Positively Charged Polymers as Promising Devices against Multidrug Resistant Gram-Negative Bacteria: A Review

Abstract

Antibiotic resistance has increased markedly in Gram-negative bacteria, causing severe infections intractable with traditional drugs and amplifying mortality and healthcare costs. Consequently, to find novel antimicrobial compounds, active on multidrug resistant bacteria, is mandatory. In this regard, cationic antimicrobial peptides (CAMPs)-able to kill pathogens on contact-could represent an appealing solution. However, low selectivity, hemolytic toxicity and cost of manufacturing, hamper their massive clinical application. In the recent years-starting from CAMPs as template molecules-less toxic and lower-cost synthetic mimics of CAMPs, including cationic peptides, polymers and dendrimers, have been developed. Although the pending issue of hemolytic toxicity and biodegradability is still left not completely solved, cationic antimicrobial polymers (CAPs), compared to small drug molecules, thanks to their high molecular weight, own appreciable selectivity, reduced toxicity toward eukaryotic cells, more long-term activity, stability and non-volatility. With this background, an updated overview concerning the main manufactured types of CAPs, active on Gram-negative bacteria, is herein reported, including synthetic procedure and action's mechanism. Information about their structures, antibacterial activity, advantages and drawbacks, was reported in the form of tables, which allow faster consultation and quicker learning concerning current CAPs state of the art, in order not to retrace reviews already available.

Keywords: Gram-negative bacteria; antibiotic resistance; hemolytic cytotoxicity; membrane disruption; positively charged polymers.

Figure 1

Structure of colistin.

Figure 2

Number of publications as a function of time that contain the phrase “antimicrobial polymer” via Scopus. These data include the cationic antimicrobial polymers literature (the scope of this review).

Figure 3

Examples of cationic antimicrobial peptides (CAMPs) not susceptible to develop resistance: (a) Structure of tachyplesin II; (b) structure of cecropin P1.

Figure 4

Schematic representation of the structure of the cell wall of Gram-negative bacteria.

Figure 5

Quaternized chitosan derivatives permanently cationic: (a) Chitosan phosphonium salt; (b) o-quaternary chitosan ammonium salts. R: –CH₂Ph (BNQAS–CS); –C₁₂H₂₅ (C₁₂QAS–CS); – C₁₄H₂₉ (C₁₄QAS–CS); – C₁₆H₃₃ (C₁₆QAS–CS); – C₁₈H₃₇ (C₁₈QAS–CS); X: Cl, Br.