Project description:Polymyxin B is considered as a last-resort antibiotic for multidrug-resistant or extensively drug-resistant gram-negative bacterial infections. Addressing Salmonella resistance to polymyxin B is crucial for global public health. In this study, transcriptomic detection and analysis were used to clarify the mechanisms by which CpxA-deleted S.typhimurium is involved in resistance to polymyxin B stress, which may be related to processes such as increased assembly of bacterial flagella.
2024-11-07 | GSE281216 | GEO
Project description:Multidrug resistant Salmonella serovars isolated from poultry
Project description:Treatment of urinary tract infections is today a challenge due to the increasing prevalence of multidrug-resistant ESBL-producing uropathogenic Escherichia coli (UPEC). There is an urgent need for new treatment strategies for multidrug-resistant UPEC and preferably with targets that have low potential for development of resistance. Carbon monoxide-releasing molecules (CORMs) are novel and potent antibacterial agents. The present study examines the transcriptomic targets of CORM-2 in a multidrug-resistant ESBL-producing UPEC isolate (ESBL7) in response to a single exposure to CORM-2 and after repeated exposure to CORM-2. The bacterial viability and minimal inhibitory concentration (MIC) were also examined after repeated exposure to CORM-2. Microarray analysis revealed that a wide range of processes were affected by CORM-2, including a general trend of down-regulation in energy metabolism and biosynthesis pathways and up-regulation of the SOS response and DNA repair. Several genes involved in virulence (ibpB), antibiotic resistance (marAB, mdtABC) and biofilm formation (bhsA, yfgF) were up-regulated, while some genes involved in virulence (kpsC, fepCEG, entABE), antibiotic resistance (evgA) and biofilm formation (artIP) were down-regulated. Repeated exposure to CORM-2 did not alter the gene expression patterns, the growth inhibitory response to CORM-2 or the MIC values for CORM-2, cefotaxime, ciprofloxacin and trimethoprim.
Project description:Salmonella enterica serotype Typhimurium produces a variety of fimbrial appendages, among which the type 1 fimbriae is the most common type. In vitro static broth culture favors S. Typhimurium to produce type 1 fimbriae, while solid agar inhibits its expression. A transposon inserted in the stbC gene, which would encode an usher protein for Stb fimbriae of a non-flagellar S. Typhimurium LB5010 strain, conferred it to agglutinate yeast cells on both cultures, and was mannose-sensitive. Reverse transcription polymerase chain reaction (RT-PCR) revealed that the expression of the fimbrial major subunit gene fimA, and fimZ, a positive regulator gene of fimA, were both increased in the stbC mutant strain when grown on LB agar; fimW, a repressor gene of fimA, exhibited lower expression. Flagella were observed in the stbC mutant and this phenotype was correlated with the motile phenotype detected by MSRV agar medium and reaction with flagella antiserum. Microarray data and RT-PCR also indicated that the expression of three genes, motA, motB, and cheM, was enhanced in the stbC mutant. The S. Typhimurium stbC mutant was resistant to a variety of antibiotics, consistent with the finding that expression of yhcQ and ramA, two genes involved in multidrug resistance, was enhanced. A complementation test revealed that transforming a recombinant plasmid possessing the coding sequence of the stbC gene restored the mannose-sensitive agglutination phenotype to the stbC mutant much as that in the parental S. Typhimurium LB5010 strain, indicating the possibility of an interplay of different fimbrial systems in coordinating their expression. Key Words: Salmonella enterica serotype Typhimurium, fimbriae, type 1 fimbriae, stbC, transposon, multidrug resistant, flagella RNA transcript of Salmonella Typhimurium LB5010 strain comparing wild-type with stbC mutant. Two-cindition experiment, wild-type vs. stbC mutant strain.
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.