The pks island: a bacterial Swiss army knife? Colibactin: beyond DNA damage and cancer

Chagneau, Camille V.; Payros, Delphine; Tang-Fichaux, Min; Auvray, Frédéric; Nougayrède, Jean-Philippe; Oswald, Éric

doi:10.1016/j.tim.2022.05.010

Cited by 13 publications

(10 citation statements)

References 75 publications

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“…Colibactin belongs to the family of hybrid polyketide/nonribosomal peptide. It is synthesized by a large nonribosomal peptide–polyketide synthetase machinery, encoded by a 54-kb gene cluster, the pks genomic island ( 54 , 55 ). Although the direct target of Hsp90 in this biosynthetic pathway is not known, it has been shown that pks+ E. coli strains devoid of Hsp90 Ec do not produce colibactin ( 22 ).…”

Section: Resultsmentioning

confidence: 99%

Uncoupling the Hsp90 and DnaK chaperone activities revealed the in vivo relevance of their collaboration in bacteria

Corteggiani

Bossuet-Greif

Nougayrède

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Chaperone proteins are essential in all living cells to ensure protein homeostasis. Hsp90 is a major adenosine triphosphate (ATP)-dependent chaperone highly conserved from bacteria to eukaryotes. Recent studies have shown that bacterial Hsp90 is essential in some bacteria in stress conditions and that it participates in the virulence of pathogenic bacteria. In vitro, bacterial Hsp90 directly interacts and collaborates with the Hsp70 chaperone DnaK to reactivate model substrate proteins; however, it is still unknown whether this collaboration is relevant in vivo with physiological substrates. Here, we used site-directed mutagenesis on Hsp90 to impair DnaK binding, thereby uncoupling the chaperone activities. We tested the mutants in vivo in two bacterial models in which Hsp90 has known physiological functions. We found that the Hsp90 point mutants were defective to support (1) growth under heat stress and activation of an essential Hsp90 client in the aquatic bacterium Shewanella oneidensis and (2) biosynthesis of the colibactin toxin involved in the virulence of pathogenic Escherichia coli . Our study therefore demonstrates the essentiality of the direct collaboration between Hsp90 and DnaK in vivo in bacteria to support client folding. It also suggests that this collaboration already functional in bacteria has served as an evolutionary basis for a more complex Hsp70–Hsp90 collaboration found in eukaryotes.

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Section: Resultsmentioning

confidence: 99%

Uncoupling the Hsp90 and DnaK chaperone activities revealed the in vivo relevance of their collaboration in bacteria

Corteggiani

Bossuet-Greif

Nougayrède

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…The predominant polyamines in bacterial cells include putrescine, spermidine, and cadaverine, and these molecules may be synthesised by the bacteria de novo or scavenged from the surrounding environment [94]. Spermidine is particularly abundant in cancer tissues, as well as in the gut where it is amply produced by intestinal microbiota [36,93,95]. It has been shown that spermidine is involved in colibactin production, and that limited availability of this polyamine results in reduced colibactin synthesis and decreased pks+ E. coli genotoxicity [93].…”

Section: Spermidinementioning

confidence: 99%

Current understandings of colibactin regulation

Addington,

Sandalli,

Roe

2024

Microbiology

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“… 11 Among these, a significant fraction of Enterobacteriaceae, extraintestinal, and commensal Escherichia coli strains have been described to harbor the pks island, which encodes for several enzymes participating in the synthesis of the genotoxin colibactin. 12 …”

Section: Introductionmentioning

confidence: 99%

Tolerance to colibactin correlates with homologous recombination proficiency and resistance to irinotecan in colorectal cancer cells

Sogari,

Rovera,

Grasso

et al. 2024

Cell Reports Medicine

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The pks island: a bacterial Swiss army knife? Colibactin: beyond DNA damage and cancer

Cited by 13 publications

References 75 publications

Uncoupling the Hsp90 and DnaK chaperone activities revealed the in vivo relevance of their collaboration in bacteria

Uncoupling the Hsp90 and DnaK chaperone activities revealed the in vivo relevance of their collaboration in bacteria

Current understandings of colibactin regulation

Tolerance to colibactin correlates with homologous recombination proficiency and resistance to irinotecan in colorectal cancer cells

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