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Bactericidal Potency and Extended Serum Life of Stereo-Chemically Engineered Peptides Against Mycobacterium

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Abstract

Tuberculosis is one of the leading causes of death, with an annual mortality rate of 2 million. The present treatment regimen for Mycobacterium species is strenuous, extending up to 12 months. Even then, rise of antibiotic resistance has limited the prognosis, with increased instances of multidrug resistant (MDR–TB) and extremely drug resistant (XDR–TB) cases reported. Peptide based antibiotics can be an effective solution due to their low toxicity, biocompatibility and predictable metabolism, but has not been employed due to their short plasma half life. In this brief communication, we demonstrate the bactericidal potency of cationic amphipathic peptides as an effective bactericidal agent against Mycobacterium smegmatis. Potency of stereo-engineered LDLD or DLDL peptides have been retained their potency, while their poly L variants rapidly lost their activity, when the experiment was repeated in human serum. To establish this as a design strategy, we further verified the results by repeating the experiment in a gram negative bacteria E. coli. One of the designed peptides were showing a minimum inhibitory concentration (MIC) value as low as 3.13 µM, suggesting the possibility of future development as a therapeutic peptide.

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Acknowledgements

Authors acknowledge Central Instrument Facility, IIT Guwahati for analytical support. Patent filed and published for antimicrobial peptide (Patent No: 333/KOL/2015 dated 26/03/2015).

Funding

This study was funded by BRNS (Project No. BSBESPNBRNS00864xxVR006), Govt. of India.

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Authors and Affiliations

  1. Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, 781 039, India

    Prakash Kishore Hazam, Anjali Singh, Nitin Chaudhary & Vibin Ramakrishnan

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  1. Prakash Kishore Hazam
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  2. Anjali Singh
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  3. Nitin Chaudhary
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  4. Vibin Ramakrishnan
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Correspondence to Vibin Ramakrishnan.

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All the testing and experiment related to human blood was performed as per the norms of ethical guidelines approved by ethical committee of Indian Institute of Technology Guwahati.

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All the subjects were informed and an informed consent was obtained as per the requirement.

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Hazam, P.K., Singh, A., Chaudhary, N. et al. Bactericidal Potency and Extended Serum Life of Stereo-Chemically Engineered Peptides Against Mycobacterium. Int J Pept Res Ther 25, 465–472 (2019). https://doi.org/10.1007/s10989-018-9690-0

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