Abstract
BackgroundsEscherichia coli K1 causes neonatal meningitis. Transcriptome studies are indispensable to comprehend the pathology and biology of these bacteria. Recently, we showed that nanoparticles loaded with Hesperidin are potential novel antibacterial agents against E. coli K1. Here, bacteria were treated with and without Hesperidin conjugated with silver nanoparticles, and silver alone, and 50% minimum inhibitory concentration was determined. Differential gene expression analysis using RNA-seq, was performed using Degust software and a set of genes involved in cell stress response and metabolism were selected for the study.Results50% minimum inhibitory concentration with silver-conjugated Hesperidin was achieved with 0.5 μg/ml of Hesperidin conjugated with silver nanoparticles at 1 h. Differential genetic analysis revealed the expression of 122 genes (≥ 2-log FC, P< 0.01) in both E. coli K1 treated with Hesperidin conjugated silver nanoparticles and E. coli K1 treated with silver alone, compared to untreated E. coli K1. Of note, the expression levels of cation efflux genes (cusA and copA) and translocation of ions, across the membrane genes (rsxB) were found to increase 2.6, 3.1, and 3.3- log FC, respectively. Significant regulation was observed for metabolic genes and several genes involved in the coordination of flagella.ConclusionsThe antibacterial mechanism of nanoparticles maybe due to disruption of the cell membrane, oxidative stress, and metabolism in E. coli K1. Further studies will lead to a better understanding of the genetic mechanisms underlying treatment with nanoparticles and identification of much needed novel antimicrobial drug candidates.
Highlights
Escherichia coli is a commensal bacteria of the gastrointestinal tract of vertebrates, including humans [1]
Effect of compounds on the growth rate of E. coli K1 Growth curve analysis revealed that untreated E. coli K1 showed the highest growth rate at 37 °C (Fig. 1)
Our analysis revealed that several genes were downregulated in E. coli K1 treated with HDN conjugated Silver nanoparticles (AgNPs), and AgNPs alone compared to untreated E. coli K1 (Fig. 6), Many of the downregulated genes showed significant decrease upon treatment
Summary
Escherichia coli is a commensal bacteria of the gastrointestinal tract of vertebrates, including humans [1]. It is a Gram-negative bacterium that is involved in extraintestinal infections [2]. In spite of the widespread use of antibiotics in recent years, the incidence of bacterial meningitis is still in the range of 5 to 40%, and the neurological sequelae rate in survivors is up to 30% [4, 5]. Previous research has revealed that meningitis caused by E. coli K1 is contributed by several vital proteins, and several genetic islands, such as sfa (S fimbriae), ksp (K1 capsule), CNF-1 and GimA. Resistance to available antibacterial agents by pathogenic bacteria has increased at an alarming rate and has become a serious problem [7]. Approaches include the development of safe bio nanocomposites that have antibacterial activity and utilization of natural products
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