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Dual RNA sequencing of group B Streptococcus-infected human monocytes reveals new insights into host–pathogen interactions and bacterial evasion of phagocytosis

Authors :
Matthew J. Sullivan
Darren Prince
Kelvin G. K. Goh
Lahiru Katupitiya
Dean Gosling
Michael R. Crowley
David K. Crossman
Glen C. Ulett
Source :
Scientific Reports, Vol 13, Iss 1, Pp 1-16 (2023)
Publication Year :
2023
Publisher :
Nature Portfolio, 2023.

Abstract

Abstract Streptococcus agalactiae, also known as Group B Streptococcus (GBS) is a frequent cause of infections, including bacteraemia and other acute diseases in adults and immunocompromised individuals. We developed a novel system to study GBS within human monocytes to define the co-transcriptome of intracellular GBS (iGBS) and host cells simultaneously using dual RNA-sequencing (RNA-seq) to better define how this pathogen responds to host cells. Using human U937 monocytes and genome-sequenced GBS reference strain 874,391 in antibiotic protection assays we validated a system for dual-RNA seq based on measures of GBS and monocyte viability to ensure that the bacterial and host cell co-transcriptome reflected mainly intracellular (iGBS) rather than extracellular GBS. Elucidation of the co-transcriptome revealed 1119 dysregulated transcripts in iGBS with most genes, including several that encode virulence factors (e.g., scpB, hvgA, ribD, pil2b) exhibiting activation by upregulated expression. Infection with iGBS resulted in significant remodelling of the monocyte transcriptome, with 7587 transcripts differentially expressed including 7040 up-regulated and 547 down-regulated. qPCR confirmed that the most strongly activated genes included sht, encoding Streptococcal Histidine Triad Protein. An isogenic GBS mutant strain deficient in sht revealed a significant effect of this gene on phagocytosis of GBS and survival of the bacteria during systemic infection in mice. Identification of a novel contribution of sht to GBS virulence shows the co-transcriptome responses elucidated in GBS-infected monocytes help to shape the host–pathogen interaction and establish a role for sht in the response of the bacteria to phagocytic uptake. This study provides comprehension of concurrent transcriptional responses that occur in GBS and human monocytes that shape the host–pathogen interaction.

Subjects

Subjects :
Medicine
Science

Details

Language :
English
ISSN :
20452322
Volume :
13
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Scientific Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.ba104a9df20644099df98bfad98b3b28
Document Type :
article
Full Text :
https://doi.org/10.1038/s41598-023-28117-x