Supramolecular Cationic Assemblies against Multidrug-Resistant Microorganisms: Activity and Mechanism of Action

Abstract

The growing challenge of antimicrobial resistance to antibiotics requires novel synthetic drugs or new formulations for old drugs. Here, cationic nanostructured particles (NPs) self-assembled from cationic bilayer fragments and polyelectrolytes are tested against four multidrug-resistant (MDR) strains of clinical importance. The non-hemolytic poly(diallyldimethylammonium) chloride (PDDA) polymer as the outer NP layer shows a remarkable activity against these organisms. The mechanism of cell death involves bacterial membrane lysis as determined from the leakage of inner phosphorylated compounds and possibly disassembly of the NP with the appearance of multilayered fibers made of the NP components and the biopolymers withdrawn from the cell wall. The NPs display broad-spectrum activity against MDR microorganisms, including Gram-negative and Gram-positive bacteria and yeast.

Simple Nanoparticles from the Assembly of Cationic Polymer and Antigen as Immunoadjuvants

“…Similar cell debris were observed by Martinez et al with 10 mM poly(allylamine hydrochloride) [31] and with linear or ramified PEI or PLL [30], suggesting a general feature of poly-cations acting by disruption of cell membranes. This also took place for multi-resistant bacteria submitted to PDDA assemblies with anionic carboxymethylcellulose (CMC) for which both the cell wall and the cell membrane were lysed allowing the leakage of intracellular compounds [32]. The effect of PDDA on morphology of the fibroblasts is presented in Figure 6.…”

“…In summary, cationic micro and nanoparticles are effectively taken up both by macrophages and dendritic cells since electrostatic attraction promotes particle binding and subsequent internalization [11,14,20,24,25]. Cationic particles and liposomes containing dioctadecyldimethylammonium bromide (DODAB) cationic lipid [13,26] carrying Mycobacterium tuberculosis [13,27], Chlamydia trachomatis [11], or Neisseria meningitides antigens enhanced the cellular and humoral immune response against them [16,28].Another important class of cationic adjuvants is represented by the cationic polymers despite their overt cytotoxicity [29][30][31][32][33]. They easily combine with oppositely charged proteins [34].…”

“…Another important class of cationic adjuvants is represented by the cationic polymers despite their overt cytotoxicity [29][30][31][32][33]. They easily combine with oppositely charged proteins [34].…”

Cationic Nanostructures against Foodborne Pathogens

“…The cationic lipid dioctadecyldimethylammonium bromide (DODAB), the antimicrobial peptide gramicidin D (Gr), the antimicrobial cationic polymer poly (diallyldimethylammonium chloride) (PDDA) and the biocompatible polymer poly (methyl methacrylate) (PMMA) can be combined to yield a variety of antimicrobial cationic nanostructures as previously described by our group (Carmona Ribeiro and Chaimovich, 1983; Martins et al, 1997; Lincopan et al, 2003, 2005; Pereira et al, 2008; Melo et al, 2010, 2011; Carvalho et al, 2012; Naves et al, 2013; Ragioto et al, 2014; Carrasco et al, 2015; Sanches et al, 2015). However, these nanostructures were not specifically evaluated against foodborne pathogens before.…”

“…These bacteria were not sensitive to the majority of the cationic assemblies tested (Table 1) with exception of PDDA (3 logs reduction in viability) or PMMA/PDDA (5 logs reduction in viability) (Table 1). Although the antibacterial effect of antimicrobial peptides and polymers was mediated by membrane disruption with leakage of intracellular compounds (Carrasco et al, 2015), it was not clear how they reached the bacterial cytoplasmic membrane, crossing barriers such as the external membrane of Gram-negative bacteria and the cell wall of Gram-positive bacteria. Possibly the peptide or polymer first targets the outer cell wall and then undergoes a self-promoted uptake (Hancock, 1997; Yaron et al, 2003).…”