Treatment Of Bacterial Pathogens Research Articles

Repurposing host-guest chemistry to sequester virulence and eradicate biofilms in multidrug resistant Pseudomonas aeruginosa and Acinetobacter baumannii

The limited diversity in targets of available antibiotic therapies has put tremendous pressure on the treatment of bacterial pathogens, where numerous resistance mechanisms that counteract their function are becoming increasingly prevalent. Here, we utilize an unconventional anti-virulence screen of host-guest interacting macrocycles, and identify a water-soluble synthetic macrocycle, Pillar[5]arene, that is non-bactericidal/bacteriostatic and has a mechanism of action that involves binding to both homoserine lactones and lipopolysaccharides, key virulence factors in Gram-negative pathogens. Pillar[5]arene is active against Top Priority carbapenem- and third/fourth-generation cephalosporin-resistant Pseudomonas aeruginosa and Acinetobacter baumannii, suppressing toxins and biofilms and increasing the penetration and efficacy of standard-of-care antibiotics in combined administrations. The binding of homoserine lactones and lipopolysaccharides also sequesters their direct effects as toxins on eukaryotic membranes, neutralizing key tools that promote bacterial colonization and impede immune defenses, both in vitro and in vivo. Pillar[5]arene evades both existing antibiotic resistance mechanisms, as well as the build-up of rapid tolerance/resistance. The versatility of macrocyclic host-guest chemistry provides ample strategies for tailored targeting of virulence in a wide range of Gram-negative infectious diseases.

Green Synthesis of ZnO Nanoparticles Using <i>Ca</i><i>esalpinia sappan</i> Leaf Extracts and its Antibacterial Activity on <i>Ralstonia solanacearum</i>

Abstract. Zinc oxide nanoparticles (ZnO NPs) are known to be one of the multifunctional inorganic nanoparticles with its application in the treatment of bacterial pathogens, especially when synthesized through green nanotechnology. In this study, ZnO NPs were successfully synthesized through co-precipitation method and its antibacterial activity against Ralstonia solanacearum was evaluated. Surface morphology through scanning electron microscope (SEM) exhibited an agglomerated rod-like structures, with a mean particle size of 180.9 nm. Phytochemical screening was performed through various chemical qualitative tests, to which the presence of terpenoids and cardiac glycosides in Caesalpinia sappan leaves was confirmed in the aqueous extract. Five treatments were evaluated against R. Solanacearum in terms of their zone of inhibition. The highest zone of inhibition from the different concentrations was observed from the positive control (Gentamicin) with a mean value of 34.47 mm, followed by 0.57 g/mL ZnO NPs with a mean value of 21.69 mm, and no zone of inhibition on the negative control, 0.28 g/mL, and 0.19 g/mL of synthesized ZnO NPs. Antibacterial activity of ZnO using disc diffusion method resulted in a significant zone of inhibition which proves that synthesized nanoparticles can be used as a potent antibacterial agent against R. solanacearum.