Antibacterianos: Principais classes, mecanismos de ação e resistência
Palavras-chave:
Antibacterianos; Resistência; GenesResumo
entender o mecanismo de ação dos fármacos antimicrobianos e compreender os mecanismos
pelos quais as bactérias conseguem resistir ao ataque destes fármacos é essencial para o desenvolvimento
de meios para potencializar a eficácia e mimetizar o desenvolvimento da resistência bacteriana. O objetivo
deste trabalho foi realizar revisão sobre os principais mecanismos de ação dos agentes antibacterianos e
mecanismos de resistência das bactérias a essas drogas. Para tal, fontes primárias e secundárias de dados
nacionais e internacionais foram consultadas. Os mecanismos de ação das principais drogas antibacterianas
foram explorados e exemplificados, bem como mecanismos de resistência bacteriana. A antibioticoterapia
como tratamento de infecções bacterianas está cada vez mais ineficiente em decorrência da emergência
de bactérias resistentes a múltiplos fármacos. Há, portanto, a necessidade global de descobertas de novas
drogas para o tratamento de infecções bacterianas.
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Referências
1. TENOVER, F. C. Mechanisms of
Antimicrobial Resistance in Bacteria. The American
Journal of Medicine. v. 119, n. 6A, p. S3-S10, jun.
2006.
2. HOWARD, S. J. et al. Antibiotic resistance:
global response needed. The Lancet Infectious
Diseases. v. 13, n. 12, p. 1001-3, dez. 2013.
3. LUPO, A.; COYNE, S.; BERENDONK, T.
U. Origin and evolution of antibiotic resistance: the
common mechanisms of emergence and spread in
water bodies. Frontiers in Microbiology. v. 3, n. 18,
jan. 2012. Disponível em: < https://www.ncbi.nlm.
nih.gov/pmc/articles/PMC3266646/>. Acesso em:
26 Out. 2016.
4. DAVIES, J.; DAVIES, D. Origins and
evolution of antibiotic resistance. Microbiology
and Molecular Biology Reviews. v. 74, n. 3, p. 417-
33, set. 2010.
5. WEI, W. J. et al. New delhi metallo-βlactamase-mediated carbapenem resistance: origin,
diagnosis, treatment and public health concern.
Chinese Medical Journal. v. 128, n. 14, p. 1969-76,
jul. 2015.
6. CARVALHO, A. A. et al. Characterization
and molecular epidemiology of extensively
prevalent, nosocomial, isolates of the drug-resistant
Acinetobacter spp. Genetics and Molecular
Research. v. 15, n. 3, ago. 2016. Disponível em: <
http://www.funpecrp.com.br/gmr/year2016/vol15-
3/pdf/gmr8608.pdf>. Acesso em: 26 Out.
7. LAXMINARAYAN, R. et al. Antibiotic
resistance - the need for global solutions. The
Lancet Infectious Diseases. v. 13, n. 12, p. 1057-
98, dez. 2013.
8. FRIEDMAN, N. D.; TEMKIN, E.;
CARMELI, Y. The negative impact of antibiotic
resistance. Clinical Microbiology and Infection. v.
22, n. 5, p. 416-22, mai. 2016.
9. BRUNTON, L. L.; CHABNER, B.
A.; KNOLLMANN, B. C. (Orgs.). Goodman
and Gilman's the Pharmacological Basis of
Therapeutics. 12. ed. New York: McGraw-Hill,
2011.
10. RANG, H. P. et al. Rang & Dale’s
Pharmacology. 8. ed. London: Elsevier Churchill
Livingstone, 2015.
11. CONSTANT, J. M. C.; CONSTANT, A. B.
L. Antibióticos e Quimioterápicos Antimicrobianos.
2. ed. São Paulo: Savier, 2015.
12. TORTORA, G. J.; FUNKE, B. R.; CASE,
C. L. Microbiology: An Introduction. 12. ed. New
York: Pearson Benjamin Cummings, 2015.
13. BERTONCHELI, C. M.; HÖRNER, R.
Uma revisão sobre metalo-β-lactamases. Revista
Brasileira de Ciências Farmacêuticas. v. 44, n. 4,
p. 577-99, out-dez. 2008.
14. AVENT, M. L. et al. Current use of
aminoglycosides: indications, pharmacokinetics
and monitoring for toxicity. Internal Medicine
Journal. v. 41, n. 6, p. 441-9, jun. 2011.
15. KAYE, K. S. et al. Agents of Last Resort:
Polymyxin Resistance. Infectious Disease Clinics
of North America. v. 30, n. 2, p. 391-414, jun. 2016.
16. MENDES, C. A. C.; BURDMANN, E.
A. Polimixinas - Revisão com ênfase na sua
nefrotoxicidade. Revista da Associação Médica
Brasileira. v. 55, n. 6, p. 752-59, 2009.
17. GIRARDELLO, R.; GALES, A. C.
Resistência às polimixinas: velhos antibióticos,
últimas opções terapêuticas. Revista de
Epidemiologia e Controle da Infecção. v. 2, n. 2, p.
66-9, 2012.
18. ALÓS, J. I. Quinolonas. Enfermedades
Infecciosas y Microbiología Clínica. v. 27, n. 5, p.
290-97, mai. 2009.
19. GÖBEL, A. et al. Occurrence and
sorption behavior of sulfonamides, macrolides,
and trimethoprim in activated sludge treatment.
Environmental Science and Technology. v. 39, n.
11, p. 3981-9, jun. 2005.
20. GÖBEL, A. et al. Fate of sulfonamides,
macrolides, and trimethoprim in different
wastewater treatment technologies. The Science of
the Total Environment. v. 372, n. 2, p. 361-71, jan.
2007.
21. BLAIR, J. M. A. et al. Molecular
mechanisms of antibiotic resistance. Nature
Reviews Microbiology. v. 13, n. 1, p. 42-51, jan.
2015.
22. CORNAGLIA, G.; GIAMARELLOU,
H.; ROSSOLINI, G. M. Metallo-β-lactamases: a
last frontier for β-lactams?. The Lancet Infectious
Diseases. v. 11, n. 5, p. 381-93, mai. 2011.
23. QUEENAN, A. M.; BUSH, K.
Carbapenemases: the Versatile β-Lactamases.
Clinical Microbiology Reviews. v. 20, n. 3, p. 440–
58, jul. 2007.
24. DJAHMI, N. et al. Epidemiology of
carbapenemase-producing Enterobacteriaceae
and Acinetobacter baumannii in Mediterranean
Countries. BioMed Research International. v. 2014,
n. 1, mai. 2014.
25. BUSH, K. Proliferation and significance of
clinically relevant β-lactamases. Annals of the New
York Academy of Sciences. v. 1277, n. 2013, p. 84-
90, jan. 2013.
26. D'ANDREA, M. M. et al. CTX-M-type
β-lactamases: a successful story of antibiotic
resistance. International Journal of Medical
Microbiology. v. 303, n. 6-7, p. 305-17, ago. 2013.
27. ALEKSHUN, M. N.; LEVY, S. B. Molecular
mechanisms of antibacterial multidrug resistance.
Cell. v. 128, n. 6, p. 1037-50, mar. 2007.
28. BHARDWAJ, A. K.; MOHANTY, P.
Bacterial efflux pumps involved in multidrug
resistance and their inhibitors: rejuvinating the
antimicrobial chemotherapy. Recent Patents on
Anti-infective Drug Discovery. v. 7, n. 1, p. 73-89,
abr. 2012.
29. LI, X. Z.; PLÉSIAT, P.; NIKAIDO, H. The
challenge of efflux-mediated antibiotic resistance
in Gram-negative bacteria. Clinical Microbiology
Reviews. v. 28, n. 2, p. 337-418, abr. 2015.
30. NIKAIDO, H.; PAGÈS, J. M. Broadspecificity efflux pumps and their role in multidrug
resistance of Gram-negative bacteria. FEMS
Microbiology Reviews. v. 36, n. 2, p. 340-63, mar.
2012.
31. YOON, E. J.; COURVALIN, P.; GRILLOTCOURVALIN, C. RND-type efflux pumps in
multidrug-resistant clinical isolates of Acinetobacter
baumannii: major role for AdeABC overexpression
and AdeRS mutations. Antimicrobial Agents and
Chemotherapy. v. 57, n. 7, p. 2989-95, abr. 2013.
32. COYNE, S.; COURVALIN, P.; PÉRICHON,
B. Efflux-mediated antibiotic resistance in
Acinetobacter spp. Antimicrobial Agents and
Chemotherapy. v. 55, n. 3, p. 947-53, mar. 2011.
33. WRIGHT, G. D. Molecular mechanisms of
antibiotic resistance. Chemical Communications. v.
47, n. 14, p. 4055-61, abr. 2011.
34. WILSON, D. N. Ribosome-targeting
antibiotics and mechanisms of bacterial resistance.
Nature Reviews Microbiology. v. 12, n. 1, p. 35-48,
jan. 2014.
35. CHEAH, S. E. et al. Colistin and polymyxin
B dosage regimens against Acinetobacter
baumannii: Differences in activity and the
emergence of resistance. Antimicrobial Agents and
Chemotherapy. v. 60, n. 7, p. 3921-33, jun. 2016.
36. CHEAH, S. E. et al. Polymyxin Resistance
in Acinetobacter baumannii: Genetic Mutations and
Transcriptomic Changes in Response to Clinically
Relevant Dosage Regimens. Scientific Reports. v.
6, n. 26233, mai. 2016. Disponível em: <http://
www.nature.com/articles/srep26233>. Acesso em:
26 Out. 2016.
37. EPAND, R. M. et al. Molecular mechanisms
of membrane targeting antibiotics. Biochimica Et
Biophysica Acta. v. 1858, n. 5, p. 980-7, mai. 2016.
38. KANETI, G.; MEIR, O.; MOR, A.
Controlling bacterial infections by inhibiting
proton-dependent processes. Biochimica Et
Biophysica Acta. v. 1858, n. 5, p. 995-1003, mai.
2016.
39. HAN, L. et al. Structure of the BAM
complex and its implications for biogenesis of
outer-membrane proteins. Nature Structural and
Molecular Biology. v. 23, n. 3, p. 192-6, mar. 2016.
40. GU, Y. et al. Structural basis of outer
membrane protein insertion by the BAM complex.
Nature. v. 531, n. 7592, p. 64-9, mar. 2016.
41. BAKELAR, J.; BUCHANAN, S. K.;
NOINAJ, N. The structure of the β-barrel assembly
machinery complex. Science. v. 351, n. 6269, p.
180-6, jan. 2016.
42. LEYTON, D. L.; BELOUSOFF, M. J.;
LITHGOW, T. The β-Barrel Assembly Machinery
Complex. Methods in Molecular Biology. v. 501, n.
7467, p. 385-90, set. 2013.
Antimicrobial Resistance in Bacteria. The American
Journal of Medicine. v. 119, n. 6A, p. S3-S10, jun.
2006.
2. HOWARD, S. J. et al. Antibiotic resistance:
global response needed. The Lancet Infectious
Diseases. v. 13, n. 12, p. 1001-3, dez. 2013.
3. LUPO, A.; COYNE, S.; BERENDONK, T.
U. Origin and evolution of antibiotic resistance: the
common mechanisms of emergence and spread in
water bodies. Frontiers in Microbiology. v. 3, n. 18,
jan. 2012. Disponível em: < https://www.ncbi.nlm.
nih.gov/pmc/articles/PMC3266646/>. Acesso em:
26 Out. 2016.
4. DAVIES, J.; DAVIES, D. Origins and
evolution of antibiotic resistance. Microbiology
and Molecular Biology Reviews. v. 74, n. 3, p. 417-
33, set. 2010.
5. WEI, W. J. et al. New delhi metallo-βlactamase-mediated carbapenem resistance: origin,
diagnosis, treatment and public health concern.
Chinese Medical Journal. v. 128, n. 14, p. 1969-76,
jul. 2015.
6. CARVALHO, A. A. et al. Characterization
and molecular epidemiology of extensively
prevalent, nosocomial, isolates of the drug-resistant
Acinetobacter spp. Genetics and Molecular
Research. v. 15, n. 3, ago. 2016. Disponível em: <
http://www.funpecrp.com.br/gmr/year2016/vol15-
3/pdf/gmr8608.pdf>. Acesso em: 26 Out.
7. LAXMINARAYAN, R. et al. Antibiotic
resistance - the need for global solutions. The
Lancet Infectious Diseases. v. 13, n. 12, p. 1057-
98, dez. 2013.
8. FRIEDMAN, N. D.; TEMKIN, E.;
CARMELI, Y. The negative impact of antibiotic
resistance. Clinical Microbiology and Infection. v.
22, n. 5, p. 416-22, mai. 2016.
9. BRUNTON, L. L.; CHABNER, B.
A.; KNOLLMANN, B. C. (Orgs.). Goodman
and Gilman's the Pharmacological Basis of
Therapeutics. 12. ed. New York: McGraw-Hill,
2011.
10. RANG, H. P. et al. Rang & Dale’s
Pharmacology. 8. ed. London: Elsevier Churchill
Livingstone, 2015.
11. CONSTANT, J. M. C.; CONSTANT, A. B.
L. Antibióticos e Quimioterápicos Antimicrobianos.
2. ed. São Paulo: Savier, 2015.
12. TORTORA, G. J.; FUNKE, B. R.; CASE,
C. L. Microbiology: An Introduction. 12. ed. New
York: Pearson Benjamin Cummings, 2015.
13. BERTONCHELI, C. M.; HÖRNER, R.
Uma revisão sobre metalo-β-lactamases. Revista
Brasileira de Ciências Farmacêuticas. v. 44, n. 4,
p. 577-99, out-dez. 2008.
14. AVENT, M. L. et al. Current use of
aminoglycosides: indications, pharmacokinetics
and monitoring for toxicity. Internal Medicine
Journal. v. 41, n. 6, p. 441-9, jun. 2011.
15. KAYE, K. S. et al. Agents of Last Resort:
Polymyxin Resistance. Infectious Disease Clinics
of North America. v. 30, n. 2, p. 391-414, jun. 2016.
16. MENDES, C. A. C.; BURDMANN, E.
A. Polimixinas - Revisão com ênfase na sua
nefrotoxicidade. Revista da Associação Médica
Brasileira. v. 55, n. 6, p. 752-59, 2009.
17. GIRARDELLO, R.; GALES, A. C.
Resistência às polimixinas: velhos antibióticos,
últimas opções terapêuticas. Revista de
Epidemiologia e Controle da Infecção. v. 2, n. 2, p.
66-9, 2012.
18. ALÓS, J. I. Quinolonas. Enfermedades
Infecciosas y Microbiología Clínica. v. 27, n. 5, p.
290-97, mai. 2009.
19. GÖBEL, A. et al. Occurrence and
sorption behavior of sulfonamides, macrolides,
and trimethoprim in activated sludge treatment.
Environmental Science and Technology. v. 39, n.
11, p. 3981-9, jun. 2005.
20. GÖBEL, A. et al. Fate of sulfonamides,
macrolides, and trimethoprim in different
wastewater treatment technologies. The Science of
the Total Environment. v. 372, n. 2, p. 361-71, jan.
2007.
21. BLAIR, J. M. A. et al. Molecular
mechanisms of antibiotic resistance. Nature
Reviews Microbiology. v. 13, n. 1, p. 42-51, jan.
2015.
22. CORNAGLIA, G.; GIAMARELLOU,
H.; ROSSOLINI, G. M. Metallo-β-lactamases: a
last frontier for β-lactams?. The Lancet Infectious
Diseases. v. 11, n. 5, p. 381-93, mai. 2011.
23. QUEENAN, A. M.; BUSH, K.
Carbapenemases: the Versatile β-Lactamases.
Clinical Microbiology Reviews. v. 20, n. 3, p. 440–
58, jul. 2007.
24. DJAHMI, N. et al. Epidemiology of
carbapenemase-producing Enterobacteriaceae
and Acinetobacter baumannii in Mediterranean
Countries. BioMed Research International. v. 2014,
n. 1, mai. 2014.
25. BUSH, K. Proliferation and significance of
clinically relevant β-lactamases. Annals of the New
York Academy of Sciences. v. 1277, n. 2013, p. 84-
90, jan. 2013.
26. D'ANDREA, M. M. et al. CTX-M-type
β-lactamases: a successful story of antibiotic
resistance. International Journal of Medical
Microbiology. v. 303, n. 6-7, p. 305-17, ago. 2013.
27. ALEKSHUN, M. N.; LEVY, S. B. Molecular
mechanisms of antibacterial multidrug resistance.
Cell. v. 128, n. 6, p. 1037-50, mar. 2007.
28. BHARDWAJ, A. K.; MOHANTY, P.
Bacterial efflux pumps involved in multidrug
resistance and their inhibitors: rejuvinating the
antimicrobial chemotherapy. Recent Patents on
Anti-infective Drug Discovery. v. 7, n. 1, p. 73-89,
abr. 2012.
29. LI, X. Z.; PLÉSIAT, P.; NIKAIDO, H. The
challenge of efflux-mediated antibiotic resistance
in Gram-negative bacteria. Clinical Microbiology
Reviews. v. 28, n. 2, p. 337-418, abr. 2015.
30. NIKAIDO, H.; PAGÈS, J. M. Broadspecificity efflux pumps and their role in multidrug
resistance of Gram-negative bacteria. FEMS
Microbiology Reviews. v. 36, n. 2, p. 340-63, mar.
2012.
31. YOON, E. J.; COURVALIN, P.; GRILLOTCOURVALIN, C. RND-type efflux pumps in
multidrug-resistant clinical isolates of Acinetobacter
baumannii: major role for AdeABC overexpression
and AdeRS mutations. Antimicrobial Agents and
Chemotherapy. v. 57, n. 7, p. 2989-95, abr. 2013.
32. COYNE, S.; COURVALIN, P.; PÉRICHON,
B. Efflux-mediated antibiotic resistance in
Acinetobacter spp. Antimicrobial Agents and
Chemotherapy. v. 55, n. 3, p. 947-53, mar. 2011.
33. WRIGHT, G. D. Molecular mechanisms of
antibiotic resistance. Chemical Communications. v.
47, n. 14, p. 4055-61, abr. 2011.
34. WILSON, D. N. Ribosome-targeting
antibiotics and mechanisms of bacterial resistance.
Nature Reviews Microbiology. v. 12, n. 1, p. 35-48,
jan. 2014.
35. CHEAH, S. E. et al. Colistin and polymyxin
B dosage regimens against Acinetobacter
baumannii: Differences in activity and the
emergence of resistance. Antimicrobial Agents and
Chemotherapy. v. 60, n. 7, p. 3921-33, jun. 2016.
36. CHEAH, S. E. et al. Polymyxin Resistance
in Acinetobacter baumannii: Genetic Mutations and
Transcriptomic Changes in Response to Clinically
Relevant Dosage Regimens. Scientific Reports. v.
6, n. 26233, mai. 2016. Disponível em: <http://
www.nature.com/articles/srep26233>. Acesso em:
26 Out. 2016.
37. EPAND, R. M. et al. Molecular mechanisms
of membrane targeting antibiotics. Biochimica Et
Biophysica Acta. v. 1858, n. 5, p. 980-7, mai. 2016.
38. KANETI, G.; MEIR, O.; MOR, A.
Controlling bacterial infections by inhibiting
proton-dependent processes. Biochimica Et
Biophysica Acta. v. 1858, n. 5, p. 995-1003, mai.
2016.
39. HAN, L. et al. Structure of the BAM
complex and its implications for biogenesis of
outer-membrane proteins. Nature Structural and
Molecular Biology. v. 23, n. 3, p. 192-6, mar. 2016.
40. GU, Y. et al. Structural basis of outer
membrane protein insertion by the BAM complex.
Nature. v. 531, n. 7592, p. 64-9, mar. 2016.
41. BAKELAR, J.; BUCHANAN, S. K.;
NOINAJ, N. The structure of the β-barrel assembly
machinery complex. Science. v. 351, n. 6269, p.
180-6, jan. 2016.
42. LEYTON, D. L.; BELOUSOFF, M. J.;
LITHGOW, T. The β-Barrel Assembly Machinery
Complex. Methods in Molecular Biology. v. 501, n.
7467, p. 385-90, set. 2013.
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Publicado
2020-12-06
Como Citar
SANTOS NOGUEIRA, H. .; ERICSSON DE OLIVEIRA XAVIER, A. R. .; DE SOUSA XAVIER, M. A. .; AMARAL CARVALHO, A. .; ATAÍDE MONÇÃO, G. .; PRATES BARRETO, N. A. . Antibacterianos: Principais classes, mecanismos de ação e resistência . Revista Unimontes Científica, [S. l.], v. 18, n. 2, p. 96–108, 2020. Disponível em: https://www.periodicos.unimontes.br/index.php/unicientifica/article/view/1811. Acesso em: 21 dez. 2024.
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