Analysis of Piscirickettsia salmonis Metabolism Using Genome-Scale Reconstruction, Modeling, and Testing.

María P Cortés,Alexis Gaete,Dante Travisany,Verónica Cambiazo,Sebastián N Mendoza,Anne Siegel,Alejandro Maass

doi:10.3389/fmicb.2017.02462

Abstract

Piscirickettsia salmonis is an intracellular bacterial fish pathogen that causes piscirickettsiosis, a disease with highly adverse impact in the Chilean salmon farming industry. The development of effective treatment and control methods for piscireckttsiosis is still a challenge. To meet it the number of studies on P. salmonis has grown in the last couple of years but many aspects of the pathogen’s biology are still poorly understood. Studies on its metabolism are scarce and only recently a metabolic model for reference strain LF-89 was developed. We present a new genome-scale model for P. salmonis LF-89 with more than twice as many genes as in the previous model and incorporating specific elements of the fish pathogen metabolism. Comparative analysis with models of different bacterial pathogens revealed a lower flexibility in P. salmonis metabolic network. Through constraint-based analysis, we determined essential metabolites required for its growth and showed that it can benefit from different carbon sources tested experimentally in new defined media. We also built an additional model for strain A1-15972, and together with an analysis of P. salmonis pangenome, we identified metabolic features that differentiate two main species clades. Both models constitute a knowledge-base for P. salmonis metabolism and can be used to guide the efficient culture of the pathogen and the identification of specific drug targets.

Highlights

Piscirickettsiosis or Salmonid Rickettsial Septicaemia (SRS) is a severe systemic fish disease that targets multiple organs and tissues (Cvitanich et al, 1991)
Reactions involved in lipopolysaccharide (LPS) biosynthesis inherited from E. coli were modified to be consistent with the reported lipid A carbohydrate backbone and fatty acid composition of P. salmonis (Vadovic et al, 2007; Vinogradov et al, 2013)
The LPS fraction in this objective function was filled by P. salmonis LPS macromolecule and the glycogen fraction was replaced by poly-3-hydroxybutanoate (PHB) as all three genes for its biosynthesis are in P. salmonis genome while no indication of glycogen biosynthesis was found

Summary

Introduction

Piscirickettsiosis or Salmonid Rickettsial Septicaemia (SRS) is a severe systemic fish disease that targets multiple organs and tissues (Cvitanich et al, 1991). While it was first observed in the late 1980’s in Coho salmon cultured in farms on the south of Chile, outbreaks were later reported in different farming countries and in other salmonid fish species such as Atlantic salmon and Rainbow trout (Bravo, 1994; Cusack et al, 2002). Studies on the fish pathogen have unveiled relevant clues, showing that it infects primarily macrophage cells and replicates inside intracellular vacuoles (McCarthy et al, 2008; Rojas et al, 2009; Ramírez et al, 2015)

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Conclusion