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2017 | 66 | 1 | 109-124
Article title

"Nowe" i "stare" antybiotyki - mechanizmy działania i strategie poszukiwania leków przeciwbakteryjnych

Title variants
The "new" and "old" antibiotics - mechanisms of action and strategies for development of novel antibacterial agents.
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Narastająca oporność bakterii na dostępne obecnie antybiotyki stanowi niezmiernie duży problem w terapii zakażeń. Na świecie zanotowano pojawienie się bakterii niosących wiele genów warunkujących oporność, efektem tego może być niewrażliwość na wszystkie dostępne klasy antybiotyków, jak to miało ostatnio miejsce w przypadku bakterii opornych na kolistynę. Kolistyna to lek ostatniej szansy w przypadku leczenia infekcji wywołanych bakteriami opornymi na antybiotyki β-laktamowe. Współcześnie dostępne klasy antybiotyków mają różne cele, takie jak osłony komórkowe, i procesy w komórce takie jak hamowanie syntezy białek, transkrypcja, replikacja, czy zaburzenia szlaków syntezy niektórych metabolitów w komórkach bakterii. Ciągle jednak trwa swojego rodzaju "wyścig zbrojeń" i poszukiwania nowych sposobów walki z opornymi mikroorganizmami. Stosowane są nowe strategie lepszego wykorzystania stosowanych już antybiotyków np. przez poszukiwanie synergistycznych oddziaływań pomiędzy lekami lub stosowanie różnego rodzaju dodatków zwiększających ich skuteczność, poszukiwanie nowych substancji i nowych celów komórkowych oraz strategie zmniejszania zjadliwości bakterii podczas infekcji.
Constantly increasing resistance of bacteria to available antibiotics is a real clinical problem. In recent years we observed a dramatic increase in number of multi resistant, so called MDR and XDR strains, causing some bacteria to become resistant to all classes of antibiotics. One recent example is the raise of collistin resistant strains while collistin has been an antibiotic of last resort in treatment of infections caused by bacteria resistant to β-lactam antibiotics. Currently available classes of antibiotics have various cellular targets. They may affect cell envelope, processes such as replication, transcription and translation and affect cellular metabolism. Today’s situation reminds the Red Queen’s Race when we try to develop new antibiotics, but constantly deal with antibiotic resistance. However, new strategies are being applied to develop active antimicrobial substances. Such strategies include: (i) better use of “old” antibiotics by using them in synergistic combinations or in combinations with small molecule additives, (ii) search for new active substances, and for new cell targets, and (iii) lowering of bacterial virulence during the infection.
Physical description
  • Zakład Epidemiologii i Mikrobiologii Klinicznej, Zakład Mikrobiologii Molekularnej, Narodowy Instytut Leków, Chełmska 30/34, 00-725 Warszawa, Polska
  • Department of Epidemiology and Clinical Microbiology, National Medicines Institute, Chełmska 30/34, 00-725 Warszawa, Poland
  • Zakład Mikrobiologii Molekularnej, Narodowy Instytut Leków, Chełmska 30/34, 00-725 Warszawa, Polska
  • Department of Molecular Microbiology, National Medicines Institute, Chełmska 30/34, 00-725 Warszawa, Poland
  • Adler A., Katz D. E., Marchaim D., 2016. The continuing plague of extended-spectrum beta-lactamase-producing Enterobacteriaceae infections. Infect. Dis. Clin. North Am. 30, 347-375.
  • Bermingham A., Derrick J. P., 2002. The folic acid biosynthesis pathway in bacteria: evaluation of potential for antibacterial drug discovery. Bioessays 24, 637-648.
  • Bialvaei A. Z., Samadi Kafil H., 2015. Colistin, mechanisms and prevalence of resistance. Curr. Med. Res. Opin. 31, 707-721.
  • Blair J. M., Richmond G. E., Piddock L. J., 2014. Multidrug efflux pumps in Gram-negative bacteria and their role in antibiotic resistance. Future Microbiol. 9, 1165-1177.
  • Bush K., 2012. Improving known classes of antibiotics: an optimistic approach for the future. Curr. Opin. Pharmacol. 12, 527-534.
  • Campbell E. A., Korzheva N., Mustaev A., Murakami K., Nair S., Goldfarb A., Darst S. A., 2001. Structural mechanism for rifampicin inhibition of bacterial RNA polymerase. Cell 104, 901-912.
  • Donovan D. M., 2007. Bacteriophage and peptidoglycan degrading enzymes with antimicrobial applications. Recent Pat. Biotechnol. 1, 113-122.
  • Edwards D. I., 1993a. Nitroimidazole drugs--action and resistance mechanisms. I. Mechanisms of action. J. Antimicrob. Chemother. 31, 9-20.
  • Edwards D. I., 1993b. Nitroimidazole drugs--action and resistance mechanisms. II. Mechanisms of resistance. J. Antimicrob. Chemother. 31, 201-210.
  • Galdiero S., Falanga A., Berisio R., Grieco P., Morelli G., Galdiero M., 2015. Antimicrobial peptides as an opportunity against bacterial diseases. Curr. Med. Chem. 22, 1665-1677.
  • Gerstmans H., Rodriguez-Rubio L., Lavigne R., Briers Y., 2016. From endolysins to Artilysin(R)s: novel enzyme-based approaches to kill drug-resistant bacteria. Biochem. Soc. Trans. 44, 123-128.
  • Hawser S., Lociuro S., Islam K., 2006. Dihydrofolate reductase inhibitors as antibacterial agents. Biochem. Pharmacol. 71, 941-948.
  • Hryniewicz W., Meszaros J., 2001. Antybiotyki w profilaktyce i leczeniu zakażeń. Wydawnictwo Lekarskie PZWL, Warszawa.
  • Izdebski R., Baraniak A., Bojarska K., Urbanowicz P., Fiett J., Pomorska-Wesolowska M., Hryniewicz W., Gniadkowski M., Zabicka D., 2016. Mobile MCR-1-associated resistance to colistin in Poland. J. Antimicrob. Chemother. doi: 10.1093/jac/dkw261.
  • Jagusztyn-Krynicka E. K., Wyszynska A., 2008. The decline of antibiotic era - new approaches for antibacterial drug discovery. Pol. J. Microbiol. 57, 91-98.
  • Janiszewska J., 2014. Naturalne peptydy przeciwdrobnoustrojowe w zastosowaniach biomedycznych. Polimery 59, 699-707.
  • Jankute M., Cox J. A., Harrison J., Besra G. S., 2015. Assembly of the mycobacterial cell wall. Annu. Rev. Microbiol. 69, 405-423.
  • Khan R., Kong H. G., Jung Y. H., Choi J., Baek K. Y., Hwang E. C., Lee S. W., 2016. Triclosan resistome from metagenome reveals diverse enoyl acyl carrier protein reductases and selective enrichment of triclosan resistance genes. Sci. Rep. 6, 32322.
  • Kocsis B., Domokos J., Szabo D., 2016. Chemical structure and pharmacokinetics of novel quinolone agents represented by avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and nemonoxacin. Ann. Clin. Microbiol. Antimicrob. 15, 34.
  • Lele A. C., Mishra D. A., Kamil T. K., Bhakta S., Degani M. S., 2016. Repositioning of DHFR inhibitors. Curr. Top. Med. Chem. 16, 2125-2143.
  • Liu Y. Y., Wang Y., Walsh T. R., Yi L. X., Zhang R., Spencer J., Doi Y., Tian G., Ding B., Huang X. i współaut., 2016. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect. Dis. 16, 161-168.
  • Ling L. L., Schneider T., Peoples A. J., Spoering A. L., Engels I., Conlon B. P., Mueller A., Schaberle T. F., Hughes D. E., Epstein S. i współaut., 2015. A new antibiotic kills pathogens without detectable resistance. Nature 517, 455-459.
  • Lofmark S., Edlund C., Nord C. E., 2010. Metronidazole is still the drug of choice for treatment of anaerobic infections. Clin. Infect. Dis. 50 (Suppl. 1), S16-S23.
  • Lu H., Tonge P. J., 2008. Inhibitors of FabI, an enzyme drug target in the bacterial fatty acid biosynthesis pathway. Acc. Chem. Res. 41, 11-20.
  • Ma C., Yang X., Lewis P. J., 2016. Bacterial transcription as a target for antibacterial drug development. Microbiol. Mol. Biol. Rev. 80, 139-160.
  • Markiewicz Z., 1993. Struktura i funkcje osłon bakteryjnych. Wydaw. Naukowe PWN, Warszawa.
  • Matteelli A., Carvalho A. C., Dooley K. E., Kritski A., 2010. TMC207: the first compound of a new class of potent anti-tuberculosis drugs. Future Microbiol. 5, 849-858.
  • McMurry L. M., Oethinger M., Levy S. B., 1998. Triclosan targets lipid synthesis. Nature 394, 531-532.
  • Mojica M. F., Bonomo R. A., Fast W., 2016. B1-metallo-beta-lactamases: Where do we stand? Curr. Drug Targets. 17, 1029-1050.
  • Moir D. T., Opperman T. J., Butler M. M., Bowin T. L., 2012. New classes of antibiotics. Curr. Opin. Pharmacol. 12, 535-544.
  • Murima P., Mc Kinney J. D., Pethe K., 2014. Targeting bacterial central metabolism for drug development. Chem. Biol. 21, 1423-1432.
  • Nelson D. C., Schmelcher M., Rodriguez-Rubio L., Klumpp J., Pritchard D. G., Dong S., Donovan D. M., 2012. Endolysins as antimicrobials. Adv. Virus. Res. 83, 299-365.
  • Nelson M. L., Dinardo A., Hochberg J., Armelagos G. J., 2010. Mass spectroscopic characterization of tetracycline in the skeletal remains of an ancient population from Sudanese Nubia 350-550 CE. Am. J. Phys. Anthropol. 143, 151-154.
  • Sheehan J. C., 1984. The enchanted ring: The untold story of penicillin. The MIT Press.
  • Palumbi S. R., 2001. Humans as the world's greatest evolutionary force. Science 293, 1786-1790.
  • Perry J., Waglechner N., Wright G., 2016. The prehistory of antibiotic resistance. Cold Spring Harb. Perspect. Med. 6, 1-8.
  • Pratt R. F., 2016. Beta-lactamases: Why and How. J. Med. Chem. 59, 8207-8220.
  • Robicsek A., Jacoby G. A., Hooper D. C., 2006. The worldwide emergence of plasmid-mediated quinolone resistance. Lancet Infect. Dis. 6, 629-640.
  • Rodriguez-Rubio L., Martinez B., Donovan D. M., Rodriguez A., Garcia P., 2013. Bacteriophage virion-associated peptidoglycan hydrolases: potential new enzybiotics. Crit. Rev. Microbiol. 39, 427-434.
  • Schmelcher M., Donovan D. M., Loessner M. J., 2012. Bacteriophage endolysins as novel antimicrobials. Future Microbiol. 7, 1147-1171.
  • Schroeder E. K., De Souza N., Santos D. S., Blanchard J. S., Basso L. A., 2002. Drugs that inhibit mycolic acid biosynthesis in Mycobacterium tuberculosis. Curr. Pharm. Biotechnol. 3, 197-225.
  • Spizek J., Sigler K., Rezanka T., Demain A., 2016. Biogenesis of antibiotics-viewing its history and glimpses of the future. Folia Microbiol. 61, 347-358.
  • Srivastava A., Talaue M., Liu S., Degen D., Ebright R. Y., Sineva E., Chakraborty A., Druzhinin S. Y., Chatterjee S., Mukhopadhyay J. i współaut., 2011. New target for inhibition of bacterial RNA polymerase: 'switch region'. Curr. Opin. Microbiol. 14, 532-543.
  • Sun H., Xu Y., Sitkiewicz I., Ma Y., Wang X., Yestrepsky B. D., Huang Y., Lapadatescu M. C., Larsen M. J., Larsen S. D. i współaut., 2012. Inhibitor of streptokinase gene expression improves survival after group A streptococcus infection in mice. Proc. Natl. Acad. Sci. USA 109, 3469-3474.
  • Tamma P. D., Cosgrove S. E., Maragakis L. L., 2012. Combination therapy for treatment of infections with gram-negative bacteria. Clin. Microbiol. Rev. 25, 450-470.
  • Taylor S.D., Palmer M., 2016. The action mechanism of daptomycin. Bioorg. Med. Chem. doi:10.1016/j.bmc.2016.05.052.
  • Tran T. T., Munita J. M., Arias C. A., 2015. Mechanisms of drug resistance: daptomycin resistance. Ann. NY Acad. Sci. 1354, 32-53.
  • Van Bambeke F., Michot J. M., Van Eldere J., Tulkens P. M., 2005. Quinolones in 2005: an update. Clin. Microbiol. Infect. 11, 256-280.
  • Walsh C., 2003. Where will new antibiotics come from? Nat. Rev. Microbiol. 1, 65-70.
  • Walsh C. T., Wencewicz T. A., 2014. Prospects for new antibiotics: a molecule-centered perspective. J. Antibiot. 67, 7-22.
  • Weber-Dąbrowska B., Jończyk-Matysiak E., Żaczek M., Łobocka M., Lusiak-Szelachowska M., Górski A., 2016. Bacteriophage procurement for therapeutic purposes. Front. Microbiol. 7, 1177.
  • Wittekind M., Schuch R., 2016. Cell wall hydrolases and antibiotics: exploiting synergy to create efficacious new antimicrobial treatments. Curr. Opin. Microbiol. 33, 18-24.
  • Żyłowska M., Wyszyńska A., Jagusztyn-Krynicka E. K., 2011. Defensyny - peptydy o aktywności przeciwbakteryjnej. Post. Mikrobiol. 50, 223-234.
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