Chanchal Kumar

We report the genome sequence of a novel species of nontuberculous mycobacterium (NTM) belonging to the Mycobacterium terrae complex (MTC). The strain SVM_VP21 was isolated from the mouthwash sample of a healthy human adult residing in Delhi, India. The strain exhibited smooth, cream-coloured colonies on Lowenstein Jensen (LJ) medium after 2 weeks of incubation and could not be identified by Hain’s Genotype Mycobacterium CM/AS line probe assay. Whole genome sequencing (WGS) of SVM_VP21 was performed using Illumina NovaSeq 6000 platform for final identification. The whole genome sequence was assembled using Shovill. Gene annotation was performed by Rapid Annotation using Subsystem Technology (RAST) and Prokaryotic Genome Annotation Pipeline (PGAP). The genome of 4,882,418 bp exhibited 67.3% GC content, 59 contigs, 4557 genes and 4502 coding sequences. The genome also encoded four rRNAs, 48 tRNAs, three non-coding RNAs and 177 pseudo genes. BLASTn analysis of the 16S rRNA and hsp65 gene sequences retrieved by WGS showed 100% and 95% identity to M. heraklionense, respectively. AutoMLST showed 93.5% average nucleotide identity of SVM_VP21 to M. virginiense. Digital DNA-DNA Hybridization, finally, identified SVM_VP21 as a novel species of the M. terrae complex. The name Mycobacterium cavoris sp. nov. is proposed for the strain in reference to its isolation from the oral cavity. The data presented here would help in understanding the novel species, which though obtained from a healthy individual in this study, may be a potential pathogen.

Mammalian cell entry (mce) operons play a vital role in cell invasion and survival of M. tuberculosis. Of the mce genes, the function of Rv0590A is still unknown. The present study was performed to investigate the function and immunogenic properties of the protein Rv0590A. Human leukemia monocytic cell line (THP-1) derived macrophages were infected with M. tuberculosis H37Rv at 3, 6, and 24 h of infection. The maximum colony forming units (CFU) were observed at 6 h (p < 0.005), followed by 3 h after infection. M. tuberculosis H37Rv and clinical isolates representative of Delhi/CAS, EAI, Beijing, Haarlem and Euro-American-superlineage were included in the study for expression analysis of mce1A, mce2A, mce3A, mce4A, and Rv0590A genes. Maximum upregulation of all mce genes was observed at 3 h of infection. All the five clinical isolates and H37Rv upregulated Rv0590A at various time points. Macrophage infection with M. tuberculosis H37Rv-overexpressing Rv0590A gene showed higher intracellular CFU as compared to that of wild-type H37Rv. Further, purified Rv0590A protein stimulated the production of TNFα, IFNγ, and IL-10 in macrophages. Thus, Rv0590A was found to be involved in cell invasion and showed good immunological response.

The tumor microenvironment can be realistically viewed as an active battle ground between the host immune system and the growing tumor cells. This reactive space surrounding the tumor possesses several possibilities and facilitates the progression of a tumor from a neoplastic stage to that of metastasis. The contemporary approach of understanding the cancer biology from a “within the cell” perspective has been largely challenged with complex and intricate “outside the cell” events. Thus understanding the biology of the tumor microenvironment has been of scientific and clinical interest. Small non-coding microRNAs with a pleotropic and wide range of cellular gene targets can be reasonably hypothesized to regulate the events of carcinogenesis and progression. MicroRNAs have been investigated in different cancer models, and evidence of their involvement in the regulation of the tumor microenvironment has been of much interest. In particular, a major interest has been exploring the role of the tumor microenvironment in regulating the interaction of cancer cells with surrounding stromal components and the effect of such interactions on the cancer cells. Fine-tuned regulation by these microRNAs extends our contemporary understanding of these small biomolecules in epigenetic regulations. This review focuses on microRNAs that are dysregulated in ovarian carcinomas, their effect on the components of the tumor microenvironment, and the correlation of their heterogeneous expression profiles with disease severity and prognosis in patients. In addition, this paper also discusses the differential expression of exosomal microRNAs that are known to link the cancer cell with its microenvironment, facilitating the development of an improved prognostic/diagnostic marker and effective therapeutic regime.