Journal Article

Adaptation to zinc restriction in Streptococcus agalactiae : role of the ribosomal protein and zinc-importers regulated by AdcR

Barbarin, P, Infectiologie et Santé Publique (ISP) ; Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Morgane Melet was supported by a doctoral fellowship of the Region Centre (France). This work was supported by the Australian Research Council (ARC) grant DP220100713 and the National Health and Medical Research Council (NHMRC) grant 2010400 to C.A.M, Melet, Morgane, Rong, V, The Peter Doherty Institute for Infection and Immunity [Melbourne] ; University of Melbourne-The Royal Melbourne Hospital, Service de Bactériologie-Virologie-Hygiène [Tours] ; Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Blanchet, S, Neville, S., L, Mcdevitt, C., A, Mereghetti, Laurent, Hiron, Aurélia, Maunders, E., A

2024

Overview

Zinc (Zn) is an essential cofactor for numerous bacterial proteins and altering Zn availability is an important component of host innate immunity. During infection, adaptation to both Zn deprivation and excess is critical for pathogenic bacteria development. To understand the adaptive responses to Zn availability of Streptococcus agalactiae , a pathogen causing invasive infections of neonates, global transcriptional profiling was conducted. Results highlight that in response to Zn limitation, genes belonging to the AdcR regulon, the master regulator of Zn homeostasis in streptococci, were overexpressed. Through a combination of in silico analysis and experimental validation, new AdcR-regulated targets were identified. Among them, we identified a duplicated ribosomal protein, RpsNb, and an ABC transporter, and examined the role of these genes in bacterial growth under Zn-restricted conditions. Our results indicated that, during Zn restriction, both the RpsNb protein and a potential secondary Zn transporter are important for S. agalactiae adaptation to Zn deficiency. IMPORTANCE Streptococcus agalactiae is a bacterial human pathobiont causing invasive diseases in neonates. Upon infection, S. agalactiae is presented with Zn limitation and excess but the genetic systems that allow bacterial adaptation to these conditions remain largely undefined. A comprehensive analysis of S. agalactiae global transcriptional response to Zn availability shows that this pathogen manages Zn limitation mainly through upregulation of the AdcR regulon. We demonstrate that several AdcR-regulated genes are important for bacterial growth during Zn deficiency, including human biological fluids. Taken together, these findings reveal new mechanisms of S. agalactiae adaptation under conditions of metal deprivation.

• Publisher: American Society for Microbiology,CCSD
• ISBN: 0013462039000