Understanding antibiotic resistance

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.

See:

Paul A. Jensen, Zeyu Zhu, Tim van Opijnen. Antibiotics Disrupt Coordination between Transcriptional and Phenotypic Stress Responses in Pathogenic Bacteria. Cell Reports, 2017; 20 (7): 1705 DOI: 10.1016/j.celrep.2017.07.062

Posted by Dr. Tim Sandle