Search

Current treatment of clostridial infections includes broad-spectrum antibiotics and antitoxins, yet antitoxins are ineffective against all Clostridium species. Moreover, rising antimicrobial resistance (AMR) threatens treatment effectiveness and public health. This study therefore aimed to discover a common drug target for four pathogenic clostridial species, Clostridium botulinum , C. difficile , C. tetani , and C. perfringens through an in-silico core genomic approach. Using four reference genomes of C. botulinum , C. difficile , C. tetani , and C. perfringens , we identified 1484 core genomic proteins (371/genome) and screened them for potential drug targets. Through a subtractive approach, four core proteins were finally identified as drug targets, represented by type III pantothenate kinase (CoaX) and, selected for further analyses. Interestingly, the CoaX is involved in the phosphorylation of pantothenate (vitamin B5), which is a critical precursor for coenzyme A (CoA) biosynthesis. Investigation of druggability analysis on the identified drug target reinforces CoaX as a promising novel drug target for the selected Clostridium species. During the molecular screening of 1201 compounds, a known agonist drug compound (Vibegron) showed strong inhibitory activity against targeted clostridial CoaX. Additionally, we identified tazobactam, a beta-lactamase inhibitor, as effective against the newly proposed target, CoaX. Therefore, identifying CoaX as a single drug target effective against all four clostridial pathogens presents a valuable opportunity to develop a cost-effective treatment for multispecies clostridial infections., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Endophytic bacteria, recognized as eco-friendly biofertilizers, have demonstrated the potential to enhance crop growth and yield. While the plant growth-promoting effects of endophytic bacteria have been extensively studied, the impact of weed endophytes remains less explored. In this study, we aimed to isolate endophytic bacteria from native weeds and assess their plant growth-promoting abilities in rice under varying chemical fertilization. The evaluation encompassed measurements of mineral phosphate and potash solubilization, as well as indole-3-acetic acid (IAA) production activity by the selected isolates. Two promising strains, tentatively identified as Alcaligenes faecalis (BTCP01) from Eleusine indica (Goose grass) and Metabacillus indicus (BTDR03) from Cynodon dactylon (Bermuda grass) based on 16S rRNA gene phylogeny, exhibited noteworthy phosphate and potassium solubilization activity, respectively. BTCP01 demonstrated superior phosphate solubilizing activity, while BTDR03 exhibited the highest potassium (K) solubilizing activity. Both isolates synthesized IAA in the presence of L-tryptophan, with the detection of nifH and ipdC genes in their genomes. Application of isolates BTCP01 and BTDR03 through root dipping and spraying at the flowering stage significantly enhanced the agronomic performance of rice variety CV. BRRI dhan29. Notably, combining both strains with 50% of recommended N, P, and K fertilizer doses led to a substantial increase in rice grain yields compared to control plants receiving 100% of recommended doses. Taken together, our results indicate that weed endophytic bacterial strains BTCP01 and BTDR03 hold promise as biofertilizers, potentially reducing the dependency on chemical fertilizers by up to 50%, thereby fostering sustainable rice production., Competing Interests: The authors declare no competing interests., (Copyright: © 2024 Fatema et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The field of fish microbiome research has rapidly been advancing, primarily focusing on farmed or laboratory fish species rather than natural or marine fish populations. This study sought to reveal the distinctive gut bacteriome composition and diversity within the anadromous fish species Tenualosa ilisha (hilsa), which holds the status of being the national fish of Bangladesh. We conducted an analysis on 15 gut samples obtained from 15 individual hilsa fishes collected from three primary habitats (e.g., freshwater = 5, brackish water = 5 and marine water = 5) in Bangladesh. The analysis utilized metagenomics based on 16S rRNA gene sequencing targeting the V3-V4 regions. Our comprehensive identification revealed a total of 258 operational taxonomic units (OTUs). The observed OTUs were represented by six phyla, nine classes, 19 orders, 26 families and 40 genera of bacteria. Our analysis unveiled considerable taxonomic differences among the habitats (freshwater, brackish water, and marine water) of hilsa fishes, as denoted by a higher level of shared microbiota (p = 0.007, Kruskal-Wallis test). Among the identified genera in the gut of hilsa fishes, including Vagococcus, Morganella, Enterobacter, Plesiomonas, Shigella, Clostridium, Klebsiella, Serratia, Aeromonas, Macrococcus, Staphylococcus, Proteus, and Hafnia, several are recognized as fish probiotics. Importantly, some bacterial genera such as Sinobaca, Synechococcus, Gemmata, Serinicoccus, Saccharopolyspora, and Paulinella identified in the gut of hilsa identified in this study have not been reported in any aquatic or marine fish species. Significantly, we observed that 67.50% (27/40) of bacterial genera were found to be common among hilsa fishes across all three habitats. Our findings offer compelling evidence for the presence of both exclusive and communal bacteriomes within the gut of hilsa fishes, exhibiting potential probiotic properties. These observations could be crucial for guiding future microbiome investigations in this economically significant fish species., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kawser et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Rice blast disease, caused by the fungus Magnaporthe oryzae, poses a severe threat to rice production, particularly in Asia where rice is a staple food. Concerns over fungicide resistance and environmental impact have sparked interest in exploring natural fungicides as potential alternatives. This study aimed to identify highly potent natural fungicides against M. oryzae to combat rice blast disease, using advanced molecular dynamics techniques. Four key proteins (CATALASE PEROXIDASES 2, HYBRID PKS-NRPS SYNTHETASE TAS1, MANGANESE LIPOXYGENASE, and PRE-MRNA-SPLICING FACTOR CEF1) involved in M. oryzae's infection process were identified. A list of 30 plant metabolites with documented antifungal properties was compiled for evaluation as potential fungicides. Molecular docking studies revealed that 2-Coumaroylquinic acid, Myricetin, Rosmarinic Acid, and Quercetin exhibited superior binding affinities compared to reference fungicides (Azoxystrobin and Tricyclazole). High throughput molecular dynamics simulations were performed, analyzing parameters like RMSD, RMSF, Rg, SASA, hydrogen bonds, contact analysis, Gibbs free energy, and cluster analysis. The results revealed stable interactions between the selected metabolites and the target proteins, involving important hydrogen bonds and contacts. The SwissADME server analysis indicated that the metabolites possess fungicide properties, making them effective and safe fungicides with low toxicity to the environment and living beings. Additionally, bioactivity assays confirmed their biological activity as nuclear receptor ligands and enzyme inhibitors. Overall, this study offers valuable insights into potential natural fungicides for combating rice blast disease, with 2-Coumaroylquinic acid, Myricetin, Rosmarinic Acid, and Quercetin standing out as promising and environmentally friendly alternatives to conventional fungicides. These findings have significant implications for developing crop protection strategies and enhancing global food security, particularly in rice-dependent regions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Moin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Non-aureus staphylococci (NAS) represent a major etiological agent in dairy animal mastitis, yet their role and impact remain insufficiently studied. This study aimed to elucidate the genomic characteristics of a newly identified multidrug-resistant NAS strain, specifically Staphylococcus warneri G1M1F, isolated from murine feces in an experimental mastitis model. Surprisingly, NAS species accounted for 54.35 % of murine mastitis cases, with S. warneri being the most prevalent at 40.0 %. S. warneri G1M1F exhibited resistance to 10 major antibiotics. Whole-genome sequencing established a genetic connection between G1M1F and S. warneri strains isolated previously from various sources including mastitis milk in dairy animals, human feces and blood across diverse geographical regions. Genomic analysis of S. warneri G1M1F unveiled 34 antimicrobial resistance genes (ARGs), 30 virulence factor genes (VFGs), and 278 metabolic features. A significant portion of identified ARGs (64 %) conferred resistance through antibiotic efflux pumps, while VFGs primarily related to bacterial adherence and biofilm formation. Inoculation with G1M1F in mice resulted in pronounced inflammatory lesions in mammary and colon tissues, indicating pathogenic potential. Our findings highlight distinctive genomic traits in S. warneri G1M1F, signifying the emergence of a novel multidrug-resistant NAS variant. These insights contribute to understanding NAS-related mastitis pathophysiology and inform strategies for effective treatment in dairy animals., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest with the contents of this article., (Copyright © 2023 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

The identification of deleterious mutations in different variants of SARS-CoV-2 and their roles in the morbidity of COVID-19 patients has yet to be thoroughly investigated. To unravel the spectrum of mutations and their effects within SARS-CoV-2 genomes, we analyzed 5,724 complete genomes from deceased COVID-19 patients sourced from the GISAID database. This analysis was conducted using the Nextstrain platform, applying a generalized time-reversible model for evolutionary phylogeny. These genomes were compared to the reference strain (hCoV-19/Wuhan/WIV04/2019) using MAFFT v7.470. Our findings revealed that SARS-CoV-2 genomes from deceased individuals belonged to 21 Nextstrain clades, with clade 20I (Alpha variant) being the most predominant, followed by clade 20H (Beta variant) and clade 20J (Gamma variant). The majority of SARS-CoV-2 genomes from deceased patients (33.4%) were sequenced in North America, while the lowest percentage (0.98%) came from Africa. The 'G' clade was dominant in the SARS-CoV-2 genomes of Asian, African, and North American regions, while the 'GRY' clade prevailed in Europe. In our analysis, we identified 35,799 nucleotide (NT) mutations throughout the genome, with the highest frequency (11,402 occurrences) found in the spike protein. Notably, we observed 4150 point-specific amino acid (AA) mutations in SARS-CoV-2 genomes, with D614G (20%) and N501Y (14%) identified as the top two deleterious mutations in the spike protein on a global scale. Furthermore, we detected five common deleterious AA mutations, including G18V, W45S, I33T, P30L, and Q418H, which play a key role in defining each clade of SARS-CoV-2. Our novel findings hold potential value for genomic surveillance, enabling the monitoring of the evolving pattern of SARS-CoV-2 infection, its emerging variants, and their impact on the development of effective vaccination and control strategies., (© 2023. The Author(s).)

Plant probiotic bacteria enhance growth and yield of crop plants when applied at the appropriate time and dose. Two rice probiotic bacteria, Paraburkholderia fungorum strain BRRh-4 and Delftia sp. strain BTL-M2 promote growth and yield of plants. However, no information is available on application of these two bacteria on growth, yield, and diversity and population of bacteriome in roots and rhizosphere soils of the treated rice plants. This study aimed to assess the effect of BRRh-4 and BTL-M2 application on growth, yield and bacteriome in roots and rhizosphere soil of rice under varying doses of N, P and K fertilizers. Application of BRRh-4 and BTL-M2 strains significantly ( p  < 0.05) increased seed germination, growth and yield of rice compared to an untreated control. Interestingly, the grain yield of rice by these bacteria with 50% less of the recommended doses of N, P, and K fertilizers were statistically similar to or better than the rice plants treated with 100% doses of these fertilizers. Targeted amplicon (16S rRNA) sequence-based analysis revealed significant differences (PERMANOVA, p  = 0.00035) in alpha-diversity between the root (R) and rhizosphere soil (S) samples, showing higher diversity in the microbial ecosystem of root samples. Additionally, the bacteriome diversity in the root of rice plants that received both probiotic bacteria and chemical fertilizers were significantly higher (PERMANOVA, p  = 0.0312) compared to the rice plants treated with fertilizers only. Out of 185 bacterial genera detected, Prevotella , an anaerobic and Gram-negative bacterium, was found to be the predominant genus in both rhizosphere soil and root metagenomes. However, the relative abundance of Prevotella remained two-fold higher in the rhizosphere soil metagenome (52.02%) than in the root metagenome (25.04%). The other predominant bacterial genera detected in the rice root metagenome were Bacillus (11.07%), Planctomyces (4.06%), Faecalibacterium (3.91%), Deinococcus (2.97%), Bacteroides (2.61%), and Chryseobacterium (2.30%). On the other hand, rhizosphere soil metagenome had Bacteroides (12.38%), Faecalibacterium (9.50%), Vibrio (5.94%), Roseomonas (3.40%), and Delftia (3.02%). Interestingly, we found the presence and/or abundance of specific genera of bacteria in rice associated with the application of a specific probiotic bacterium. Taken together, our results indicate that improvement of growth and yield of rice by P. fungorum strain BRRh-4 and Delftia sp. strain BTL-M2 is likely linked with modulation of diversity, structures, and signature of bacteriome in roots and rhizosphere soils. This study for the first time demonstrated that application of plant growth promoting bacteria significantly improve growth, yield and increase the diversity of bacterial community in rice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Islam, Fatema, Hoque, Gupta, Mahmud, Sakif and Sharpe.)

Magnaporthe oryzae causes destructive blast disease in more than 50 species of the major cereal crops rice, wheat and maize and destroys food of millions of people worldwide. Application of synthetic chemical fungicides are environmentally hazardous and unreliable in controlling M. oryzae . Conversely, naturally occurring biofungicides with multiple modes of actions are needed to be discovered for combatting the blast fungus. To find the effective biofungicides, we performed molecular docking study of some potential antifungal natural compounds targeting two proteins including a single-stranded DNA binding protein MoSub1 (4AGH), and an effector protein AVR-Pik (5E9G) of M. oryzae that regulates transcription in fungus and/or suppresses the host cell immunity. The thirty-nine natural compounds previously shown to inhibit M. oryzae growth and reproduction were put under molecular docking against these two proteins followed by simulation, free energy, and interaction analysis of protein-ligand complexes. The virtual screening revealed that two alkaloidal metabolites, camptothecin and GKK1032A2 showed excellent binding energy with any of these target proteins compared to reference commercial fungicides, azoxystrobin and strobilurin. Of the detected compounds, GKK1032A2 bound to both target proteins of M. oryzae . Both compounds showed excellent bioactivity scores as compared to the reference fungicides. Results of our computational biological study suggest that both camptothecin and GKK1032A2 are potential fungicides that could also be considered as lead compounds to design novel fungicides against the blast fungus. Furthermore, the GKK1032A2 acted as a multi-site mode of action fungicide against M. oryzae ., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)