Curcumin is the principal curcuminoid obtained from the plant Curcuma longa and has been extensively studied for its biological and chemical properties. Curcumin displays a vast range of pharmacological properties, including antimicrobial, anti-inflammatory, antioxidant, and antitumor activity. Specifically, curcumin has been linked to the improvement of the outcome of tuberculosis. There are many reviews on the pharmacological effects of curcumin; however, reviews of the antitubercular activity are comparatively scarcer. In this review, we attempt to discuss the different aspects of the research on the antitubercular activity of curcumin. These include antimycobacterial activity, modulation of the host immune response, and enhancement of BCG vaccine efficacy. Recent advances in the antimycobacterial activity of curcumin synthetic derivatives, the role of computer aided drug design in identifying curcumin targets, the hepatoprotective role of curcumin, and the dosage and toxicology of curcumin will be discussed. While growing evidence supports the use of curcumin and its derivatives for tuberculosis therapy, further preclinical and clinical investigations are of pivotal importance before recommending the use of curcumin formulations in public health.

The uncontrolled emergence of multidrug-resistant mycobacterial strains presents as the primary determinant of the present crisis in antimycobacterial therapeutics and underscores tuberculosis (TB) as a daunting global health concern. There is an urgent requirement for drug development for the treatment of TB. Numerous novel molecules are presently undergoing clinical investigation as part of TB drug development. However, the complex cell wall and the lifecycle of M. tuberculosis within the host pose a significant challenge to the development of new drugs and, therefore, led to a shift in research focus towards alternative antibacterial compounds, notably nanotechnology. A novel approach to TB therapy utilizing silver nanoparticles (AgNPs) holds the potential to address the medical limitations imposed by drug resistance commonly associated with currently available antibiotics. Their broad-spectrum antimicrobial activity presents the utilization of AgNPs as a promising avenue for the development of therapeutics targeting mycobacterial-induced diseases, which can effectively target Mycobacterium tuberculosis, including drug-resistant strains. AgNPs can enhance the effectiveness of traditional antibiotics, potentially leading to better treatment outcomes and a shorter duration of therapy. However, the successful implementation of this complementary strategy is contingent upon addressing several pivotal therapeutic challenges, including suboptimal delivery, variability in intra-macrophagic antimycobacterial effect, and potential toxicity. Future perspectives may involve developing targeted delivery systems that maximize therapeutic effects and minimize side effects, as well as exploring combinations with existing TB medications to enhance treatment outcomes. We have attempted to provide a comprehensive overview of the antimycobacterial activity of AgNPs, and critically analyze the advantages and limitations of employing silver nanoparticles in the treatment of TB.

In this review, we highlight the variations of gut resistome studies, which may preclude comparisons and translational interpretations. Of 22 included studies, a range of 12 to 2000 antibiotic resistance (AR) genes were profiled. Overall, studies defined a healthy gut resistome as subjects who had not taken antibiotics in the last three to 12 months prior to sampling. In studies with de novo assembly, AR genes were identified based on variable nucleotide or amino acid sequence similarities. Different marker genes were used for defining resistance to a given antibiotic class. Validation of phenotypic resistance in the laboratory is frequently lacking. Cryptic resistance, collateral sensitivity and the interaction with repressors or promotors were not investigated. International consensus is needed for selecting marker genes to define resistance to a given antibiotic class in addition to uniformity in phenotypic validation and bioinformatics pipelines.

The invasion of skin tissue by Staphylococcus aureus is mediated by mechanisms that involve sequential breaching of the different stratified layers of the epidermis. Induction of cell death in keratinocytes is a measure of virulence and plays a crucial role in the infection progression. We established a 3D-organotypic keratinocyte-fibroblast co-culture model to evaluate whether a 3D-skin model is more effective in elucidating the differences in the induction of cell death by Methicillin-resistant Staphylococcus aureus (MRSA) than in comparison to 2D-HaCaT monolayers. We investigated the difference in adhesion, internalization, and the apoptotic index in HaCaT monolayers and our 3D-skin model using six strains of MRSA representing different clonal types, namely, ST8, ST30, ST59, ST22, ST45 and ST239. All the six strains exhibited internalization in HaCaT cells. Due to cell detachment, the invasion study was limited up to two and a half hours. TUNEL assay showed no significant difference in the cell death induced by the six MRSA strains in the HaCaT cells. Our 3D-skin model provided a better insight into the interactions between the MRSA strains and the human skin during the infection establishment as we could study the infection of MRSA in our skin model up to 48 h. Immunohistochemical staining together with TUNEL assay in the 3D-skin model showed co-localization of the bacteria with the apoptotic cells demonstrating the induction of apoptosis by the bacteria and revealed the variation in bacterial transmigration among the MRSA strains. The strain representing ST59 showed maximum internalization in HaCaT cells and the maximum cell death as measured by Apoptotic index in the 3D-skin model. Our results show that 3D-skin model might be more likely to imitate the physiological response of skin to MRSA infection than 2D-HaCaT monolayer keratinocyte cultures and will enhance our understanding of the difference in pathogenesis among different MRSA strains.

In this study, antimycobacterial activity of a set of synthesized chalcone derivatives against Mycobacterium tuberculosis H37Rv was investigated by quantitative structure–activity relationship (QSAR) analysis using density functional theory (DFT) and molecular mechanics (MM+)‐based descriptors in both gas and solvent phases. The best molecular descriptors identified were hardness, E_HOMO, MR_A‐4 and MR_B‐4′ that contributed to the antimycobacterial activity of the chalcones as independent factors. The correlation of these four descriptors with their antimycobacterial activity increases with the inclusion of solvent medium, indicating their importance in studying biological activity. QSAR models revealed that in gas phase, lower values of E_HOMO, MR_A‐4 and MR_B‐4′ increase the antimycobacterial activity of the chalcone molecules. However, in solvent phase, lower values of E_HOMO and MR_B‐4′ and higher values of MR_A‐4 increase their activity.