TY - JOUR
KW - Antisense RNA
KW - Consortia
KW - Gastrointestinal tract
KW - Gene expression
KW - Shigella
KW - Shigella flexneri
KW - Shigellosis
KW - Virulence Factors
AU - Thibault Frisch
AU - Petra Geiser
AU - Margarita Komi
AU - Philip A. Karlsson
AU - Anjeela Bhetwal
AU - Laura Jenniches
AU - Lars Barquist
AU - Erik Holmqvist
AU - André Mateus
AU - Mikael E. Sellin
AU - Maria Letizia Di Martino
AB - The enteropathogen Shigella flexneri employs a Type Three Secretion System (T3SS) to colonize intestinal epithelial cells. Genes encoding the T3SS are located on a large IncFII virulence plasmid, pINV. T3SS expression comes at the expense of slowed Shigella growth and is therefore strictly controlled by both transcriptional and post-transcriptional mechanisms. Following up on a recent genome-wide screen, we here show that the chromosomal gene pcnB, encoding the poly-A polymerase I (PAP-I), slows Shigella growth at 37°C, while it at the same time promotes early colonization of a human epithelial enteroid model. Proteomic profiling revealed that pcnB drives global increase of the Shigella T3SS virulence program. Accordingly, pcnB upholds pINV replication to a level favourable for Shigella virulence. This is achieved through increased degradation of the antisense RNA CopA, involved in plasmid replication control. The pcnB effect on pINV replication was found to also ensure longer-term intraepithelial expansion of Shigella following human intestinal epithelium invasion. Our findings exemplify how an adequate pINV level, sustained by pcnB, underpins the successful execution of Shigella´s infection cycle.
BT - PLOS Pathogens
DA - Nov 20, 2025
DO - 10.1371/journal.ppat.1013727
IS - 11
LA - en
N2 - The enteropathogen Shigella flexneri employs a Type Three Secretion System (T3SS) to colonize intestinal epithelial cells. Genes encoding the T3SS are located on a large IncFII virulence plasmid, pINV. T3SS expression comes at the expense of slowed Shigella growth and is therefore strictly controlled by both transcriptional and post-transcriptional mechanisms. Following up on a recent genome-wide screen, we here show that the chromosomal gene pcnB, encoding the poly-A polymerase I (PAP-I), slows Shigella growth at 37°C, while it at the same time promotes early colonization of a human epithelial enteroid model. Proteomic profiling revealed that pcnB drives global increase of the Shigella T3SS virulence program. Accordingly, pcnB upholds pINV replication to a level favourable for Shigella virulence. This is achieved through increased degradation of the antisense RNA CopA, involved in plasmid replication control. The pcnB effect on pINV replication was found to also ensure longer-term intraepithelial expansion of Shigella following human intestinal epithelium invasion. Our findings exemplify how an adequate pINV level, sustained by pcnB, underpins the successful execution of Shigella´s infection cycle.
PY - 0
EP - e1013727
T2 - PLOS Pathogens
TI - The pcnB gene sustains Shigella flexneri virulence
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013727
VL - 21
Y2 - 2026-04-06
SN - 1553-7374
ER -