Chitooligosaccharides as Antibacterial, Antibiofilm, Antihemolytic and Anti-Virulence Agent against Staphylococcus aureus

Author(s): Fazlurrahman Khan, Jang-Won Lee, Dung T.N. Pham, Young-Mog Kim*

Journal Name: Current Pharmaceutical Biotechnology

Volume 20 , Issue 14 , 2019


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Abstract:

Background: Staphylococcus aureus nosocomial infections with a high mortality rate in human and animals have been reported to associate with bacterial biofilm formation, along with the secretion of numerous virulence factors. Therefore, the inhibition of biofilm formation and attenuation of virulence determinants are considered as a promising solution to combat the spread of S. aureus infections. Modern trends in antibiofilm therapies have opted for the active agents that are biocompatible, biodegradable, non-toxic and cost-effective. Owning the aforementioned properties, chitosan, a natural N-acetylated carbohydrate biopolymer derived from chitin, has been favorably employed. Recently, the chitosan structure has been chemically modified into Chitooligosaccharides (COS) to overcome its limited solubility in water, thus widening chitosan applications in modern antibiofilm research. In the present study, we have investigated the antibacterial, antibiofilm and anti-virulence activities against S. aureus of COS of different molecular weights dissolved in neutral water.

Methods: The study of bactericidal activity was performed using the micro-dilution method while the biofilm inhibition assay was performed using crystal-violet staining method and confirmed by scanning electron microscopic analysis. The inhibition of amyloid protein production was confirmed by Congo Red staining.

Results: Results showed that low molecular weight COS exhibited bactericidal activity and reduced the bacterial amylogenesis, hemolytic activity as well as H2O2 resistance properties, while slightly inhibiting biofilm formation. The present study provides a new insight for further applications of the water-soluble COS as a safe and cost-effective drug for the treatment of S. aureus biofilm-associated infections.

Conclusion: Reducing the molecular weight of chitosan in the form of COS has become an effective strategy to maintain chitosan biological activity while improving its water solubility. The low molecular weight COS investigated in this study have effectively performed antibacterial, antibiofilm and antivirulence properties against S. aureus.

Keywords: Antibacterial, antibiofilm, anti-virulence, chitooligosaccharides, S. aureus, e-DNA.

[1]
Chemmugil, P.; Lakshmi, P.T.V.; Annamalai, A. Exploring Morin as an anti-quorum sensing agent (anti-QSA) against resistant strains of Staphylococcus aureus. Microb. Pathog., 2019, 127, 304-315.
[http://dx.doi.org/10.1016/j.micpath.2018.12.007] [PMID: 30529513]
[2]
McConoughey, S.J.; Howlin, R.; Granger, J.F.; Manring, M.M.; Calhoun, J.H.; Shirtliff, M.; Kathju, S.; Stoodley, P. Biofilms in periprosthetic orthopedic infections. Future Microbiol., 2014, 9(8), 987-1007.
[http://dx.doi.org/10.2217/fmb.14.64] [PMID: 25302955]
[3]
Paharik, A.E.; Horswill, A.R. The staphylococcal biofilm: Adhesins, regulation, and host response. Microbiol. Spectr., 2016, 4(2)
[http://dx.doi.org/10.1128/microbiolspec.VMBF-0022-2015] [PMID: 27227309]
[4]
McGuinness, W.A.; Malachowa, N.; DeLeo, F.R. Vancomycin resistance in Staphylococcus aureus. Yale J. Biol. Med., 2017, 90(2), 269-281.
[PMID: 28656013]
[5]
Foster, T.J. Antibiotic resistance in Staphylococcus aureus. Current status and future prospects. FEMS Microbiol. Rev., 2017, 41(3), 430-449.
[http://dx.doi.org/10.1093/femsre/fux007] [PMID: 28419231]
[6]
Hall-Stoodley, L.; Stoodley, P. Evolving concepts in biofilm infections. Cell. Microbiol., 2009, 11(7), 1034-1043.
[http://dx.doi.org/10.1111/j.1462-5822.2009.01323.x] [PMID: 19374653]
[7]
Singh, R.; Ray, P.; Das, A.; Sharma, M. Role of persisters and small-colony variants in antibiotic resistance of planktonic and biofilm-associated Staphylococcus aureus: An in vitro study. J. Med. Microbiol., 2009, 58(Pt 8), 1067-1073.
[http://dx.doi.org/10.1099/jmm.0.009720-0] [PMID: 19528167]
[8]
Zhou, K.; Li, C.; Chen, D.; Pan, Y.; Tao, Y.; Qu, W.; Liu, Z.; Wang, X.; Xie, S. A review on nanosystems as an effective approach against infections of Staphylococcus aureus. Int. J. Nanomedicine, 2018, 13, 7333-7347.
[http://dx.doi.org/10.2147/IJN.S169935] [PMID: 30519018]
[9]
Archer, N.K.; Mazaitis, M.J.; Costerton, J.W.; Leid, J.G.; Powers, M.E.; Shirtliff, M.E. Staphylococcus aureus biofilms: Properties, regulation, and roles in human disease. Virulence, 2011, 2(5), 445-459.
[http://dx.doi.org/10.4161/viru.2.5.17724] [PMID: 21921685]
[10]
Lister, J.L.; Horswill, A.R. Staphylococcus aureus biofilms: Recent developments in biofilm dispersal. Front. Cell. Infect. Microbiol., 2014, 4, 178.
[http://dx.doi.org/10.3389/fcimb.2014.00178] [PMID: 25566513]
[11]
Costerton, J.W.; Stewart, P.S.; Greenberg, E.P. Bacterial biofilms: A common cause of persistent infections. Science, 1999, 284(5418), 1318-1322.
[http://dx.doi.org/10.1126/science.284.5418.1318] [PMID: 10334980]
[12]
Hall, C.W.; Mah, T-F. Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria. FEMS Microbiol. Rev., 2017, 41(3), 276-301.
[http://dx.doi.org/10.1093/femsre/fux010] [PMID: 28369412]
[13]
Khatoon, Z.; McTiernan, C.D.; Suuronen, E.J.; Mah, T.F.; Alarcon, E.I. Bacterial biofilm formation on implantable devices and approaches to its treatment and prevention. Heliyon, 2018, 4(12)e01067
[http://dx.doi.org/10.1016/j.heliyon.2018.e01067] [PMID: 30619958]
[14]
Pragman, A.A.; Schlievert, P.M. Virulence regulation in Staphylococcus aureus: the need for in vivo analysis of virulence factor regulation. FEMS Immunol. Med. Microbiol., 2004, 42(2), 147-154.
[http://dx.doi.org/10.1016/j.femsim.2004.05.005] [PMID: 15364098]
[15]
Kiedrowski, M.R.; Horswill, A.R. New approaches for treating staphylococcal biofilm infections. Ann. N. Y. Acad. Sci., 2011, 1241, 104-121.
[http://dx.doi.org/10.1111/j.1749-6632.2011.06281.x] [PMID: 22191529]
[16]
Liu, G.Y.; Nizet, V. Color me bad: microbial pigments as virulence factors. Trends Microbiol., 2009, 17(9), 406-413.
[http://dx.doi.org/10.1016/j.tim.2009.06.006] [PMID: 19726196]
[17]
Kong, C.; Chee, C.F.; Richter, K.; Thomas, N.; Abd Rahman, N.; Nathan, S. Suppression of Staphylococcus aureus biofilm formation and virulence by a benzimidazole derivative, UM-C162. Sci. Rep., 2018, 8(1), 2758.
[http://dx.doi.org/10.1038/s41598-018-21141-2] [PMID: 29426873]
[18]
Allen, R.C.; Popat, R.; Diggle, S.P.; Brown, S.P. Targeting virulence: Can we make evolution-proof drugs? Nat. Rev. Microbiol., 2014, 12(4), 300-308.
[http://dx.doi.org/10.1038/nrmicro3232] [PMID: 24625893]
[19]
Paul, P.; Kolesinska, B.; Sujka, W. Chitosan and its derivatives - biomaterials with diverse biological activity for manifold applications. Mini Rev. Med. Chem., 2019, 19(9), 737-750.
[http://dx.doi.org/10.2174/1389557519666190112142735] [PMID: 30648508]
[20]
Rubini, D.; Farisa Banu, S.; Veda Hari, B.N.; Ramya Devi, D.; Gowrishankar, S.; Karutha Pandian, S.; Nithyanand, P. Chitosan extracted from marine biowaste mitigates staphyloxanthin production and biofilms of methicillin- resistant Staphylococcus aureus. Food Chem. Toxicol., 2018, 118, 733-744.
[http://dx.doi.org/10.1016/j.fct.2018.06.017] [PMID: 29908268]
[21]
Bellich, B.; D’Agostino, I.; Semeraro, S.; Gamini, A.; Cesàro, A. “The good, the bad and the ugly” of Chitosans. Mar. Drugs, 2016, 14(5)E99
[http://dx.doi.org/10.3390/md14050099] [PMID: 27196916]
[22]
Hamed, I.; Özogul, F.; Regenstein, J.M. Industrial applications of crustacean by-products (chitin, chitosan, and chitooligosaccharides): A review. Trends Food Sci. Technol., 2016, 48, 40-50.
[http://dx.doi.org/10.1016/j.tifs.2015.11.007]
[23]
Olicón-Hernández, D.; Zepeda Giraud, L.F.; Guadalupe, G-S. Current applications of chitosan and chito-oligosaccharides. J. Drug Design Res., 2017, 4, 1039.
[24]
Naveed, M.; Phil, L.; Sohail, M.; Hasnat, M.; Baig, M.M.F.A.; Ihsan, A.U.; Shumzaid, M.; Kakar, M.U.; Mehmood Khan, T.; Akabar, M.D.; Hussain, M.I.; Zhou, Q.G. Chitosan oligosaccharide (COS): An overview. Int. J. Biol. Macromol., 2019, 129, 827-843.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.01.192] [PMID: 30708011]
[25]
Zhang, G.; Liu, J.; Li, R.; Jiao, S.; Feng, C.; Wang, Z.A.; Du, Y. Conjugation of inulin improves anti-biofilm activity of chitosan. Mar. Drugs, 2018, 16(5)E151
[http://dx.doi.org/10.3390/md16050151] [PMID: 29734657]
[26]
Asli, A.; Brouillette, E.; Ster, C.; Ghinet, M.G.; Brzezinski, R.; Lacasse, P.; Jacques, M.; Malouin, F. Antibiofilm and antibacterial effects of specific chitosan molecules on Staphylococcus aureus isolates associated with bovine mastitis. PLoS One, 2017, 12(5)e0176988
[http://dx.doi.org/10.1371/journal.pone.0176988] [PMID: 28486482]
[27]
Konwar, A.; Kalita, S.; Kotoky, J.; Chowdhury, D. Chitosan-Iron oxide coated graphene oxide nanocomposite hydrogel: A robust and soft antimicrobial biofilm. ACS Appl. Mater. Interfaces, 2016, 8(32), 20625-20634.
[http://dx.doi.org/10.1021/acsami.6b07510] [PMID: 27438339]
[28]
He, X.; Hwang, H.M.; Aker, W.G.; Wang, P.; Lin, Y.; Jiang, X.; He, X. Synergistic combination of marine oligosaccharides and azithromycin against Pseudomonas aeruginosa. Microbiol. Res., 2014, 169(9-10), 759-767.
[http://dx.doi.org/10.1016/j.micres.2014.01.001] [PMID: 24529598]
[29]
Khan, F.; Manivasagan, P.; Lee, J.W.; Pham, D.T.N.; Oh, J.; Kim, Y.M. Fucoidan-stabilized gold nanoparticle-mediated biofilm inhibition, attenuation of virulence and motility properties in Pseudomonas aeruginosa PAO1. Mar. Drugs, 2019, 17(4)E208
[http://dx.doi.org/10.3390/md17040208] [PMID: 30987163]
[30]
Khan, F.; Manivasagan, P.; Pham, D.T.N.; Oh, J.; Kim, S.K.; Kim, Y.M. Antibiofilm and antivirulence properties of chitosan-polypyrrole nanocomposites to Pseudomonas aeruginosa. Microb. Pathog., 2019, 128, 363-373.
[http://dx.doi.org/10.1016/j.micpath.2019.01.033] [PMID: 30684638]
[31]
Salinas, N.; Colletier, J-P.; Moshe, A.; Landau, M. Extreme amyloid polymorphism in Staphylococcus aureus virulent PSMα peptides. Nat. Commun., 2018, 9(1), 3512.
[http://dx.doi.org/10.1038/s41467-018-05490-0] [PMID: 30158633]
[32]
Blanco, L.P.; Evans, M.L.; Smith, D.R.; Badtke, M.P.; Chapman, M.R. Diversity, biogenesis and function of microbial amyloids. Trends Microbiol., 2012, 20(2), 66-73.
[http://dx.doi.org/10.1016/j.tim.2011.11.005] [PMID: 22197327]
[33]
Lee, J.H.; Cho, M.H.; Lee, J. 3-Indolylacetonitrile decreases Escherichia coli O157:H7 biofilm formation and Pseudomonas aeruginosa virulence. Environ. Microbiol., 2011, 13(1), 62-73.
[http://dx.doi.org/10.1111/j.1462-2920.2010.02308.x] [PMID: 20649646]
[34]
Lee, J.H.; Cho, H.S.; Kim, Y.; Kim, J.A.; Banskota, S.; Cho, M.H.; Lee, J. Indole and 7-benzyloxyindole attenuate the virulence of Staphylococcus aureus. Appl. Microbiol. Biotechnol., 2013, 97(10), 4543-4552.
[http://dx.doi.org/10.1007/s00253-012-4674-z] [PMID: 23318836]
[35]
Vandenesch, F.; Lina, G.; Henry, T. Staphylococcus aureus hemolysins, bi-component leukocidins, and cytolytic peptides: A redundant arsenal of membrane-damaging virulence factors? Front. Cell. Infect. Microbiol., 2012, 2, 12.
[http://dx.doi.org/10.3389/fcimb.2012.00012] [PMID: 22919604]
[36]
Wang, J.; Zhou, X.; Li, W.; Deng, X.; Deng, Y.; Niu, X. Curcumin protects mice from Staphylococcus aureus pneumonia by interfering with the self-assembly process of α-hemolysin. Sci. Rep., 2016, 6, 28254.
[http://dx.doi.org/10.1038/srep28254] [PMID: 27345357]
[37]
Hall, J.W.; Yang, J.; Guo, H.; Ji, Y. The Staphylococcus aureus AirSR two-component system mediates reactive oxygen species resistance via transcriptional regulation of staphyloxanthin production. Infect. Immun., 2017, 85(2), e00838-e16.
[http://dx.doi.org/10.1128/IAI.00838-16] [PMID: 27872240]
[38]
Gaupp, R.; Ledala, N.; Somerville, G.A. Staphylococcal response to oxidative stress. Front. Cell. Infect. Microbiol., 2012, 2, 33.
[http://dx.doi.org/10.3389/fcimb.2012.00033] [PMID: 22919625]
[39]
Zhang, H.; Zheng, Y.; Gao, H.; Xu, P.; Wang, M.; Li, A.; Miao, M.; Xie, X.; Deng, Y.; Zhou, H.; Du, H. Identification and characterization of Staphylococcus aureus strains with an incomplete hemolytic phenotype. Front. Cell. Infect. Microbiol., 2016, 6, 146.
[http://dx.doi.org/10.3389/fcimb.2016.00146] [PMID: 27917374]
[40]
Li, J.; Cai, C.; Li, J.; Li, J.; Li, J.; Sun, T.; Wang, L.; Wu, H.; Yu, G. Chitosan-based nanomaterials for drug delivery. Molecules, 2018, 23(10)E2661
[http://dx.doi.org/10.3390/molecules23102661] [PMID: 30332830]
[41]
Naskar, S.; Koutsu, K.; Sharma, S. Chitosan-based nanoparticles as drug delivery systems: A review on two decades of research. J. Drug Target., 2018, 1-15.
[PMID: 30103626]
[42]
Raafat, D.; von Bargen, K.; Haas, A.; Sahl, H.G. Insights into the mode of action of chitosan as an antibacterial compound. Appl. Environ. Microbiol., 2008, 74(12), 3764-3773.
[http://dx.doi.org/10.1128/AEM.00453-08] [PMID: 18456858]
[43]
Muslim, S.N.; Kadmy, I.; Ali, A.N.M.; Salman, B.K.; Ahmad, M.; Khazaal, S.S.; Hussein, N.H.; Muslim, S.N. Chitosan extracted from Aspergillus flavus shows synergistic effect, eases quorum sensing mediated virulence factors and biofilm against nosocomial pathogen Pseudomonas aeruginosa. Int. J. Biol. Macromol., 2018, 107(Pt A), 52-58.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.08.146]
[44]
Felipe, V.; Breser, M.L.; Bohl, L.P.; Rodrigues da Silva, E.; Morgante, C.A.; Correa, S.G.; Porporatto, C. Chitosan disrupts biofilm formation and promotes biofilm eradication in Staphylococcus species isolated from bovine mastitis. Int. J. Biol. Macromol., 2019, 126, 60-67.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.12.159] [PMID: 30586583]
[45]
Yusof, N.A.A.; Zain, N.M.; Pauzi, N. Synthesis of ZnO nanoparticles with chitosan as stabilizing agent and their antibacterial properties against Gram-positive and Gram-negative bacteria. Int. J. Biol. Macromol., 2019, 124, 1132-1136.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.11.228] [PMID: 30496864]
[46]
Liu, H.; Du, Y.; Wang, X.; Sun, L. Chitosan kills bacteria through cell membrane damage. Int. J. Food Microbiol., 2004, 95(2), 147-155.
[http://dx.doi.org/10.1016/j.ijfoodmicro.2004.01.022] [PMID: 15282127]
[47]
Bernkop-Schnürch, A.; Dünnhaupt, S. Chitosan-based drug delivery systems. Eur. J. Pharm. Biopharm., 2012, 81(3), 463-469.
[http://dx.doi.org/10.1016/j.ejpb.2012.04.007] [PMID: 22561955]
[48]
Wang, J.J.; Zeng, Z.W.; Xiao, R.Z.; Xie, T.; Zhou, G.L.; Zhan, X.R.; Wang, S.L. Recent advances of chitosan nanoparticles as drug carriers. Int. J. Nanomedicine, 2011, 6, 765-774.
[PMID: 21589644]
[49]
Bowman, K.; Leong, K.W. Chitosan nanoparticles for oral drug and gene delivery. Int. J. Nanomedicine, 2006, 1(2), 117-128.
[http://dx.doi.org/10.2147/nano.2006.1.2.117] [PMID: 17722528]
[50]
Mohammed, M.A.; Syeda, J.T.M.; Wasan, K.M.; Wasan, E.K. An overview of chitosan nanoparticles and its application in non-parenteral drug delivery. Pharmaceutics, 2017, 9(4)E53
[http://dx.doi.org/10.3390/pharmaceutics9040053] [PMID: 29156634]
[51]
Alves, N.M.; Mano, J.F. Chitosan derivatives obtained by chemical modifications for biomedical and environmental applications. Int. J. Biol. Macromol., 2008, 43(5), 401-414.
[http://dx.doi.org/10.1016/j.ijbiomac.2008.09.007] [PMID: 18838086]
[52]
El Knidri, H.; Belaabed, R.; Addaou, A.; Laajeb, A.; Lahsini, A. Extraction, chemical modification and characterization of chitin and chitosan. Int. J. Biol. Macromol.,, 2018, 120(pt A), 1181-1189.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.08.139]
[53]
Zhang, J.; Xia, W.; Liu, P.; Cheng, Q.; Tahirou, T.; Gu, W.; Li, B. Chitosan modification and pharmaceutical/biomedical applications. Mar. Drugs, 2010, 8(7), 1962-1987.
[http://dx.doi.org/10.3390/md8071962] [PMID: 20714418]
[54]
Muanprasat, C.; Chatsudthipong, V. Chitosan oligosaccharide: Biological activities and potential therapeutic applications. Pharmacol. Ther., 2017, 170, 80-97.
[http://dx.doi.org/10.1016/j.pharmthera.2016.10.013] [PMID: 27773783]
[55]
Wu, Z.; Huang, X.; Li, Y.C.; Xiao, H.; Wang, X. Novel chitosan films with laponite immobilized Ag nanoparticles for active food packaging. Carbohydr. Polym., 2018, 199, 210-218.
[http://dx.doi.org/10.1016/j.carbpol.2018.07.030] [PMID: 30143123]
[56]
Park, H.H.; Ko, S.C.; Oh, G.W.; Jang, Y.M.; Kim, Y.M.; Park, W.S.; Choi, I.W.; Jung, W.K. Characterization and biological activity of PVA hydrogel containing chitooligosaccharides conjugated with gallic acid. Carbohydr. Polym., 2018, 198, 197-205.
[http://dx.doi.org/10.1016/j.carbpol.2018.06.070] [PMID: 30092991]
[57]
Liaqat, F.; Eltem, R. Chitooligosaccharides and their biological activities: A comprehensive review. Carbohydr. Polym., 2018, 184, 243-259.
[http://dx.doi.org/10.1016/j.carbpol.2017.12.067] [PMID: 29352917]
[58]
Laokuldilok, T.; Potivas, T.; Kanha, N.; Surawang, S.; Seesuriyachan, P.; Wangtueai, S.; Phimolsiripol, Y.; Regenstein, J.M. Physicochemical, antioxidant, and antimicrobial properties of chitooligosaccharides produced using three different enzyme treatments. Food Biosci., 2017, 18, 28-33.
[http://dx.doi.org/10.1016/j.fbio.2017.03.004]
[59]
Tsai, G.J.; Zhang, S.L.; Shieh, P.L. Antimicrobial activity of a low-molecular-weight chitosan obtained from cellulase digestion of chitosan. J. Food Prot., 2004, 67(2), 396-398.
[http://dx.doi.org/10.4315/0362-028X-67.2.396] [PMID: 14968977]
[60]
Raafat, D.; Sahl, H.G. Chitosan and its antimicrobial potential--a critical literature survey. Microb. Biotechnol., 2009, 2(2), 186-201.
[http://dx.doi.org/10.1111/j.1751-7915.2008.00080.x] [PMID: 21261913]
[61]
Naqvi, S.; Moerschbacher, B.M. The cell factory approach toward biotechnological production of high-value chitosan oligomers and their derivatives: An update. Crit. Rev. Biotechnol., 2017, 37(1), 11-25.
[http://dx.doi.org/10.3109/07388551.2015.1104289] [PMID: 26526199]
[62]
Geisberger, G.; Gyenge, E.B.; Hinger, D.; Käch, A.; Maake, C.; Patzke, G.R. Chitosan-thioglycolic acid as a versatile antimicrobial agent. Biomacromolecules, 2013, 14(4), 1010-1017.
[http://dx.doi.org/10.1021/bm3018593] [PMID: 23470196]
[63]
Rzhepishevska, O.; Hakobyan, S.; Ruhal, R.; Gautrot, J.; Barbero, D.; Ramstedt, M. The surface charge of anti-bacterial coatings alters motility and biofilm architecture. Biomater. Sci., 2013, 1(6), 589-602.
[http://dx.doi.org/10.1039/c3bm00197k]
[64]
Zhang, A.; Mu, H.; Zhang, W.; Cui, G.; Zhu, J.; Duan, J. Chitosan coupling makes microbial biofilms susceptible to antibiotics. Sci. Rep., 2013, 3, 3364.
[http://dx.doi.org/10.1038/srep03364] [PMID: 24284335]
[65]
Schwartz, K.; Syed, A.K.; Stephenson, R.E.; Rickard, A.H.; Boles, B.R. Functional amyloids composed of phenol soluble modulins stabilize Staphylococcus aureus biofilms. PLoS Pathog., 2012, 8(6)e1002744
[http://dx.doi.org/10.1371/journal.ppat.1002744] [PMID: 22685403]
[66]
Periasamy, S.; Joo, H.S.; Duong, A.C.; Bach, T.H.; Tan, V.Y.; Chatterjee, S.S.; Cheung, G.Y.; Otto, M. How 7tgc o biofilms develop their characteristic structure. Proc. Natl. Acad. Sci. USA, 2012, 109(4), 1281-1286.
[http://dx.doi.org/10.1073/pnas.1115006109] [PMID: 22232686]
[67]
Selkoe, D.J. Folding proteins in fatal ways. Nature, 2003, 426(6968), 900-904.
[http://dx.doi.org/10.1038/nature02264] [PMID: 14685251]
[68]
Selkoe, D.J. Normal and abnormal biology of the beta-amyloid precursor protein. Annu. Rev. Neurosci., 1994, 17, 489-517.
[http://dx.doi.org/10.1146/annurev.ne.17.030194.002421] [PMID: 8210185]
[69]
Liu, H.; Ojha, B.; Morris, C.; Jiang, M.; Wojcikiewicz, E.P.; Rao, P.P.; Du, D. Positively charged chitosan and N-trimethyl chitosan inhibit Aβ40 fibrillogenesis. Biomacromolecules, 2015, 16(8), 2363-2373.
[http://dx.doi.org/10.1021/acs.biomac.5b00603] [PMID: 26125953]
[70]
Jia, S.; Lu, Z.; Gao, Z.; An, J.; Wu, X.; Li, X.; Dai, X.; Zheng, Q.; Sun, Y. Chitosan oligosaccharides alleviate cognitive deficits in an amyloid-β1-42-induced rat model of Alzheimer’s disease. Int. J. Biol. Macromol., 2016, 83, 416-425.
[http://dx.doi.org/10.1016/j.ijbiomac.2015.11.011] [PMID: 26601759]
[71]
Lee, S.H.; Park, J.S.; Kim, S.K.; Ahn, C.B.; Je, J.Y. Chitooligosaccharides suppress the level of protein expression and acetylcholinesterase activity induced by Abeta25-35 in PC12 cells. Bioorg. Med. Chem. Lett., 2009, 19(3), 860-862.
[http://dx.doi.org/10.1016/j.bmcl.2008.12.019] [PMID: 19097785]
[72]
Dai, X.; Chang, P.; Zhu, Q.; Liu, W.; Sun, Y.; Zhu, S.; Jiang, Z. Chitosan oligosaccharides protect rat primary hippocampal neurons from oligomeric β-amyloid 1-42-induced neurotoxicity. Neurosci. Lett., 2013, 554, 64-69.
[http://dx.doi.org/10.1016/j.neulet.2013.08.046] [PMID: 23999027]
[73]
Dai, X.; Hou, W.; Sun, Y.; Gao, Z.; Zhu, S.; Jiang, Z. Chitosan oligosaccharides inhibit/disaggregate fibrils and attenuate amyloid β-mediated neurotoxicity. Int. J. Mol. Sci., 2015, 16(5), 10526-10536.
[http://dx.doi.org/10.3390/ijms160510526] [PMID: 26006224]
[74]
Hoque, J.; Adhikary, U.; Yadav, V.; Samaddar, S.; Konai, M.M.; Prakash, R.G.; Paramanandham, K.; Shome, B.R.; Sanyal, K.; Haldar, J. Chitosan derivatives active against multidrug-resistant bacteria and pathogenic fungi: In vivo evaluation as topical antimicrobials. Mol. Pharm., 2016, 13(10), 3578-3589.
[http://dx.doi.org/10.1021/acs.molpharmaceut.6b00764] [PMID: 27589087]


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VOLUME: 20
ISSUE: 14
Year: 2019
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DOI: 10.2174/1389201020666190902130722
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