Current understandings of colibactin regulation

Addington, Emily; Sandalli, Sofia; Roe, Andrew J.

doi:10.1099/mic.0.001427

Cited by 2 publications

(2 citation statements)

References 103 publications

(223 reference statements)

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“…ClbA Phosphopantetheinyl transferase for activation of megasynthases [93] ClbB Biosynthesis of NRPS/pks hybrids [94] ClbC Biosynthesis of pks [94] ClbD Hydroxyl-acyl-CoA dehydrogenase [95] ClbE Freestanding acyl carrier protein (ACP) [95] ClbF α β dehydrogenase (αβdhg) [96] ClbG Acyltransferase (AT) [96] ClbH Cyclopropane-formatting synthetase [92] ClbI Cyclopropane-formatting synthetase [92] ClbJ Biosynthesis of NRPS [96] ClbK Biosynthesis of NRPS/pks hybrids [94] ClbL Amidase (role not fully known) [96] ClbM Efflux pump for exporting pre-colibactin [94] ClbN Initiates synthesis using asparagine to generate the prodrug motif N-myristoyl-d-asparagine (NMDA) [92] ClbO Final enzymatic module of the assembly line and completes the extension stage of the pre-colibactin skeleton [92] ClbP Periplasmic peptidase associated with bacterial cytoplasmic membrane [96] ClbQ Thioesterase (TE) [96] ClbR LuxR-type transcriptional activator [92] ClbS Protects colibactin-producing bacterium from genotoxic effects [96] The pks enzyme would participate in the maturation of the compound in the periplasmic compartment [96].…”

Section: Gene Name Function Referencesmentioning

confidence: 99%

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Contribution of pks+ Escherichia coli (E. coli) to Colon Carcinogenesis

Sadeghi,

Mestivier,

Sobhani

2024

Microorganisms

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Colorectal cancer (CRC) stands as a significant global health concern, ranking second in mortality and third in frequency among cancers worldwide. While only a small fraction of CRC cases can be attributed to inherited genetic mutations, the majority arise sporadically due to somatic mutations. Emerging evidence reveals gut microbiota dysbiosis to be a contributing factor, wherein polyketide synthase-positive Escherichia coli (pks+ E. coli) plays a pivotal role in CRC pathogenesis. pks+ bacteria produce colibactin, a genotoxic protein that causes deleterious effects on DNA within host colonocytes. In this review, we examine the role of the gut microbiota in colon carcinogenesis, elucidating how colibactin-producer bacteria induce DNA damage, promote genomic instability, disrupt the gut epithelial barrier, induce mucosal inflammation, modulate host immune responses, and influence cell cycle dynamics. Collectively, these actions foster a microenvironment conducive to tumor initiation and progression. Understanding the mechanisms underlying pks+ bacteria-mediated CRC development may pave the way for mass screening, early detection of tumors, and therapeutic strategies such as microbiota modulation, bacteria-targeted therapy, checkpoint inhibition of colibactin production and immunomodulatory pathways.

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Section: Gene Name Function Referencesmentioning

confidence: 99%

“…The pks genomic island includes 19 genes that code for the complex enzymatic machinery responsible for the synthesis of colibactin ( Table 3 , Figure 2 ). It includes 54 kb of a chromosomal region located in the asnW tRNA locus, a site of DNA insertion and exchange [ 36 , 92 ].…”

Section: Role Of E Coli In Crc Developmentmentioning

confidence: 99%