Hope for fighting bacteria lies in bacteriophage biology


Our ability to fight bacteria using antibiotics is limited by the rise of resistant strains. However, understanding the mechanisms of bacteria’s natural enemy, the bacteriophage, may lead to a new treatment. “Bacteriophage phi812 … can infect at least 95% of Staphylococcus aureus strains, including those strains resistant to antibiotics” writes Dr Nováček, a lead scientist at the Czech Instruct Centre, in his paper. The key to being able to use this bacteriophage as a treatment is understanding how it infects cells. Dr Nováček’s team generated high resolution 3D models of phi812 in each of the stages of infection using cryo-electron microscopy.



Figure 1 of the paper showing virions of the bacteriophage phi812 in native conformation (A) and after tail contraction (B). 


Bacteriophages eject their genome form their capsid into the bacteria cell through the tail. To ensure that the ejection process is successful phi812 must recognise when it has come into contact with a bacteria cell. The role of the baseplate is to trigger the ejection process under the right circumstances. Changes to the baseplate cause the outer layer of the tail, called the tail sheath, to contract. This contraction causes the inner tail tube to be inserted into the bacterial cell. Once this change has occurred genome of the bacteriophage is ready to enter the bacterial cell. 

 

One question still remained; does the ejection of the genome occur as a single step? Dr Nováček and his colleagues began their investigation by identifying bacteriophages with DNA within the capsid despite having contracted the tail sheath. This told the researchers that the DNA ejection happens in two steps. Further analysis of the 3D structural changes showed that the first step of ejection is triggered by the tail sheath, and the second is triggered by the tail tube. Understanding this precise mechanism could lead to bacteriophage use in medical treatments.

 

Dr Nováček presented a high resolution bacteriophage structure at theInstruct-ULTRA General Assembly in March 2018, click here to watch the video podcast.

 

Read about Cryo-EM facilities at Instruct-ERIC.

 

Read Dr Nováček’s paper: Nováček J., et al., 2016, Structure and genome release of Twort-like Myoviridae phage with a double-layered baseplate, Proceedings of the National Academy of Sciences, 113 (33) 9351-9356