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Conserved bacterial de novo guanine biosynthesis pathway enables microbial survival and colonization in the environmental niche of the urinary tract


In bacteria, guaA encodes guanosine monophosphate synthetase that confers an ability to biosynthesize guanine nucleotides de novo. This enables bacterial colonization in different environments and, while guaA is widely distributed among Bacteroidetes and Firmicutes, its contribution to the inhabitation of the human microbiome by commensal bacteria is unclear. We studied Streptococcus as a commensal urogenital tract bacterium and opportunistic pathogen, and explored the role of guaA in bacterial survival and colonization of urine. Analysis of guaA-deficient Streptococcus revealed guanine utilization is essential for bacterial colonization of this niche. The genomic location of guaA in other commensals of the human urogenital tract revealed substantial cross-phyla diversity and organizational structures of guaA that are divergent across phyla. Essentiality of guaA for Streptococcus colonization in the urinary tract establishes that purine biosynthesis is a critical element of the ability of this bacterium to survive and colonize in the host as part of the resident human microbiome.

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Fig. 1: guaA supports S. agalactiae growth in urine and colonization of the mouse bladder.
Fig. 2: Cross-phyla genetic organization and sequence diversity of guaA among commensal bacterial genera of the human urogenital tract microbiota.


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This work was supported by funding from a Griffith University New Researcher Grant (MSC GUNRG 219152; to DSI), the National Health and Medical Research Council (Project Grant APP1146820; to GCU), the Griffith Health Institute and a Future Fellowship from the Australian Research Council (FT110101048; to GCU). The authors thank Harry Sakelaris and James A. Fraser for helpful discussions.

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Correspondence to Glen C. Ulett.

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Ipe, D.S., Sullivan, M.J., Goh, K.G.K. et al. Conserved bacterial de novo guanine biosynthesis pathway enables microbial survival and colonization in the environmental niche of the urinary tract. ISME J 15, 2158–2162 (2021).

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