16
Lipid A inhibitors
10.1128/9781555815929/f1253-01_thmb.gif
10.1128/9781555815929/f1253-01.gif
Figure 16
Lipid A inhibitors
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig17
Figure 17
Lipid A inhibitors
10.1128/9781555815929/f1253-02_thmb.gif
10.1128/9781555815929/f1253-02.gif
Figure 17
Lipid A inhibitors
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig18
Figure 18
TTPS inhibitors
10.1128/9781555815929/f1254-01_thmb.gif
10.1128/9781555815929/f1254-01.gif
Figure 18
TTPS inhibitors
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig19
Figure 19
ERM methylase inhibitors: triazine analogs
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10.1128/9781555815929/f1254-02.gif
Figure 19
ERM methylase inhibitors: triazine analogs
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig20
Figure 20
ERM methylase inhibitors: S-adenosyl-l-homocysteine
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10.1128/9781555815929/f1254-03.gif
Figure 20
ERM methylase inhibitors: S-adenosyl-l-homocysteine
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig21
Figure 21
ERM methylase inhibitors: analogs of S-adenosyl-l-homocysteine
10.1128/9781555815929/f1255-01_thmb.gif
10.1128/9781555815929/f1255-01.gif
Figure 21
ERM methylase inhibitors: analogs of S-adenosyl-l-homocysteine
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig22
Figure 22
Mar inhibitors
10.1128/9781555815929/f1255-02_thmb.gif
10.1128/9781555815929/f1255-02.gif
Figure 22
Mar inhibitors
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig23
Figure 23
Collagenase inhibitor
10.1128/9781555815929/f1255-03_thmb.gif
10.1128/9781555815929/f1255-03.gif
Figure 23
Collagenase inhibitor
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig24
Figure 24
Collagenase inhibitor
10.1128/9781555815929/f1256-01_thmb.gif
10.1128/9781555815929/f1256-01.gif
Figure 24
Collagenase inhibitor
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51fig25
Figure 25
OPT-80
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10.1128/9781555815929/f1256-02.gif
Figure 25
OPT-80
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
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Tables
In Pursuit of New Antibiotics
[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555815929.ch51-1,webId=/content/author/10.1128/9781555815929.ch51-1,properties={foaf_givenname=André, foaf_name=André Bryskier, foaf_surname=Bryskier}]]
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51tab01
Table 1
Affinity for TTPS
Table 1
Affinity for TTPS
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51tab02
Table 2
Mar inhibitor activities in vitro of selected benzimidazoles
a
Table 2
Mar inhibitor activities in vitro of selected benzimidazoles a
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51tab03
Table 3
In vitro activity of OPT-80
a
Table 3
In vitro activity of OPT-80 a
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51
/content/10.1128/9781555815929.ch51.ch51tab04
Table 4
In vitro susceptibility of C. bolteae
Table 4
In vitro susceptibility of C. bolteae
Citation:
Bryskier A.
2005.
In Pursuit of New Antibiotics,
p 1242-1259.
In
Bryskier, M.D. A (ed),
Antimicrobial Agents.
ASM Press, Washington, DC.
doi: 10.1128/9781555815929.ch51