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

Autor:	Melet M; ISP, Université de Tours, Tours, France., Blanchet S; ISP, Université de Tours, Tours, France., Barbarin P; ISP, Université de Tours, Tours, France., Maunders EA; Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia., Neville SL; Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia., Rong V; ISP, Université de Tours, Tours, France., Mereghetti L; ISP, Université de Tours, Tours, France.; CHRU de Tours, Service de Bactériologie-Virologie Hygiène, Tours, France., McDevitt CA; Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia., Hiron A; ISP, Université de Tours, Tours, France.
Jazyk:	angličtina
Zdroj:	MSphere [mSphere] 2024 Nov 21; Vol. 9 (11), pp. e0061424. Date of Electronic Publication: 2024 Oct 31.
DOI:	10.1128/msphere.00614-24
Abstrakt:	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. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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