Researchers
have uncovered new insights into how bacteria respond to stress. When deprived
of nutrients, strains of the bacterium Streptococcus pneumoniae mount a
coordinated defense. When exposed to antibiotics, the bacterial response is
highly disorganized, revealing the bacteria are far less familiar with
antibiotics and do not recognize how to respond.
When
facing a common -- or historic -- threat such as deprivation of nutrients, the
deadly bacterium Streptococcus pneumoniae
exerts a highly organized response -- one influenced by the bacteria's genetic
evolution and powered by genes that respond cooperatively to stress, the
researchers found. But when confronted with antibiotics -- a relatively new
form of stress -- the bacterium mounts a confused defense, according to the
study "Antibiotics Disrupt Coordination Between Transcriptional and
Phenotypic Stress Responses in Pathogenic Bacteria," published today in
the journal Cell Reports.
Scienitsts
used a process known as RNA sequencing, or RNA-Seq, to assess bacterial genes
that are provoked to change, a process known as transcription. This activity
has long been viewed as central to understanding how bacteria combat
antibiotics and other stressors.
The
team paired that analysis with its own technique: transposon insertion
sequencing, or Tn-Seq. Developed by van Opijnen, Tn-Seq combs through millions
of genetic sequences and singles-out gene functions in bacteria. The advantage
of Tn-Seq is that it is able to begin to pinpoint which genes play the most
important defensive roles.
During
the course of more than two years, the team's RNA-Seq experiments analyzed 800
million genetic sequences and produced 150,000 data points. Tn-Seq analyzed 1.2
billion sequences and produced 300 million data points. The researchers
constructed a metabolic model of the coordinated response to deprivation, which
placed the responding genes in close proximity to each other. When challenged
with antibiotics, the model shows that the response of the physical network
breaks down in disorganization and those genes are no longer in close
proximity.
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