Browsing by Author "Mugweru, Julius N."

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    Annotations of novel antennae-expressed genes in male Glossina morsitans morsitans tsetse flies
    (Plos 1, 2022-08) Bwana, Billiah K.; Mireji, Paul O.; Obiero, George F.; Gakii, Consolata; Akoth, Modesta O.; Mugweru, Julius N.; Nyabuga, Franklin N.; Wachira, Benson M.; Bateta, Rosemary; Ng’ang’a, Margaret M.; Hassanali, Ahmed
    Tsetse flies use antennal expressed genes to navigate their environment. While most canonical genes associated with chemoreception are annotated, potential gaps with important antennal genes are uncharacterized in Glossina morsitans morsitans. We generated antennae-specific transcriptomes from adult male G. m. morsitans flies fed/unfed on bloodmeal and/or exposed to an attractant (ε-nonalactone), a repellant (δ-nonalactone) or paraffin diluent. Using bioinformatics approach, we mapped raw reads onto G. m. morsitans geneset from VectorBase and collected un-mapped reads (constituting the gaps in annotation). We de novo assembled these reads (un-mapped) into transcript and identified corresponding genes of the transcripts in G. m. morsitans gene-set and protein homologs in UniProt protein database to further annotate the gaps. We predicted potential protein-coding gene regions associated with these transcripts in G. m. morsitans genome, annotated/curated these genes and identified their putative annotated orthologs/homologs in Drosophila melanogaster, Musca domestica or Anopheles gambiae genomes. We finally evaluated differential expression of the novel genes in relation to odor exposures relative to no-odor control (unfed flies). About 45.21% of the sequenced reads had no corresponding transcripts within G. m. morsitans gene-set, corresponding to the gap in existing annotation of the tsetse fly genome. The total reads assembled into 72,428 unique transcripts, most (74.43%) of which had no corresponding genes in the UniProt database. We annotated/curated 592 genes from these transcripts, among which 202 were novel while 390 were improvements of existing genes in the G. m. morsitans genome. Among the novel genes, 94 had orthologs in D. melanogaster, M. domestica or An. gambiae while 88 had homologs in UniProt. These orthologs were putatively associated with oxidative regulation, protein synthesis, transcriptional and/or translational regulation, detoxification and metal ion binding, thus providing insight into their specific roles in antennal physiological processes in male G. m. morsitans. A novel gene (GMOY014237.R1396) was differentially expressed in response to the attractant. We thus established significant gaps in G. m. morsitans genome annotation and identified novel male antennae-expressed genes in the genome, among which > 53% (108) are potentially G. m. morsitans specific.
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    Assessment of Clofazimine and TB47 Combination Activity against Mycobacterium abscessus Using a Bioluminescent Approach
    (American Society for Microbiology, 2020-02) Liu, Yang; Tan, Yaoju; Islam, Mahmudul M.; Cao, Yuanyuan; Lu, Xiaoyun; Zeng, Sheng; Hameed, H. M. Adnan; Zhou, Peipei; Cai, Xingshan; Wang, Shuai; Mugweru, Julius N.; Zhang, Guoliang; Yin, Huancai; Liu, Jianxiong; Nuermberger, Eric; Zhang, Tianyu
    Mycobacterium abscessus is intrinsically resistant to most antimicrobial agents. The emerging infections caused by M. abscessus and the lack of effective treatment call for rapid attention. Here, we intended to construct a selectable marker-free autoluminescent M. abscessus strain (designated UAlMab) as a real-time reporter strain to facilitate the discovery of effective drugs and regimens for treating M. abscessus. The UAlMab strain was constructed using the dif/Xer recombinase system. In vitro and in vivo activities of several drugs, including clofazimine and TB47, a recently reported cytochrome bc1 inhibitor, were assessed using UAlMab. Furthermore, the efficacy of multiple drug combinations, including the clofazimine and TB47 combination, were tested against 20 clinical M. abscessus isolates. The UAlMab strain enabled us to evaluate drug efficacy both in vitro and in live BALB/c mice in a real-time, noninvasive fashion. Importantly, although TB47 showed marginal activity either alone or in combination with clarithromycin, amikacin, or roxithromycin, the drug markedly potentiated the activity of clofazimine, both in vitro and in vivo. This study demonstrates that the use of the UAlMab strain can significantly facilitate rapid evaluation of new drugs and regimens. The clofazimine and TB47 combination is effective against M. abscessus, and dual/triple electron transport chain (ETC) targeting can be an effective therapeutic approach for treating mycobacterial infections.
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    Staff Profile: Dr. Julius N. Mugweru .
    (UoEm, 2023) Mugweru, Julius N.
    Julius N. Mugweru is the Chair of the Department/Lecturer. Department of Biological Sciences, School: Pure and Applied Sciences (SPAS). Area of Specialization: Molecular Biology, Biochemistry, Immunology and Microbiology. Dr. Mugweru Holds a PhD in Molecular Biology and Biochemistry from the State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences and a Master of Science degree in Immunology from Jomo Kenyatta University of Agriculture and Technology. He has been a Research Fellow at the Okayama University’s Institute of Plant Sciences and Resources Japan, and a postdoctoral fellow at Georg-August-Universität Göttingen. Research Interests: Recombinant DNA techniques, Bacteria prospecting studies, In vitro drug testing assessment studies, In vivo vaccine testing studies using mouse models, Development of molecular markers, Metagenomics