Tuberculosis (TB) is a highly infectious, air-borne disease caused by Mycobacterium tuberculosis. Tuberculosis usually affects the lungs but can also affect other parts of the body such as kidney, spine, or brain. In our bid to find New Chemical Entities (NCE) with anti-tubercular activities, we recently identified a novel imizaothiazole-3-carboxamide analogues with excellent anti-TB properties. Herein, we aim to investigate the anti-microbial properties of these novel analogues against eight bacteria strains (four Gram-positive and four Gram-negative bacteria strains) using the broth microdilution method. The MIC (Minimum Inhibitory Concentration) of these analogues will be determined using the colorimetric assay (Neomycin will be used as positive control).

Human T-cell Leukemia Virus type 1 (HTLV-1) is the retrovirus responsible for the aggressive cancer, Adult T-cell Lymphoma. Within this malignant evolution, the virally-encoded oncoprotein Tax acts as a transcriptive promoter in the signaling pathways of CREB and p300 through the KIX domain. Despite the extensive research into Tax's interactions with cellular co-activators, potential interactions have yet to be completely explored, likely caused by the difficulty in using conventional molecular modus operandi when characterizing Tax. However, genetically optimizing the oncoprotein possesses the possibility of facilitating further examination into Tax-coactivator interactions. This optimization is executed through the sequential application of three distinct peptide tags: poly-histidine, strep, and a small ubiquitin-like modifier, known as SUMO. This set of modifications includes the integration of two distinct affinity tags, as well as a cleavage site for further purification that provides an enhancement for protein stability. The molecularly engineered gene is then translocated from a T5 lac-operator vector to a previously modified T7 pET expression vector, creating a new recombinant plasmid. In previous procedures, the expression of Tax is purposefully kept within a low range due to the protein's toxicity; However, within the new context of a T7 vector, the induction of IPTG and increased lac-operon transcription warrants further exploration of protein activity and host interactions. This genetically optimized Tax variant and its associated modifications offer a promising platform for deciphering the intricate molecular events underpinning Tax-induced oncogenesis.

Angiotensin-converting enzyme (ACE) is best known for its role in regulating blood pressure through its function in the renin-angiotensin pathway. However, a role for ACE in innate immunity has only recently been discovered. We have previously shown that upon activation, myeloid cells display increased expression of ACE. ACE over-expression in murine macrophages was also shown to cause increased pro-inflammatory gene expression and enhanced mitochondrial metabolism. While these results have been observed in murine cells, the effects of ACE over-expression in human myeloid cells haven’t been evaluated. To assess the role of ACE in human macrophage function and metabolism, we generated THP-1 human monocytic cells over-expressing ACE. Utilizing gene expression analysis and respirometry, we demonstrate that THP-1 cells over-expressing ACE display increased inflammatory activation and enhanced mitochondrial respiration. These results suggest a previously underappreciated role of ACE in regulating human macrophage inflammation and metabolism.