Project description:Iodine is one of the oldest antimicrobial agents. Until now, there have been no reports on acquiring resistance to iodine. Recent studies showed promising results on application of iodine-containing nano-micelles, FS-1, against antibiotic-resistant pathogens as a supplement to antibiotic therapy. The mechanisms of the action, however, remain unclear. The aim of this study was to perform a holistic analysis and comparison of gene regulation in three phylogenetically distant multidrug-resistant reference strains representing pathogens associated with nosocomial infections from the ATCC culture collection: Escherichia coli BAA-196, Staphylococcus aureus BAA-39, and Acinetobacter baumannii BAA-1790. These cultures were treated by a 5-min exposure to sublethal concentrations of the iodine-containing drug FS-1 applied in the late lagging phase and the middle of the logarithmic growth phase. Complete genome sequences of these strains were obtained in the previous studies. Gene regulation was studied by total RNA extraction and Ion Torrent sequencing followed by mapping the RNA reads against the reference genome sequences and statistical processing of read counts using the DESeq2 algorithm. It was found that the treatment of bacteria with FS-1 profoundly affected the expression of many genes involved in the central metabolic pathways; however, alterations of the gene expression profiles were species specific and depended on the growth phase. Disruption of respiratory electron transfer membrane complexes, increased penetrability of bacterial cell walls, and osmotic and oxidative stresses leading to DNA damage were the major factors influencing the treated bacteria.IMPORTANCE Infections caused by antibiotic-resistant bacteria threaten public health worldwide. Combinatorial therapy in which antibiotics are administered together with supplementary drugs improving susceptibility of pathogens to the regular antibiotics is considered a promising way to overcome this problem. An induction of antibiotic resistance reversion by the iodine-containing nano-micelle drug FS-1 has been reported recently. This drug is currently under clinical trials in Kazakhstan against multidrug-resistant tuberculosis. The effects of released iodine on metabolic and regulatory processes in bacterial cells remain unexplored. The current work provides an insight into gene regulation in the antibiotic-resistant nosocomial reference strains treated with iodine-containing nanoparticles. This study sheds light on unexplored bioactivities of iodine and the mechanisms of its antibacterial effect when applied in sublethal concentrations. This knowledge will aid in the future design of new drugs against antibiotic-resistant infections.
Project description:1.BackgroundIodine is a broad-spectrum antimicrobial disinfectant for topical application. Recent studies have shown promising results on the applicability of an iodine-containing complex, FS-1, against antibiotic-resistant pathogens. It was hypothesized that the antimicrobial activity of iodine-containing complexes may be modulated by the organic moiety of the complex, i.e., amino acids. 2.MethodsGene regulation and metabolic alterations were studied in two model multidrug-resistant microorganisms, Staphylococcus aureus ATCC BAA-39, and Escherichia coli ATCC BAA-196, treated with three complexes containing iodine and three different amino acids: glycine, L-alanine, and L-isoleucine. The bacterial cultures were exposed to sub-lethal concentrations of the complexes in the lagging and logarithmic growth phases. Gene regulation was studied by total RNA sequencing and differential gene expression analysis. 3.ResultsThe central metabolism of the treated bacteria was affected. An analysis of the regulation of genes involved in stress responses suggested the disruption of cell wall integrity, DNA damage, and oxidative stress in the treated bacteria. 4.ConclusionsPrevious studies showed that the application of iodine-containing complexes, such as FS-1, serves as a supplement to common antibiotics and can be a promising way to combat antibiotic-resistant pathogens. Current results shed light on possible mechanisms of this action by disrupting the cell wall barriers and imposing oxidative stress. It was also found that the effect of the complexes on metabolic pathways varied in the tested microorganisms depending on the organic moiety of the complexes and the growth phase when the complexes had been applied.
Project description:We report here the whole-genome sequence of the USA300 strain of methicillin-resistant Staphylococcus aureus (MRSA), designated ATCC BAA-1680, and commonly referred to as community-associated MRSA (CA-MRSA). This clinical MRSA isolate is commercially available from the American Type Culture Collection (ATCC) and is widely utilized as a control strain for research applications and clinical diagnosis. The isolate was propagated in ATCC medium 18, tryptic soy agar, and has been utilized as a model S. aureus strain in several studies, including MRSA genetic analysis after irradiation with 470-nm blue light.