In silico analysis of essential tricarboxylic acid cycle enzymes from biofilm-forming bacteria

Abstract

The Tricarboxylic Acid Cycle (TCA) cycle is the central point in the metabolism of living organisms and is important for the survival of infectious biofilms. The inhibition of this vital point could be a promising strategy for the control of infectious biofilms. Therefore, this study was carried out to identify the potential drug targets from the TCA cycle of several Biofilm-Forming Bacteria (BFB) and to identify the available small molecule drugs against the TCA cycle enzymes. Based on the in silico substractive genomic approach, citrate lyase subunit alpha/citrate CoA-transferase [EC: 4.1.3.6], succinate dehydrogenase iron-sulfur subunit (EC: 1.3.99.1) and 2-oxoglutarate ferredoxin oxidoreductase subunit delta [EC: 1.2.7.3] were found to be essential and exclusively present in the BFB. Further in silico analyses showed that most of them are chemically regulated by myristoylation, phosphorylation, glycosylation and amidation. Based on the sequence search against DrugBank database, the potential small molecule drugs for biofilm treatment are 2-[l-methylhexyl]-4, 6-dinitrophenol, Atpenin A5 and Ubiquinone-2 which all target the succinate dehydrogenase enzyme of BFB. This study demonstrates the rapid identification of potential drug targets and small molecule drugs which could be useful in biofilm control strategies.