The Two-Component System YesMN Promotes Pneumococcal Host-to-Host Transmission and Regulates Genes Involved in Zinc Homeostasis

Zafar, M. Ammar; Costa-Terryl, Alicia; Young, Taylor M

doi:10.1128/iai.00375-22

Cited by 1 publication

(1 citation statement)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While some studies have effectively used phosphomimetics ( 63 ), it is noteworthy that that while phosphorylation typically promotes subunit oligomerization and DNA binding, exceptions do exist ( 64 ). Our experience has shown that overexpressing native RRs in conjunction with RNA-sequencing reliably identifies RR targets; findings later confirmed by other studies ( 47 , 65 ). Consequently, the same methodology was adopted for this study.…”

Section: Discussionsupporting

confidence: 84%

A comprehensive analysis of pneumococcal two-component system regulatory networks

Pettersen,

Nielsen,

Andreassen

et al. 2024

NAR Genomics and Bioinformatics

View full text Add to dashboard Cite

Two-component systems are key signal-transduction systems that enable bacteria to respond to a wide variety of environmental stimuli. The human pathogen, Streptococcus pneumoniae (pneumococcus) encodes 13 two-component systems and a single orphan response regulator, most of which are significant for pneumococcal pathogenicity. Mapping the regulatory networks governed by these systems is key to understand pneumococcal host adaptation. Here we employ a novel bioinformatic approach to predict the regulons of each two-component system based on publicly available whole-genome sequencing data. By employing pangenome-wide association studies (panGWAS) to predict genotype-genotype associations for each two-component system, we predicted regulon genes of 11 of the pneumococcal two-component systems. Through validation via next-generation RNA-sequencing on response regulator overexpression mutants, several top candidate genes predicted by the panGWAS analysis were confirmed as regulon genes. The present study presents novel details on multiple pneumococcal two-component systems, including an expansion of regulons, identification of candidate response regulator binding motifs, and identification of candidate response regulator-regulated small non-coding RNAs. We also demonstrate a use for panGWAS as a complementary tool in target gene identification via identification of genotype-to-genotype links. Expanding our knowledge on two-component systems in pathogens is crucial to understanding how these bacteria sense and respond to their host environment, which could prove useful in future drug development.

show abstract