NDLI: Cell-penetrating peptide and antibiotic combination therapy: a potential alternative to combat drug resistance in methicillin-resistant Staphylococcus aureus

Content Provider	Springer Nature Link
Author	Randhawa, Harmandeep Kaur Gautam, Ankur Sharma, Minakshi Bhatia, Rakesh Varshney, Grish C. Raghava, Gajendra Pal Singh Nandanwar, Hemraj
Copyright Year	2016
Abstract	The diverse pattern of resistance by methicillin-resistant Staphylococcus aureus (MRSA) is the major obstacle in the treatment of its infections. The key reason of resistance is the poor membrane permeability of drug molecules. Over the last decade, cell-penetrating peptides (CPPs) have emerged as efficient drug delivery vehicles and have been exploited to improve the intracellular delivery of numerous therapeutic molecules in preclinical studies. Therefore, to overcome the drug resistance, we have investigated for the first time the effects of two CPPs (P3 and P8) in combination with four antibiotics (viz. oxacillin, erythromycin, norfloxacin, and vancomycin) against MRSA strains. We found that both CPPs internalized into the MRSA efficiently at very low concentration (<10 μM) which was non-toxic to bacteria as well as mammalian cells and showed no significant hemolytic activity. However, the combinations of CPPs (≤10 μM) and antibiotics showed high toxicity against MRSA as compared to antibiotics alone. The significant finding is that P3 and P8 could lower the MICs against oxacillin, norfloxacin, and vancomycin to susceptible levels (generally <1 μg/mL) for almost all five clinical isolates. Further, the bacterial cell death was confirmed by scanning electron microscopy as well as propidium iodide uptake assay. Simultaneously, time-kill kinetics revealed the increased uptake of antibiotics. In summary, CPPs assist to restore the effectiveness of antibiotics at much lower concentration, eliminate the antibiotic toxicity, and represent the CPP-antibiotic combination therapy as a potential novel weapon to combat MRSA infections.
Starting Page	4073
Ending Page	4083
Page Count	11
File Format	PDF
ISSN	01757598
Journal	Applied Microbiology and Biotechnology
Volume Number	100
Issue Number	9
e-ISSN	14320614
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2016-02-02
Publisher Place	Berlin, Heidelberg
Access Restriction	Subscribed
Subject Keyword	Methicillin-resistant Staphylococcus aureus Drug resistance Drug delivery Cell-penetrating peptides Microbiology Microbial Genetics and Genomics Biotechnology
Content Type	Text
Resource Type	Article
Subject	Medicine Applied Microbiology and Biotechnology Biotechnology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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