Background: Salmonella Typhimurium (S.Typhimurium) adapts to the broad fluctuations of oxygen concentrations encountered in the host. The transition from aerobic to microaerobic/anaerobic condition encountered in the intestine is mainly regulated by fumarate and nitrate reductase (fnr) regulatory gene and aerobic respiratory control A (arcA) gene. Aim is to appraise the role of fnr gene under anaerobic conditions.Methods: In this study, we deleted fnr gene from S.Typhimurium using lambda red-recombinase mediated gene knockout protocol. Further carried out in vitro characterization and analyzed the differential protein expression in wild type (WT) and isogenic Δfnr null mutant (Δfnr) using SDS-PAGE and MALDI-TOF mass spectrometry under anaerobic conditions.Result: In growth competition, WT strain outcompeted the Δfnr and biofilm-forming ability of Δfnr was significantly reduced compared to WT strain. Swimming motility was reduced in Δfnr strain. Besides, differential protein expression revealed the global changes in the expression of many proteins in fnr strain. One differentially expressed protein was identified as TolA, an inner membrane envelope protein. It points out that fnr may regulate the genes responsible for motility and biofilm formation. FNR protein positively regulates TolA, which is important for bacterial virulence, maintenance of membrane integrity, LPS production and replication of bacteria.
Salmonella Typhimurium (STM) is a facultative anaerobe of zoonotic
importance and one of the causative agents of non-typhoidal
salmonellosis (NTS). During infection, STM must adapt to the changes in
oxygen concentration encountered in the crucial niches of host like gut
lumen and intramacrophage environments. But being a
chemo-organoheterotroph, STM is capable of obtaining its energy from
organic sources via redox reactions. NarL, a transcription factor and
the response regulator of the two-component regulatory system NarX/L,
gets activated under nitrate rich anaerobic condition. Upon activation,
it upregulates the nitrate reduction during anaerobic respiration.
However, in this study, we observed a significant attenuation of
virulence in the narL-knockout strain of STM, while the respective
morphotypes got rescued upon genetic complementation. Along with
motility and biofilm forming ability, the mutant strain displayed
reduced intracellular replication in either intestinal epithelial cells
or monocyte-derived macrophages of poultry origin. Further, in vivo
competitive assay in the murine model showed that wild type STM
significantly outcompeted its isogenic narL null mutant.
Background: Leishmania infantum, one important intracellular parasite causes most potentially lethal diseases such as leishmaniasis i.e. Visceral leishmaniasis in dogs. Although certain chemical drugs such as pentostam, amphotericin B, miltefosine have been trailed against this disease, but all these drugs induced antibiotic resistance and toxicity in the host. Further, the trypanothione synthetase, a key enzyme of this parasite which catalyzes a reaction, maintaining thiol redox within the cell Methods: The binding study was carried out with selected natural/synthetic phytocompounds/drugs against the modeled trypanothione synthetase though molecular docking. Result: The generated protein model with lowest discrete potential energy (DOPE) -19960.97 was found good in quality with z score of -5.19 and quality factor of 61.83% and it was found that the natural inhibitors glycyrrhetic acid (GRA) and Theaflavin (TFN) showed highest binding energies of -7.34 and -6.95 Kcal/mol. This study may be concluded that the natural inhibitors glycyrrhetic acid (GRA) and Theaflavin (TFN) would be potential regimen in treatment of canine leishmaniasis.
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