Antimicrobial activity of α/β hybrid peptides incorporating tBu-β3,3Ac6c against methicillin-resistant Staphylococcus aureus | The Journal of Antibiotics

Oct 29, 2024

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The incorporation of β-amino acids into peptides is a promising approach to develop proteolytically stable therapeutic agents. Short α/β hybrid peptides containing tBu-β3,3Ac6cː H2N-Lys-tBu-β3,3Ac6c-PEA, P1; H2N-Orn-tBu-β3,3Ac6c-PEA, P2; H2N-Arg-tBu-β3,3Ac6c-PEA, P3; LA-Lys-tBu-β3,3Ac6c-PEA, P4; LA-Orn-tBu-β3,3Ac6c-PEA, P5; LA-Arg-tBu-β3,3Ac6c-PEA, P6; LAu-Lys-tBu-β3,3Ac6c-PEA, P7; LAu-Orn-tBu-β3,3Ac6c-PEA, P8; and LAu-Arg-tBu-β3,3Ac6c-PEA, P9 were prepared. The antimicrobial efficacies of all the peptides were evaluated against ESKAPE pathogens, along with a small panel of multi-drug resistant (MDR) clinical isolates of S. aureus. Among all the peptides, P4, P6, and P7 showed significant efficacies against P. aeruginosa, S. aureus, and MRSA with an MIC value ranging from 6.25 to 12.5 μM. Further, in vitro, anti-staphylococcal assessment with their antimicrobial synergy of the peptides P4, P6, and P7 was carried out against MRSA, due to its better efficacy. The peptides P6 and P7 exhibited MRSA biofilm inhibition of 70% and 77%, respectively, at 4×MIC concentration. At its MIC concentration, about 19% hemolysis was observed for P4, P6, and P7.

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The authors are grateful to the Director, CSIR-IIIM, Jammu, for providing laboratory facilities to conduct this research. The work was supported by the internal institutional grant (MLP-110011) and (IIRP-0715/2023) from the Council of Scientific and Industrial Research (CSIR) and the Indian Council for Medical Research (ICMR) Government of India. ARS and RM thanks CSIR-IIIM for providing the project fellowship. JK and RC thank the Council of Scientific and Industrial Research (CSIR), India, for providing the fellowship. AR and SF thank the University Grant Commission (UGC), India, for providing the fellowship. The institutional publication number of the article is CSIR-IIIM/IPR/00727.

These authors contributed equally: Aminur Rahman Sarkar, Jyoti Kumari

Natural Products and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, Jammu and Kashmir, India

Aminur Rahman Sarkar, Rubina Chowdhary & Rajkishor Rai

Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India

Aminur Rahman Sarkar, Jyoti Kumari, Arti Rathore, Rubina Chowdhary, Shifa Firdous, Avisek Mahapa & Rajkishor Rai

Infectious Diseases Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, Jammu and Kashmir, India

Jyoti Kumari, Arti Rathore, Rakshit Manhas, Shifa Firdous & Avisek Mahapa

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Correspondence to Avisek Mahapa or Rajkishor Rai.

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Sarkar, A.R., Kumari, J., Rathore, A. et al. Antimicrobial activity of α/β hybrid peptides incorporating tBu-β3,3Ac6c against methicillin-resistant Staphylococcus aureus. J Antibiot (2024). https://doi.org/10.1038/s41429-024-00773-9

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Received: 18 April 2024

Revised: 05 August 2024

Accepted: 11 September 2024

Published: 29 October 2024

DOI: https://doi.org/10.1038/s41429-024-00773-9

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