RT Journal Article
SR Electronic
T1 Bacteriophage adaptation to a mammalian mucosa reveals a trans-domain evolutionary axis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.05.11.443681
DO 10.1101/2021.05.11.443681
A1 Wai Hoe Chin
A1 Ciaren Kett
A1 Oren Cooper
A1 Deike Müseler
A1 Yaqi Zhang
A1 Rebecca Bamert
A1 Ruzeen Patwa
A1 Laura C. Woods
A1 Citsabehsan Devendran
A1 Joe Tiralongo
A1 Trevor Lithgow
A1 Mike J. McDonald
A1 Adrian Neild
A1 Jeremy J. Barr
YR 2021
UL http://biorxiv.org/content/early/2021/05/11/2021.05.11.443681.abstract
AB The majority of viruses within the human gut are obligate bacterial viruses known as bacteriophages (phages)1. Their bacteriotropism underscores the study of phage ecology in the gut, where they sustain top-down control2–4 and co-evolve5 with gut bacterial communities. Traditionally, these were investigated empirically via in vitro experimental evolution6–8 and more recently, in vivo models were adopted to account for gut niche effects4,9. Here, we probed beyond conventional phage-bacteria co-evolution to investigate the potential evolutionary interactions between phages and the mammalian “host”. To capture the role of the mammalian host, we recapitulated a life-like mammalian gut mucosa using in vitro lab-on-a-chip devices (to wit, the gut-on-a-chip) and showed that the mucosal environment supports stable phage-bacteria co-existence. Next, we experimentally evolved phage populations within the gut-on-a-chip devices and discovered that phages adapt by de novo mutations and genetic recombination. We found that a single mutation in the phage capsid protein Hoc – known to facilitate phage adherence to mucus10 – caused altered phage binding to fucosylated mucin glycans. We demonstrated that the altered glycan-binding phenotype provided the evolved mutant phage a competitive fitness advantage over their ancestral wildtype phage in the gut-on-a-chip mucosal environment. Collectively, our findings revealed that phages – in addition to their evolutionary relationship with bacteria – are also able to engage in evolution with the mammalian host.Competing Interest StatementThe authors have declared no competing interest.