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CodY Is a Global Transcriptional Regulator Required for Virulence in Group B Streptococcus

Authors :
Angelica Pellegrini
Germana Lentini
Agata Famà
Andrea Bonacorsi
Viola Camilla Scoffone
Silvia Buroni
Gabriele Trespidi
Umberto Postiglione
Davide Sassera
Federico Manai
Giampiero Pietrocola
Arnaud Firon
Carmelo Biondo
Giuseppe Teti
Concetta Beninati
Giulia Barbieri
Source :
Frontiers in Microbiology, Vol 13 (2022)
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

Abstract

Group B Streptococcus (GBS) is a Gram-positive bacterium able to switch from a harmless commensal of healthy adults to a pathogen responsible for invasive infections in neonates. The signals and regulatory mechanisms governing this transition are still largely unknown. CodY is a highly conserved global transcriptional regulator that links nutrient availability to the regulation of major metabolic and virulence pathways in low-G+C Gram-positive bacteria. In this work, we investigated the role of CodY in BM110, a GBS strain representative of a hypervirulent lineage associated with the majority of neonatal meningitis. Deletion of codY resulted in a reduced ability of the mutant strain to cause infections in neonatal and adult animal models. The observed decreased in vivo lethality was associated with an impaired ability of the mutant to persist in the blood, spread to distant organs, and cross the blood-brain barrier. Notably, the codY null mutant showed reduced adhesion to monolayers of human epithelial cells in vitro and an increased ability to form biofilms, a phenotype associated with strains able to asymptomatically colonize the host. RNA-seq analysis showed that CodY controls about 13% of the genome of GBS, acting mainly as a repressor of genes involved in amino acid transport and metabolism and encoding surface anchored proteins, including the virulence factor Srr2. CodY activity was shown to be dependent on the availability of branched-chain amino acids, which are the universal cofactors of this regulator. These results highlight a key role for CodY in the control of GBS virulence.

Details

Language :
English
ISSN :
1664302X
Volume :
13
Database :
Directory of Open Access Journals
Journal :
Frontiers in Microbiology
Publication Type :
Academic Journal
Accession number :
edsdoj.2a565a165b3740278e49914fb859bab9
Document Type :
article
Full Text :
https://doi.org/10.3389/fmicb.2022.881549