Differential Expression of lncRNAs in HIV Patients with TB and HIV-TB with Anti-Retroviral Treatment.

Tuberculosis (TB) is the leading cause of death among people with HIV-1 infection. To improve the diagnosis and treatment of HIV-TB patients, it is important to understand the mechanisms underlying these conditions. Here, we used an integrated genomics approach to analyze and determine the lncRNAs that are dysregulated in HIV-TB patients and HIV-TB patients undergoing anti-retroviral therapy (ART) using a dataset available in the public domain. The analyses focused on the portion of the genome transcribed into non-coding transcripts, which historically have been poorly studied and received less focus. This revealed that Mtb infection in HIV prominently up-regulates the expression of long non-coding RNA (lncRNA) genes DAAM2-AS1, COL4A2-AS1, LINC00599, AC008592.1, and CLRN1-AS1 and down-regulates the expression of lncRNAs AC111000.4, AC100803.3, AC016168.2, AC245100.7, and LINC02073. It also revealed that ART down-regulates the expression of some lncRNA genes (COL4A2-AS1, AC079210.1, MFA-AS1, and LINC01993) that are highly up-regulated in HIV-TB patients. Furthermore, the interrogation of the genomic regions that are associated with regulated lncRNAs showed enrichment for biological processes linked to immune pathways in TB-infected conditions. However, intriguingly, TB patients treated with ART showed completely opposite and non-overlapping pathways. Our findings suggest that lncRNAs could be used to identify critical diagnostic, prognostic, and treatment targets for HIV-TB patients.

Mycobacterium smegmatis secreting methionine sulfoxide reductase A (MsrA) modulates cellular processes in mouse macrophages.

Methionine sulfoxide reductase A (MsrA) is an antioxidant repair enzyme that reduces the oxidized methionine (Met-O) in proteins to methionine (Met). Its pivotal role in the cellular processes has been well established by overexpressing, silencing, and knocking down MsrA or deleting the gene encoding MsrA in several species. We are specifically interested in understanding the role of secreted MsrA in bacterial pathogens. To elucidate this, we infected mouse bone marrow-derived macrophages (BMDMs) with recombinant Mycobacterium smegmatis strain (MSM), secreting a bacterial MsrA or M. smegmatis strain (MSC) carrying only the control vector. BMDMs infected with MSM induced higher levels of ROS and TNF-α than BMDMs infected with MSC. The increased ROS and TNF-α levels in MSM-infected BMDMs correlated with elevated necrotic cell death in this group. Further, RNA-seq transcriptome analysis of BMDMs infected with MSC and MSM revealed differential expression of protein and RNA coding genes, suggesting that bacterial-delivered MsrA could modulate the host cellular processes. Finally, KEGG pathway enrichment analysis identified the down-regulation of cancer-related signaling genes in MSM-infected cells, indicating that MsrA can potentially regulate the development and progression of cancer.

Tackling Multiple-Drug-Resistant Bacteria With Conventional and Complex Phytochemicals.

Emerging antibiotic resistance in bacteria endorses the failure of existing drugs with chronic illness, complicated treatment, and ever-increasing expenditures. Bacteria acquire the nature to adapt to starving conditions, abiotic stress, antibiotics, and our immune defense mechanism due to its swift evolution. The intense and inappropriate use of antibiotics has led to the development of multidrug-resistant (MDR) strains of bacteria. Phytochemicals can be used as an alternative for complementing antibiotics due to their variation in metabolic, genetic, and physiological fronts as well as the rapid evolution of resistant microbes and lack of tactile management. Several phytochemicals from diverse groups, including alkaloids, phenols, coumarins, and terpenes, have effectively proved their inhibitory potential against MDR pathogens through their counter-action towards bacterial membrane proteins, efflux pumps, biofilms, and bacterial cell-to-cell communications, which are important factors in promoting the emergence of drug resistance. Plant extracts consist of a complex assortment of phytochemical elements, against which the development of bacterial resistance is quite deliberate. This review emphasizes the antibiotic resistance mechanisms of bacteria, the reversal mechanism of antibiotic resistance by phytochemicals, the bioactive potential of phytochemicals against MDR, and the scientific evidence on molecular, biochemical, and clinical aspects to treat bacterial pathogenesis in humans. Moreover, clinical efficacy, trial, safety, toxicity, and affordability investigations, current status and developments, related demands, and future prospects are also highlighted.