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01-12-2022 | Streptococci | Research article

Analysis of host-pathogen gene association networks reveals patient-specific response to streptococcal and polymicrobial necrotising soft tissue infections

Authors: Sanjeevan Jahagirdar, Lorna Morris, Nirupama Benis, Oddvar Oppegaard, Mattias Svenson, Ole Hyldegaard, Steinar Skrede, Anna Norrby-Teglund, Vitor A. P. Martins dos Santos, Edoardo Saccenti, INFECT Study group

Published in: BMC Medicine | Issue 1/2022

Abstract

Background

Necrotising soft tissue infections (NSTIs) are rapidly progressing bacterial infections usually caused by either several pathogens in unison (polymicrobial infections) or Streptococcus pyogenes (mono-microbial infection). These infections are rare and are associated with high mortality rates. However, the underlying pathogenic mechanisms in this heterogeneous group remain elusive.

Methods

In this study, we built interactomes at both the population and individual levels consisting of host-pathogen interactions inferred from dual RNA-Seq gene transcriptomic profiles of the biopsies from NSTI patients.

Results

NSTI type-specific responses in the host were uncovered. The S. pyogenes mono-microbial subnetwork was enriched with host genes annotated with involved in cytokine production and regulation of response to stress. The polymicrobial network consisted of several significant associations between different species (S. pyogenes, Porphyromonas asaccharolytica and Escherichia coli) and host genes. The host genes associated with S. pyogenes in this subnetwork were characterised by cellular response to cytokines. We further found several virulence factors including hyaluronan synthase, Sic1, Isp, SagF, SagG, ScfAB-operon, Fba and genes upstream and downstream of EndoS along with bacterial housekeeping genes interacting with the human stress and immune response in various subnetworks between host and pathogen.

Conclusions

At the population level, we found aetiology-dependent responses showing the potential modes of entry and immune evasion strategies employed by S. pyogenes, congruent with general cellular processes such as differentiation and proliferation. After stratifying the patients based on the subject-specific networks to study the patient-specific response, we observed different patient groups with different collagens, cytoskeleton and actin monomers in association with virulence factors, immunogenic proteins and housekeeping genes which we utilised to postulate differing modes of entry and immune evasion for different bacteria in relationship to the patients’ phenotype.

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Title: Analysis of host-pathogen gene association networks reveals patient-specific response to streptococcal and polymicrobial necrotising soft tissue infections
Authors: Sanjeevan Jahagirdar
Lorna Morris
Nirupama Benis
Oddvar Oppegaard
Mattias Svenson
Ole Hyldegaard
Steinar Skrede
Anna Norrby-Teglund
Vitor A. P. Martins dos Santos
Edoardo Saccenti
INFECT Study group
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Streptococci
Soft Tissue Infection
Published in: BMC Medicine / Issue 1/2022
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/s12916-022-02355-8

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Analysis of host-pathogen gene association networks reveals patient-specific response to streptococcal and polymicrobial necrotising soft tissue infections

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

﻿Abstract

Background

Methods

Results

Conclusions

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