Read on Twitter
1/14 Excited to share our work on experimental evolution of pneumococcus in mouse infection models. The result of a big effort from the whole lab, but led by @GreenAngharad and @DanielNeill85 with great collaborators @jay_salsa, @ChrispinChaguza, @StephenBentley5, Jason Rosch lab https://twitter.com/biorxiv_micrbio/status/1303548383198679043
2/14 We passaged pneumo 20x through mouse models of upper airway colonisation, generating 10 independently-evolved bacterial lineages adapted to nasopharynx. We did the same in a pneumonia model, generating 10 lineages evolved within lungs. (Thanks @eliza_coli for the image).
3/14 Nasopharynx-passaged pneumococci became more effective colonisers, whilst those passaged through lungs showed attenuated virulence.
4/14 We mapped SNPs in the passaged lineages to the genome sequence of the ancestor strain. These differed depending on the niche in which the pneumococci were evolved.
5/14 We found examples of parallel evolution, where the same SNP was identified in independently evolved lineages (gene names in boxes). With the exception of yknX, where we found SNPs in both lung & nasopharynx passaged pneumo, examples of parallel evolution were niche specific.
6/14 Three lineages of lung-passaged pneumococci acquired the same SNP in lafA (P0_00979), which encodes a glycosyltransferase involved in cell wall modification. These sweep to fixation in all 3 lineages (maroon colour in Muller plots).
7/14 In nasopharynx-passaged pneumococci we observed fixed SNPs in pneumococcal vaccine antigen A (pvaA - P0_01029) in two independent lineages.
8/14 Some inspired suggestions from a very talented undergraduate student visiting the lab led us to focus our attention on gpsA, a gene in which we identified the same non-synonymous mutation in two independently evolved nasopharynx-passaged lineages.
9/14 We reproduced the identified gpsA SNP in the ancestor strain (D39:gpsAG208R) and found that it conferred increased potential to colonise mouse nasopharynx. A gpsA knockout strain (D39:deltaGpsA) was rapidly cleared from nasopharynx.
10/14 The SNP increased functional activity of the gpsA encoded glycerol-6-phosphate dehydrogenase, mediating resistance to oxidative stress. Pneumo produce H2O2 as part of their central metabolism and encounter oxidative stress from co-colonising microbes and neutrophil defences
11/14 What drives the rapid adaptation in this experimental model? Our chosen strain (D39) is a poor coloniser and may have lost many adaptations to host. Is the loss of selective pressures and populations bottlenecks associated with transmission also a factor?
12/14 Have we just adapted pneumo to the mouse? Work by @ChrispinChaguza suggests many genes highlighted in our study are targets of mutation and selection in natural colonisation in infants: https://www.nature.com/articles/s41467-020-17327-w. GpsA was the 23rd (of 592) most frequently mutated gene.
13/14 A great paper by @vscooper et al describes similar in vivo exp evo work with pneumo: https://msystems.asm.org/content/5/3/e00352-20. Lots of interesting shared findings between the two studies, but the importance of ABC transporters and pyruvate metabolism to adaptation to nasopharynx stood out.
14/14 We really enjoyed this study and big thanks go to our collaborators who helped make it possible. The exciting thing for us is that there are lots of findings to follow up on and new potential colonisation and virulence factors to explore. END.
