The human gut microbiota is an important reservoir of ESBL-producing Escherichia coli (ESBL-Ec). Community surveillance studies of ESBL-Ec to monitor circulating clones and ESBL genes are logistically challenging and costly.
 
  To evaluate if isolates obtained in routine clinical practice can be used as an alternative to monitor the distribution of clones and ESBL genes circulating in the community.
 
  WGS was performed on 451 Dutch ESBL-Ec isolates (2014-17), including 162 community faeces and 289 urine and blood isolates. We compared proportions of 10 most frequently identified STs, PopPUNK-based sequence clusters (SCs) and ESBL gene subtypes and the degree of similarity using Czekanowski's proportional similarity index (PSI).
 
  Nine out of 10 most prevalent STs and SCs and 8/10 most prevalent ESBL genes in clinical ESBL-Ec were also the most common types in community faeces. The proportions of ST131 (39% versus 23%) and SC131 (40% versus 25%) were higher in clinical isolates than in community faeces (P < 0.01). Within ST131, H30Rx (C2) subclade was more prevalent among clinical isolates (55% versus 26%, P < 0.01). The proportion of ESBL gene blaCTX-M-1 was lower in clinical isolates (5% versus 18%, P < 0.01). Czekanowski's PSI confirmed that the differences in ESBL-Ec from community faeces and clinical isolates were limited.
 
  Distributions of the 10 most prevalent clones and ESBL genes from ESBL-Ec community gut colonization and extra-intestinal infection overlapped in majority, indicating that isolates from routine clinical practice could be used to monitor ESBL-Ec clones and ESBL genes in the community.
 Distributions of the 10 most prevalent clones and ESBL genes from ESBL-Ec community gut colonization and extra-intestinal infection overlapped in majority, indicating that isolates from routine clinical practice could be used to monitor ESBL-Ec clones and ESBL genes in the community.Biotin is a covalently attached enzyme cofactor required for intermediary metabolism in all three domains of life. Several important human pathogens (e.g. Mycobacterium tuberculosis) require biotin synthesis for pathogenesis. Humans lack a biotin synthetic pathway hence bacterial biotin synthesis is a prime target for new therapeutic agents. The biotin synthetic pathway is readily divided into early and late segments. Although pimelate, a 7-carbon α,ω-dicarboxylic acid that contributes 7 of the 10 biotin carbons atoms, was long known to be a biotin precursor, its biosynthetic pathway was a mystery until the Escherichia colipathway was discovered in 2010. Since then, diverse bacteria encode evolutionarily distinct enzymes that replace enzymes in the E.  https://www.selleckchem.com/products/pomhex.html  coli pathway. Two new bacterial pimelate synthesis pathways have been elucidated. In contrast to the early pathway, the late pathway, assembly of the fused rings of the cofactor, was long thought settled. However, a new enzyme that bypasses a canonical enzyme was recently discovered as well as homologs of another canonical enzyme that functions in synthesis of another protein-bound coenzyme, lipoic acid. Most bacteria tightly regulate transcription of the biotin synthetic genes in a biotin-responsive manner. The bifunctional biotin ligases which catalyze attachment of biotin to its cognate enzymes and repress biotin gene transcription are best understood regulatory system.
  Campylobacter spp. and Arcobacter butzleri are foodborne pathogens associated with the consumption of contaminated raw chicken meat. At the industry level, the combination of new and common antimicrobials could be used as a strategy to control the presence of pathogens in chicken carcasses. The objective of this study was to determine the bacteriostatic and bactericidal effects of a mixture of chlorine (Cl) and sodium gallate (SG) on a mixture of two Campylobacter species (Campylobacter jejuni and Campylobacter coli) and A. butzleri. Using a central composite experimental design, it was established that the optimum inhibitory SG-Cl concentration for Campylobacter spp. was 44 to 45 ppm. After 15 h of incubation, Campylobacter species growth was reduced by 37.5% and the effect of Cl was potentiated by SG at concentrations above 45 ppm. In the case of A. butzleri, optimum levels of 28 and 41 ppm were observed for SG and Cl, respectively; no synergism was reported, as this bacterium was more sensitive to lower Cl concentrations than Campylobacter. After a 20-min pretreatment with peracetic acid (50 ppm), the optimum condition to achieve a >1.0-Log CFU/mL reduction of Campylobacter spp. was exposure to 177 ppm of Cl and 44 ppm of SG for 56 min. As A. butzleri showed lower resistance to the bacteriostatic effect of the Cl-SG combination, it was assumed that optimum bactericidal conditions for Campylobacter spp. were effective to control the former; this was confirmed with subsequent validation of the model. The SG-Cl combination has bactericidal properties against Campylobacter and A. butzleri, and it may be a useful strategy to improve sanitary practices applied in the poultry industry.
 CRISPR/Cas9 multigene editing is an active and widely studied topic in the fields of biomedicine and biology. It involves a simultaneous participation of multiple single-guide RNAs (sgRNAs) to edit multiple target genes in a way that each gene is edited by one of these sgRNAs. There are possibly numerous sgRNA candidates capable of on-target editing on each of these genes with various efficiencies. Meanwhile, each of these sgRNA candidates may cause unwanted off-target editing at many other genes. Therefore, selection optimization of these multiple sgRNAs is demanded so as to minimize the number of sgRNAs and thus reduce the collective negative effects caused by the off-target editing. This survey reviews wet-laboratory approaches to the implementation of multigene editing and their needs of computational tools for better design. We found that though off-target editing is unavoidable during the gene editing, those disfavored cuttings by some target genes' sgRNAs can potentially become on-target editing sites for some other genes of interests. This off-to-on role conversion is beneficial to optimize the sgRNA selection in multigene editing. We present a preference cutting score to assess those beneficial off-target cutting sites, which have a few mismatches with their host genes' on-target editing sites. These potential sgRNAs can be prioritized for recommendation via ranking their on-target average cutting efficiency, the total off-target site number and their average preference cutting score. We also present case studies on cancer-associated genes to demonstrate tremendous usefulness of the new method.