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Histone acetyltransferases derived RW20 protects and promotes rapid clearance of Pseudomonas aeruginosa in zebrafish larvae

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Abstract

Pseudomonas is a group of bacteria that can cause a wide range of infections, particularly in people with weakened immune systems, such as those with cystic fibrosis or who are hospitalized. It can also cause infections in the skin and soft tissue, including cellulitis, abscesses and wound infections. Antimicrobial peptides (AMPS) are the alternative strategy due to their broad spectrum of activity and act as effective treatment against multi-drug resistance pathogens. In this study, we have used an AMP, RW20 (1RPVKRKKGWPKGVKRGPPKW20). RW20 peptide is derived from the histone acetyltransferases (HATs) of the freshwater teleost, Channa striatus. The antimicrobial prediction tool has been utilized to identify the RW20 sequence from the HATs sequence. We synthesized the peptide to explore its mechanism of action. In an in vitro assay, RW20 was challenged against P. aeruginosa and we showed that RW20 displayed antibacterial properties and damaged the cell membrane. The mechanism of action of RW20 against P. aeruginosa has been established via field emission scanning electron microscopy (FESEM) as well as fluorescence assisted cell sorter (FACS) analysis. Both these experiments established that RW20 caused bacterial membrane disruption and cell death. Moreover, the impact of RW20, in-vivo, was tested against P. aeruginosa-infected zebrafish larvae. In the infected larvae, RW20 showed protective effect against P. aeruginosa by increasing the larval antioxidant enzymes, reducing the excess oxidative stress and apoptosis. Thus, it is possible that HATs-derived RW20 can be an efficient antimicrobial molecule against P. aeruginosa.

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The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Conceptualization: AG and JA; animal experiment and data collection: AG and RM; formal analysis and original draft preparation: AG; review and editing: RM and JA. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Jesu Arockiaraj.

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The fishes were collected, transported and handled for the experiment as per the Institute Animal Ethical Committee Guidelines and Approval (SAF/IAEC/211215/004).

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Guru, A., Murugan, R. & Arockiaraj, J. Histone acetyltransferases derived RW20 protects and promotes rapid clearance of Pseudomonas aeruginosa in zebrafish larvae. Int Microbiol 27, 25–35 (2024). https://doi.org/10.1007/s10123-023-00391-9

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  • DOI: https://doi.org/10.1007/s10123-023-00391-9

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