Search

The key to bacterial virulence relies on an exquisite balance of signals between microbe and hosts. Bacterial toxin–antitoxin (TA) system is known to play a vital role in response to stress adaptation, drug resistance, biofilm formation, intracellular survival, persistence as well as pathogenesis. In the present study, we investigated the role of Hha-TomB TA system in regulating virulence of Salmonella enterica serovar Typhimurium (S. Typhimurium) in a host model system, where we showed that deletion of hha and tomB genes displayed impaired cell adhesion, invasion, and uptake. The isogenic hha and tomB mutant strain was also found to be deficient in intracellular replication in vitro, with a highly repressed Salmonella Pathogenicity Island-2 (SPI-2) genes and downregulation of Salmonella Pathogenicity Island-1 (SPI-1) genes. In addition, the Δhha and ΔtomB did not show acute colitis in C57BL/6 mice and displayed less dissemination to systemic organs followed by their cecal pathology. The TA mutants also showed reduction in serum cytokine and nitric oxide levels both in vitro and in vivo. However, the inflammation phenotype was restored on complementing strain of TA gene to its mutant strain. In silico studies depicted firm interaction of Hha–TomB complex and the regulatory proteins, namely, SsrA, SsrB, PhoP, and PhoQ. Overall, we demonstrate that this study of Hha–TomB TA system is one of the prime regulating networks essential for S. Typhimurium pathogenesis.

Acute/chronic gastroenteritis is caused by a few serovars of Salmonella enterica. Among different serovars, S. enterica Typhimurium is a potent pathogen that contributes significantly to self-limiting diarrhea related mortality worldwide. With no successful vaccine in hand against this pathogen, antibiotics are used as for gold standard for treatment against Salmonella induced gastroenteritis. Indispensably, rise in multi drug resistance against Salmonella Typhimurium poses challenge to treatment options. South East Asia, with 11 different countries, stands 3rd as super region for global burden of Salmonella induced gastroenteritis. In this review, we made an attempt to discuss on prevalence and multidrug resistance in Salmonella Typhimurium in 11 countries of South East Asia—the issue that has not been seriously addressed so far. By thorough analysis of reported data, we found varying frequencies for prevalence of Salmonella Typhimurium as well as subtle evidences on resistance of this pathogen to multiple antibiotics in different countries. Vietnam ranked top in terms of reports for prevalence and antimicrobial resistance. However, in countries such as Brunei and Timor Leste, no study has been performed so far to track the frequency of incidence and drug resistance of this pathogen. Our review, the first of its kind, emphasizes that, although the pathogen was not found as dominant serovar in South East Asia in last 20 years unlike sub-Saharan Africa, it may be still considered as a major threat in this region due to available evidences for infection in humans as well as contamination in several animal and food sources. More importantly, the importance as a public threat in this subregion of Asia is also due to resistance of this pathogen to multiple antibiotics. South East Asian countries showing incidence and multi drug resistance of Salmonella enterica Typhimurium in human and non-human sources (1969–2020). —Drug resistant S. enterica Typhimurium.

Cervical cancer is the fourth most common cause of mortality in women worldwide. In this study we investigated the effect of a tumour suppressor microRNA miR-214 in modulating the cell death against chemotherapeutic drugs like Doxorubicin, Cisplatin and Paclitaxel. CRISPR-facilitated knockdown and plasmid-based overexpression of miR-214 was performed in cervical cancer cell lines HeLa, C33A and CaSki. It was observed that knocking out miR-214 resulted in reduced apoptosis and cell migration upon drug treatments; while overexpression of miR-214 resulted in marginal increase in apoptosis and cell migration when treated with drugs. However, miR-214 had very little effect on production of reactive oxygen species. Our results also indicate that Doxorubicin was least effective and Paclitaxel most effective in inducing cell death. A combination of miR-214 overexpression and Paclitaxel treatment was found to be most effective in inducing cell death in cervical cancer cells. Analysis of cell cycle phases followed by apoptotic markers also showed that miR-214 overexpression along with Paclitaxel treatment caused an increase in PARP and decline of PI-3 kinase/Akt levels. Therefore, miR-214 levels determine the fate of the cancer cell during chemotherapeutic treatment.