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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.)

Escherichia coli is one of the major pathogens causing mastitis in lactating mammals. We hypothesized that E. coli from the gut and mammary glands may have similar genomic characteristics in the causation of mastitis. To test this hypothesis, we used whole genome sequencing to analyze two multidrug resistant E. coli strains isolated from mammary tissue (G2M6U) and fecal sample (G6M1F) of experimentally induced mastitis mice. Both strains showed resistance to multiple (>7) antibiotics such as oxacillin, aztreonam, nalidixic acid, streptomycin, gentamicin, cefoxitin, ampicillin, tetracycline, azithromycin and nitrofurantoin. The genome of E. coli G2M6U had 59 antimicrobial resistance genes (ARGs) and 159 virulence factor genes (VFGs), while the E. coli G6M1F genome possessed 77 ARGs and 178 VFGs. Both strains were found to be genetically related to many E. coli strains causing mastitis and enteric diseases originating from different hosts and regions. The G6M1F had several unique ARGs (e.g., Qnr S1, sul 2, tet A, tet R, emr K, bla TEM-1/105, and aph (6)-Id, aph (3″)-Ib) conferring resistance to certain antibiotics, whereas G2M6U had a unique heat-stable enterotoxin gene ( ast A) and 7192 single nucleotide polymorphisms. Furthermore, there were 43 and 111 unique genes identified in G2M6U and G6M1F genomes, respectively. These results indicate distinct differences in the genomic characteristics of E. coli strain G2M6U and G6M1F that might have important implications in the pathophysiology of mammalian mastitis, and treatment strategies for mastitis in dairy animals., 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 The Authors.)

Mothers in developing countries are nutritionally vulnerable due to an undiversified diet. Dietary diversity and healthy dietary patterns of mothers are necessary for the health and nutrition of both the mother and the child. Keeping these in mind, the study was designed to investigate the determinants of mothers' dietary diversity in the capital city (Dhaka) of Bangladesh. A total 613 mothers who had at least one child aged 6-59 months were surveyed in 2020. Dietary diversity (DD) was measured by 24 h recall period following the established guidelines. To explore the determinants of dietary diversity, a log linear regression model was employed. The findings revealed that the overall DD of mothers was low, with less than 15% of respondents consuming more than 5 of the 9 food groups. The study found that if a mother receives one more year of formal education, her DD, on average, would increase by 0.70%. Receiving antenatal care (ANC) for four or more times during pregnancy increases DD by 5.13% compared to mothers who receive ANC less than four times. The findings also showed that mothers with access to assets have 10.18% higher DD than mothers without access to assets. On the other hand, mothers' employment status was negatively associated with DD. Redistributing the household workload between mother and other household members can play a critical role in increasing mothers' DD. Providing care facilities and counseling to mothers about the nutritional value of consuming different food groups can substantially improve the situation., 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.)

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.)