Microbiol Spectr. 2023 Feb 14:e0410222. doi: 10.1128/spectrum.04102-22. Online ahead of print.

ABSTRACT

India is one of the largest consumers and producers of antibiotics and a hot spot for the emergence and proliferation of antimicrobial resistance genes (ARGs). Indian hospital wastewater (HWW) accumulates ARGs from source hospitals and often merges with urban wastewater, with the potential for environmental and human contamination. Despite its putative clinical importance, there is a lack of high-resolution resistome profiling of Indian hospital wastewater, with most studies either relying on conventional PCR-biased techniques or being limited to one city. In this study, we comprehensively analyzed antibiotic resistomes of wastewater from six Indian hospitals distributed in rural and urban areas of northern India through shotgun metagenomics. Our study revealed the predominance of ARGs against aminoglycoside, macrolide, carbapenem, trimethoprim, and sulfonamide antibiotics in all the samples through both read-based analysis and assembly-based analysis. We detected the mobile colistin resistance gene mcr-5.1 for the first time in Indian hospital sewage. blaNDM-1 was present in 4 out of 6 samples and was carried by Pseudomonas aeruginosa in HWW-2, Klebsiella pneumoniae in HWW-4 and HWW-6, and Acinetobacter baumanii in HWW-5. Most ARGs were plasmid-mediated and hosted by Proteobacteria. We identified virulence factors and transposable elements flanking the ARGs, highlighting the role of horizontal gene transmission of ARGs. IMPORTANCE There is a paucity of research on detailed antibiotic resistome and microbiome diversity of Indian hospital wastewater. This study reports the predominance of clinically concerning ARGs such as the beta-lactamases blaNDM and blaOXA and the colistin resistance gene mcr and their association with the microbiome in six different Indian hospital wastewaters of both urban and rural origin. The abundance of plasmid-mediated ARGs and virulence factors calls for urgent AMR crisis management. The lack of proper wastewater management strategies meeting international standards and open drainage systems further complicates the problem of containing the ARGs at these hospitals. This metagenomic study presents the current AMR profile propagating in hospital settings in India and can be used as a reference for future surveillance and risk management of ARGs in Indian hospitals.

PMID:36786639 | DOI:10.1128/spectrum.04102-22

Microb Biotechnol. 2023 Feb 14. doi: 10.1111/1751-7915.14222. Online ahead of print.

ABSTRACT

Practical experiments drive important scientific discoveries in biology, but theory-based research studies also contribute novel-sometimes paradigm-changing-findings. Here, we appraise the roles of theory-based approaches focusing on the experiment-dominated wet-biology research areas of microbial growth and survival, cell physiology, host-pathogen interactions, and competitive or symbiotic interactions. Additional examples relate to analyses of genome-sequence data, climate change and planetary health, habitability, and astrobiology. We assess the importance of thought at each step of the research process; the roles of natural philosophy, and inconsistencies in logic and language, as drivers of scientific progress; the value of thought experiments; the use and limitations of artificial intelligence technologies, including their potential for interdisciplinary and transdisciplinary research; and other instances when theory is the most-direct and most-scientifically robust route to scientific novelty including the development of techniques for practical experimentation or fieldwork. We highlight the intrinsic need for human engagement in scientific innovation, an issue pertinent to the ongoing controversy over papers authored using/authored by artificial intelligence (such as the large language model/chatbot ChatGPT). Other issues discussed are the way in which aspects of language can bias thinking towards the spatial rather than the temporal (and how this biased thinking can lead to skewed scientific terminology); receptivity to research that is non-mainstream; and the importance of theory-based science in education and epistemology. Whereas we briefly highlight classic works (those by Oakes Ames, Francis H.C. Crick and James D. Watson, Charles R. Darwin, Albert Einstein, James E. Lovelock, Lynn Margulis, Gilbert Ryle, Erwin R.J.A. Schrödinger, Alan M. Turing, and others), the focus is on microbiology studies that are more-recent, discussing these in the context of the scientific process and the types of scientific novelty that they represent. These include several studies carried out during the 2020 to 2022 lockdowns of the COVID-19 pandemic when access to research laboratories was disallowed (or limited). We interviewed the authors of some of the featured microbiology-related papers and-although we ourselves are involved in laboratory experiments and practical fieldwork-also drew from our own research experiences showing that such studies can not only produce new scientific findings but can also transcend barriers between disciplines, act counter to scientific reductionism, integrate biological data across different timescales and levels of complexity, and circumvent constraints imposed by practical techniques. In relation to urgent research needs, we believe that climate change and other global challenges may require approaches beyond the experiment.

PMID:36786388 | DOI:10.1111/1751-7915.14222

J Oncol. 2023 Feb 4;2023:8268955. doi: 10.1155/2023/8268955. eCollection 2023.

ABSTRACT

Gastric cancer (GC) is one of the most lethal cancers in South Korea, and it is a cancer of concern worldwide. 5-fluorouracil (5-Fu) is commonly used as the first-line therapy for advanced GC; however, its side effects often limit the dosage range and impair patients' quality of life. Due to the limitations of current chemotherapy, new anticancer therapies are urgently needed. 3,3'-diindolylmethane (DIM) has been reported to have the ability to protect against various types of cancer. Our study aimed to elucidate the anticancer effect of DIM in GC when treated with the chemotherapeutic agent 5-Fu. In our results, combined treatment with DIM and 5-Fu resulted in higher apoptosis and lower cell proliferation than treatment with 5-Fu in SNU484 and SNU638 cell lines. Furthermore, when DIM and 5-Fu were administered together, cell invasion was diminished by mediated E-cadherin, MMP-9, and uPA; p-Akt and p-GSK-3β levels were reduced more significantly than when 5-Fu was administered alone. Moreover, in the Wnt signaling pathway, combined treatment of DIM and 5-Fu diminished β-catenin levels in the nucleus and inhibited cyclin D1and c-Myc protein levels. The Akt inhibitor, wortmannin, further inhibited the levels of β-catenin and c-Myc that were inhibited by DIM and 5-Fu. Furthermore, an animal xenograft model demonstrated that DIM combined with 5-Fu considerably reduced tumor growth without any toxic effects by regulating the Akt/GSK-3β and β-catenin levels. Our findings suggest that DIM significantly potentiates the anticancer effects of 5-Fu by targeting the Akt/GSK-3β and WNT/β-catenin because the combination therapy is more effective than 5-Fu alone, thereby offering an innovative potential therapy for patients with GC.

PMID:36785670 | PMC:PMC9922186 | DOI:10.1155/2023/8268955

Biophys J. 2023 Feb 10;122(3S1):8a-9a. doi: 10.1016/j.bpj.2022.11.277.

NO ABSTRACT

PMID:36785075 | DOI:10.1016/j.bpj.2022.11.277

Biophys J. 2023 Feb 10;122(3S1):78a-79a. doi: 10.1016/j.bpj.2022.11.631.

NO ABSTRACT

PMID:36785013 | DOI:10.1016/j.bpj.2022.11.631

Biophys J. 2023 Feb 10;122(3S1):78a. doi: 10.1016/j.bpj.2022.11.627.

NO ABSTRACT

PMID:36785009 | DOI:10.1016/j.bpj.2022.11.627

Biophys J. 2023 Feb 10;122(3S1):69a. doi: 10.1016/j.bpj.2022.11.581.

NO ABSTRACT

PMID:36784962 | DOI:10.1016/j.bpj.2022.11.581

Biophys J. 2023 Feb 10;122(3S1):68a. doi: 10.1016/j.bpj.2022.11.576.

NO ABSTRACT

PMID:36784957 | DOI:10.1016/j.bpj.2022.11.576

Biophys J. 2023 Feb 10;122(3S1):57a-58a. doi: 10.1016/j.bpj.2022.11.520.

NO ABSTRACT

PMID:36784894 | DOI:10.1016/j.bpj.2022.11.520

Biophys J. 2023 Feb 10;122(3S1):50a-51a. doi: 10.1016/j.bpj.2022.11.483.

NO ABSTRACT

PMID:36784636 | DOI:10.1016/j.bpj.2022.11.483

Biophys J. 2023 Feb 10;122(3S1):464a-465a. doi: 10.1016/j.bpj.2022.11.2492.

NO ABSTRACT

PMID:36784380 | DOI:10.1016/j.bpj.2022.11.2492

Biophys J. 2023 Feb 10;122(3S1):447a-448a. doi: 10.1016/j.bpj.2022.11.2414.

NO ABSTRACT

PMID:36784293 | DOI:10.1016/j.bpj.2022.11.2414

Biophys J. 2023 Feb 10;122(3S1):421a. doi: 10.1016/j.bpj.2022.11.2280.

NO ABSTRACT

PMID:36784152 | DOI:10.1016/j.bpj.2022.11.2280

Biophys J. 2023 Feb 10;122(3S1):36a. doi: 10.1016/j.bpj.2022.11.410.

NO ABSTRACT

PMID:36783875 | DOI:10.1016/j.bpj.2022.11.410

Biophys J. 2023 Feb 10;122(3S1):301a. doi: 10.1016/j.bpj.2022.11.1699.

NO ABSTRACT

PMID:36783510 | DOI:10.1016/j.bpj.2022.11.1699

Biophys J. 2023 Feb 10;122(3S1):300a. doi: 10.1016/j.bpj.2022.11.1693.

NO ABSTRACT

PMID:36783502 | DOI:10.1016/j.bpj.2022.11.1693

Biophys J. 2023 Feb 10;122(3S1):285a. doi: 10.1016/j.bpj.2022.11.1619.

NO ABSTRACT

PMID:36783413 | DOI:10.1016/j.bpj.2022.11.1619

Biophys J. 2023 Feb 10;122(3S1):283a. doi: 10.1016/j.bpj.2022.11.1610.

NO ABSTRACT

PMID:36783407 | DOI:10.1016/j.bpj.2022.11.1610

Biophys J. 2023 Feb 10;122(3S1):247a. doi: 10.1016/j.bpj.2022.11.1438.

NO ABSTRACT

PMID:36783216 | DOI:10.1016/j.bpj.2022.11.1438

Biophys J. 2023 Feb 10;122(3S1):203a. doi: 10.1016/j.bpj.2022.11.1227.

NO ABSTRACT

PMID:36782985 | DOI:10.1016/j.bpj.2022.11.1227