Project description:Multidrug-resistant (MDR; resistance to >3 antimicrobial classes) Salmonella enterica serovar I 4,[5],12:i:- strains were linked to a 2015 foodborne outbreak from pork. Strain USDA15WA-1, associated with the outbreak, harbors an MDR module and the metal tolerance element Salmonella Genomic Island 4 (SGI-4). Characterization of SGI-4 revealed that conjugational transfer of SGI-4 resulted in the mobile genetic element (MGE) replicating as a plasmid or integrating into the chromosome. Tolerance to copper, arsenic, and antimony compounds was increased in Salmonella strains containing SGI-4 compared to strains lacking the MGE. Following Salmonella exposure to copper, RNA-seq transcriptional analysis demonstrated significant differential expression of diverse genes and pathways, including induction of numerous metal tolerance genes (copper, arsenic, silver, and mercury). Evaluation of swine administered elevated concentrations of zinc oxide (2,000 mg/kg) and copper sulfate (200 mg/kg) as an antimicrobial feed additive (Zn+Cu) in their diet for 4 weeks prior to and 3 weeks post-inoculation with serovar I 4,[5],12:i:- indicated that Salmonella shedding levels declined at a slower rate in pigs receiving in-feed Zn+Cu compared to control pigs (no Zn+Cu). The presence of metal tolerance genes in MDR Salmonella serovar I 4,[5],12:i:- may provide benefits for environmental survival or swine colonization in metal-containing settings.
Project description:The emergence of multidrug resistant (MDR) Mycobacterium tuberculosis (Mtb) strains, resistant to the frontline anti-tubercular drugs rifampicin and isoniazid, forces treatment with less effective and toxic second-line drugs and stands to derail TB control efforts. However, the immune response to MDR Mtb infection remains poorly understood. Here, we determined the RNA transcriptional profile of in vitro generated macrophages to infection with either drug susceptible Mtb HN878 or MDR Mtb W_7642 infection.
Project description:We examined the microRNA profiles of THP-1 macrophages upon the MTB infection of (1) Beijing/W and non-Beijing/W clinical strains, and (2) susceptible and multidrug-resistant (MDR-) MTB strains.
Project description:Efforts to eradicate TB are largely threatened by drug-resistant tuberculosis, particularly, multidrug-resistant tuberculosis (MDR-TB). It is imperative to find one or more specific biomarkers for diagnosing MDR-TB earlier and declining the incidence. Growing evidences have showed lncRNAs are widely expressed and take part in the genesis and development of many diseases, including tuberculosis. Therefore, to screen the differential lncRNAs among MDR-TB, drug-sensitive tuberculosis(DS-TB) and healthy controls(HCs) is a good strategy to acquire potential biomarkers for MDR-TB diagnosis and partly describe the mechanism of MDR-TB. Here, the present study aimed to investigate the differential expression profile of lncRNAs in serum among patients with MDR-TB ,DS-TB and HCs using lncRNA microarray
Project description:We examined the microRNA profiles of THP-1 macrophages upon the MTB infection of (1) Beijing/W and non-Beijing/W clinical strains, and (2) susceptible and multidrug-resistant (MDR-) MTB strains. THP-1 cells were induced differentiation into a macrophage phenotype. Then cells were infected with three MDR (INHR, RIFR) Beijing/W, three sensitive (INHS, RIFS) Beijing/W, three MDR(INHR, RIFR) non-Beijing/W, and three sensitive (INHS, RIFS) non-Beijing/W strains. Total RNA were extracted and transfered into cDNA for miRNA profile analysis. Non-infected cells were used as control.
Project description:In the face of escalating challenges posed by infections with multiple drug-resistant (MDR) pathogens, the use of bacteriophages in therapeutic applications has emerged as a critically relevant and often sole alternative to traditional antibiotics. The most promising results of phage therapy have been demonstrated in the case of Staphylococcus aureus. It should be noted that the S. aureus population is characterized by a high degree of clonality. Strains belonging to sequence type 239 are among the main epidemic strains of methicillin-resistant S. aureus, identified worldwide. Many ST239 strains are characterized by MDR and resistance to virulent bacteriophages, and can become a serious problem in medicine. The purpose of this study was to investigate the resistance of clinical strains of S. aureus SA191REV of ST239 to bacteriophages of the Herelleviridae family using systems biology methods, starting from microbiological data on the interaction of strains with bacteriophages to transcriptomic and proteomic analysis. As results, the main changes in the cells of the resistant strain caused by phage infection are related to the energy metabolism in the cell. Significant changes were found in the functioning of the tricarboxylic acid cycle, glycolytic process, and glucose metabolic process. The most likely mechanism of resistance in the case of SA191REV strains is the premature death of infected cells due to the type I toxin-antitoxin system, as well as the hyperexpression of the lrgA and lrgB genes.
