We are proud to announce the result of a collaborative effort of the PerMIT consortium (supported by the ERA PerMed) on applying a personalised medicine approach to necrotising soft tissue infections.
Lorna Morris, senior researcher at LifeGlimmer, played a leading role in designing and executing this interdisciplinary study.
Read the full abstract here:
Jahagirdar, Sanjeevan, Lorna Morris, Nirupama Benis, Oddvar Oppegaard, Mattias Svenson, Ole Hyldegaard, Steinar Skrede, Anna Norrby-Teglund, Vitor AP Martins dos Santos, and Edoardo Saccenti. "Analysis of host-pathogen gene association networks reveals patient-specific response to streptococcal and polymicrobial necrotising soft tissue infections." BMC medicine 20, no. 1 (2022): 1-18.
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 mecha‑
nisms in this heterogeneous group remain elusive. Methods: In this study, we built interactomes at both the population and individual levels consisting of host-patho‑
gen interactions inferred from dual RNA-Seq gene transcriptomic profles of the biopsies from NSTI patients. Results: NSTI type-specifc 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 signifcant associations between diferent 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 diferentiation and proliferation. After stratifying the patients based on the subject-specifc networks to study the patient-specifc response, we observed diferent patient groups with diferent collagens, cytoskeleton and actin monomers in association with virulence factors, immunogenic proteins and housekeeping genes which we utilised to postulate difering modes of entry and immune evasion for diferent bacteria in relationship to the patients’ phenotype.