Protective Action of Linear Polyethylenimine against Staphylococcus aureus Colonization and Exaggerated Inflammation in Vitro and in Vivo

Abstract

Increased evolution of multidrug resistant pathogens necessitates the development of multifunctional antimicrobials. There is a perceived need for developing new antimicrobials that can interfere with acute inflammation after bacterial infections. Here, we investigated the therapeutic potential of linear polyethylenimine (LPEI) in vitro and in vivo. The minimum inhibitory concentration of LPEI ranged from 8 to 32 μg/mL and elicited rapid bactericidal activity against clinical isolates of meticillin-resistant Staphylococcus aureus (MRSA). The polymer was biocompatible for human cultured ocular and dermal cells. Prophylactic addition of LPEI inhibited the bacterial colonization of human primary dermal fibroblasts (hDFs). In a scratch wound cell migration assay, LPEI attenuated the migration inhibitory effects of bacterial secretions. The polymer neutralized the cytokine release by hDFs exposed to bacterial secretions, possibly by blocking their accessibility to host cell receptors. Topical instillation of LPEI (1 mg/ mL) was noncytotoxic and did not affect the re-epithelialization of injured porcine cornea. In a prophylactic in vivo model of S. aureus keratitis, LPEI was superior to gatifloxacin in terms of reducing stimulation of cytokines, corneal edema, and overall severity of the infection. These observations demonstrate therapeutic potential of LPEI for antimicrobial prophylaxis.

Amphiphilic Polymethyloxazoline–Polyethyleneimine Copolymers: Interaction with Lipid Bilayer and Antibacterial Properties

“…In comparison, the branch PEI displays broad molecular weight distribution which can influence variation of antibacterial activity. The L‐PEI demonstrates good selectivity toward bacteria ( Escherichia coli and Staphylococcus aureus ) in comparison to red blood cells (RBCs) or IOBA cell line . The limited reports available discuss L‐PEI hydrophobic modifications for use as antibacterial surface coatings, typically in the form of covalently bonded polymers or paints .…”

Cationic Lignin-Based Hyperbranched Polymers to Circumvent Drug Resistance in Pseudomonas Keratitis

“…At 24 h post infection, 50 μL of 0.3% (w/v) copolymer (in PBS, pH 7.0, n = 6 eyes), comparator antibiotics (gatifloxaxin, 0.3% w/v, n = 4 eyes), or PBS ( n = 5 eyes) was applied topically to the infected eyes four times/day. Slit-lamp photographs and AS-OCT scans were taken before and after infection as well as during the course of treatment. , The preinoculation and postinoculation corneal thicknesses (CTs) were measured perpendicular to the anterior corneal surfaces, and the average CT was reported . At 72 h post treatment, bacterial bioburden was enumerated, following the protocol reported before.…”

“…Slit-lamp photographs and AS-OCT scans were taken before and after infection as well as during the course of treatment. 28,29 The preinoculation and postinoculation corneal thicknesses (CTs) were measured perpendicular to the anterior corneal surfaces, and the average CT was reported. 30 At 72 h post treatment, bacterial bioburden was enumerated, following the protocol reported before.…”

Nature-inspired antimicrobial nanofibers for infection control

“…Secretome proteins such as receptors, transporters, adhesins, complex cell structures, secreted enzymes, toxins, and virulence factors allow bacteria to interact with, and adapt to their environment will affect wound healing. Bacterial secretome process several important roles in virulence as well as cell to cell communication and later play a core role in bacterial pathogenesis [148,149].…”

“…The supernatants were analyzed for the absence of any bacteria by microscopic examination. A suitable volume of bacterial secretomes was combined with the DMEM, added to single layers of hDFs with (0.1% w/v) or without εPL, and incubated at 37 °C for 24 h to examined wound closure[148,149].…”