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/...
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
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 💟
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 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.
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.
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.
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??
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.
QR code to access 'Structural diversification of phage tail fibres enables recognition of diverse type IV pili'
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
Cracked, but still there: the glass ceiling persists for senior women in science www.nature.com/articles/d41...
They don't want the link posted for security reasons but you can sign up here! docs.google.com/forms/d/e/1F...
Aqs1's mode of binding can inform development of allosteric inhibitors of PilB-like enzymes that power important virulence traits in many bacterial pathogens. This work also revealed the stabilizing role of the PilB linker which is absent in xray and cryo structures and poorly modeled by AI. Enjoy!
Even though DMS3 is a #Pseudomonas #phage, Nathan showed that Aqs1 could inhibit the function of other #T4P family ATPases, including #T2SS GspE, PilB from #Stenotrophomonas (twitching) and PilB from #Acinetobacter (DNA uptake). These data point to a new allosteric vulnerability of PilB homologues.
Nathan found that Aqs1 binds a hydrophobic pocket on the N2 domain of PilB, displacing the poorly characterized hydrophobic linker segment connecting N1 and N2 that is important for stabilizing the hexamer. Vero Taylor (Maxwell lab) showed that adding Aqs1 causes PilB hexamers to break apart!
New paper alert! Outstanding work by PhD candidate Nathan Roberge, great collab with the Ellison and Maxwell labs. #Pseudomonas #phage DMS3 encodes Aqs1, an inhibitor of #T4P assembly ATPase PilB, but how it binds and leads to loss of function was unknown. @mcmasteriidr.bsky.social
You're right - starts at NOON EDT!
Correction on the start time - NOON EDT! Clearly I'm not awake because of the recent switch to daylight savings time.
webinar speaker descriptions
Join us online tomorrow 11am EDT to catch PhD candidate Veronica Tran talking about work from her recently accepted mBio paper on #Pseudmonas mutants selected by type IV pilus-targeting #phages! @mcmasteriidr.bsky.social @mcmasternexus.bsky.social
🧵 Proud to present a tour de force by postdoc @gregbwhitfield.bsky.social solving the mystery of how bacterial Tad pili can extend and retract with a single motor ATPase. Great collaboration with Lynne Howell, @dr-lori-burrows.bsky.social, @ianyyen.bsky.social www.biorxiv.org/content/10.6...
Beautiful, now I can retire 😁
Happy International Day for Women and Girls in Science! @mcmasteriidr.bsky.social @mcmasternexus.bsky.social @mcmasteruniversity.bsky.social
A bar graph showing the differences in fractional inhibitory concentrations of beta lactam-adjuvant combinations against MRSA versus MSSA, where synergy is lost in MSSA.
Are you trying to kill #MRSA? The Burrows & the Pinho labs are too, and we found that an old anti-inflammatory compound can resensitize it to pen G and other beta lactams in a wall teichoic acid-dependent way, but unlike other WTA adjuvants. @mcmasteriidr.bsky.social www.biorxiv.org/cgi/content/...
Now available - PhD student Veronica Tran reviews the importance of identifying & reporting #phage receptors to build better therapeutic cocktails with diverse #bacteriophages for tough pathogens like #Pseudomonas
journals.asm.org/doi/epub/10....
@mcmasteriidr.bsky.social @mcmasternexus.bsky.social
The report, issued Tuesday by the Council of Canadian Academies, takes a comprehensive look at the state of science and technology in Canada – the first such assessment since 2018. At its focus is the role that research and development plays in economic growth across the country.
New paper alert! PhD candidate Veronica Tran asked what types of resistance mutations were selected in #Pseudomonas by type IV pilus-specific #phages & whether they were reversible, Qs relevant to #phagetherapy - she got some interesting answers! Read the paper here: www.biorxiv.org/cgi/content/...
New paper alert! We used our fav technique, genetic suppression, to understand how FimX controls function of the T4P PilB motor ATPase in Pseudomonas aeruginosa. Great collab with the Ellison lab at U Georgia who helped with some fancy microscopy to capture pilus dynamics! doi.org/10.1371/jour...
New paper! Specific PilA and PilY1 sequences make PilU dispensable for T4P-dependent twitching motility in P. aeruginosa. However, most suppressors still had high cAMP levels from loss of PilU, showing that motility and surface sensing responses can be uncoupled.🧐 ⏩ journals.asm.org/doi/10.1128/...
