GNAT Toxin may have a Potential Role in Pseudomonas Aeruginosa Persistence: An In vitro and in Silico Study

Abstract

Aims: Persistent cells are primarily responsible for developing antibiotic resistance and the recurrence of Pseudomonas aeruginosa. This study investigated the possible role of GNAT toxin in persistence. Materials & methods: P. aeruginosa was exposed to five MIC concentrations of ciprofloxacin. The expression levels of target genes were assessed. The GNAT/HTH system was bioinformatically studied, and an inhibitory peptide was designed to disrupt this system. Results: Ciprofloxacin can induce bacterial persistence. There was a significant increase in the expression of the GNAT toxin during the persistence state. A structural study of the GNAT/HTH system determined that an inhibitory peptide could be designed to block this system effectively. Conclusion: The GNAT/HTH system shows promise as a novel therapeutic target for combating P. aeruginosa infections.

Plain language summary

Antibiotics are used to treat infections caused by bacteria. Over time, some of these infections have become more difficult to treat. This is because the bacteria can slow their growth and tolerate the antibiotic, known as persistence. It is important to find new ways to treat infections caused by persistent bacteria. This study researched a toxin–antitoxin system, called GNAT/HTH, that may play a role in bacterial persistence. This system could be a target for new antibiotics.

Keywords::

• GNAT/HTH system
• GNAT toxin
• inhibitory peptides
• molecular docking
• P. aeruginosa
• persistence

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/fmb-2023-0134

Financial disclosure

This study was financially supported by ilam University of Medical Sciences (Ilam, Iran), for which we are very grateful.

Conflict of interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This study was financially supported by ilam University of Medical Sciences (Ilam, Iran), for which we are very grateful.