Xenobiotic Binding Domain of Glutathione S-Transferase Has Cryptic Antimicrobial Peptides
- 33 Downloads
Antimicrobial peptides are one of the important components of innate immune defense system and play a critical role in controlling infections. Although vast sequence and structural diversities exist, AMPs share several common features like cationicity, amphipathicity and membrane permeabilisation as mode of action. In this study, a moderately short cationic and hydrophobic peptides derived from the conserved domains of human glutathione S-transferase (GST) have been shown to have antimicrobial activity against Staphylococcus aureus ATCC 29213 and Klebsiella pneumoniae ATCC 7637 in physiological conditions without any toxicity issues. We further shown here that human GST, a C-terminal region which showed the higher antimicrobial activity, is conserved in the vertebrates. Our results demonstrate the potential of human GST derived peptides as a template for the development of anti-infective therapeutics.
KeywordsESKAPE Glutathione S-transferase Antimicrobial peptides Host defence peptides S. aureus K. pneumonia
MP is grateful to the Director, CDRI, Lucknow, India for providing the seed grant to establish the group and constant encouragement during the study. MP is thankful to DST-SERB, New Delhi [grant no.: SB/YS/LS-321/2013] for financial assistance. SH and VCT are grateful to UGC, India for the financial support. SR is thankful to ICMR, New Delhi, India for senior research fellowship. We are very thankful to RK Purshottam, SAIF, CSIR-CDRI for recording the flow cytometry profiles. We great fully acknowledge Mr A.Lal for technical support. CSIR-CDRI communication number: 9779.
Compliance with Ethical Standards
Conflict of interest
The authors declare no conflict of interest.
- Arockiaraj J, Chaurasia MK, Kumaresan V, Palanisamy R, Harikrishnan R, Pasupuleti M, Kasi M (2015) Macrobrachium rosenbergii mannose binding lectin: synthesis of MrMBL-N20 and MrMBL-C16 peptides and their antimicrobial characterization, bioinformatics and relative gene expression analysis. Fish Shellfish Immunol 43(2):364–374PubMedGoogle Scholar
- Aslam RM, Caline C, Christian J, Franaois D, Franaois VD, Alain P, Gilles H, Youssef T, Corinne S, Marie MF H (2013) Cateslytin, a chromogranin a derived peptide is active against staphylococcus aureus and resistant to degradation by its proteases. PLoS ONE 8(7):e68993PubMedPubMedCentralGoogle Scholar
- Beter M, Kara HK, Topal AE, Dana A, Tekinay AB, Guler MO (2017) Multivalent presentation of cationic peptides on supramolecular nanofibers for antimicrobial activity. Mol Pharmacol 14(11):3660–3668Google Scholar
- Boucher HW, Talbot GH, Benjamin DK Jr, Bradley J, Guidos RJ, Jones RN, Murray BE, Bonomo RA, Gilbert D, Infectious Diseases Society of A (2013) 10 x ‘20 progress-development of new drugs active against gram-negative bacilli: an update from the Infectious Diseases Society of America. Clin Infect Dis 56(12):1685–1694PubMedPubMedCentralGoogle Scholar
- Hilpert K, Fjell CD, Cherkasov A (2008) Short linear cationic antimicrobial peptides: screening, optimizing, and prediction. Peptide-based drug design. L. Otvos. Humana Press, Totowa, pp 127–159Google Scholar
- Jaskiewicz M, Neubauer D, Kamysz W (2017) Comparative study on antistaphylococcal activity of lipopeptides in various culture media. Antibiotics (Basel) 6(3):15Google Scholar
- Kacprzyk L, Rydengård V, Mörgelin M, Davoudi M, Pasupuleti M, Malmsten M, Schmidtchen A (2007) Antimicrobial activity of histidine-rich peptides is dependent on acidic conditions. Biochim Biophys Acta-Biomembr 1768(11):2667–2680Google Scholar
- Krause A, Sillard R, Kleemeier B, Kluver E, Maronde E, Conejo-García JR, Forssmann WG, Schulz-Knappe P, Nehls MC, Wattler F, Wattler S, Adermann K (2003) Isolation and biochemical characterization of LEAP-2, a novel blood peptide expressed in the liver. Protein Sci 12(1):143–152PubMedPubMedCentralGoogle Scholar
- Magzoub M, Kilk K, Eriksson L, Langel U, Gräslund A (2001) Interaction and structure induction of cell-penetrating peptides in the presence of phospholipid vesicles. Biochim Biophys Acta-Biomembr 1512(1):77–89Google Scholar
- Sader HS, Mendes RE, Jones RN, Flamm RK (2016) Antimicrobial susceptibility patterns of community- and hospital-acquired methicillin-resistant Staphylococcus aureus from United States Hospitals: results from the AWARE Ceftaroline Surveillance Program (2012–2014). Diagn Microbiol Infect Dis 86(1):76–79PubMedGoogle Scholar
- Setty SC, Horam S, Pasupuleti M, Haq W (2017) Modulating the antimicrobial activity of temporin l through introduction of fluorinated phenylalanine. Int J Pept Res Ther 23(2):213–225Google Scholar
- Svensson SL, Pasupuleti M, Walse B, Malmsten M, Mörgelin M, Sjögren C, Olin AI, Collin M, Schmidtchen A, Palmer R (2010) Midkine and pleiotrophin have bactericidal properties: preserved antibacterial activity in a family of heparin-binding growth factors during evolution. J Biol Chem 285(21):16105–16115PubMedPubMedCentralGoogle Scholar