Ibsenlaustsen0494

Sulfolobus islandicus codes for four DNA polymerases three are of the B-family (Dpo1, Dpo2, and Dpo3), and one is of the Y-family (Dpo4). Western analysis revealed that among the four polymerases, only Dpo2 exhibited DNA damage-inducible expression. To investigate how these DNA polymerases could contribute to DNA damage tolerance in S. islandicus, we conducted genetic analysis of their encoding genes in this archaeon. Plasmid-borne gene expression revealed that Dpo2 increases cell survival upon DNA damage at the expense of mutagenesis. Gene deletion studies showed although dpo1 is essential, the remaining three genes are dispensable. Furthermore, although Dpo4 functions in housekeeping translesion DNA synthesis (TLS), Dpo2, a B-family DNA polymerase once predicted to be inactive, functions as a damage-inducible TLS enzyme solely responsible for targeted mutagenesis, facilitating GC to AT/TA conversions in the process. Together, our data indicate that Dpo2 is the main DNA polymerase responsible for DNA damage tolerance and is the primary source of targeted mutagenesis. Given that crenarchaea encoding a Dpo2 also have a low-GC composition genome, the Dpo2-dependent DNA repair pathway may be conserved in this archaeal lineage.The aim of this study was to investigate the characteristics of a fosA3 carrying IncC-IncN plasmid from a multidrug-resistant Salmonella isolate HNK130. HNK130 was isolated from a chicken and identified as ST17 Salmonella enterica serovar Indiana and exhibited resistance to 13 antibiotics including the cephalosporins and fosfomycin. S1 nuclease pulsed-field gel electrophoresis and Southern blot assays revealed that HNK130 harbored only one ∼180-kb plasmid carrying fosA3 and blaCTX-M-14, which was not transferable via conjugation. We further examined 107 Escherichia coli electro-transformants and identified 3 different plasmid variants, pT-HNK130-1 (69), pT-HNK130-2 (15), and pT-HNK130-3 (23), in which pT-HNK130-1 seemed to be the same as the plasmid harbored in HNK130. DIRECT RED 80 concentration We completely sequenced an example of each of these variants, and all three variants were IncC-IncN multi-incompatible plasmid and showed a mosaic structure. The fosA3 gene was present in all three and bounded by IS26 elements in the same orientation (IS26-322bp-fosA3-1758bp-IS26) that could form a minicircle containing fosA3. The blaCTX-M-14 gene was located within an IS15DI-ΔIS15DI-iroN-IS903B-blaCTX-M-14-ΔISEcp1-IS26 structure separated from the fosA3 gene in pT-HNK130-1, but was adjacent to fosA3 in pT-HNK130-3 in an inverted orientation. Linear comparison of the three variants showed that pT-HNK130-2 and pT-HNK130-3 resulted from the sequence deletion and inversion of pT-HNK130-1. Stability tests demonstrated that pT-HNK130-1 and pT-HNK130-3 could be stably maintained in the transformants without antibiotic selection but pT-HNK130-2 was unstable. This is the first description of an IncC-IncN hybrid plasmid from an ST17 S. Indiana strain and indicates that this plasmid may further facilitate dissemination of fosfomycin and cephalosporin resistance in Salmonella.In recent years, the treatment of tuberculosis is once again facing a severe situation because the existing antituberculosis drugs have become weaker and weaker with the emergence of drug-resistant Mycobacterium tuberculosis (Mtb). The studies of cell division and cell cycle-related factors in Mtb are particularly important for the development of new drugs with broad-spectrum effects. Mycobacterium smegmatis (Msm) has been used as a model organism to study the molecular, physiological, and drug-resistant mechanisms of Mtb. Bioinformatics analysis has predicted that MSMEG_6171 is a MinD-like protein of the septum site-determining protein family associated with cell division in Mycobacterium smegmatis. In our study, we use ultrastructural analysis, proteomics, metabolomics, and molecular biology techniques to comprehensively investigate the function of MSMEG_6171. Overexpression of MSMEG_6171 in Msm resulted in elongated cells, suggesting an important role of MSMEG_6171 in regulating cell wall morphology. The MSMEG_6171 overexpression could enhance the bacterial resistance to vancomycin, ethionamide, meropenem, and cefamandole. The MSMEG_6171 overexpression could alter the lipid metabolism of Msm to cause the changes on cellular biofilm property and function, which enhances bacterial resistance to antibiotics targeting cell wall synthesis. MSMEG_6171 could also induce the glyceride and phospholipid alteration in vivo to exhibit the pleiotropic phenotypes and various cellular responses. The results showed that amino acid R249 in MSMEG_6171 was a key site that can affect the level of bacterial drug resistance, suggesting that ATPase activity is required for function.Neurological complications occurring due to Salmonella infection in some typhoid patients remain a relatively unexplored serious complication. This study firstly aimed to explore whether disseminative ability of Salmonella from gut to brain is strain specific or not and on the basis of bacterial load, histopathology, and behavioral changes, it was observed that Salmonella enterica serovar Typhimurium NCTC 74 did not cause brain infection in murine model in contrast to Salmonella Typhimurium SL1344. Simultaneously, alarming escalation in antimicrobial resistance, making the existing antibiotics treatment inefficacious, prompted us to evaluate other bio-compatible strategies as a potential treatment option. In this context, the role of gut microbiota in influencing behavior, brain neurochemistry, and physiology by modulating key molecules associated with gut-brain axis has captured the interest of the scientific community. Followed by in vitro screening of potential probiotic strains for beneficial attributes, efficacy of the selected strain was systematically evaluated at various levels of gut-brain axis against Salmonella induced brain infection. Analysis of behavioral (depression, anxiety, and locomotor), neurochemical [gamma amino butyric acid and acetylcholinesterase (AChE)], neuropathological (brain and intestinal histology; bacterial burden), and immunohistochemical studies (tight junction proteins expression) revealed its role in preventing serious manifestations and proving its potential as "psychobiotic." To the best of our knowledge, this is the first report elaborating strain specificity of Salmonella in causing post-typhoidal neurological manifestations and simultaneous use of probiotic in managing the same by influencing the pathophysiology at gut-brain axis.