  We studied in silico effects of structural stress in Mycoplasma pneumoniae, a
genome-reduced model bacterial organism, by tracking the damage propagating on
its metabolic network after a deleterious perturbation. First, we analyzed
failure cascades spreading from individual reactions and pairs of reactions and
compared the results to those in Staphylococcus aureus and Escherichia coli. To
alert to the potential damage caused by the failure of individual reactions, we
propose a generic predictor based on local information that identifies target
reactions for structural vulnerability. With respect to the simultaneous
failure of pairs of reactions, we detected strong non-linear amplification
effects that can be predicted by the presence of specific motifs in the
intersection of single cascades. We further connected the metabolic and gene
co-expression networks of M. pneumoniae through enzyme activities, and studied
the consequences of knocking out individual genes and clusters of genes. Damage
caused by single gene knockouts reveals a strong correlation between
genome-scale cascades of large impact and gene essentiality. At the same time,
we found that genes controlling high-damage reactions tend to operate in
functional isolation, as a metabolic protection mechanism. We conclude that the
architecture of M. pneumoniae, both at the level of metabolism and genome,
seems to have evolved towards increased structural robustness, similarly to
other more complex model bacterial organisms, despite its reduced genome size
and its greater metabolic network linearity. Our approach, although motivated
biochemically, is generic enough to be of potential use toward analyzing and
predicting spreading of structural stress in any bipartite complex network.
