Sunday 8 November 2020

Genetic analysis system yields new insights into bacterial pneumonia


A team of infectious disease researchers has developed a new method to identify virulence genes in Streptococcus pneumoniae, the leading cause of bacterial pneumonia. Using this technique in a mouse model of pneumonia, they were able to gain new insights into the progression of the disease and its interaction with the flu virus.


The researchers developed a new method for performing functional gene analysis to identify the genes that drive virulence in S. pneumoniae. Their method builds on the powerful gene editing technology known as CRISPR, which can be modified to selectively silence targeted genes with a technique called CRISPR interference. The researchers created a pooled library of S. pneumoniae strains in which each of the bacteria's genes was targeted by CRISPR interference in one of the bacterial strains.


The CRISPR interference system was inducible by the antibiotic doxycycline, so the genes were not silenced until the bacteria (which were resistant to the antibiotic) were introduced into mice given doxycycline-containing feed. In addition, a genetic "barcode" on the guide RNAs used to target the silenced genes enabled the researchers to easily track each strain after infection. With a single sequencing step, they could identify which strains had survived and caused infections in the mice.


The results pointed to several genes as having important roles in pneumococcal infections, including genes identified as virulence factors in previous studies, such as the bacterial capsule genes. Surprisingly, the gene for the bacteria's main toxin, pneumolysin, did not appear to be necessary for the development of infections. Together with other recent findings, this suggests that pneumolysin may be more important for transmission than for survival in the host.




Xue Liu, Jacqueline M. Kimmey, Laura Matarazzo, Vincent de Bakker, Laurye Van Maele, Jean-Claude Sirard, Victor Nizet, Jan-Willem Veening. Exploration of Bacterial Bottlenecks and Streptococcus pneumoniae Pathogenesis by CRISPRi-Seq. Cell Host & Microbe, 2020; DOI: 10.1016/j.chom.2020.10.001


Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (

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