Susceptibility of Multidrug-Resistant Bacteria, Isolated from Water and Plants in Nigeria, to Ceragenins

Abstract

The continuous emergence of multidrug resistant pathogens is a major global health concern. Although antimicrobial peptides (AMPs) have shown promise as a possible means of combatting multidrug resistant strains without readily engendering resistance, costs of production and targeting by proteases limit their utility. Ceragenins are non-peptide AMP mimics that overcome these shortcomings while retaining broad-spectrum antimicrobial activity. To further characterize the antibacterial activities of ceragenins, their activities against a collection of environmental isolates of bacteria were determined. These isolates were isolated in Nigeria from plants and water. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of selected ceragenins and currently available antimicrobials against these isolates were measured to determine resistance patterns. Using scanning electron microscopy (SEM), we examined the morphological changes in bacterial membranes following treatment with ceragenins. Finally, we investigated the effectiveness of ceragenins in inhibiting biofilm formation and destroying established biofilms. We found that, despite high resistance to many currently available antimicrobials, including colistin, environmental isolates in planktonic and biofilm forms remain susceptible to ceragenins. Additionally, SEM and confocal images of ceragenin-treated cells confirmed the effective antibacterial and antibiofilm activity of ceragenins.

<p>NDM-1 Carbapenemase-Producing Enterobacteriaceae are Highly Susceptible to Ceragenins CSA-13, CSA-44, and CSA-131</p>

“…Therefore, CSAs can be considered as a new approach to eradicate MDR pathogens. 16,20,29,38,39 Moreover, bacteria are unable to achieve high levels of resistance to CSAs. It should be pointed out that ceragenins appear to be well tolerated and exhibits no degradation in the presence of bacterial and host proteases, making these properties a significant area of the antimicrobial research.…”

“…It should be pointed out that ceragenins appear to be well tolerated and exhibits no degradation in the presence of bacterial and host proteases, making these properties a significant area of the antimicrobial research. 20 An important criterion in the assessment of effectiveness of CSAs is maintenance of the sufficient antibacterial activity with highly drug-resistant organisms. MIC values were determined for this purpose.…”

“…Accordingly, all ceragenins tested (CSA-13, CSA-44, CSA-131) have been shown to penetrate the extracellular matrix and eradicate a biofilm in a dose-dependent manner. 20,25 Importantly, even non-toxic doses of ceragenins (at least 5-10 μg/mL) inhibit the biofilm formation in the 40-50% range.…”

“…16 So far, no bacteria have accomplished high levels of resistance to ceragenins. 20 Apart from antibacterial effects, these molecules also display antibiofilm, sporicidal, antiviral, antiparasitic, and anticancer activities. [21][22][23][24] The therapeutic potential of CSAs is also underlined by their low toxicity, good stability under physiological conditions, and relatively inexpensive production.…”

“…[21][22][23][24] The therapeutic potential of CSAs is also underlined by their low toxicity, good stability under physiological conditions, and relatively inexpensive production. 20,25 Because of promising therapeutic properties of CSAs, we investigated antibacterial features of CSA-13, CSA-44, and CSA-131 against rods belonging to Enterobacteriaceae family producing NDM-1.…”