Broad-Spectrum Anti-biofilm Peptide That Targets a Cellular Stress Response
Bacteria colonize most environments, including the host by forming biofilms, which are extremely (adaptively) resistant to conventional antibiotics. Biofilms cause at least 65% of all human infections, being particularly prevalent in device-related infections, infections on body surfaces and in chronic infections. Currently there is a severe problem with antibiotic-resistant organisms, given the explosion of antibiotic resistance whereby our entire arsenal of antibiotics is gradually losing effectiveness, combined with the paucity of truly novel compounds under development or entering the clinic. Thus the even greater resistance of biofilms adds to the major concerns being expressed by physicians and medical authorities. Consequently, there is an urgent need for new strategies to treat biofilm infections and we demonstrate in the present study an approach, based on the inhibition of (p)ppGpp by a small peptide, that eradicates biofilms formed by four of the so-called ESKAPE pathogens, identified by the Infectious Diseases Society of America as the most recalcitrant and resistant organisms in our society. The strategy presented here represents a significant advance in the search for new agents that specifically target bacterial biofilms.
Vyšlo v časopise:
Broad-Spectrum Anti-biofilm Peptide That Targets a Cellular Stress Response. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004152
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004152
Souhrn
Bacteria colonize most environments, including the host by forming biofilms, which are extremely (adaptively) resistant to conventional antibiotics. Biofilms cause at least 65% of all human infections, being particularly prevalent in device-related infections, infections on body surfaces and in chronic infections. Currently there is a severe problem with antibiotic-resistant organisms, given the explosion of antibiotic resistance whereby our entire arsenal of antibiotics is gradually losing effectiveness, combined with the paucity of truly novel compounds under development or entering the clinic. Thus the even greater resistance of biofilms adds to the major concerns being expressed by physicians and medical authorities. Consequently, there is an urgent need for new strategies to treat biofilm infections and we demonstrate in the present study an approach, based on the inhibition of (p)ppGpp by a small peptide, that eradicates biofilms formed by four of the so-called ESKAPE pathogens, identified by the Infectious Diseases Society of America as the most recalcitrant and resistant organisms in our society. The strategy presented here represents a significant advance in the search for new agents that specifically target bacterial biofilms.
Zdroje
1. CostertonJW, StewartPS, GreenbergEP (1999) Bacterial biofilms: a common cause of persistent infections. Science 284: 1318–22.
2. de la Fuente-NúñezC, ReffuveilleF, FernándezL, HancockREW (2013) Bacterial biofilm development as a multicellular adaptation: antibiotic resistance and new therapeutic strategies. Curr Opin Microbiol 16: 580–9.
3. PotrykusK, CashelM (2008) (p)ppGpp: still magical? Annu Rev Microbiol 62: 35–51.
4. MagnussonLU, FarewellA, NyströmT (2005) ppGpp: a global regulator in Escherichia coli. Trends Microbiol 13: 236–42.
5. AbergA, ShinglerV, BalsalobreC (2006) (p)ppGpp regulates type 1 fimbriation of Escherichia coli by modulating the expression of the site-specific recombinase FimB. Mol Microbiol 60: 1520–33.
6. BalzerGJ, McLeanRJ (2002) The stringent response genes relA and spoT are important for Escherichia coli biofilms under slow-growth conditions. Can J Microbiol 48: 675–80.
7. Chávez de PazLE, LemosJA, WickströmC, SedgleyCM (2012) Role of (p)ppGpp in biofilm formation by Enterococcus faecalis. Appl Environ Microbiol 78: 1627–30.
8. HeH, CooperJN, MishraA, RaskinDM (2012) Stringent response regulation of biofilm formation in Vibrio cholerae. J Bacteriol 194: 2962–72.
9. LemosJA, BrownTAJr, BurneRA (2004) Effects of RelA on key virulence properties of planktonic and biofilm populations of Streptococcus mutans. Infect Immun 72: 1431–40.
10. SugisakiK, HanawaT, YonezawaH, OsakiT, FukutomiT, et al. (2013) Role of (p)ppGpp in biofilm formation and expression of filamentous structures in Bordetella pertussis. Microbiology 159: 1379–89.
11. TaylorCM, BeresfordM, EptonHA, SigeeDC, ShamaG, et al. (2002) Listeria monocytogenes relA and hpt mutants are impaired in surface-attached growth and virulence. J Bacteriol 184: 621–8.
12. NguyenD, Joshi-DatarA, LepineF, BauerleE, OlakanmiO, et al. (2011) Active starvation responses mediate antibiotic tolerance in biofilms and nutrient-limited bacteria. Science 334: 982–6.
13. OverhageJ, CampisanoA, BainsM, TorfsEC, RehmBH, et al. (2008) Human host defense peptide LL-37 prevents bacterial biofilm formation. Infect Immun 76: 4176–82.
14. de la Fuente-NúñezC, KorolikV, BainsM, NguyenU, BreidensteinEB, et al. (2012) Inhibition of bacterial biofilm formation and swarming motility by a small synthetic cationic peptide. Antimicrob Agents Chemother 56: 2696–704.
15. Rivas-SantiagoB, Castañeda-DelgadoJE, Rivas SantiagoCE, WaldbrookM, González-CurielI, et al. (2013) Ability of innate defence regulator peptides IDR-1002, IDR-HH2 and IDR-1018 to protect against Mycobacterium tuberculosis infections in animal models. PLoS One 8: e59119.
16. TosaT, PizerLI (1971) Biochemical bases for the antimetabolite action of L-serine hydroxamate. J Bacteriol 106: 972–82.
17. YanH, HancockREW (2001) Synergistic interactions between mammalian antimicrobial defense peptides. Antimicrob Agents Chemother 45: 1558–60.
18. DahlJL, KrausCN, BoshoffHI, DoanB, FoleyK, et al. (2003) The role of RelMtb-mediated adaptation to stationary phase in long-term persistence of Mycobacterium tuberculosis in mice. Proc Natl Acad Sci U S A 100: 10026–31.
19. VogtSL, GreenC, StevensKM, DayB, EricksonDL, et al. (2011) The stringent response is essential for Pseudomonas aeruginosa virulence in the rat lung agar bead and Drosophila melanogaster feeding models of infection. Infect Immun 79: 4094–104.
20. ErlichH, LafflerT, GallantJ (1971) ppGpp formation in Escherichia coli treated with rifampicin. J Biol Chem 246: 6121–3.
21. KhanSR, YamazakiH (1972) Trimethoprim-induced accumulation of guanosine tetraphosphate (ppGpp) in Escherichia coli. Biochem Biophys Res Commun 48: 169–74.
22. CortayJC, CozzoneAJ (1983) Accumulation of guanosine tetraphosphate induced by polymixin and gramicidin in Escherichia coli. Biochim Biophys Acta 755: 467–73.
23. IkeharaK, KamitaniE, KoarataC, OguraA (1985) Induction of stringent response by streptomycin in Bacillus subtilis cells. J Biochem 97: 697–700.
24. GilbertP, CollierPJ, BrownMR (1990) Influence of growth rate on susceptibility to antimicrobial agents: biofilms, cell cycle, dormancy, and stringent response. Antimicrob Agents Chemother 34: 1865–8.
25. WexselblattE, Oppenheimer-ShaananY, KaspyI, LondonN, Schueler-FurmanO, et al. (2012) Relacin, a novel antibacterial agent targeting the Stringent Response. PLoS Pathog 8: e1002925.
26. PompilioA, ScocchiM, PomponioS, GuidaF, Di PrimioA, et al. (2011) Antibacterial and anti-biofilm effects of cathelicidin peptides against pathogens isolated from cystic fibrosis patients. Peptides 32: 1807–14.
27. FjellCD, HissJA, HancockREW, SchneiderG (2011) Designing antimicrobial peptides: form follows function. Nat Rev Drug Discov 11: 37–51.
28. FriedrichCL, MoylesD, BeveridgeTJ, HancockREW (2000) Antibacterial action of structurally diverse cationic peptides on Gram-positive bacteria. Antimicrob Agents Chemother 44: 2086–92.
29. BetznerAS, FerreiraLC, HöltjeJV, KeckW (1990) Control of the activity of the soluble lytic transglycosylase by the stringent response in Escherichia coli. FEMS Microbiol Lett 55: 161–4.
30. GeigerT, GoerkeC, FritzM, SchäferT, OhlsenK, et al. (2010) Role of the (p)ppGpp synthase RSH, a RelA/SpoT homolog, in stringent response and virulence of Staphylococcus aureus. Infect Immun 78: 1873–83.
31. TedinK, NorelF (2001) Comparison of DeltarelA strains of Escherichia coli and Salmonella enterica serovar Typhimurium suggests a role for ppGpp in attenuation regulation of branched-chain amino acid biosynthesis. J Bacteriol 183: 6184–96.
32. SvitilAL, CashelM, ZyskindJW (1993) Guanosine tetraphosphate inhibits protein synthesis in vivo. A possible protective mechanism for starvation stress in Escherichia coli. J Biol Chem 268: 2307–11.
33. XiaoH, KalmanM, IkeharaK, ZemelS, GlaserG, et al. (1991) Residual guanosine 3',5'-bispyrophosphate synthetic activity of relA null mutants can be eliminated by spoT null mutations. J Biol Chem 266: 5980–90.
34. QiuD, DamronFH, MimaT, SchweizerHP, YuHD (2008) PBAD-based shuttle vectors for functional analysis of toxic and highly regulated genes in Pseudomonas and Burkholderia spp. and other bacteria. Appl Environ Microbiol 74: 7422–6.
35. WiegandI, HilpertK, HancockREW (2008) Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat Protoc 3: 163–75.
36. SunS, KjellebergS, McDougaldD (2013) Relative contributions of Vibrio polysaccharide and quorum sensing to the resistance of Vibrio cholerae to predation by heterotrophic protists. PLoS One 8: e56338.
37. HilpertK, McLeodB, YuJ, ElliottMR, RautenbachM, et al. (2010) Short cationic antimicrobial peptides interact with ATP. Antimicrob Agents Chemother 54: 4480–3.
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
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