A rationally designed synthetic antimicrobial peptide against Pseudomonas-associated corneal keratitis: Structure-function correlation

Mohid, Sk Abdul; Sharma, Prerana; Alghalayini, Amani; Saini, Tripti; Datta, Debarun; Willcox, Mark; Ali, Haydar; Raha, Sreyan; Singha, Achintya; Lee, Dong‐Kuk; Sahoo, Nirakar; Cranfield, Charles G.; Roy, Sanhita; Bhunia, Anirban

doi:10.1016/j.bpc.2022.106802

Cited by 8 publications

(6 citation statements)

References 62 publications

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“…Extensive biophysical studies indicated that the peptide selectively acts in a membranolytic fashion against negatively charged bacterial membrane or liposomes [172]. The high-resolution NMR structures in presence of bacterial outer and inner membrane mimicking systems revealed that the peptide can adopt a well-folded amphipathic structure that displays a complementary surface for interactions with LPS [172]. These results motivated us to proceed further to evaluate the pre-clinical potential of the VR18 peptide in near future.…”

Section: De Novo Designed Synthetic Peptidesmentioning

confidence: 97%

“…Thus, the KG18 (KNKSR-VARGWGRKCPLFG) and VR18 (VARGWGRKCPLFG-KNKSR) peptides were synthesized which showed more promising activity than the parent peptides [171]. The VR18 peptide was effective against invasive P. aeruginosa strain which is the major causal agent of human corneal keratitis [172]. A recent study showed that VR18 can effectively kill P. aeruginosa PAO1 and 6294 strains in an in vitro, ex vivo, and in vivo set-up [172].…”

Section: De Novo Designed Synthetic Peptidesmentioning

confidence: 99%

“…The VR18 peptide was effective against invasive P. aeruginosa strain which is the major causal agent of human corneal keratitis [172]. A recent study showed that VR18 can effectively kill P. aeruginosa PAO1 and 6294 strains in an in vitro, ex vivo, and in vivo set-up [172]. Extensive biophysical studies indicated that the peptide selectively acts in a membranolytic fashion against negatively charged bacterial membrane or liposomes [172].…”

Section: De Novo Designed Synthetic Peptidesmentioning

confidence: 99%

“…A recent study showed that VR18 can effectively kill P. aeruginosa PAO1 and 6294 strains in an in vitro, ex vivo, and in vivo set-up [172]. Extensive biophysical studies indicated that the peptide selectively acts in a membranolytic fashion against negatively charged bacterial membrane or liposomes [172]. The high-resolution NMR structures in presence of bacterial outer and inner membrane mimicking systems revealed that the peptide can adopt a well-folded amphipathic structure that displays a complementary surface for interactions with LPS [172].…”

Section: De Novo Designed Synthetic Peptidesmentioning

confidence: 99%

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Atomic-Resolution Structures and Mode of Action of Clinically Relevant Antimicrobial Peptides

Bhattacharjya

Mohid

Bhunia

2022

IJMS

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Global rise of infections and deaths caused by drug-resistant bacterial pathogens are among the unmet medical needs. In an age of drying pipeline of novel antibiotics to treat bacterial infections, antimicrobial peptides (AMPs) are proven to be valid therapeutics modalities. Direct in vivo applications of many AMPs could be challenging; however, works are demonstrating encouraging results for some of them. In this review article, we discussed 3-D structures of potent AMPs e.g., polymyxin, thanatin, MSI, protegrin, OMPTA in complex with bacterial targets and their mode of actions. Studies on human peptide LL37 and de novo-designed peptides are also discussed. We have focused on AMPs which are effective against drug-resistant Gram-negative bacteria. Since treatment options for the infections caused by super bugs of Gram-negative bacteria are now extremely limited. We also summarize some of the pertinent challenges in the field of clinical trials of AMPs.

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Section: De Novo Designed Synthetic Peptidesmentioning

confidence: 97%

Section: De Novo Designed Synthetic Peptidesmentioning

confidence: 99%

Section: De Novo Designed Synthetic Peptidesmentioning

confidence: 99%

Section: De Novo Designed Synthetic Peptidesmentioning

confidence: 99%

See 2 more Smart Citations

Atomic-Resolution Structures and Mode of Action of Clinically Relevant Antimicrobial Peptides

Bhattacharjya

Mohid

Bhunia

2022

IJMS

Self Cite

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“…Antimicrobial peptides produced by living organisms including humans as a self-defense mechanism are promising candidates for a novel class of antibacterial agents because they are effective against a broad range of microorganisms, including multidrug-resistant bacteria, and the emergence of resistant bacteria is difficult. − These merits result from their general mode of action: membrane permeabilization. The polycationic and amphiphilic peptides bind to negatively charged bacterial membranes, both outer and inner, and disrupt their structures, leading to bactericidal activity.…”

mentioning

confidence: 99%

Development of Antimicrobial Peptide–Antibiotic Conjugates to Improve the Outer Membrane Permeability of Antibiotics Against Gram-Negative Bacteria

et al. 2022

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Antibiotics have been widely used in the medical field as a treatment for infectious diseases, but they are not effective against all Gram-negative bacteria because of their low permeability to the outer membrane. One of the strategies to improve the antibacterial activity of antibiotics is the coadministration of antibiotics and membraneperturbing antimicrobial peptides for their synergistic effects. However, because of their different pharmacokinetics, their coadministration may not exert expected effects in the clinical stage. Here, we designed various antimicrobial peptide−antibiotic conjugates as a novel approach to improve the antimicrobial activity of antibiotics. Ampicillin was chosen as a model antibiotic with poor outer membrane permeability, and the effects of the chemistry and position of conjugation and the choice of antimicrobial peptides were examined. One of the ampicillin conjugates exhibited significantly improved antimicrobial activity against ampicillin-resistant Gram-negative bacteria without exerting cytotoxicity against human cultured cells, demonstrating that our novel approach is an effective strategy to improve the antimicrobial activity of antibiotics with low outer membrane permeability.

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Advances of Antimicrobial Peptide‐Based Biomaterials for the Treatment of Bacterial Infections

Lai

Shan

2023

Advanced Science

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Owing to the increase in multidrug-resistant bacterial isolates in hospitals globally and the lack of truly effective antimicrobial agents, antibiotic resistant bacterial infections have increased substantially. There is thus an urgent need to develop new antimicrobial drugs and their related formulations. In recent years, natural antimicrobial peptides (AMPs), AMP optimization, self-assembled AMPs, AMP hydrogels, and biomaterial-assisted delivery of AMPs have shown great potential in the treatment of bacterial infections. In this review, it is focused on the development prospects and shortcomings of various AMP-based biomaterials for treating animal model infections, such as abdominal, skin, and eye infections. It is hoped that this review will inspire further innovations in the design of AMP-based biomaterials for the treatment of bacterial infections and accelerate their commercialization.

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A rationally designed synthetic antimicrobial peptide against Pseudomonas-associated corneal keratitis: Structure-function correlation

Cited by 8 publications

References 62 publications

Atomic-Resolution Structures and Mode of Action of Clinically Relevant Antimicrobial Peptides

Atomic-Resolution Structures and Mode of Action of Clinically Relevant Antimicrobial Peptides

Development of Antimicrobial Peptide–Antibiotic Conjugates to Improve the Outer Membrane Permeability of Antibiotics Against Gram-Negative Bacteria

Advances of Antimicrobial Peptide‐Based Biomaterials for the Treatment of Bacterial Infections

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