Abstract

Colistin is a re-emergent antibiotic peptide used as a last resort in clinical practice to overcome multi-drug resistant (MDR) Gram-negative bacterial infections. Unfortunately, the dissemination of colistin-resistant strains has increased in recent years and is considered a public health problem worldwide. Strategies to reduce resistance to antibiotics such as nanotechnology have been applied successfully. In this work, colistin was characterized physicochemically by surface tension measurements. Subsequently, nanoliposomes coated with highly deacetylated chitosan were prepared with and without colistin. The nanoliposomes were characterized using dynamic light scattering and zeta potential measurements. Both physicochemical parameters fluctuated relatively to the addition of colistin and/or polymer. The antimicrobial activity of formulations increased by four-fold against clinical isolates of susceptible Pseudomona aeruginosa but did not have antimicrobial activity against multidrug-resistant (MDR) bacteria. Interestingly, the free coated nanoliposomes exhibited the same antibacterial activity in both sensitive and MDR strains. Finally, the interaction of colistin with phospholipids was characterized using molecular dynamics (MD) simulations and determined that colistin is weakly associated with micelles constituted by zwitterionic phospholipids.

Highlights

  • Colistin (CST) is an antimicrobial peptide that was reintroduced into clinical practice as a last resort for the treatment of infections caused by multi-drug resistant (MDR) Gramnegative bacteria [1]

  • P. aeruginosa ATCC® 27853 TM was obtained from the American Type Culture Collection (ATCC; Rockville, molecular dynamics (MD), USA)

  • Pa02MDR and Pa03MDR clinical isolates were resistant to all the antibiotics evaluated according to the clinical breakpoints defined by the CLSI guidelines [23]

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Summary

Introduction

Colistin (CST) is an antimicrobial peptide that was reintroduced into clinical practice as a last resort for the treatment of infections caused by multi-drug resistant (MDR) Gramnegative bacteria [1]. CST is a cyclic heptapeptide consisting of a tripeptide side-chain acylated at the N terminus by a fatty acid tail and has a cationic charge at neutral pH [2]. This antibiotic has been used to control and prevent infectious diseases in animals for decades, but its excessive use has contributed to the emergence of CST-resistant Enterobacteriaceae [3,4], and possibly to the horizontal transmission of CST resistance from farm animals to humans [5]. Pharmaceutics 2021, 13, 41 genes such as Extended spectrum beta-lactamases (ESBL) and New Delhi metallo-betalactamase (NDM) [7]. This situation poses a major challenge for the treatment of life-threatening Gram-negative bacterial infections

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