Helicobacter pylori Biofilm-Related Drug Resistance and New Developments in Its Anti-Biofilm Agents

Figures & data

Figure 1 Steps of H. pylori biofilm formation. Planktonic H. pylori (green) adhere to the surface of gastric epithelial cells and secrete molecules to create extracellular polymeric substances (EPS) to form an early biofilm structure and biofilm H. pylori (blue) are protected from the adverse external environment. After the biofilm matures, dead H. pylori (red) gradually appear due to the lack of nutrients in the biofilm and the biofilm dispersal into the next cycle.

Table 1 Natural Anti-Biofilm Agents Targeting H. pylori Infection

Natural Anti-Biofilm Agents	H. pylori Strains	In vivo/in vitro	Antibacterial Activity	Synergistic Antibiotics	References
Chelidonium majus and Corydalis cheilanthifolia Extracts	H. pylori 8064	in vitro	√	AMX	[88]
Atractylodes lancea volatile oils	NCTC 11637	in vitro	√		[89]
Pistacia vera L. oleoresin	clinical strains	in vitro and in vivo	√	LVX	[56]
Dihydrotanshinone I	G27 ATCC 43504 26,695 NSH57 clinical strains BHKS159	in vitro and in vivo	√	MTZ	[57]
Armeniaspirol A	G27 Hp159 clinical strains BHKS159	in vitro and in vivo	√		[12]
curcumin	ATCC 43504	in vitro			[90]
3-Bromopyruvate or Sertraline	ATCC 51932 H. pylori 8064	in vitro	√		[91]
Antimicrobial Peptide Cathelicidin	SS1 H. pylori 10,783	in vitro	√		[92]
Alginate Lyase	ATCC 43629	in vitro		CLR	[93]
Aloe vera inner gel	H. pylori 3/2013/A H. pylori 21/2011/A H. pylori 16/2012/A ATCC 43629	in vitro	√		[60]
Amu-ru 7	ATCC 43503 NCTC 11638 clinical strains	in vitro and in vivo	√		[58]
Hibiscus rosa sinensis L. Flower	ATCC 43504 ATCC 51932 clinical strains	in vitro	√		[94]
Rhamnolipid	SS1	in vitro	√	CLR, AMX	[95]
Sodium Lauryl Sulfate	SS1	in vitro	√		[96]
Lactobacillus salivarius LN12	SS1 ATCC43504 clinical strains	in vitro	√	CLR, AMX	[64]
Resveratrol	ATCC 43629 clinical strains	in vitro	√	LVX	[97]
Myricetin	ATCC 700824 ATCC 51932	in vitro	√	CLR, AMX LVX, MTZ, TET	[65]
Casearia sylvestris leaf derivatives	ATCC 43504	in vitro and in vivo	√		[59]
Lactobacillus plantarum LN66	ATCC 43504	in vitro		CLR, LVX	[98]
Nimbolide	G27 26,695 HPAG1 SS1 J99 7.13 USU101 USU103UA1182 (ATCC 700684)	in vitro	√		[99]
Carvacrol and Thymol	NCTC 11637 (ATCC 43504)	in vitro			[100]
Dioscin	H. pylori J99	in vitro	√	CLR, MTZ, LVX	[101]

Krzyzek P, Junka A, Slupski W, et al. Antibiofilm and antimicrobial-enhancing activity of Chelidonium majus and Corydalis cheilanthifolia extracts against multidrug-resistant Helicobacter pylori. Pathogens. 2021;10(8):1033. doi:10.3390/pathogens10081033

 Web of Science ®Google Scholar

Yu M, Wang X, Ling F, Wang H, Zhang P, Shao S. Atractylodes lancea volatile oils attenuated helicobacter pylori NCTC11637 growth and biofilm. Microb Pathog. 2019;135:103641. doi:10.1016/j.micpath.2019.103641

 Web of Science ®Google Scholar

Di Lodovico S, Napoli E, Di Campli E, et al. Pistacia vera L. Oleoresin and levofloxacin is a synergistic combination against resistant Helicobacter pylori strains. Sci Rep. 2019;9(1):4646. doi:10.1038/s41598-019-40991-y

 Web of Science ®Google Scholar

Luo P, Huang Y, Hang X, et al. Dihydrotanshinone I is effective against drug-resistant Helicobacter pylori in vitro and in vivo. Antimicrob Agents Chemother. 2021;65(3). doi:10.1128/AAC.01921-20

 PubMed Web of Science ®Google Scholar

Jia J, Zhang C, Liu Y, et al. Armeniaspirol A: a novel anti-Helicobacter pylori agent. Microb Biotechnol. 2021;15(2):442–454. doi:10.1111/1751-7915.13807

 Web of Science ®Google Scholar

Vetvicka V, Vetvickova J, Fernandez-Botran R. Effects of curcumin on Helicobacter pylori infection. Ann Transl Med. 2016;4(24):479. doi:10.21037/atm.2016.12.52

 Web of Science ®Google Scholar

Krzyzek P, Gosciniak G, Fijalkowski K, et al. Potential of bacterial cellulose chemisorbed with anti-metabolites, 3-bromopyruvate or sertraline, to fight against Helicobacter pylori lawn biofilm. Int J Mol Sci. 2020;21(24):9507. doi:10.3390/ijms21249507

 Web of Science ®Google Scholar

Zhang L, Wu WK, Gallo RL, et al. Critical role of antimicrobial peptide cathelicidin for controlling helicobacter pylori survival and infection. J Immunol. 2016;196(4):1799–1809. doi:10.4049/jimmunol.1500021

 PubMed Web of Science ®Google Scholar

Bugli F, Palmieri V, Torelli R, et al. In vitro effect of clarithromycin and alginate lyase against helicobacter pylori biofilm. Biotechnol Prog. 2016;32(6):1584–1591. doi:10.1002/btpr.2339

 Web of Science ®Google Scholar

Cataldi V, Di Bartolomeo S, Di Campli E, Nostro A, Cellini L, Di Giulio M. In vitro activity of Aloe vera inner gel against microorganisms grown in planktonic and sessile phases. Int J Immunopathol Pharmacol. 2015;28(4):595–602. doi:10.1177/0394632015600594

 Web of Science ®Google Scholar

Bai CL, Osaki T, Yonezawa H, et al. In vitro and in vivo effects of the Mongolian drug Amu-ru 7 on Helicobacter pylori growth and viability. Microbiol Immunol. 2010;54(9):508–515. doi:10.1111/j.1348-0421.2010.00246.x

 Web of Science ®Google Scholar

Tran TH, Truong THH, Nguyen TTL, Nguyen VMH, Thi NM, Luong TM. Growth-inhibiting, bactericidal, antibiofilm, and urease inhibitory activities of Hibiscus rosa sinensis L. flower constituents toward antibiotic sensitive- and resistant-strains of Helicobacter pylori. ACS Omega. 2020;5(32):20080–20089. doi:10.1021/acsomega.0c01640

 PubMed Web of Science ®Google Scholar

Chen X, Li P, Shen Y, Zou Y, Yuan G, Hu H. Rhamnolipid-involved antibiotics combinations improve the eradication of Helicobacter pylori biofilm in vitro: a comparison with conventional triple therapy. Microb Pathog. 2019;131:112–119. doi:10.1016/j.micpath.2019.04.001

 PubMed Web of Science ®Google Scholar

Shen Y, Li P, Chen X, et al. Activity of sodium lauryl sulfate, rhamnolipids, and N-Acetylcysteine against biofilms of five common pathogens. Microb Drug Resist. 2020;26(3):290–299. doi:10.1089/mdr.2018.0385

 Web of Science ®Google Scholar

Jin F, Yang H. Effects of Lactobacillus salivarius LN12 in Combination with amoxicillin and clarithromycin on Helicobacter pylori biofilm in vitro. Microorganisms. 2021;9(8):1611. doi:10.3390/microorganisms9081611

 Web of Science ®Google Scholar

Di Fermo P, Di Lodovico S, Amoroso R, et al. Searching for new tools to counteract the helicobacter pylori resistance: the positive action of resveratrol derivatives. Antibiotics. 2020;9(12). doi:10.3390/antibiotics9120891

 Web of Science ®Google Scholar

Krzyzek P, Migdal P, Paluch E, Karwanska M, Wieliczko A, Gosciniak G. Myricetin as an antivirulence compound interfering with a morphological transformation into coccoid forms and potentiating activity of antibiotics against Helicobacter pylori. Int J Mol Sci. 2021;22(5):2695. doi:10.3390/ijms22052695

 Web of Science ®Google Scholar

Sposito L, Oda FB, Vieira JH, et al. In vitro and in vivo anti-Helicobacter pylori activity of Casearia sylvestris leaf derivatives. J Ethnopharmacol. 2019;233:1–12. doi:10.1016/j.jep.2018.12.032

 PubMed Web of Science ®Google Scholar

Ji J, Yang H. In vitro effects of lactobacillus plantarum ln66 and antibiotics used alone or in combination on Helicobacter pylori mature biofilm. Microorganisms. 2021;9(2):424. doi:10.3390/microorganisms9020424

 Web of Science ®Google Scholar

Wylie MR, Windham IH, Blum FC, Wu H, Merrell DS. In vitro antibacterial activity of nimbolide against Helicobacter pylori. J Ethnopharmacol. 2022;285:114828. doi:10.1016/j.jep.2021.114828

 Web of Science ®Google Scholar

Grande R, Carradori S, Puca V, et al. Selective inhibition of helicobacter pylori carbonic anhydrases by carvacrol and thymol could impair biofilm production and the release of outer membrane vesicles. Int J Mol Sci. 2021;22(21):11583. doi:10.3390/ijms222111583

 PubMed Web of Science ®Google Scholar

Spiegel M, Krzyzek P, Dworniczek E, Adamski R, Sroka Z. In silico screening and in vitro assessment of natural products with anti-virulence activity against Helicobacter pylori. Molecules. 2021;27(1):20. doi:10.3390/molecules27010020

 Web of Science ®Google Scholar