Identification and qualitative characterization of new therapeutic targets in Stenotrophomonas maltophilia through in silico proteome exploration

Abstract

Stenotrophomonas maltophilia is an emerging opportunistic pathogen, and immunocompromised patients are at a higher risk of getting infected with this nosocomial bacterium. The biggest concern is its inherent resistance to most of the commonly used antibiotics, leaving a few options for treatment. Moreover, recent studies have reported the emergence of its resistance to trimethoprim/sulfamethoxazole (TMP/SMX), the drugs of choice against this pathogen. In this study, we employed a subtractive proteome analysis approach to identify new drug targets against Stenotrophomonas maltophilia K279a. We identified 56 proteins to be essential for the survival of this pathogen, 33 of which are exclusively involved in its metabolism. We identified their subcellular locations and performed broad-spectrum analysis, interactome analysis, and functional analysis. Drug targeting properties and docking energy showed that 29 out of 33 proteins have the potential to serve as potential new therapeutic targets, and four proteins (dCTP deaminase, NAD(P)H:quinone oxidoreductase, dihydroneopterin aldolase, and α, α-trehalose-phosphate synthase) bind with high affinity to already approved or experimental drugs. Based on the broad-spectrum analysis and interactome analysis, we identified NAD(P)H:quinone oxidoreductase, dCTP deaminase, Phosphotransferase, and ATP-dependent Clp protease adapter (ClpS) as the most potential therapeutic targets. Notably, phosphotransferase and ClpS are new targets, i.e., they do not interact with any experimental or approved drugs. Overall, our study will guide the development of new and effective drugs for the treatment of Stenotrophomonas maltophilia infection.

Keywords: Druggability; New therapeutic targets; Stenotrophomonas maltophilia; subtractive Proteomics.