Temporin-SHa and Its Analogs as Potential Candidates for the Treatment of Helicobacter pylori.

Hamza Olleik,Marine Manzoni,Arif Iftikhar Khan,Muhammad Iqbal Choudhary,Muhammad Nadeem-Ul-Haque,Philippe Sockeel,Eric Di Pasquale,Akram Hijazi,Hunain Ali,Lucas Dupuis,Farzana Shaheen,Ghislain Pauleau,Marc Maresca,Géraldine Goin,Josette Raymond,Yvain Goudard,Elias Baydoun,Bruno De La Villéon,Josette Perrier

doi:10.3390/biom9100598

Abstract

Helicobacterpylori is one of the most prevalent pathogens colonizing 50% of the world’s population and causing gastritis and gastric cancer. Even with triple and quadruple antibiotic therapies, H. pylori shows increased prevalence of resistance to conventional antibiotics and treatment failure. Due to their pore-forming activity, antimicrobial peptides (AMP) are considered as a good alternative to conventional antibiotics, particularly in the case of resistant bacteria. In this study, temporin-SHa (a frog AMP) and its analogs obtained by Gly to Ala substitutions were tested against H. pylori. Results showed differences in the antibacterial activity and toxicity of the peptides in relation to the number and position of D-Ala substitution. Temporin-SHa and its analog NST1 were identified as the best molecules, both peptides being active on clinical resistant strains, killing 90–100% of bacteria in less than 1 h and showing low to no toxicity against human gastric cells and tissue. Importantly, the presence of gastric mucins did not prevent the antibacterial effect of temporin-SHa and NST1, NST1 being in addition resistant to pepsin. Taken together, our results demonstrated that temporin-SHa and its analog NST1 could be considered as potential candidates to treat H. pylori, particularly in the case of resistant strains.

Highlights

Helicobacter pylori is a Gram-negative microaerophilic bacterium able to establish a lifelong infection in humans after its acquisition during childhood [1]
The activity of temporin-SHa and its analogs NST1, NST2, and NST3 was tested on clinical strains of H. pylori obtained from patients and resistant to conventional antibiotics such as clarithromycin and metronidazole (Table 5, Figure 7)
To know if the higher minimal inhibitory concentration (MIC) found on clinical strains compared to the ATCC strain were due to the presence of fetal bovine serum (FBS) in the media, MIC of the four peptides were repeated on the reference H. pylori strain (ATCC 43504) in the same media

Summary

Introduction

Helicobacter pylori is a Gram-negative microaerophilic bacterium able to establish a lifelong infection in humans after its acquisition during childhood [1]. H. pylori is one of the most prevalent pathogens, which colonizes 50% of the world’s population (and more than 90% of the population in a developing country) and survives in the human stomach if not treated. H. pylori causes many gastrointestinal diseases including peptic ulcers and gastritis in 10% of patients. H. pylori infection has been associated to gastric carcinoma in 1% of the case, causing. In addition to health issues, H. pylori infection has important economic consequences with approximately six billion losses annually [2]. Prevention of health and economic complications associated with H. pylori depends on its successful eradication [3,4]

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