microbiologist, McMaster U 🇨🇦 • type IV pili, phages, biofilms, antibiotic resistance • equestrian🐴 • cancer survivor🎗️
Lori L. Burrows
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This work shows how closely related phages can evolve to recognize a wide range of hosts using tail fibre modules tolerant of receptor modifications, and links host range to tail fibre architecture. It can inform the selection of broad-host-range phages for treating tough #Pseudomonas infections.
Ikram did a deep bioinformatic dive and found that JBD26-like and DMS-like tails were modular, diverging sharply at the C-terminal receptor recognition domain. JBD26-like tails were conserved while DMS3-like were diverse and found in many phage families, consistent with broad receptor recognition.
Ikram and Hanjeong tested additional members of the JBD26-like and DMS3-like classes and showed they followed the same pattern of sensitivity to changes in pilin sequence, with DMS3-like being tolerant of mutations as well as post-translational modifications.
Using a related pair of phages with narrow (JBD26) and broad (DMS3) pilin recognition, plus a chimeric phage (JBD26 expressing DMS3 tail fibres), we examined whether pilus electrostatics impacted recognition. Mutation of specific charged residues dramatically reduced infectivity, but only for JBD26.
We are really interested in #phages that use the type IV pilus as receptors, and the ways in which bacteria - like #Pseudomonas - try to escape those phages without crippling themselves permanently in the process. healthsci.mcmaster.ca/hiding-in-pl... @mcmasteriidr.bsky.social
To study the implications, we built a pilin library in PAO1, and compared the ability of polyclonal #antisera vs #phages to recognize diverse pilins. While antibodies were highly selective for their cognate antigens, some phages could recognize almost all of the pilins! But how could they do that??
New paper showing how tailed #phages recognize diverse #Pseudomonas #T4P! Outstanding work by PhD candidate Ikram Qaderi, building on work started a decade ago during my sabbatical in the McArthur lab and in collaboration with the Guarné lab, now at #McGill. @mcmasteriidr.bsky.social
Footnote: Thanks to the @guarnelab.bsky.social for solving the structure of the most common group I pilin, back in the pre-Alphafold days!! We must remember that Alphafold only works well now because people painstakingly solved experimental structures to train it in the first place 💟
During my sabbatical I wanted to learn more bioinformatics, so spent 2 months learning Python and building a dataset from over 1360 genomes of 5 groups of highly diverse T4aP #Pseudomonas #pilins mapped to the strains' MLSTs. We identified over 50 distinct pilins and over 300 pilin-MLST combos.
Lori L. Burrows
Excited to share our new paper out today in @science.org 🎉
We show that HGT via natural competence drives diversification of chromosomal integrons in V. cholerae 🤩
Below a 🧵 on key findings incl. background on natural competence in V. cholerae 1/
#microsky #phagesky
www.science.org/doi/10.1126/...
