@pierrelebury
Multi-omics enthusiast & official plague doctor, focused on physiopathology, immunology and molecular pathogenesis. Postdoctoral researcher | ImVA-HB / IDMIT @cea.fr | @yersiniaunit.bsky.social @pasteur.fr.
Pour chaque vie, la science agit. Le Pasteurdon, c’est maintenant ! Soutenez la recherche et celles et ceux qui la font avancer. Faites un don sur pasteurdon.fr
Pour chaque vie, la science agit.
Le Pasteurdon, c’est maintenant !
Soutenez la recherche et celles et ceux qui la font avancer ↘️ pasteurdon.fr
#Pasteurdon
Happy to share that the paper describing Autocycler is now 100% up:
doi.org/10.1093/bioi...
(1/3)
💊 🧬 Insightful dive into in-host bacterial evolution under antimicrobial pressure, a work from @csavin.bsky.social and @pierrelebury.bsky.social in our lab at @pasteur.fr
Great collaboration with @csavin.bsky.social at @yersiniaunit.bsky.social in @pasteur.fr, as well as @julmini.bsky.social @chrudetours.bsky.social @univparissaclay.bsky.social @cea.fr @ap-hp.bsky.social
📖 Out in @natcomms.nature.com @natureportfolio.nature.com 👇
www.nature.com/articles/s41...
8/8 🙏 Many thanks to all the contributors of this study !
@csavin.bsky.social @julmini.bsky.social
@yersiniaunit.bsky.social @pasteur.fr @chrudetours.bsky.social @univparissaclay.bsky.social @cea.fr @ap-hp.bsky.social @natureportfolio.nature.com @natcomms.nature.com
7/8 - Conclusion
💊 A fascinating case of in-host bacterial evolution — and a warning about long-term antibiotic exposure.
6/8 - Selection
🚫 We also identified positive selection signals:
- a truncation in the phosphate transporter PitA which probably impairs its activity
- an amino acid substitution interfering with the active site and diminishing the catalytic activity of the acyl-CoA thioesterase II TesB
5/8 - Metabolic adaptation
🍔 Omics analysis also unraveled:
- a progressive genome reduction
- metabolic changes in amino acid and carbon utilization
- a disturbed stringent response
which could contribute to the observed slower growth and antibiotic tolerance preceding resistance.
4/8 - Antibiotics resistance mechanisms
🧪 By analysing Ye.1 to Ye.4 genomes and proteomes, we could identify:
- a novel gyrA mutation leading to quinolone resistance
- ceftriaxone resistance via OmpF loss and β-lactamase activity
3/8 - Phylogenetic reconstruction
🧫 Ye.1 to Ye.4 belong to the Ye genotype 4 (bioserotype 4/O:3) and a form a unique clade separated from other Ye strains, strongly suggesting that the patient suffered from a chronic infection due to a unique evolving Ye 4/O:3 strain.
2/8 - Clinical case
🏥 Thanks to the National Reference Center for Plague and other Yersiniosis in @pasteur.fr, we collected 4 clinical isolates — Ye.1 to Ye.4, which evolved antibiotics tolerance and resistance — from a rare chronic infection in an elderly patient from @chrudetours.bsky.social.
1/8 - New in @natcomms.nature.com !
☣️ Meet Yersinia enterocolitica (Ye) — a lesser-known but still dangerous cousin of Yersinia pestis.
We uncover how this invasive pathogen can survive and adapt for 14 years inside a human host under constant antibiotic pressure 👇
www.nature.com/articles/s41...
Very clear explanation by @alicelebreton.bsky.social of our article about plague virulence reduction, in Le Monde (in French)!
#NatMicroPicks
The plague virulence! 💀🦠
During plague epidemics, virulence gene pla in Yersinia pestis often becomes depleted, which reduces the pathogen's lethality and may help it survive in less susceptible hosts when transmission conditions worsen.
#MicroSky
www.science.org/doi/10.1126/...
🦠 The plague bacillus became less virulent, extending the duration of two major pandemics. @yersiniaunit.bsky.social @pierrelebury.bsky.social @mcmasteruniversity.bsky.social @ravneetksidhu.bsky.social
Additional disclaimer: we did not SOLVE a mystery, it is just another small brick added on the top of all the knowledge accumulated since then...
Picking up our publication on Black Death and plague pandemics: here are interesting historical thoughs about the well known but deceptive (not so) medieval plague doctor costume
Our work on the facial skin microbiome of non-human primates is out in mSystems!
We show there is no close relative of Cutibacterium on the faces of gorillas and chimps at the Lincoln Park Zoo, furthering the mysterious origin of the dominant human skin colonizer.
journals.asm.org/doi/10.1128/...
IIDR researchers have discovered that a single gene in Yersinia pestis — the bacteria that causes bubonic #plague — was responsible for keeping pandemics like the Black Death burning for hundreds of years. Learn more about this evolutionary phenomenon in our all-new explainer video. #IDSky
Two great papers in @science.org this month on the #evolution of #vector-borne #pathogens
1 #Yersinia pestis attenuates virulence over 3 pandemics
2 Ancient #Borrelia genomes trace the rise of louse-borne relapsing fever
Fascinating reads (links below)
A short animation to better understand our paper:
www.youtube.com/watch?v=o8nf...
New in 𝘚𝘊𝘐𝘌𝘕𝘊𝘌:
Plague Plays the Long Game
As plague pandemics decimated rodent populations, 𝘠𝘦𝘳𝘴𝘪𝘯𝘪𝘢 𝘱𝘦𝘴𝘵𝘪𝘴 adapted
Virulence gene 𝘱𝘭𝘢 lost late in outbreaks ➡️ strains with reduced lethality ➡️ pathogen can persist, spread across highly fragmented host networks
www.science.org/doi/10.1126/...
More details here 👇https://bsky.app/profile/pierrelebury.bsky.social/post/3lqdcuo5gwk2v
12/12 🙏 Many thanks to the contributors of this study!
@ravneetksidhu.bsky.social @gmasfiol.bsky.social @bbolker.bsky.social @yersiniaunit.bsky.social
#ScienceResearch
11/12 - Impact
Our study highlights the importance of reservoir dynamics and structures to better understand virulence evolution of a zoonotic pathogen.
10/12 - Conclusion
Pla depletion may reflect adaptive evolution during declining host populations throughout a pandemic, while full virulence remains crucial for long-term survival in sylvatic reservoirs between pandemics.
9/12 - Our hypothesis
💡 Y. pestis is typically transmitted during late-stage, fatal bacteremia: a lower mortality should reduce transmission. However, in structured rodent populations, delayed host death may help spread Y. pestis across dispersed groups, enabling longer epidemic persistence.
8/12 - Wet lab findings
🧪 Pla enzyme activity scales with pla gene dosage. pla-depleted strains remain virulent but cause slightly lower mortality and delayed death in bubonic plague.
7/12 - Genomic findings
🧬 pla depletion is mediated by integration of the high-copy-number pPCP1 plasmid into low-copy replicons. This is combined with pla excision from the high-copy-number pPCP1 possibly via Xer recombination sites.
6/12 - Phylogenomic findings
🌍 pla copy number reduction occured during the 1st, the 2nd but also during the 3rd pandemic.
