Surface Grafted MSI-78A Antimicrobial Peptide has High Potential for Gastric Infection Management

Abstract

As we approach the end of the antibiotic era, newer therapeutic options, such as antimicrobial peptides (AMPs), are in urgent demand. AMP surface grafting onto biomaterials has been described as a good strategy to overcome problems associated with their in vivo stability. Helicobacter pylori is among the bacteria that pose greatest threat to human health, being MSI-78A one of the few bactericidal AMPs against this bacterium. Here, we report that MSI-78A grafted onto model surfaces (Self-Assembled Monolayers –SAMs), in a concentration of 30.3 ± 1.2 ng/cm2 determined by quartz crystal microbalance with dissipation (QCM-D), was able to kill, by contact, 98% of planktonic H. pylori in only 2 h. This fact was not verified against the control bacteria (Staphylococcus epidermidis), although the minimal inhibitory concentration (MIC) of MSI-78A in solution is much lower for S. epidermidis (2 μg/mL) than for H. pylori (64 μg/mL). Our results also demonstrated that, in opposite to other bacteria, H. pylori cells were attracted to ethylene glycol terminated (antiadhesive) surfaces, which can explain the high bactericidal potential of grafted MSI-78A. This proof of concept study establishes the foundations for development of MSI-78A grafted nanoparticles for gastric infection management within a targeted nanomedicine concept.

Adhesive Antimicrobial Peptides Containing 3,4-Dihydroxy-L-Phenylalanine Residues for Direct One-Step Surface Coating

“…Various coating methods have been used to physically or chemically bind AMPs to the surface of materials, such as implants, catheters, and contact lenses. These methods include layer-by-layer assembly [ 8 ], adsorption [ 9 ], covalent bonding [ 10 , 11 ], and polymer brushing [ 12 , 13 ]. Although these methods facilitate efficient immobilization of peptides, most of these approaches are suitable only for specific surfaces.…”

Antimicrobial peptide-based materials: opportunities and challenges

“…Despite the development of antimicrobial coating technologies, implant-associated infections are still a major problem in the healthcare sector. [269][270][271][272] This problem is further complicated by the presence of MDR-bacteria. Kazemzadeh-Narbat et al modified Ti implants with calcium phosphate (CaP) using the electrostatic deposition method followed by loading of an AMP, Tet213, through a simple soaking technique.…”

“…To improve the selectivity and activity of AMPs, Parreira et al replaced one amino acid of MSI-78 (pexiganan) with Cys and added an aminohexanoic acid spacer. 272 MSI-78 AMPs grafted onto the self-assembled monolayers of biotin and tetraethylene glycol (EG4) strongly adhere to H. pylori bacteria and kill 98% of planktonic H. pylori within 2 h of exposure. 272 Chitosan NPs loaded with cryptdin-2 AMP showed 83% survivability and a two-long reduction in bacterial load in a Salmonella enterica serovar Typhimurium ( S. Typhimurium ) infected mouse model.…”

“…272 MSI-78 AMPs grafted onto the self-assembled monolayers of biotin and tetraethylene glycol (EG4) strongly adhere to H. pylori bacteria and kill 98% of planktonic H. pylori within 2 h of exposure. 272 Chitosan NPs loaded with cryptdin-2 AMP showed 83% survivability and a two-long reduction in bacterial load in a Salmonella enterica serovar Typhimurium ( S. Typhimurium ) infected mouse model. Cryptidin-2-chitosan NPs reduced the oxidants, particularly nitrite by 3.25 folds and increased catalase antioxidant by two folds as compared to the free peptide.…”

Microbial resistance to nanotechnologies: An important but understudied consideration using antimicrobial nanotechnologies in orthopaedic implants

“…Different material compositions and strategies to enable AMP-conjugated nano antimicrobials can be found in other review papers [ 171 , 172 ]. Despite enhanced stability and antibacterial performance by surface decoration relative to encapsulation by nanocarriers [ 173 ], the potent cytotoxicity of AMPs remains a significant risk factor yet to be resolved, which might lead to antimicrobial resistance.…”