In Silico Characterization of the Interaction between the PBP2a "Decoy" Protein of Resistant Staphylococcus aureus and the Monomeric Units of Eudragit E-100 and Poly(Maleic Acid-alt-Octadecene) Polymers.

Yamil Liscano,Astrid González,Jose Oñate-Garzón,Constain H Salamanca,Ana Amú

doi:10.3390/polym13142320

Yamil Liscano, Astrid González + Show 3 more

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https://doi.org/10.3390/polym13142320

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Journal: Polymers	Publication Date: Jul 15, 2021
Citations: 4	License type: CC BY 4.0

Affiliation: Universidad Santiago de Cali, University of Antioquia

Abstract

Antimicrobial treatment alternatives for methicillin-resistant Staphylococcus aureus (MRSA) are increasingly limited. MRSA strains are resistant to methicillin due to the formation of β-lactamase enzymes, as well as the acquisition of the mecA gene, which encodes the penicillin-binding protein (PBP2a) that reduces the affinity for β-lactam drugs. Previous studies have shown that the use of ampicillin-loaded nanoparticles can improve antimicrobial activity on resistant S. aureus strains. However, the biological mechanism of this effect has not yet been properly elucidated. Therefore, this short communication focused on characterizing the in silico interactions of the PBP2a membrane receptor protein from S. aureus against the monomeric units of two polymeric materials previously used in the development of different nanoparticles loaded with ampicillin. Such polymers correspond to Eudragit E-100 chloride (EuCl) and the sodium salt of poly(maleic acid-alt-octadecene) (PAM-18Na). For this, molecular coupling studies were carried out in the active site of the PBP2a protein with the monomeric units of both polymers in neutral and ionized form, as well as with ampicillin antibiotic (model β-lactam drug). The results showed that ampicillin, as well as the monomeric units of EuCl and PAM18Na, described a slight binding free energy to the PBPa2 protein. In addition, it was found that the amino acids of the active site of the PBPa2 protein have interactions of different types and intensities, suggesting, in turn, different forms of protein–substrate coupling.

Highlights

Regarding the pharmacological mechanism of ampicillin, it is based on its union with PBP proteins (Penicillin-Binding Proteins), which are enzymes anchored on the cell membrane that contribute to the construction of peptidoglycan as a component of the cell wall
In accordance with the aforementioned, some of our studies have focused on evaluating the effect of several ampicillin-loaded NPs against S. aureus strains with different degrees of antibiotic resistance (ATCC 25923-sensitive strain, ATCC 29213-β-lactamase producing strain and ATCC 43300-encoding the mecA gene and β-lactamase producing strain)
The results showed that ampicillin has several interaction positions with the PBP2a protein, corresponding to five hydrophobic interactions (HI), one hydrogen bond (HB) and one attractive charge (AC) interaction with a total binding free energy of −6.4 kcal/mol (Figure 3B)

Summary

Introduction

The biological mechanism of this effect has not yet been properly elucidated This short communication focused on characterizing the in silico interactions of the PBP2a membrane receptor protein from S. aureus against the monomeric units of two polymeric materials previously used in the development of different nanoparticles loaded with ampicillin. Such polymers correspond to Eudragit E-100 chloride (EuCl) and the sodium salt of poly(maleic acid-alt-octadecene) (PAM18Na). Such resistance can be acquired for several reasons, where bacterial evolutionary processes and the inappropriate use of antibiotics stand out [7], such as self-medication, which is conjunctural with the lack of knowledge of the antibiotic dose and the time of treatment, variables that contribute to the development of resistance mechanisms [8]

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