Invertible promoters mediate bacterial phase variation, antibiotic resistance, and host adaptation in the gut.
Jiang X, Hall AB, Arthur TD, Plichta DR, Covington CT, Poyet M, Crothers J, Moses PL, Tolonen AC, Vlamakis H, Alm EJ, Xavier RJ
Science. Jan 2019. doi: 10.1126/science.aau5238
COMMENT: This article is centered around the study of inversion-mediated phase variation. In this inversion events a DNA sequence is inverted, resulting in an ON to OFF switch or vice versa resulting in the expression or not of the gene/genes located close to this switch. The authors use the new concept "INVERTONS" defined as invertible regions containing promoters oriented such that in the ON orientation, the promoter activates the transcription of an operon and in the opposite OFF orientation the promoter is oriented in such a way that the operon is not transcribed. This work analyzes with the PhaseFinder algorithm the events of inversion-mediated phase variation in a set of 54,875 bacterial genomes.
(i) How prevalent are invertons?
(ii) What are the functions of genes regulated by invertons?
(iii) In the context of a host, do individual-specific selective pressures modulate inverton orientation?
The authors search for invertons in 54,875 bacterial genomes using PhaseFinder and provide the number of invertons per phylum.
These are some interesting findings about invertons in ulcerative colitis patients after Faecal Microbiome Transplantation (FMT):
We observed the influence of the individual on the orientations of invertons in a cohort of patients with ulcerative colitis who were the recipients of FMT from healthy donors.
The main genes regulated by invertons are genes that encode extracellular proteins exposed to the host immune system or genes involved in important adaptive processes as antibiotic resistance:
Our findings highlight the role of invertons in host-microbe coexistence. Genes regulated by invertons were highly enriched for products located on the exterior of the cell where they are exposed to the host immune system and phages, indicating that they may be primary targets for selection that are beneficial for gut commensals to diversify their surface architectures or essential processes, such as antibiotic resistance, whose expression has a high fitness cost
The high prevalence of antibiotic resistance genes regulated by invertons containing promoters suggests that this is an example of bet-hedging. This could lead to longer persistence of antibiotic resistance genes in a microbial community, further increasing the burden to combat antibiotic resistance. Our results indicate that in the human gut, invertons help bacterial populations regain heterogeneity after bottlenecks encountered during colonization of a new host or severe perturbations. Overall, our study provides insights into a mechanism allowing adaptive tradeoffs in bacteria that have evolved to successfully colonize host-associated niches