Identification of putative drug targets of Listeria monocytogenes F2365 by subtractive genomics approach

MD. M. HOSSAIN, A.T.M.J. MOSNAZ, A. M. SAJIB, P. K. ROY, S. K. SHAKIL, S.M. SARID ULLAH and S. H. PRODHAN

ABSTRACT
The prolonged and uncontrolled use of antibiotics in treatment against many pathogens causes the multiple drug resistance. The drug resistance of Listeria monocytogenes F2365 has been evolved, which cause a major disease listeriosis. The drug dose limit against that pathogen was also increased for currently prescribed antibiotics and more often combinational therapy was preferred. Therefore, identification of an extensive novel drug target, unique and essential to the microorganism and subjected to its validation and drug development is imperative. Availability of the total proteome of L. monocytogenes F2365 enabled in silico identification of putative common drug targets and their subcellular localization by subtractive genomics approach. In the present work subtractive genomics approach is used to identify vaccine and drug targets of L. monocytogenes F2365 to speed up the rational drug and vaccine design. It has revealed that out of 2821 reference sequences of the pathogen, 744 represent essential proteins and among them 274 are human non-homolog proteins. Besides, all predicted human non-homologs were then analyzed by subcellular localization servers, in which 46 proteins were identified as surface exposed proteins and can be considered as potential drug and vaccine targets for the pathogen. The 3D structure of two human non-homolog putative drug targets, pantothenate kinase (LmPK) and holliday junction resolvase-like protein (LmHJR) of L. monocytogenes F2365 were generated by homology modeling program Easymodeller 4.0; a GUI version of modeller. Generated structures were also validated by several online servers. The overall stereochemical quality of the model was assessed by Ramachandran plot analysis that was provided by PROCHECK. ProQ, ERRAT, Pro-SA web and VERIFY 3D of SAVES programs were also used to compute several validation parameters during the evaluation of the model. This protein structure information is important in structure-based drug and vaccine design. This study provides information about putative drug targets of L. monocytogenes F2365 and 3D structures (LmPK and LmHJR), which emphasizes future perspective to design rational drugs and vaccines.

Key words: drug targets, Listeria monocytogenes, subtractive genomics approach, LmPK, LmHJR

Volume 2, Number 1 (2013) pp. 63-71   [ Full Text (PDF) ]