Prospects for the use of antimicrobial peptides as antihelicobacterial agents in pediatric practice

Authors

  • T.V. Sorokman Bukovinian State Medical University, Ukraine
  • P.M. Moldova Bukovinian State Medical University, Ukraine
  • О.V. Makarova Bukovinian State Medical University, Ukraine

Abstract

Purpose – to analise of literature data on the prospects of using antimicrobial peptides.

The article presents a literature review antimicrobial peptides. We searched for published and unpublished research using Pubmed as the search engine by the key words: antimicrobial peptides, defensins, cathelicidins, children, Helicobacter pylori (H. pylori), antibiotic resistance taking into consideration studies conducted in the last 20 years, citation review of relevant primary and review articles, conference abstracts, personal files, and contact with expert informants. The criterion for the selection of articles for the study was based on their close relevance to the topic, thus out of 2256 analyzed articles, the findings of the researchers covered in 75 articles were crucial. An urgent task of modern scientific and practical medicine is to overcome resistance to the world's most common H. pylori infection. Resistance to the main antimicrobial drugs included in the first line of treatment is quite high. The presence of cross-antibiotic resistance and the direct association of H. pylori infection with the development of gastric and duodenal diseases in childhood have led to the urgency of this problem. It is with the increase in resistance of H. pylori to antibacterial drugs associated with the growth of diseases and complications caused by pathology of the gastroduodenal area, and hence — a significant increase in treatment costs, which is not only medical but also socio-economic problem. Therefore, antimicrobial peptides, which can replace traditional antibacterial drugs, are considered a new class of anti-infectives today. The most promising developments in this direction are the study of the antibacterial effect of endogenous antimicrobial peptides.

The main attention is paid to the clinical role of the recently described antimicrobial factors — difensins and cathelicidins, which are endogenously synthesized by neutrophils and many epithelial cells of the human body, including the gastrointestinal tract. The range of their action is quite wide — antioxidant, antihypertensive, antifungal, antiviral, antibacterial, antitumor, immunoregulatory. In particular, H. pylori infection leads to a significant induction of β-defensins, which play a key role in the immune response of the gastrointestinal epithelium to H. pylori infection, affecting and activating the adaptive immune system. Although most antimicrobial peptides are directly synthesized in their active forms, posttranslational modification is required to perform their functions. Some drugs of antimicrobial peptides are already used in clinical practice.

 

References

Alalwani SM, Sierigk J, Herr Ch, Pinkenburg O et al. (2010). The antimicrobial peptide LL-37 modulates the inflammatory and host defense response of human neutrophils. Eur J Immunol. 40 (4): 1118-1126. https://doi.org/10.1002/eji.200939275; PMid:20140902 PMCid:PMC2908514

Arslan N, Yilmaz O, Demiray-Gurbuz E. (2017). World Importance of antimicrobial susceptibility testing for the management of eradication in Helicobacter pylori infection. J Gastroenterol. 2823 (16): 2854-2869. https://doi.org/10.3748/wjg.v23.i16.2854; PMid:28522904 PMCid:PMC5413781

Bandurska K, Berdowska A, Barczynska-Felusiak R, Krupa P. (2015). Unique features of human cathelicidin LL-37. Biofactors. 41 (5): 289-300. https://doi.org/10.1002/biof.1225; PMid:26434733

Barksdale SM, Hrifko EJ, van Hoek ML. (2017). Cathelicidin antimicrobial peptide from Alligator mississippiensis has antibacterial activity against multi-drug resistant Acinetobacter baumanii and Klebsiella pneumoniae. Dev Comp Immunol. 70: 135-144. https://doi.org/10.1016/j.dci.2017.01.011; PMid:28089718

Bauer B, Wex T, Kuester D, Meyer T, Malfertheiner P. (2013). Differential expression of human beta defensin 2 and 3 in gastric mucosa of Helicobacter pylori-infected individuals. Helicobacter. 18 (1): 6-12. https://doi.org/10.1111/hel.12000; PMid:23067102

Bilgilier C, Stadlmann A, Makristathis A et al. (2018). Austrian Helicobacter Study Group of the Austrian Society of Gastroenterology and Hepatology. Prospective multicentre clinical study on inter- and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori. Clin Microbiol Infect. 24: 267-272. https://doi.org/10.1016/j.cmi.2017.06.025; PMid:28669844

Brannan AM, Whelan WA, Cole E, Booth V. (2015). Differential scanning calorimetry of whole Escherichia coli treated with the antimicrobialpeptide MSI-78 indicate a multi-hit mechanism with ribosomes as a novel target. Peer J. 3: 516. https://doi.org/10.7717/peerj.1516; PMid:26713257 PMCid:PMC4690349

Buda De Cesare G, Cristy SA, Garsin DA, Lorenz MC. (2020). Antimicrobial Peptides: a New Frontier in Antifungal Therapy mBio. 11 (6): e02123-20. https://doi.org/10.1128/mBio.02123-20; PMid:33144376 PMCid:PMC7642678

Chen D, Cunningham SA, Cole NC, Peggy C. (2017). Antimicrob Agents Chemother. 61 (4): e02530-16. https://doi.org/10.1128/AAC.02530-16; PMid:28167563 PMCid:PMC5365656

Chromek M, Arvidsson I, Karpman DT. (2012). The antimicrobial peptide cathelicidin protects mice from Escherichia coli O157: H7-mediated disease. PLoS One. 7 (10): e46476. https://doi.org/10.1371/journal.pone.0046476; PMid:23077510 PMCid:PMC3471911

Chung C, Silwal P, Kim I, Modlin RL, Jo EK. (2020). Vitamin d-cathelicidin axis: at the Crossroads between Protective Immunity and Pathological Inflammation during Infection. Immune Netw. 20 (2): e12. https://doi.org/10.4110/in.2020.20.e12; PMid:32395364 PMCid:PMC7192829

Cuadrado-Lavin A, Salcines-Caviedes JR, Carrascosa MF et al. (2012). Antimicrobial susceptibility of Helicobacter pylori to six antibiotics currently used in Spain. J Antimicrob Chemother. 67: 170-173. https://doi.org/10.1093/jac/dkr410; PMid:21965436

Cunliffe RN. (2003). Alpha-defensins in the gastrointestinal tract. Mol Immunol. 40 (7): 463-467. https://doi.org/10.1016/S0161-5890(03)00157-3

Czaplewski L, Bax R, Clokie M et al. (2016). Alternatives to antibiotics a pipeline portfolio review. Lancet Infect Dis. 16 (2): 239-251. https://doi.org/10.1016/S1473-3099(15)00466-1

Davidson DJ, Currie AJ, Reid GS. (2004). The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization. J Immunol. 172 (2): 1146-1156. https://doi.org/10.4049/jimmunol.172.2.1146; PMid:14707090

Doss M, White MR, Tecle T, Hartshorn KL. (2010). Human defensins and LL-37 in mucosal immunity. J Leukoc Biol. 87: 79-92. https://doi.org/10.1189/jlb.0609382; PMid:19808939 PMCid:PMC7167086

Droin N, Hendra JB, Ducoroy P, Solary E. (2009). Human defensins as cancer biomarkers and antitumour molecules. J Proteomics. 72 (6): 918-927. https://doi.org/10.1016/j.jprot.2009.01.002; PMid:19186224

Dudnyk VM, Khromykh KV, Fedchushen OP. (2017). Changes in the lung function depending on the 25-hydroxycholecalciferol and cathelitcidin LL-37 serum level in children with asthma. Fundamentalis scientiam. 4 (5): 97-100.

Fabisiak A, Murawska N, Fichna J. (2016). LL-37: cathelicidin-related antimicrobial peptide with pleiotropic activity. Pharmacol Rep. 68: 802-808. https://doi.org/10.1016/j.pharep.2016.03.015; PMid:27117377

Fan D, Coughlin LA, Neubauer MM et al. (2020). Activation of HIF-1α and LL-37 by commensal bacteria inhibits Candida albicans colonization. Nat Med. 21: 808-814. https://doi.org/10.1038/nm.3871; PMid:26053625 PMCid:PMC4496259

Faye I, Lindberg BG. (2016). Towards a paradigm shift in innate immunity-seminal work by Hans G Boman and co-workers. Philos Trans R Soc Lond B Biol Sci. 371 (1695): 20150303. https://doi.org/10.1098/rstb.2015.0303; PMid:27160604 PMCid:PMC4874399

Gisbert JP. (2020). Empirical or susceptibility-guided treatment for Helicobacter pylori infection? A comprehensive review. Therap Adv Gastroenterol. 13: https://doi.org/10.1177/1756284820968736; PMid:33240392 PMCid:PMC7675893

Hans M, Madaan Hans V. (2014). Epithelial antimicrobial peptides: guardian of the oral cavity. International Journal of Peptides: 1-13. https://doi.org/10.1155/2014/370297; PMid:25435884 PMCid:PMC4243596

Hase K, Murakami M, Iimura M et al. (2003). Expression of LL-37 by human gastric epithelial cells as a potential host defense mechanism against Helicobacter pylori. Gastroenterology. 125 (6): 1613-1625. https://doi.org/10.1053/j.gastro.2003.08.028; PMid:14724813

Hazlett L, Wu M. (2011). Defensins in innate immunity. Cell Tissue Res. 343 (1): 175-188. https://doi.org/10.1007/s00441-010-1022-4; PMid:20730446

Hunt RH, Xiao SD, Megraud F et al. (2011). World Gastroenterology Organization. Helicobacter pylori in developing countries. World Gastroenterology Organisation Global Guideline. J Gastrointestin Liver Dis. 20: 299-304.

Kahlenberg JM, Kaplan MJ. (2013). Little peptide, big effects: the role of LL-37 in inflammation and autoimmune disease. J Immunol. 191: 4895-4901. https://doi.org/10.4049/jimmunol.1302005; PMid:24185823 PMCid:PMC3836506

Kawauchi K, Yagihashi A, Tsuji N et al. (2006). Human beta-defensin-3 induction in H. pylori-infected gastric mucosal tissues. World J Gastroenterol. 12 (36): 5793-5797. https://doi.org/10.3748/wjg.v12.i36.5793; PMid:17007044 PMCid:PMC4100659

Kim SY, Chung JW. (2020). Best Helicobacter pylori Eradication Strategy in the Era of Antibiotic Resistance. Antibiotics (Basel). 9 (8): 436. https://doi.org/10.3390/antibiotics9080436; PMid:32717826 PMCid:PMC7459868

Krzyzek P, Grande R. (2020). Transformation of Helicobacter pylori into Coccoid Forms as a Challenge for Research Determining Activity of Antimicrobial Substances. Pathogens. 9 (3): 184. https://doi.org/10.3390/pathogens9030184; PMid:32143312 PMCid:PMC7157236

Leszczynska K, Namiot A, Fein DE et al. (2009). Bactericidal activities of the cationic steroid CSA-13 and the cathelicidin peptide ll-37 against Helicobacter pylori in simulated gastric juice. BMC Microbiol. 9: 187. https://doi.org/10.1186/1471-2180-9-187; PMid:19728885 PMCid:PMC2748089

Lezhenko GO, Abaturov AE, Pashkova OE, Kraynya HV. (2017). The role of endogenous antibacterial peptides in pneumonia occurrence among children of young age. Zdorov'e rebenka. 12: 104-108. https://doi.org/10.22141/2224-0551.12.2.2017.99762

Li Y, Osterhus S, Johnsen IB. (2018). Human metapneumovirus infection inhibits cathelicidin antimicrobial peptide expression in human macrophages. Front Immunol. 9: 902. https://doi.org/10.3389/fimmu.2018.00902; PMid:29780383 PMCid:PMC5946005

Liscano Y, Onate-Garzon J, Delgado JP. (2020). Peptides with Dual Antimicrobial-Anticancer Activity: Strategies to Overcome Peptide Limitations and Rational Design of Anticancer Peptides. Molecules (Basel, Switzerland). 25 (18): 4245. https://doi.org/10.3390/molecules25184245; PMid:32947811 PMCid:PMC7570524

Luthje P, Brauner A. (2016). Novel Strategies in the Prevention and Treatment of Urinary Tract Infections. Pathogens. 5 (1): 13. https://doi.org/10.3390/pathogens5010013; PMid:26828523 PMCid:PMC4810134

Malik E, Dennison SR, Harris F, Phoenix DA. (2016). pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents. Pharmaceuticals (Basel). 9 (4): 67. https://doi.org/10.3390/ph9040067; PMid:27809281 PMCid:PMC5198042

Mascellino MT, Oliva A, Miele MC et al. (2020). Antibiotics (Basel). 9 (9): 549. https://doi.org/10.3390/antibiotics9090549; PMid:32872117 PMCid:PMC7560230

Mascellino MT, Porowska B, Angelis MDe, Oliva A. (2017). Antibiotic susceptibility, heteroresistance, and updated treatment strategies in Helicobacter pylori infection. Drug Des Devel Ther. 11: 2209-2220. https://doi.org/10.2147/DDDT.S136240; PMid:28814829 PMCid:PMC5546184

Matsumoto H, Shiotani A, Graham DY. (2019). Current and Future Treatment of Helicobacter pylori Infections. Adv Exp Med Biol. 1149: 211-225. https://doi.org/10.1007/5584_2019_367; PMid:31016626 PMCid:PMC6918954

Matsuzaki K. (1999). Why and how are peptide-lipid interactions utilized for self-defense? Magainins and tachyplesins as archetypes. Biochim Biophys Acta. 1462: 1-10. https://doi.org/10.1016/S0005-2736(99)00197-2

Megraud F, Coenen S, Versporten A et al. (2013). Study Group participants. Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption. Gut. 62: 34-42. https://doi.org/10.1136/gutjnl-2012-302254; PMid:22580412

Memarpoor-Yazdia M, Asoodehbc A, Chamania JK. (2012). A novel antioxidant and antimicrobial peptide from hen egg white lysozyme hydrolysates. Journal of Functional Foods on ScienceDirect. 4: 278-228. https://doi.org/10.1016/j.jff.2011.12.004

Nigro E, Colavita I, Sarnataro D et al. (2015). An ancestral host defence peptide within human â-defensin 3 recapitulates the antibacterial and antiviral activity of the full-length molecule. Sci Rep. 1 (5): 18450. https://doi.org/10.1038/srep18450; PMid:26688341 PMCid:PMC4685272

Niyonsaba F, Nagaoka I, Ogawa H, Okumura K. (2009). Multifunctional antimicrobial proteins and peptides: natural activators of immune systems. Curr Pharm Des. 15 (21): 2393-2413. https://doi.org/10.2174/138161209788682271; PMid:19601839

Otte JM, Neumann HM, Brand S et al. (2020). Schmitz F. Expression of beta-defensin 4 is increased in human gastritis. Eur J Clin Invest. 39 (2): 126-138. https://doi.org/10.1111/j.1365-2362.2008.02071.x; PMid:19200166

Padra M, Benktander J, Robinson K, Linden SK. (2019). Carbohydrate-Dependent and Antimicrobial Peptide Defence Mechanisms Against Helicobacter pylori Infections, Molecular Mechanisms of Inflammation: Induction, Resolution and Escape by Helicobacter pylori. Curr Top Microbiol Immunol. 421: 179-207. https://doi.org/10.1007/978-3-030-15138-6_8; PMid:31123890

Patel SR, Smith K, Letley DP et al. (2013). Helicobacter pylori downregulates expression of human â-defensin 1 in the gastric mucosa in a type IV secretion-dependent fashion. Cell Microbiol. 15 (12): 2080-2092. https://doi.org/10.1111/cmi.12174; PMid:23870035 PMCid:PMC4028989

Patil A, Hughes AL, Zhang G. (2004). Rapid evolution and diversification of mammalian alpha-defensins as revealed by comparative analysis of rodent and primate genes. Physiol Genomics. 15, 20 (1): 1-11 https://doi.org/10.1152/physiolgenomics.00150.2004; PMid:15494476

Perederiy VG, Volodicheva YA, Kuzenko YUG, Kostenko IG. (2011). Bacteriological method for determining the sensitivity of Helicobacter pylori to antibacterial drugs. Suchasna hastroenterolohiya. 3 (59): 34.

Pero R, Coretti L, Nigro E et al. (2017). Scudiero β-Defensins in the Fight against Helicobacter pylori. Molecules. 22 (3): 424. https://doi.org/10.3390/molecules22030424; PMid:28272373 PMCid:PMC6155297

Roszczenko-Jasinska, Wojtys MІ, Jagusztyn-Krynicka EK. (2020). Helicobacter pylori treatment in the post-antibiotics era searching for new drug targets. Appl Microbiol Biotechnol. 104 (23): 9891-9905. https://doi.org/10.1007/s00253-020-10945-w; PMid:33052519 PMCid:PMC7666284

Sakamoto N, Mukae H, Fujii T. (2005). Differential effects of alpha- and beta-defensin on cytokine production by cultured human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol. 288 (3): 508-513. https://doi.org/10.1152/ajplung.00076.2004; PMid:15557089

Saracino IM, Zullo A, Holton J et al. (2012). High prevalence of primary antibiotic resistance in Helicobacter pylori isolates in Italy. J Gastrointestin Liver Dis. 21: 363-365.

Sass V, Schneider T, Wilmes M et al. (2010). Human beta-defensin 3 inhibits cell wall biosynthesis in Staphylococci. Infect Immun. 78 (6): 2793-2800. https://doi.org/10.1128/IAI.00688-09; PMid:20385753 PMCid:PMC2876548

Schneider JJ, Unholzer A, Schaller M, Schafer-Korting M, Korting HC. (2005). Human defensins. J Mol Med (Berl). 83 (8): 587-595. https://doi.org/10.1007/s00109-005-0657-1; PMid:15821901

Schnupf P, Gaboriau-Routhiau V, Sansonetti PJ, Cerf-Bensussan N. (2017). Segmented filamentous bacteria, Th17 induc Curr Opin Microbiol. 35: 100-109. https://doi.org/10.1016/j.mib.2017.03.004; PMid:28453971

Sechet E, Telford E, Bonamy C, Sansonetti PJ, Sperandio B. (2018). Natural molecules induce and synergize to boost expression of the human antimicrobial peptide β-defensin-3. Proc Natl Acad Sci USA. 115 (42): E9869-E9878. https://doi.org/10.1073/pnas.1805298115; PMid:30275324 PMCid:PMC6196494

Seppanen EJ, Thornton RB, Corscadden KJ et al. High concentrations of middle ear antimicrobial peptides and proteins and proinflammatory cytokines are associated with detection of middle ear pathogens in children with recurrent acute otitis media. (2019). PLoS One. 14 (12): e0227080. https://doi.org/10.1371/journal.pone.0227080; PMid:31877198 PMCid:PMC6932785

Shahane G, Ding W, Palaiokostas M et al. (2019). Interaction of Antimicrobial Lipopeptides with Bacterial Lipid Bilayers. J Membrane Biol. 252: 317-329. https://doi.org/10.1007/s00232-019-00068-3; PMid:31098677 PMCid:PMC6790193

Shai Y. (1999). Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by á-helical antimicrobial and cell non-selective membrane-lytic peptides. Biochim Biophys Acta. 1462: 55-70. https://doi.org/10.1016/S0005-2736(99)00200-X

Sheh A, Fox JG. (2013). The role of the gastrointestinal microbiome in Helicobacter pylori pathogenesis. Gut Microbes. 4 (6): 505-531. https://doi.org/10.4161/gmic.26205; PMid:23962822 PMCid:PMC3928162

Smyth D, Cameron A, Davies MR et al. (2020). DrsG from Streptococcus dysgalactiae subsp equisimilis inhibits the antimicrobial peptide LL-37. Infect Immun. 82: 2337-2344. https://doi.org/10.1128/IAI.01411-13; PMid:24664506 PMCid:PMC4019180

Subbalakshmi C, Sitaram N. (1998). Mechanism of antimicrobial action of indolicidin. FEMS Microbiol. Lett. 60: 91-96. https://doi.org/10.1111/j.1574-6968.1998.tb12896.x; PMid:9495018

Suzuki S, Esaki M, Kusano C, Ikehara H, Gotoda T. (2019). Development of Helicobacter pylori treatment: How do we manage antimicrobial resistance? World J Gastroenterol. 25 (16): 1907-1912. https://doi.org/10.3748/wjg.v25.i16.1907; PMid:31086459 PMCid:PMC6487377

Taha AS, Faccenda E, Angerson WJ, Balsitis M, Kelly RW. (2005). Gastric epithelial anti-microbial peptides-histological correlation and influence of anatomical site and peptic ulcer disease. Dig Liver Dis. 37 (1): 51-56. https://doi.org/10.1016/j.dld.2004.07.019; PMid:15702860

Tavano R, Sega D, Gobbo M, Papini E. (2011). The honeybee antimicrobial peptide apidaecin differentially immunomodulates human-macrophages, monocytes and dendritic cells. J Innate Immun. 3: 614-622. https://doi.org/10.1159/000327839; PMid:21677421

Thung H, Aramin V, Vavinskaya S. (2016). Review article: the global emergence of Helicobacter pylori antibiotic resistance. Aliment Pharmacol Ther. 43 (4): 514-533. https://doi.org/10.1111/apt.13497; PMid:26694080 PMCid:PMC5064663

Treneva MS, Pampura AN. (2011). Antimicrobial peptides in the pathogenesis of atopic dermatitis. Rossiyskiy vestnik perinatologii i pediatrii. 2: 80-83.

Tuerkova A, Kabelka I, Kralova T et al. (2020). Effect of helical kink in antimicrobial peptides on membrane pore formation. Elife. 9: e47946. https://doi.org/10.7554/eLife.47946; PMid:32167466 PMCid:PMC7069690

Walker CR, Hautefort I, Dalton JE et al. (2013). Intestinal intraepithelial lymphocyte-enterocyte crosstalk regulates production of bactericidal angiogenin 4 by Paneth cells upon microbial challenge. PLoS One. 8 (12): e84553. https://doi.org/10.1371/journal.pone.0084553; PMid:24358364 PMCid:PMC3866140

Wan M, van der Does AM, Tang X et al. (2014). Antimicrobial peptide LL-37 promotes bacterial phagocytosis by human macrophages. J Leukoc Biol. 95 (6): 971-981. https://doi.org/10.1189/jlb.0513304; PMid:24550523

Woods EC, Edwards AN, Childress KO, Jones JB, McBride SM. (2018). The C difficile clnRAB operon initiates adaptations to the host environment in response to LL-37. PLoS Pathog. 14: e1007153. https://doi.org/10.1371/journal.ppat.1007153; PMid:30125334 PMCid:PMC6117091

Yousr M, Howell N. (2015). Antioxidant and ACE Inhibitory Bioactive Peptides Purified from Egg Yolk Proteins. Int J Mol Sci. 16 (12): 29161-29178. https://doi.org/10.3390/ijms161226155; PMid:26690134 PMCid:PMC4691102

Zasloff M. (2002). Antimicrobial peptides of multicellular organisms. Nature. 415: 389-395. https://doi.org/10.1038/415389a; PMid:11807545

Zuberbier T, Orlow SJ, Paller AS et al. (2006). A perspective on the benefit of p10 in atopic dermatitis. The Journal of Allergy and Clinical Immunology. 11 (1): 226-223. https://doi.org/10.1016/j.jaci.2006.02.031; PMid:16815160

Published

2021-01-02