Polydim-I antimicrobial activity against MDR bacteria and its model membrane interaction

Author(s)

Rangel, Marisa ; dos Santos Castro, Fabiola Fernandes ; Mota-Lima, Lilian Daiene ; Clissa, Patricia Bianca ; Martins, Danubia Batista ; dos Santos Cabrera, Marcia Perez ; Mortari, Marcia Renata

• Document type: Journal article
• Source: PLoS One; v. 12, n. 6 JUN 1 2017.
• Web of Science Citations: 0

Abstract

The rapid spread of multi-drug resistant pathogens represents a serious threat to public health, considering factors such as high mortality rates, treatment restrictions and high prevalence of multi-drug resistant bacteria in the hospital environment. Antimicrobial peptides (AMPs) may exhibit powerful antimicrobial activity against different and diverse microorganisms, also presenting the advantage of absence or low toxicity towards animal cells. In this study, the evaluation of the antimicrobial activity against multi-drug resistant bacteria of a recently described AMP from wasp, Polydim-I, was performed. Polydim-I presented activity against standard strains (non-carriers of multi-resistant genes) that are susceptible to commercial antimicrobials, and also against multi-drug resistant strains at concentrations bellow 1 mu g/ml (0.41 mu M). This is a rather low concentration among those reported for AMPs. At this concentration we found out that Polydim-I inhibits almost 100% of the tested pathogens growth, while with the ATCC strains the minimum inhibitory concentration (MIC100) is 400 times higher. Also, in relation to in vitro activity of conventional drugs against multi-drug resistant bacteria strains, Polydim-I is almost 10 times more efficient and with broader spectrum. Cationic AMPs are known as multi-target compounds and specially for targeting the phospholipid matrix of bacterial membranes. Exploring the interactions of Polydim-I with lipid bilayers, we have confirmed that this interaction is involved in the mechanism of action. Circular dichroism experiments showed that Polydim-I undergoes a conformational transition from random coil to a mostly helical conformation in the presence of membrane mimetic environments. Zeta potential measurements confirmed the binding and partial charge neutralization of anionic asolectin vesicles, and also suggested a possible aggregation of peptide molecules. FTIR experiments confirmed that some peptide aggregation occurs, which is minimized in the presence of strongly anionic micelles of sodium dodecyl sulfate. Also, Polydim-I induced channel-like structures formation to asolectin lipid bilayers, as demonstrated in the electrophysiology experiments. We suggest that cationic Polydim-I targets the membrane lipids due to electrostatic attraction, partially accumulates, neutralizing the opposite charges and induces pore formation. Similar mechanism of action has already been suggested for other peptides from wasp venoms, especially mastoparans. (AU)

• FAPESP's process: 12/24259-0 - Peptide and chitosan conjugates with pharmacological potential: synthesis, prospecting of activity in membrane mimetic systems, and evaluation in cells
• Grantee: Marcia Perez dos Santos Cabrera
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 14/08372-7 - Peptide and chitosan conjugates with pharmacological potential: synthesis, prospecting of activity in membrane mimetic systems, and evaluation in cells
• Grantee: Marcia Perez dos Santos Cabrera
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 08/00173-4 - Prospection of antimicrobial channel forming natural peptides on cellular membranes and artificial lipid bilayers.
• Grantee: Marisa Rangel
• Support Opportunities: Regular Research Grants