Title:Structural Insights to the Pathophysiology of Effector Induced Immunostimulation
in Salmonella Typhimurium: Biocomputational Methods
Volume: 17
Issue: 2
Author(s): Abhigyan Choudhury*
Affiliation:
- Department of Biochemistry, University of Calcutta, Kolkata, 700019, West Bengal, India
Keywords:
Salmonella typhimurium, septicemia, inflammation, TLR, effector, molecular docking, therapeutic targets.
Abstract:
Introduction: The worldwide impact of the foodborne pathogen Salmonella can never
be overstated, nor can be the fatal threat of septicemia in patients infected with its Typhimurium
serovar. Behind the hyperimmune response in the case of septicemia lies a critical phenomenon of
the bacterial pathogenic signals being sensed by different pattern recognition receptors, such as the
Typhimurium effector proteins that are detected by toll-like receptors.
Methods: To mitigate such a threat, precise structural and functional description of these effectors
is necessary. The same has been addressed in this article using accelerated biocomputational techniques,
beginning with the identification of the functional niche of the effectors and their influence
over other proteins.
Results: The molecular crystal structures were retrieved, and rigorous molecular docking experiments
were conducted among the TLRs and effector proteins in order to examine the interactions.
The interactions were thereby evaluated and screened according to their respective strengths using
parameters including binding affinity, dissociation constant, hydropathy variation, etc. SopB effectors
were found to be detected by three different TLR proteins and GtgE by two other TLRs,
while SifA, SrfJ, and SsaV had only a single interacting TLR partner each. Interestingly, TLR9
presented lower sensitivity towards PAMPs of this bacterium.
Conclusion: Normal modal analyses in combination with atomistic molecular dynamics simulations
that tend to imitate natural cytosolic environments reveal stable and consistent interactions
and realistic conformations among the effector-bound TLR complexes. The findings open up new
avenues for the development of targeted therapies against Salmonella, which could significantly
reduce the global burden of this foodborne pathogen.
