Gencefe Client Article | Novel Therapeutic Strategies for Drug-Resistant Helicobacter pylori — Investigating the Role of tmRNA in Zinc Acetate

Helicobacter pylori (H. pylori) infection is a major contributor to chronic inflammation in the stomach, rendering individuals susceptible to peptic ulcers and gastric cancer [1-3]. Over half of the global population harbors H. pylori within the gastric mucosa, with prevalence exceeding 80% in certain regions such as Asia [4, 5]. Eradication of H. pylori has been shown to reduce the long-term risk of peptic ulcers and gastric cancer [6, 7]. However, the rapid increase in H. pylori antibiotic resistance hinders antibiotic-based treatment methods. Metal chelating compounds, such as bismuth, are commonly added to H. pylori combination therapies in clinical treatment [8]. The addition of zinc-based complexes, such as polaprezinc (a chelate compound of zinc and l-carnosine), has been proven to improve the eradication of H. pylori [9, 10]. Currently, research on the impact of zinc acetate on H. pylori growth and antibiotic sensitivity is limited.

In November 2022, Professor Gangshi Wang and his research team from the 301 Hospital published an article in the "Microbiology Spectrum" journal titled "Transcriptomic and Functional Approaches Unveil the Role of tmRNA in Zinc Acetate Mediated Levofloxacin Sensitivity in Helicobacter pylori." The research demonstrated the inhibitory effect of zinc acetate on in vitro H. pylori growth, explored the transcriptomic changes induced by zinc acetate treatment in H. pylori, and investigated the knockdown effects of differentially expressed tmRNA (ssrA) on antibiotic sensitivity [11].

In this study, siRNA against ssrA designed and synthesized by GenCefe Biotech was used to successfully knock down the ssrA gene.

Result:

1. Zinc acetate inhibits the growth of Helicobacter pylori and increases its sensitivity to levofloxacin

2. Transcriptomic Changes Induced by Zinc Acetate Treatment in Helicobacter pylori

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RNA sequencing was employed to assess changes in gene expression between the control group and H. pylori cultured with zinc acetate for 3 days. A total of 227 differentially expressed genes (DEGs) were identified between the zinc acetate treatment group and the control group, with nominal significance (P < 0.05). Further validation through qRT-PCR was conducted on six DEGs exhibiting the highest absolute fold changes. Significant and consistent changes in the expression of ssrA (DQL14_RS05110, also known as transfer-messenger RNA, tmRNA) were observed, aligning with the results obtained from RNA sequencing.

3. Knockdown of ssrA Restores Helicobacter pylori Sensitivity to Levofloxacin

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A knockdown of ssrA was performed in Helicobacter pylori, resulting in a 46% reduction in ssrA expression due to siRNA ssrA knockdown. Following the knockdown of ssrA, the minimum inhibitory concentration (MIC) of levofloxacin in the zinc acetate treatment group was restored to levels similar to the control group. This observation aligns with the hypothesis that ssrA is a driving factor in zinc acetate-mediated levofloxacin sensitivity.

Discussion:

This study reveals the impact of zinc acetate on the expression of the ssrA gene in extracellular Helicobacter pylori. Zinc acetate, by upregulating the tmRNA system and inducing various distinct transcriptomic changes, as well as modulating translational systems, inhibits the growth of Helicobacter pylori and enhances sensitivity to levofloxacin. The findings from this research support the notion that zinc acetate serves as a useful adjunct in the treatment of levofloxacin-resistant Helicobacter pylori, particularly in conjunction with fluoroquinolone antibiotics.

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GENCEFE BIOTECH with its expertise in siRNA synthesis technology, has an experienced team capable of assisting users in designing siRNA sequences or customizing siRNA synthesis according to user requirements.

Gencefe also provides modified oligonucleotides to meet specific customer needs.

Reference：

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