Justyna Śmiałek-Bartyzel, Monika Bzowska, Alicja Frączek, Iwona Wojda, Renata Mężyk-Kopeć, Piotr Bonarek, Artur Blat, Jan Rak, Paweł Mak
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引用次数: 0
Abstract
This study describes the interactions between two different pro-inflammatory factors produced by bacteria, lipopolysaccharide (LPS) from Gram-negative bacteria and the peptide BacSp222 produced by a Gram-positive zoonotic strain, Staphylococcus pseudintermedius 222. We demonstrate that the mentioned molecules interact, forming a complex, and this phenomenon selectively reduces their biological activities in vitro and in vivo. Specifically, the levels of tumor necrosis factor (TNF) and nitric oxide (NO) produced by monocyte-macrophage cells were lower in samples treated with both LPS and BacSp222 compared to those treated with LPS alone. This is most likely because BacSp222 limited the ability of LPS to stimulate the TLR4 receptor. In the Galleria mellonella larvae injected simultaneously with LPS and BacSp222, the activity of hemolymph phenoloxidase, a key component of the insect immune response, was lower than that observed in larvae injected with either LPS or BacSp222 alone. Moreover, LPS inhibited the antibacterial activity of the bacteriocin, while BacSp222 limited LPS's ability to activate a proenzyme in the Limulus amebocyte lysate test. The changes in the activities of BacSp222 and LPS were attributed to the electrostatic interactions between LPS micelles and bacteriocin molecules, resulting in a decrease in LPS aggregate size and the direct formation of a complex between them, as revealed by gel filtration and isothermal microcalorimetry.
期刊介绍:
ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to:
* Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials.
* Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets.
* Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance.
* Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents.
* Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota.
* Small molecule vaccine adjuvants for infectious disease.
* Viral and bacterial biochemistry and molecular biology.