Nowe strategie walki z chorobami zakaźnymi - leki skierowane przeciwko czynnikom wirulencji

• Authors: Elżbieta Jagusztyn-Krynicka , Magdalena Grzeszczuk , Patrycja Kobierecka

Title variants

EN

New strategies to combat infecious diseases - antivirulence drugs.

• Languages of publication: PL EN

Abstracts

PL

Stale rosnąca liczba szczepów bakterii patogennych opornych na stosowane w terapiach ludzi antybiotyki stanowi zagrożenie dla ludzkości. Zgodnie z danymi Europejskiego Centrum ds. Zapobiegania i Kontroli Chorób tylko w Europie odnotowywanych jest rocznie około 25.000 zgonów z powodu chorób będącymi konsekwencją infekcji powodowanych przez mikroorganizmy oporne na antybiotyki. Pomiędzy rokiem 1930 a 1962 zidentyfikowano i wprowadzono do terapii ponad 20 klas antybiotyków. Od tego czasu zarejestrowano tylko dwie nowe klasy antybiotyków. Skuteczna walka z chorobami zakaźnymi wymaga opracowania i wprowadzenia na rynek nowych klas leków o odmiennych od antybiotyków mechanizmach działania. Praca przeglądowa prezentuje najnowsze osiągnięcia dotyczące identyfikacji nowej klasy leków antybakteryjnych, tzw. leków blokujących procesy wirulencji. Omówione są zarówno leki blokujące konkretne czynniki wirulencji, jak i te, których celem działania są globalne procesy zachodzące w komórkach, istotne także dla procesów patogenezy.

EN

The rapid emergence of resistant bacteria occurring in many parts of the world constitutes an increasing risk to public health. According to European Centre for Disease Prevention and Control (ECDC), in 2009 infections caused by a subset of resistant bacteria were responsible for about 25 000 deaths in Europe. The issue of resistance concerns both gram-positive and gram-negative pathogens that cause infections in the hospitals and in the community. The success in combat against infectious diseases depends upon development of effective anti-infective drugs. More than 20 novel classes of antibiotics were introduced into market between 1930 and 1962. Since then only two new classes of antibiotics have been approved for clinical use. This review presents recent advances toward the development of alternative medicines to classical antibiotics, antivirulence drugs, and highlights their benefits and disadvantages over conventional antibacterials. There are described both potential drugs aimed at single targets as well as those able to inhibit global cellular processes essential for virulence.

Keywords

EN

antybiotyki; bakterie; choroby zakaźne; leki blokujące procesy wirulencji

• Journal: Kosmos
• Year: 2017
• Volume: 66
• Issue: 1
• Pages: 93-107

Dates

published

2017

Contributors

author

Elżbieta Jagusztyn-Krynicka

• Zakład Genetyki Bakterii, Instytut Mikrobiologii, Wydział Biologii, Uniwersytet Warszawski, Miecznikowa 1, 02-096 Warszawa, Polska
• Department of Bacterial Genetics, Institute of Microbiology, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warszawa, Poland

author

Magdalena Grzeszczuk

• Zakład Genetyki Bakterii, Instytut Mikrobiologii, Wydział Biologii, Uniwersytet Warszawski, Miecznikowa 1, 02-096 Warszawa, Polska
• Department of Bacterial Genetics, Institute of Microbiology, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warszawa, Poland

author

Patrycja Kobierecka

• Zakład Genetyki Bakterii, Instytut Mikrobiologii, Wydział Biologii, Uniwersytet Warszawski, Miecznikowa 1, 02-096 Warszawa, Polska
• Department of Bacterial Genetics, Institute of Microbiology, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warszawa, Poland

References

• Aberg V., Fallman E., Axner O., Uhlin B. E., Hultgren S. J., Almqvist F., 2007. Pilicides regulate pili expression in E. coli without affecting the functional properties of the pilus rod. Mol. Biosyst. 3, 214-218.
• Becattini S., Taur Y., Pamer E. G., 2016. Antibiotic-induced changes in the intestinal microbiota and disease. Trends. Mol. Med. 22, 458-478.
• Bem A. E., Velikova N., Pellicer M. T., Baarlen P., Marina A., Wells J. M., 2015. Bacterial histidine kinases as novel antibacterial drug targets. ACS Chem. Biol. 10, 213-224.
• Berkmen M., 2012. Production of disulfide-bonded proteins in Escherichia coli. Protein Expr. Purif. 82, 240-251.
• Boucher H. W., Talbot G. H., Bradley J. S., Edwards J. E., Gilbert D., Rice L. B., Scheld M., Spellberg B., Bartlett J., 2009. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin. Infect. Dis. 48, 1-12.
• Brackman G., Coenye T., 2015. Quorum sensing inhibitors as anti-biofilm agents. Curr. Pharm. Des. 21, 5-11.
• Cai S., Singh B. R., 2007. Strategies to design inhibitors of Clostridium botulinum neurotoxins. Infect Disord. Drug Targets. 7, 47-57.
• Cdcp (Center for Disease Control and Prevention), 2013. Antibiotic resistance threats in the United States, 2013. http://cdc.gov/drugresistance/threat-report-2013.
• Chagnot C., Zorgani M. A., Astruc T., Desvaux M., 2013. Proteinaceous determinants of surface colonization in bacteria: bacterial adhesion and biofilm formation from a protein secretion perspective. Front. Microbiol. 4, 303.
• Coates A. R., Halls G., Hu Y., 2011. Novel classes of antibiotics or more of the same? Br. J. Pharmacol. 163, 184-194.
• Falagas M. E., Kasiakou S. K., 2005. Colistin: the revival of polymyxins for the management of multidrug-resistant Gram-negative bacterial infections. Clin. Infect. Dis. 40, 1333-1341.
• Friebe S., van der Goot F. G., Burgi J., 2016. The ins and outs of anthrax toxin. Toxins (Basel). 8, 1-15
• Galan J. E., Lara-Tejero M., Marlovits T. C., Wagner S., 2014. Bacterial type III secretion systems: specialized nanomachines for protein delivery into target cells. Annu. Rev. Microbiol. 68, 415-438.
• Gauthier A., Robertson M. L., Lowden M., Ibarra J. A., Puente J. L., Finlay B. B., 2005. Transcriptional inhibitor of virulence factors in enteropathogenic Escherichia coli. Antimicrob. Agents Chemother. 49, 4101-4109.
• Gotoh Y., Eguchi Y., Watanabe T., Okamoto S., Doi A., Utsumi R., 2010. Two-component signal transduction as potential drug targets in pathogenic bacteria. Curr. Opin. Microbiol. 13, 232-239.
• Halili M. A., Bachu P., Lindahl F., Bechara C., Mohanty B., Reid R. C., Scanlon M. J., Robinson C. V., Fairlie D. P., Martin J. L., 2015. Small molecule inhibitors of disulfide bond formation by the bacterial DsbA-DsbB dual enzyme system. ACS Chem. Biol. 10, 957-964.
• Hatahet F., Boyd D., Beckwith J., 2014. Disulfide bond formation in prokaryotes: history, diversity and design. Biochim. Biophys. Acta. 1844, 1402-1414.
• Heras B., Shouldice S. R., Totsika M., Scanlon M. J., Schembri M. A., Martin J. L., 2009. DSB proteins and bacterial pathogenicity. Nat. Rev. Microbiol. 7, 215-225.
• Holmes A. H., Moore L. S., Sundsfjord A., Steinbakk M., Regmi S., Karkey A., Guerin P. J., Piddock L. J., 2016. Understanding the mechanisms and drivers of antimicrobial resistance. Lancet. 387, 176-187.
• Idsa (Infectious Diseases Society of America), 2010. The 10 x '20 Initiative: pursuing a global commitment to develop 10 new antibacterial drugs by 2020. Clin. Infect. Dis. 50, 1081-1083.
• Inaba K., Ito K., 2008. Structure and mechanisms of the DsbB-DsbA disulfide bond generation machine. Biochim. Biophys. Acta. 1783, 520-529.
• Kalia V. C., 2013. Quorum sensing inhibitors: an overview. Biotechnol Adv. 31, 224-245.
• Kauppi A. M., Nordfelth R., Uvell H., Wolf-Watz H., Elofsson M., 2003. Targeting bacterial virulence: inhibitors of type III secretion in Yersinia. Chem. Biol. 10, 241-249.
• Keyser P., Elofsson M., Rosell S., Wolf-Watz H., 2008. Virulence blockers as alternatives to antibiotics: type III secretion inhibitors against Gram-negative bacteria. J. Intern. Med. 264, 17-29.
• Kinoshita M., Kato H., Yasumoto H., Shimizu M., Hamaoka S., Naito Y., Akiyama K., Moriyama K., Sawa T., 2016. The prophylactic effects of human IgG derived from sera containing high anti-PcrV titers against pneumonia-causing Pseudomonas aeruginosa. Hum. Vaccin. Immunother., 1-14.
• Kiris E., Burnett J. C., Kane C. D., Bavari S., 2014. Recent advances in botulinum neurotoxin inhibitor development. Curr. Top. Med. Chem. 14, 2044-2061.
• Klemm P., Vejborg R. M., Hancock V., 2010. Prevention of bacterial adhesion. Appl. Microbiol. Biotechnol. 88, 451-459.
• Kostyanev T., Bonten M. J., O'Brien S., Steel H., Ross S., Francois B., Tacconelli E., Winterhalter M., Stavenger R. A., Karlen A., Harbarth S., Hackett J., Jafri H. S., Vuong C., MacGowan A., Witschi A., Angyalosi G., Elborn J. S., deWinter R., Goossens H., 2016. The Innovative Medicines Initiative's New Drugs for Bad Bugs programme: European public-private partnerships for the development of new strategies to tackle antibiotic resistance. J. Antimicrob. Chemother. 71, 290-295.
• Krachler A. M., Orth K., 2013. Targeting the bacteria-host interface: strategies in anti-adhesion therapy. Virulence 4, 284-294.
• Landeta C., Blazyk J. L., Hatahet F., Meehan B. M., Eser M., Myrick A., Bronstain L., Minami S., Arnold H., Ke N., Rubin E. J., Furie B. C., Furie B., Beckwith J., Dutton R., Boyd D., 2015. Compounds targeting disulfide bond forming enzyme DsbB of Gram-negative bacteria. Nat. Chem. Biol. 11, 292-298.
• Lasica A. M., Jagusztyn-Krynicka E. K., 2007. The role of Dsb proteins of Gram-negative bacteria in the process of pathogenesis. FEMS Microbiol. Rev. 31, 626-636.
• Lillington J., Geibel S., Waksman G., 2014. Biogenesis and adhesion of type 1 and P pili. Biochim. Biophys. Acta. 1840, 2783-2793.
• 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., Jones M., Lazarides L., Steadman V. A., Cohen D. R., Felix C. R., Fetterman K. A., Millett W. P., Nitti A. G., Zullo A. M., Chen C., Lewis K., 2015. A new antibiotic kills pathogens without detectable resistance. Nature. 517, 455-459.
• Magiorakos A. P., Srinivasan A., Carey R. B., Carmeli Y., Falagas M. E., Giske C. G., Harbarth S., Hindler J. F., Kahlmeter G., Olsson-Liljequist B., Paterson D. L., Rice L. B., Stelling J., Struelens M. J., Vatopoulos A., Weber J. T., Monnet D. L., 2012. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin. Microbiol. Infect. 18, 268-281.
• Maresso A. W., Schneewind O., 2008. Sortase as a target of anti-infective therapy. Pharmacol. Rev. 60, 128-141.
• McMahon R. M., Premkumar L., Martin J. L., 2014. Four structural subclasses of the antivirulence drug target disulfide oxidoreductase DsbA provide a platform for design of subclass-specific inhibitors. Biochim. Biophys. Acta. 1844, 1391-1401.
• McShan A. C., De Guzman R. N., 2015. The bacterial type III secretion system as a target for developing new antibiotics. Chem. Biol. Drug Des. 85, 30-42.
• Negrea A., Bjur E., Ygberg S. E., Elofsson M., Wolf-Watz H., Rhen M., 2007. Salicylidene acylhydrazides that affect type III protein secretion in Salmonella enterica serovar typhimurium. Antimicrob. Agents Chemother. 51, 2867-2876.
• Nestorovich E. M., Bezrukov S. M., 2014. Designing inhibitors of anthrax toxin. Expert. Opin. Drug Discov. 9, 299-318.
• Nordfelth R., Kauppi A. M., Norberg H. A., Wolf-Watz H., Elofsson M., 2005. Small-molecule inhibitors specifically targeting type III secretion. Infect Immun. 73, 3104-3114.
• Normark B. H., Normark S., 2002. Evolution and spread of antibiotic resistance. J. Intern. Med. 252, 91-106.
• Normark S., Nilsson C., Normark B. H., 2005. Microbiology. A pathogen attacks while keeping up defense. Science. 307, 1211-1212.
• Norrby S. R., Nord C. E., Finch R., 2005. Lack of development of new antimicrobial drugs: a potential serious threat to public health. Lancet Infect. Dis. 5, 115-119.
• Pinkner J. S., Remaut H., Buelens F., Miller E., Aberg V., Pemberton N., Hedenstrom M., Larsson A., Seed P., Waksman G., Hultgren S. J., Almqvist F., 2006. Rationally designed small compounds inhibit pilus biogenesis in uropathogenic bacteria. Proc. Natl. Acad. Sci. USA 103, 17897-17902.
• Portaliou A. G., Tsolis K. C., Loos M. S., Zorzini V., Economou A., 2016. Type III Secretion: Building and Operating a Remarkable Nanomachine. Trends Biochem Sci. 41, 175-189.
• Rasmussen T. B., Givskov M., 2006. Quorum-sensing inhibitors as anti-pathogenic drugs. Int. J. Med. Microbiol. 296, 149-161.
• Rice L. B., 2008. Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE. J. Infect. Dis. 197, 1079-1081.
• Rossetto O., Pirazzini M., Montecucco C., 2014. Botulinum neurotoxins: genetic, structural and mechanistic insights. Nat. Rev. Microbiol. 12, 535-549.
• Rutherford S. T., Bassler B. L., 2012. Bacterial quorum sensing: its role in virulence and possibilities for its control. Cold Spring Harb. Perspect. Med. 2, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543102/
• Shouldice S. R., Heras B., Walden P. M., Totsika M., Schembri M. A., Martin J. L., 2011. Structure and function of DsbA, a key bacterial oxidative folding catalyst. Antioxid. Redox Signal. 14, 1729-1760.
• Velikova N., Fulle S., Manso S., Mechkarska M., Finn P., Conlon J. M., Oggioni M. R., Wells J. K., Marina A., 2016. Putative histidine kinase inhibitors with antibacterial effect against multi-drug resistant clinical isolates identified by in vitro and in silico screens. Scientific Reports. 6; doi: 10.1038/srep26085.
• Ventola C. L., 2015a. The antibiotic resistance crisis. Part 1. Causes and threats. Pharmacy Tcherap. 40, 277-283.
• Ventola C. L., 2015b. The antibiotic resistance crisis: part 2: management strategies and new agents. Pharmacy Tcherap. 40, 344-352.
• Zalewska-Piatek B. M., 2011. Urinary tract infections of Escherichia coli strains of chaperone-usher system. Pol. J. Microbiol. 60, 279-285.