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

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 1μg/ml (0.41 μM). 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.

Assessing Barriers for Antimicrobial Penetration in Complex Asymmetric Bacterial Membranes: A Case Study with Thymol

“…Natural small molecules from the extract of herbs and spices have shown good antibacterial effects, , and thymol is one among them, a monoterpene phenol found in the oil of plants from the Lamiaceae family. , It has also been found that thymol in synergy with synthetic antibiotics decreases antibacterial resistance . There are many reports available on the action of antimicrobials and small molecules on live bacteria as well as model phospholipid membrane systems. − Despite these investigations, microscopic insights into the preferred pathways for molecules to cross the outer membrane (OM) are not well explored. In order to understand the origins of the resistance to the translocation of small molecules across the bacterial cell envelope, it is not sufficient to create realistic in vitro bacterial membrane platforms but also devise means to determine the transport of molecules across the membrane.…”

Therapeutics Approaches of Invertebrate Animal Toxins: A Review

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“…In addition, CrTX displayed anti-angiogenic effects in vivo [85]. Snake venom-derived drug cerivastatin also reduces the proliferation and invasion of aggressive breast cancer cells [86]. DisBa-01, a low molecular weight recombinant protein, specifically interacted with alpha(v)beta3 integrin and shows potent anti-metastatic and anti-angiogenic properties.…”

Wasp Venom Biochemical Components and Their Potential in Biological Applications and Nanotechnological Interventions

“…The peptide prevents bacterial growth through the inhibition of protein synthesis, did not result in visible morphological changes. Polydim-I treatment at 2 mg/kg/mLW showed significant reduction of the bacterial load in in the lungs, spleen, and liver [ 15 ], and the antimicrobial properties against S. aureus , E. coli , Enterococcus faecalis , Acinetobacter calcoaceticus-baumannii were displayed with MIC 50 values of 4.1, 50.7, 73.2, and 84.0 μg/mL, respectively [ 73 ].…”