Dataset Information

Identification of potential inhibitors for Penicillinbinding protein (PBP) from Staphylococcus aureus.

ABSTRACT: Staphylococcus aureus is an infectious agent that causes severe skin and soft tissue infection in hospitalized patients. Therefore, it is of interest to develop potent inhibitors for S. aureus. Penicillin Binding protein (PBP) is a known drug target for inhibition of cell wall biosynthesis in S. aureus. Hence, PBP was screened with compounds from six databases using virtual screening approaches. Results shows that the screened lead compound produced higher docking score (-9.87 kcal/mol) compared to resistant drugs. Antimicrobial activity using screened lead compounds and resistant drugs showed maximum activity in potential screened compounds compared to resistant compounds.

SUBMITTER: Kulanthaivel L

PROVIDER: S-EPMC6563657 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Identification of potential inhibitors for Penicillinbinding protein (PBP) from Staphylococcus aureus.

Kulanthaivel Langeswaran L Jeyaraman Jeyakanthan J Biswas Abir A Subbaraj Gowtham Kumar GK Santhoshkumar S S

Bioinformation 20181102 9

<i>Staphylococcus aureus</i> is an infectious agent that causes severe skin and soft tissue infection in hospitalized patients. Therefore, it is of interest to develop potent inhibitors for S. aureus. Penicillin Binding protein (PBP) is a known drug target for inhibition of cell wall biosynthesis in S. aureus. Hence, PBP was screened with compounds from six databases using virtual screening approaches. Results shows that the screened lead compound produced higher docking score (-9.87 kcal/mol) c ...[more]

PMID: 31223205

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Project description:Exogenous spermine was reported to enhance the killing of methicillin-resistant Staphylococcus aureus (MRSA) by ?-lactams through a strong synergistic effect of unknown nature. Spermine alone also exerts an antimicrobial activity against S. aureus in a pH-dependent manner. MIC measurements revealed stronger effects of spermine under alkaline conditions, suggesting the nucleophilic property of spermine instead of its positive charge as the cause of adverse effects. A spontaneous suppressor mutant (MuM) of MRSA Mu50 was selected for spermine resistance and conferred complete abolishment of spermine-?-lactam synergy. In comparison to that in Mu50, the spermine MIC in MuM remained constant (64 mM) at pH 6 to 8; however, MuM, a heat-sensitive mutant, also grew in a very narrow pH range. Furthermore, MuM acquired a unique phenotype of vancomycin-spermine synergy. Genome resequencing revealed a 7-bp deletion in pbpB, which results in a truncated penicillin-binding protein 2 (PBP 2) without the transpeptidase domain at the C terminus while the N-terminal transglycosidase domain remains intact. The results of fluorescent Bocillin labeling experiments confirmed the presence of this defective PBP 2 in MuM. All the aforementioned phenotypes of MuM were reverted to those of Mu50 after complementation by the wild-type pbpB carried on a recombinant plasmid. The anticipated changes in cell wall metabolism and composition in MuM were evidenced by observations that the cell wall of MuM was more susceptible to enzyme hydrolysis and that MuM exhibited a lower level of autolytic activities. Pleiotropic alterations in gene expression were revealed by microarray analysis, suggesting a remarkable flexibility of MuM to circumvent cell wall damage by triggering adaptations that are complex but completely different from that of the cell wall stress stimulon. In summary, these results reveal phenotypic changes and transcriptome adaptations in a unique pbpB mutant and provide evidence to support the idea that exogenous spermine may perturb normal cell wall formation through its interactions with PBP 2.

Dataset Information

Identification of potential inhibitors for Penicillinbinding protein (PBP) from Staphylococcus aureus.

Publications

Identification of potential inhibitors for Penicillinbinding protein (PBP) from Staphylococcus aureus.

Similar Datasets

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