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Updated: Sep 24, 2025
A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
Published on: February 19, 2019
Analysis of host-pathogen gene association networks reveals patient-specific response to streptococcal and
Sanjeevan Jahagirdar1, Lorna Morris2, Nirupama Benis1,3
1Laboratory of Systems and Synthetic Biology, Wageningen University & Research, Stippeneng 4, 6708, WE, Wageningen, the Netherlands.
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.
Insights
Necrotising soft tissue infections (NSTIs) involve complex host-pathogen interactions. This study reveals distinct bacterial and host responses in monomicrobial versus polymicrobial NSTIs, highlighting patient-specific mechanisms.
Area of Science:
- Microbiology
- Immunology
- Genomics
Background:
- Necrotising soft tissue infections (NSTIs) are severe bacterial infections with high mortality.
- Pathogenic mechanisms in NSTIs, whether monomicrobial (e.g., Streptococcus pyogenes) or polymicrobial, remain poorly understood.
- Understanding host-pathogen interactions is crucial for developing effective treatments.
Purpose of the Study:
- To elucidate the underlying pathogenic mechanisms of NSTIs.
- To build host-pathogen interactomes at population and individual levels.
- To identify aetiology-dependent and patient-specific responses in NSTIs.
Main Methods:
- Dual RNA-Seq transcriptomic profiling of patient biopsies.
- Construction of host-pathogen interaction networks at population and individual levels.
- Analysis of gene expression patterns to infer pathogenic mechanisms and host responses.
Main Results:
- Distinct host responses were identified for monomicrobial (S. pyogenes) and polymicrobial NSTIs.
- The S. pyogenes subnetwork showed enrichment in cytokine production and stress response genes.
- Polymicrobial networks revealed interactions between multiple bacterial species and host genes involved in immune responses.
- Specific virulence factors and bacterial housekeeping genes were found to interact with host stress and immune pathways.
Conclusions:
- Host responses to NSTIs are dependent on the causative aetiology (monomicrobial vs. polymicrobial).
- Patient-specific networks revealed variations in host factors (collagens, cytoskeleton) interacting with bacterial virulence factors.
- These findings suggest differing bacterial entry and immune evasion strategies tailored to individual patient phenotypes.
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