Activated sludges were sampled from five sewage treatment plants (STPs) distributed in three geographically isolated areas, i.e., Hong Kong (Shatin, Stanley), Shanghai (Minhang) in China, and the bay area in California (Palo Alto and San Jose) of the United States. Among the tested 14 tetracycline resistance (tet) genes, nine genes encompassing efflux pumps (tetA, tetC, tetE, and tetG), ribosomal protection proteins (tetM, tetO, tetQ, and tetS), and enzymatic modification (tetX) were commonly detected in the STP sludge samples, whereas five genes encompassing efflux pumps [tetB, tetD, tetL, tetK, and tetA(P)] were not detected in any sludge sample. Additionally, 109 lactose-fermenting Enterobacteriaceae (LFE) strains were isolated from the activated sludge of the Shatin STP. Tetracycline-resistant (TR) LFE accounted for 32% of the total 109 LFE strains. The occurrence frequencies of tet genes among all TR-LEF strains varied from 0 to 91%, i.e., tetC (91%), tetA (46%), tetE (9%), tetG (6%), and tetD (6%). Finally, quantitative real-time polymerase chain reaction was used to quantify the change of tetC and tetA genes as the indicator of TR-LEF in the Shatin and Stanley STPs. The results showed that the concentrations of tetC and tetA genes in STP effluent ranged from 10(4) to 10(5) copies/mL, significantly lower than those in the influent by 3 orders of magnitude.

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The release of sulfonamide antibiotics into the environment is alarming because the existence of these antibiotics in the environment may promote resistance in clinically relevant microorganisms, which is a potential threat to the effectiveness of antibiotic therapies. Controllable biodegradation processes are of particular significance for the inexpensive yet effective restoration of sulfonamide-contaminated environments. Cultivation-based techniques have already made great strides in successfully isolating bacteria with promising sulfonamide degradation abilities, but the implementation of these isolates in bioremediation has been limited by unknown microbial diversity, vast population responsiveness, and the impact of perturbations from open and complex environments. Advances in DNA sequencing technologies and metagenomic analyses are being used to complement the information derived from cultivation-based procedures. In this Review, we provide an overview of the growing understanding of isolated sulfonamide degraders and identify shortcomings of the prevalent literature in this field. In addition, we propose a technical paradigm that integrates experimental testing with metagenomic analysis to pave the way for improved understanding and exploitation of these ecologically important isolates. Overall, this Review aims to outline how metagenomic studies of isolated sulfonamide degraders are being applied for the advancement of bioremediation strategies for sulfonamide contamination.

As one of the largest biotechnological applications, activated sludge (AS) systems in wastewater treatment plants (WWTPs) harbor enormous viruses, with 10-1,000-fold higher concentrations than in natural environments. However, the compositional variation and host-connections of AS viruses remain poorly explored. Here, we report a catalogue of ~50,000 prokaryotic viruses from six WWTPs, increasing the number of described viral species of AS by 23-fold, and showing the very high viral diversity which is largely unknown (98.4-99.6% of total viral contigs). Most viral genera are represented in more than one AS system with 53 identified across all. Viral infection widely spans 8 archaeal and 58 bacterial phyla, linking viruses with aerobic/anaerobic heterotrophs, and other functional microorganisms controlling nitrogen/phosphorous removal. Notably, Mycobacterium, notorious for causing AS foaming, is associated with 402 viral genera. Our findings expand the current AS virus catalogue and provide reference for the phage treatment to control undesired microorganisms in WWTPs.

2ϩ storage and release, transcription factors, and ion channels. The major isoform of CaMKII in the heart is CaMKII␦. Two cardiac splice variants, CaMKII␦ B and ␦ C , differ in whether they contain a nuclear localization sequence. Our laboratory has examined the hypothesis that the nuclear ␦ B and the cytoplasmic ␦ C isoforms respond to different Ca 2ϩ stimuli and have distinct effects on hypertrophic cardiac growth and Ca 2ϩ handling. We have shown that pressure overload-induced hypertrophy differentially affects the nuclear ␦ B and the cytoplasmic ␦ C isoforms of CaMKII. Additionally, using isolated myocytes and transgenic mouse models, we demonstrated that the nuclear CaMKII␦ B isoform plays a key role in cardiac gene expression associated with cardiac hypertrophy. The cytoplasmic CaMKII␦ C isoform phosphorylates substrates involved in Ca 2ϩ handling. Dysregulation of intracellular Ca 2ϩ and resulting changes in excitation-contraction coupling characterize heart failure and can be induced by in vivo overexpression of CaMKII␦ C and phosphorylation of its substrates. The differential location of CaMKII isoforms and their relative activation by physiological vs. pathological stimuli may provide a paradigm for exploring and elucidating how Ca 2ϩ /CaMKII pathways can serve as both friends and foes in the heart.

To comprehensively understand the profile of free-living bacteria and potential bacterial pathogens in sewage treatment plants (STPs), this study applied high-throughput sequencing-based metagenomics approaches to investigate the effects of activated sludge (AS) treatment process and ultraviolet (UV) disinfection on the community of bacterial pathogens in two full-scale STPs. A total of 23 bacterial genera were identified as free-living bacteria, and 243 species/OTU were identified as potential bacterial pathogens, 6 of which were confidently detected in the STPs (with the total abundances ranging from 0.02 to 14.19%). Both diversity and relative abundance of the detected bacterial pathogens decreased obviously after AS treatment process (p < 0.05), and increased slightly after sedimentation (p < 0.05). UV disinfection shows no obvious effects on the total relative abundance of the free-living pathogenic bacteria in sewage. Although large amounts of the particle-bound pathogens were eliminated through the sewage treatment process, the STPs could not effectively remove the free-living bacterial pathogens, and some pathogenic bacteria (e.g., Pseudomonas aeruginosa) present in the effluent had higher relative abundance after UV disinfection. Overall, the results extend our knowledge regarding the community of potential pathogens (especially free-living pathogens) in STPs.

Background Our interconnected world and the ability of bacteria to quickly swap antibiotic resistance genes (ARGs) make it particularly important to establish the epidemiological links of multidrug resistance (MDR) transfer between wastewater treatment plant (WWTP)- and human/animal-associated bacteria, under the One Health framework. However, evidence of ARGs exchange and potential factors that contribute to this transfer remain limited. Results Here, by combining culture-based population genomics and genetic comparisons with publicly available datasets, we reconstructed the complete genomes of 82 multidrug-resistant isolates from WWTPs and found that most WWTP-associated isolates were genetically distinct from their closest human/animal-associated relatives currently available in the public database. Even in the minority of lineages that were closely related, WWTP-associated isolates were characterized by quite different plasmid compositions. We identified a high diversity of circular plasmids (264 in total, of which 141 were potentially novel), which served as the main source of resistance, and showed potential horizontal transfer of ARG-bearing plasmids between WWTP- and humans/animal-associated bacteria. Notably, the potentially transferred ARGs and virulence factors (VFs) with different genetic backgrounds were closely associated with flanking insertion sequences (ISs), suggesting the importance of synergy between plasmids and ISs in mediating a multilayered hierarchical transfer of MDR and potentiating the emergence of MDR-hypervirulent clones. Conclusion Our findings advance the current efforts to establish potential epidemiological links of MDR transmission between WWTP- and human/animal-associated bacteria. Plasmids play an important role in mediating the transfer of ARGs and the IS-associated ARGs that are carried by conjugative plasmids should be prioritized to tackle the spread of resistance.

Motivation The driver genes play a key role in the evolutionary process of cancer. Effectively identifying these driver genes is crucial to cancer diagnosis and treatment. However, due to the high heterogeneity of cancers, it remains challenging to identify the driver genes for individual patients. Although some computational methods have been proposed to tackle this problem, they seldom consider the fact that the genes functionally similar to the well-established driver genes may likely play similar roles in cancer process, which potentially promotes the driver gene identification. Thus, here we developed a novel approach of IMCDriver to promote the driver gene identification both for cohorts and individual patients. Results IMCDriver first considers the well-established driver genes as prior information, and adopts the using multi-omics data (e.g., somatic mutation, gene expression and protein-protein interaction) to compute the similarity between patients/genes. Then, IMCDriver prioritizes the personalized mutated genes according to their functional similarity to the well-established driver genes via Inductive Matrix Completion. Finally, IMCDriver identifies the highly rank-ordered genes as the personalized driver genes. The results on five cancer datasets from TCGA show that our IMCDriver outperforms other existing state-of-the-art methods both in the cohort and patient-specific driver gene identification. IMCDriver also reveals some novel driver genes that potentially drive cancer development. In addition, even for the driver genes rarely mutated among a population, IMCDriver can still identify them and prioritize them with high priorities. Availability Code available at https://github.com/NWPU-903PR/IMCDriver Supplementary information Supplementary data are available at Bioinformatics online.