Salmonella invasion is controlled through the secondary structure of the hilD transcript

Autor: Staci L. Nugent, Paulina D. Pavinski Bitar, Elaine M. Handley, Chien Che Hung, Colleen R. Eade, Michael I. Betteken, Rimi Chowdhury, Craig Altier
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Bacterial Diseases
Salmonella typhimurium
Transcription
Genetic
RNA Stability
Regulator
Gene Expression
Pathology and Laboratory Medicine
Biochemistry
Mice
Salmonella
Medicine and Health Sciences
Biology (General)
Regulation of gene expression
0303 health sciences
education.field_of_study
Mice
Inbred BALB C
Virulence
Messenger RNA
030302 biochemistry & molecular biology
Cell biology
Bacterial Pathogens
Nucleic acids
RNA
Bacterial
Infectious Diseases
Medical Microbiology
Salmonella Infections
Female
Pathogens
Anatomy
Research Article
QH301-705.5
Virulence Factors
Immunology
Population
DNA transcription
Biology
Microbiology
Bacterial genetics
03 medical and health sciences
Enterobacteriaceae
Bacterial Proteins
Gene Types
Virology
Genetics
Point Mutation
Animals
Secretion
RNA
Messenger
education
Molecular Biology
Gene
Psychological repression
Microbial Pathogens
030304 developmental biology
Bacteria
Base Sequence
Organisms
Biology and Life Sciences
Gene Expression Regulation
Bacterial
RC581-607
Gastrointestinal Tract
Mutation
Regulator Genes
RNA
Nucleic Acid Conformation
Parasitology
Immunologic diseases. Allergy
Digestive System
Transcription Factors
Zdroj: PLoS Pathogens
PLoS Pathogens, Vol 15, Iss 4, p e1007700 (2019)
ISSN: 1553-7374
1553-7366
Popis: Virulence functions of bacterial pathogens are often energetically costly and thus are subjected to intricate regulatory mechanisms. In Salmonella, invasion of the intestinal epithelium, an essential early step in virulence, requires the production of a multi-protein type III secretion apparatus. The pathogen mitigates the overall cost of invasion by inducing it in only a fraction of its population. This constitutes a successful virulence strategy as invasion by a small number is sufficient to promote the proliferation of the non-invading majority. Such a system suggests the existence of a sensitive triggering mechanism that permits only a minority of Salmonella to reach a threshold of invasion-gene induction. We show here that the secondary structure of the invasion regulator hilD message provides such a trigger. The 5’ end of the hilD mRNA is predicted to contain two mutually exclusive stem-loop structures, the first of which (SL1) overlaps the ribosome-binding site and the ORF start codon. Changes that reduce its stability enhance invasion gene expression, while those that increase stability reduce invasion. Conversely, disrupting the second stem-loop (SL2) represses invasion genes. Although SL2 is the energetically more favorable, repression through SL1 is enhanced by binding of the global regulator CsrA. This system thus alters the levels of hilD mRNA and is so sensitive that changing a single base pair within SL1, predicted to augment its stability, eliminates expression of invasion genes and significantly reduces Salmonella virulence in mice. This system thus provides a possible means to rapidly and finely tune an essential virulence function.
Author summary Pathogenic bacteria tightly regulate the expression of their virulence functions to balance survival and proliferation within an animal host against the fitness costs that these functions engender. Salmonella has evolved an energetically favorable means to invade the intestinal epithelium, required for its virulence, with only a small proportion of its population expressing the needed genes, while the remainder reaps the benefits. This work shows that the threshold of invasion induction is finely controlled through the message secondary structure of the activator hilD in conjunction with the invasion repressor CsrA. This sensitive system may thus allow Salmonella rapidly to adjust the dynamics of its invading population in response to signals within the animal.
Databáze: OpenAIRE
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