Pseudomonas aeruginosa reverse diauxie is a multidimensional, optimized, resource utilization strategy

S Lee Mcgill,Michael A Henson,Luke Hanley,Kristopher A Hunt,Ross P Carlson,Yeni Yung

doi:10.1038/s41598-020-80522-8

Abstract

Pseudomonas aeruginosa is a globally-distributed bacterium often found in medical infections. The opportunistic pathogen uses a different, carbon catabolite repression (CCR) strategy than many, model microorganisms. It does not utilize a classic diauxie phenotype, nor does it follow common systems biology assumptions including preferential consumption of glucose with an ‘overflow’ metabolism. Despite these contradictions, P. aeruginosa is competitive in many, disparate environments underscoring knowledge gaps in microbial ecology and systems biology. Physiological, omics, and in silico analyses were used to quantify the P. aeruginosa CCR strategy known as ‘reverse diauxie’. An ecological basis of reverse diauxie was identified using a genome-scale, metabolic model interrogated with in vitro omics data. Reverse diauxie preference for lower energy, nonfermentable carbon sources, such as acetate or succinate over glucose, was predicted using a multidimensional strategy which minimized resource investment into central metabolism while completely oxidizing substrates. Application of a common, in silico optimization criterion, which maximizes growth rate, did not predict the reverse diauxie phenotypes. This study quantifies P. aeruginosa metabolic strategies foundational to its wide distribution and virulence including its potentially, mutualistic interactions with microorganisms found commonly in the environment and in medical infections.

Highlights

Pseudomonas aeruginosa is a globally-distributed bacterium often found in medical infections
P. aeruginosa utilizes a carbon catabolite repression (CCR) strategy termed ‘reverse diauxie’ or reverse CCR which is defined by a hierarchy of preferred carbon sources that is nearly reverse that of classic carbon catabolite repression’ (cCCR) preferences[8,15]
The cultures did not exhibit an overflow metabolism defined by the secretion of reduced metabolic byproducts like acetate, as is typical of microorganisms expressing cCCR p henotypes[17,30]

Summary

Introduction

Pseudomonas aeruginosa is a globally-distributed bacterium often found in medical infections. The opportunistic pathogen uses a different, carbon catabolite repression (CCR) strategy than many, model microorganisms It does not utilize a classic diauxie phenotype, nor does it follow common systems biology assumptions including preferential consumption of glucose with an ‘overflow’ metabolism. In silico and in vitro studies of E. coli quantified acclimation to carbon, nitrogen, or iron limitation along a metabolic tradeoff surface by optimizing the functional return on the limiting nutrient, at the expense of substrates found in excess[21,31] This strategy resulted in ‘overflow metabolisms’ with the secretion of byproducts like acetate and lactate; overflow metabolisms are known as the Warburg or Crabtree effect in e ukaryotes[32]. Given the large genomic potential and phenotypic plasticity of P. aeruginosa, these approaches hold potential for decoding the metabolic organization of this problematic bacterium

Methods

Results

Conclusion