Pseudomonas aeruginosa: the making of a pathogen

Reconstruction of the metabolic network of Pseudomonas aeruginosa to interrogate virulence factor synthesis

“…While infection-based Tn-seq screens have demonstrated that mutants incapable of VF synthesis lack the ability to infect, it is challenging to discern whether this occurs due to the inhibited gene's essentiality for the expression of virulence-linked compound(s), essentiality for growth, or essentiality for both728. To address this gap in knowledge, we employed genome-scale metabolic network modelling.…”

“…In targeting the synthesis of these metabolites, resistance may develop more slowly because of weakened selection pressure versus traditional targets that directly impact growth-essential catabolism of substrates or cell wall construction and repair3. However, our understanding of the role of virulence-linked genes is evolving7—significant links between virulence and pathogen metabolism are now emerging. For example, antibiotic pigments called phenazines enable opportunistic bacteria to combat the effects of immune cell oxidative bursts, but these pigments may also induce rewiring of redox-linked pathways within the pathogen8.…”

“…Furthermore, the production of virulence-linked compounds relies on essential components of central metabolism that connect substrate catabolism to VF synthesis pathways. A clear division between therapeutic targets impacting growth and virulence is therefore not straightforward7. We need to map the interconnectivity of these systems to identify genes that contribute to either or both systems, determine their function and essentiality in a clinically relevant environment, and estimate the impact of their inhibition on virulence versus growth.…”

Latest developments in foodborne pathogen risk assessment

“…On the other hand, Gale et al [40] explored the possibility of building a dose-response model for RNA virus but they could not succeed in having a quantitative estimation of probability of infection on the basis of omic data. Finally, metabolomics and more specifically fluxomics seems a valuable technique to progress on hazard characterization [41], even if reconstructing causal gene-metabolite network will be always difficult [42].…”

Manipulating virulence factor availability can have complex consequences for infections

“…The pervasive idea that virulence—the damage a host experiences during infection—follows more or less directly from pathogen load has shaped our view of infectious disease since the early days of germ theory (Anderson & May, ; Bastian, ; Evans, ; Frank, ; Pasteur, ; Stearns & Koella, ) and has underpinned our clinical quest to eradicate harmful microbes (Allison, Brynildsen, & Collins, ; Dagan, Klugman, Craig, & Baquero, ; Russell, ). However, advances over the years have revealed that the severity of an infectious disease depends on much more than just the sheer number of pathogens present; rather, it derives from complex interactions between the pathogen, its host and the prevailing abiotic and biotic ecological conditions (Bull & Lauring, ; de Lorenzo, ; Méthot & Alizon, ; Schmid‐Hempel, ). In other words, a microbe's pathogenicity is not so much about what it is and how abundant it is, but what it does, when it does it and to whom.…”