Genome-Scale Metabolic Modelling Approach to Understand the Metabolism of the Opportunistic Human Pathogen Staphylococcus epidermidis RP62A.

Teresa Díaz Calvo,Dipali Singh,Noemi Tejera,Mark Poolman,John Wain,Iain Mcnamara,Gemma C Langridge

doi:10.3390/metabo12020136

Abstract

Staphylococcus epidermidis is a common commensal of collagen-rich regions of the body, such as the skin, but also represents a threat to patients with medical implants (joints and heart), and to preterm babies. Far less studied than Staphylococcus aureus, the mechanisms behind this increasingly recognised pathogenicity are yet to be fully understood. Improving our knowledge of the metabolic processes that allow S. epidermidis to colonise different body sites is key to defining its pathogenic potential. Thus, we have constructed a fully curated, genome-scale metabolic model for S. epidermidis RP62A, and investigated its metabolic properties with a focus on substrate auxotrophies and its utilisation for energy and biomass production. Our results show that, although glucose is available in the medium, only a small portion of it enters the glycolytic pathways, whils most is utilised for the production of biofilm, storage and the structural components of biomass. Amino acids, proline, valine, alanine, glutamate and arginine, are preferred sources of energy and biomass production. In contrast to previous studies, we have shown that this strain has no real substrate auxotrophies, although removal of proline from the media has the highest impact on the model and the experimental growth characteristics. Further study is needed to determine the significance of proline, an abundant amino acid in collagen, in S. epidermidis colonisation.

Highlights

Staphylococci are non-motile Gram-positive cocci, and ubiquitous commensals of the skin and mucous membranes
The model was constructed on the basis of the BioCyc Pathway/Genome Database (PGDB) [19,20] for S. epidermidis RP62A, version 20.1, using the ScrumPy metabolic modelling package [21] and in a modular fashion, using the approach described by Tejera et al [18], Ahmad et al [22], and was comprised of the following: The top level module, which serves to import the modules listed below
The curated Genome-scale metabolic models (GSMs) of S. epidermidis RP62A consists of 895 reactions and 864 internal metabolites, with an additional 95 transport reactions and 74 external metabolites (Supplementary File SIII)

Summary

Introduction

Staphylococci are non-motile Gram-positive cocci, and ubiquitous commensals of the skin and mucous membranes. They are opportunistic pathogens and the most frequent cause of nosocomial infections associated with implanted medical devices. Cycle (which lacks the glyoxylate shunt) [6] They mainly catabolise carbohydrates through the glycolysis and the pentose phosphate pathway, while the activity of the TCA cycle and electron transport chain depends on the availability of nutrients, as well as that of oxygen, nitrate or nitrite, all of which can serve as terminal electron acceptors [6,7,8]

Methods

Results

Discussion

Conclusion