A bacterial pan-genome makes gene essentiality strain-dependent and evolvable

Rosconi, F.; Rudmann, E.; Li, J.; Surujon, D.; Anthony, J.; Frank, M.; Jones, D. S.; Rock, C.; Rosch, J. W.; Johnston, C. D.; van Opijnen, T.

doi:10.1101/2022.02.08.479609

bioRxiv · 10.1101/2022.02.08.479609

A bacterial pan-genome makes gene essentiality strain-dependent and evolvable

Rosconi, F.·Rudmann, E.·Li, J.·Surujon, D.·Anthony, J.·Frank, M.·Jones, D. S.·Rock, C.·Rosch, J. W.·Johnston, C. D.·van Opijnen, T.

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Abstract

Many bacterial species are represented by a pan-genome, whose genetic repertoire far outstrips that of any single bacterial genome. Here we investigate how a bacterial pan-genome might influence gene essentiality, and whether essential genes that are initially critical for the survival of an organism can evolve to become non-essential. By using Tn-Seq, whole-genome sequencing, and RNA-Seq on a set of 36 clinical Streptococcus pneumoniae strains representative of >68% of the species pan-genome, we identify a species-wide essentialome that can be subdivided into universal, strain-specific and accessory essential genes. By employing forced-evolution experiments we show that specific genetic changes allow bacteria to bypass essentiality. Moreover, by untangling several genetic mechanisms we show that gene-essentiality can be highly influenced and/or dependent on: 1) the composition of the accessory genome; 2) the accumulation of toxic intermediates; 3) functional redundancy; 4) efficient recycling of critical metabolites; and 5) pathway rewiring. While this functional characterization underscores the evolvability-potential of many essential genes, we also show that genes with differential essentiality remain important antimicrobial drug target candidates, as their inactivation almost always has a severe fitness cost in vivo.

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Rosconi, F., Rudmann, E., Li, J., Surujon, D., Anthony, J., Frank, M., Jones, D. S., Rock, C., Rosch, J. W., Johnston, C. D., van Opijnen, T.. 2022-02-09. A bacterial pan-genome makes gene essentiality strain-dependent and evolvable. https://doi.org/10.1101/2022.02.08.479609

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