Trueperella pyogenes is a Gram-positive opportunistic pathogen that causes severe cases of mastitis, metritis, and pneumonia in a wide range of animals, resulting in significant economic losses. Although little is known about the virulence factors involved in the disease pathogenesis, a comprehensive comparative genome analysis of T. pyogenes genomes has not been performed till date. Hence, present investigation was carried out to characterize and compare 19 T. pyogenes genomes originating in different geographical origins including the draftgenome of the first Indian origin strain T. pyogenes Bu5. Additionally, candidate virulence determinants that could be crucial for their pathogenesis were also detected and analyzed by using various bioinformatics tools. The pan-genome calculations revealed an open pan-genome of T. pyogenes. In addition, an inventory of virulence related genes, 190 genomic islands, 31 prophage sequences, and 40 antibiotic resistance genes that could play a significant role in organism’s pathogenicity were detected. The core-genome based phylogeny of T. pyogenes demonstrates a polyphyletic, host-associated group with a high degree of genomic diversity. The identified core-genome can be further used for screening of drug and vaccine targets. The investigation has provided unique insights into pan-genome, virulome, mobiliome, and resistome of T. pyogenes genomes and laid the foundation for future investigations.

Mycobacterium tuberculosis (Mtb) harbors a high number of Toxin-Antitoxin (TA) systems, wherein half of them belong to virulence associated proteins B and C (VapBC) family that has a characteristic PilT N-terminus domain and ribonuclease activity. Functional insights into Mtb VapBC TA modules unraveled their role in adaptation to various host-mediated stressors, including oxidative/nitrosative, chemical and nutrient starvation as well as multidrug tolerance and establishment of persistence. To understand the intricacies of Mtb's pathogenesis, absolute cellular targets of 19 VapC(s) were determined. Some exhibit a shared ribonuclease activity, whereas others harbor tRNAse and 23S rRNA cleavage activity. The detailed functional characterization of VapBC4, VapBC12 and VapBC22, including in vivo deletion mutant studies revealed their role in Mtb's virulence/persistence. For example, the VapC22 mutant was attenuated for Mtb's growth in mice and elicited a decreased T_H1 response, whereas mice infected with VapC12 mutant displayed a substantially higher bacillary load and pro-inflammatory response than the wild type, showing a hyper-virulent phenotype. Further experimental studies are needed to decode the functional role of VapBC systems and unravel their cellular targets. Taken together, Mtb VapBC TA systems seem to be promising drug targets owing to their key role in enduring stressors, antibiotic resistance and persistence.

Environmental causes of lung cancer are often overlooked, despite being one of the most common forms of cancer. This review critically analyzes both existing and emerging literature on the impact of human activity on the presence of heavy metals such as arsenic, nickel, chromium, and cadmium in the environment, and assesses their effects on lung cancer. While more research is needed to understand the genomic and epigenomic mechanisms by which these metals affect oxidative stress responses, inflammatory responses, and DNA damage response systems, this work emphasizes the importance of regulating their emissions to protect public health from harmful concentrations or chronic exposure. This study highlights the need to reconstruct toxicity studies not only based on exposure levels but also by considering fluctuations and the synergistic effects of these metals. This approach can lead to a better understanding of lung cancer risk and help in developing more accurate preventive and regulatory policies.