Single Cell Stochastic Regulation of Pilus Phase Variation by an Attenuation-like Mechanism
Abstract
The molecular triggers leading to virulence of a number of human-adapted commensal bacteria such as
Streptococcus
gallolyticus
are largely unknown. This opportunistic pathogen is responsible for endocarditis in the elderly and associated
with colorectal cancer. Colonization of damaged host tissues with exposed collagen, such as cardiac valves and pre-
cancerous polyps, is mediated by appendages referred to as Pil1 pili. Populations of
S. gallolyticus
are heterogeneous
with the majority of cells weakly piliated while a smaller fraction is hyper piliated. We provide genetic evidences
that heterogeneous
pil1
expression depends on a phase variation mechanism involving addition/deletion of GCAGA
repeats that modifies the length of an upstream leader peptide. Synthesis of longer leader peptides potentiates
the transcription of the
pil1
genes through ribosome-induced destabilization of a premature stem-loop transcription
terminator. This study describes, at the molecular level, a new regulatory mechanism combining phase variation in a leader
peptide-encoding gene and transcription attenuation. This simple and robust mechanism controls a stochastic
heterogeneous pilus expression, which is important for evading the host immune system while ensuring optimal tissue
colonization.
Domains
Bacteriology
Origin : Publication funded by an institution
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