Molecular drilling to combat salmonella typhi biofilm using L-Asparaginase via multiple targeting process

ABSTRACT

Objectives

Salmonella Typhibiofilm condition is showing as a major public health problem due to the development of antibiotic resistance and less available druggable target proteins. Therefore, we aimed to identify some more druggable targets of S. Typhibiofilm using computational drilling at the genome/proteome level so that the target shortage problem could be overcome and more antibiofilm agents could be designed in the future against the disease.

Methods

We performed protein–protein docking and interaction analysis between the homological identified target proteins of S.Typhi biofilm and a therapeutic protein L-Asparaginase.

Results

We have identified some druggable targets CsgD, BcsA, OmpR, CsgG, CsgE, and CsgF in S.Typhi. These targets showed high-binding affinity BcsA (−219.8 Kcal/mol) >csgF (−146.52 Kcal/mol) >ompR (−135.68 Kcal/mol) >CsgE (−134.66 Kcal/mol) >CsgG (−113.81 Kcal/mol) >CsgD(−95.39 Kcal/mol) with therapeutic enzyme L-Asparaginase through various hydrogen-bonds and salt-bridge. We found six proteins of S. Typhi biofilm from the Csg family as druggable multiple targets. 

Conclusion

This study provides insight into the idea of identification of new druggable targets and their multiple targeting with L-Asparaginase to overcome target shortage in S. Typhibiofilm-mediated infections. Results further indicated that L-Asparaginase could potentially be utilized as an antibiofilm biotherapeutic agent against S.Typhi.

GRAPHICAL ABSTRACT

KEYWORDS:

• Salmonella typhi
• biofilm
• multiple targets
• L-Asparaginase
• protein–protein interaction
• antibiofilm bio-therapeutics

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Authors’ contributions

Conception and design: A Kumar and D Pal. Performed experiments and analysis: A Upadhyay. Drafting the article: A Upadhyay. Critically revising the article: A Upadhyay and A Kumar. Creating the figures: A Upadhyay and A Kumar. Reviewed submitted version of manuscript: A Upadhyay, D Pal and A Kumar. Approved the final version of the manuscript on behalf of all authors: A Kumar. Article supervision: A Kumar and D Pal.

Data availability statement

Data are openly available in a public repository and related links are provided in the manuscript.

Additional information

Funding

This paper was not funded.