Metabolic and genetic basis for auxotrophies in Gram-negative species

Proceedings of the National Academy of Sciences of the United States of America
Yara SeifBernhard Ø Palsson

Abstract

Auxotrophies constrain the interactions of bacteria with their environment, but are often difficult to identify. Here, we develop an algorithm (AuxoFind) using genome-scale metabolic reconstruction to predict auxotrophies and apply it to a series of available genome sequences of over 1,300 Gram-negative strains. We identify 54 auxotrophs, along with the corresponding metabolic and genetic basis, using a pangenome approach, and highlight auxotrophies conferring a fitness advantage in vivo. We show that the metabolic basis of auxotrophy is species-dependent and varies with 1) pathway structure, 2) enzyme promiscuity, and 3) network redundancy. Various levels of complexity constitute the genetic basis, including 1) deleterious single-nucleotide polymorphisms (SNPs), in-frame indels, and deletions; 2) single/multigene deletion; and 3) movement of mobile genetic elements (including prophages) combined with genomic rearrangements. Fourteen out of 19 predictions agree with experimental evidence, with the remaining cases highlighting shortcomings of sequencing, assembly, annotation, and reconstruction that prevent predictions of auxotrophies. We thus develop a framework to identify the metabolic and genetic basis for auxotrophies in Gr...Continue Reading

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Citations

Jun 25, 2020·MSystems·Morgan N PriceAdam P Arkin
Jun 11, 2020·FEMS Microbiology Ecology·Winifred M JohnsonHeidi Smith
Feb 10, 2021·Current Opinion in Biotechnology·Livia S ZaramelaKarsten Zengler
Feb 10, 2021·Journal of Cell Science·Lena Pernas
Feb 20, 2021·Genome Biology·David B BernsteinDaniel Segrè
Jun 22, 2021·Frontiers in Microbiology·Lacey R LopezJanelle C Arthur
Nov 5, 2021·The ISME Journal·Dasith PereraMatthew Ramsey

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Methods Mentioned

BETA
insertion-site sequencing
PCR

Software Mentioned

PHAge Search Tool ( PHAST )
TRADIS
BLASTn
rapid multi - alignment ( ParSNP )
Basic nucleotide Local Alignment Search Tool ( BLASTn )
BiGG
AuxoFind
PATRIC

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