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

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

doi:10.1007/s10989-018-9690-0

Cited by 14 publications

(7 citation statements)

References 63 publications

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“…Traditionally peptide based antimicrobials have two main issues, which limit their potential utility as therapeutic solutions. First is the uncertainty of the designed sequence forming prescribed structure while encountering the membrane and second is the proteolytic stability of the peptides while administering intravenously 15 . Different mechanisms were proposed for membrane lysis of bacterial cell, but the interesting fact is that, the membrane composition is different in different bacterial species.…”

Section: Resultsmentioning

confidence: 99%

“…The antibacterial activity of the peptides was also tested in the presence of 50 percent serum. The serum is a representative bio-fluid comprised of multiple factors responsible for reduced therapeutic activity under in vivo conditions 15 . Insertion of D-enantiomers within a peptide sequence has been reported to address issues like enzymatic degradation, ion sensitivity and mammalian cytotoxicity 16 .…”

Section: Resultsmentioning

confidence: 99%

“…The serum sensitivity experiment was similar to antibacterial activity. In this experiment, 50% serum containing media was used, instead of media alone 15 . The experiment with human serum was performed as per IHEC (Institute Human Ethics Committee) guidelines, at IIT Guwahati hospital, from healthy adult donors.…”

Section: Methodsmentioning

confidence: 99%

“…These enzymes are ubiquitous in different levels of cellular organizations, in body fluid and extracellular spaces 12 . Usage of D-amino acids and cyclization of peptides has been reported to resist enzymatic degradation and ion sensitivity to a significant extent, which would probably result in better activity in biological fluids 13 – 15 . The choice of opting peptide based antibacterial agents as a case study for stereo-chemically engineered peptide, pivot around this acute necessity in supplementing new therapeutic options and transforming the option of using peptide drugs to a more potent and effective solution.…”

Section: Introductionmentioning

confidence: 99%

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Antimicrobial effects of syndiotactic polypeptides

Hazam

Phukan

Akhil

et al. 2021

Sci Rep

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We present design and antibacterial studies of stereochemically diversified antimicrobial peptides against multidrug-resistant bacterial pathogens. Syndiotactic polypeptides are polymers of alternating L and D amino acids with LDLD or DLDL backbone stereochemical sequence, which can form stable gramicidin like helical conformations. We designed, synthesized and characterized eight model molecular systems with varied electrostatic fingerprints, modulated through calibrated sequence positioning. Six out of eight model systems showed very impressive antimicrobial activity against three difficult to treat bacterial species, Gentamicin resistant MRSA, E. coli and Mycobacterium. More importantly, the designed LDLD peptides were equally potent in serum, an important drawback of poly L peptide sequences due to enzyme mediated degradation and ion sensitivity. Further, we tested the activity of the designed peptides against drug-resistant clinical isolates of Staphylococcus aureus and Escherichia coli. Molecular dynamics simulation studies suggest formation of an assembly of individual peptides, preceding the membrane interaction and deformation. The activity estimates are comparable with the available peptide based antimicrobials, and are also highly specific and less toxic as per standard estimates. Incorporation of D amino-acids can significantly expand the peptide design space, which can in turn manifest in future biomaterial designs, especially antimicrobials.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antimicrobial effects of syndiotactic polypeptides

Hazam

Phukan

Akhil

et al. 2021

Sci Rep

Self Cite

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“…Fresh Nile tilapia blood was collected and washed three times in normal saline by centrifuging at 800× g. Then, 50 µL of 2% blood suspension was treated with 50 µL of test peptide for 1 h at room temperature. The incubated mixture was then centrifuged, and hemoglobin release was recorded using a spectroscope at 570 nm [13].…”

Section: Fish Blood Haemolysismentioning

confidence: 99%

Development of Bactericidal Peptides against Multidrug-Resistant Acinetobacter baumannii with Enhanced Stability and Low Toxicity

Hazam

Cheng

Hsieh

et al. 2022

IJMS

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Pathogenic superbugs are the root cause of untreatable complex infections with limited or no treatment options. These infections are becoming more common as clinical antibiotics have lost their effectiveness over time. Therefore, the development of novel antibacterial agents is urgently needed to counter these microbes. Antimicrobial peptides (AMPs) are a viable treatment option due to their bactericidal potency against multiple microbial classes. AMPs are naturally selected physiological microbicidal agents that are found in all forms of organisms. In the present study, we developed two tilapia piscidin 2 (TP2)-based AMPs for antimicrobial application. Unlike the parent peptide, the redesigned peptides showed significant antimicrobial activity against multidrug-resistant bacterial species. These peptides also showed minimal cytotoxicity. In addition, they were significantly active in the presence of physiological salts, 50% human serum and elevated temperature. The designed peptides also showed synergistic activity when combined with clinical antibiotics. The current approach demonstrates a fruitful strategy for developing potential AMPs for antimicrobial application. Such AMPs have potential for progression to further trials and drug development investigations.

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Antimicrobial Assay

Redkar

Ramakrishnan

2023

Springer Protocols Handbooks

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

Cited by 14 publications

References 63 publications

Antimicrobial effects of syndiotactic polypeptides

Antimicrobial effects of syndiotactic polypeptides

Development of Bactericidal Peptides against Multidrug-Resistant Acinetobacter baumannii with Enhanced Stability and Low Toxicity

Antimicrobial Assay

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