Defining Host Responses during Systemic Bacterial Infection through Construction of a Murine Organ Proteome Atlas

Abstract

Group A Streptococcus (GAS) remains one of the top 10 deadliest human pathogens worldwide despite its sensitivity to penicillin. Although the most common GAS infection is pharyngitis (strep throat), it also causes life-threatening systemic infections. A series of complex networks between host and pathogen drive invasive infections, which have not been comprehensively mapped. Attempting to map these interactions, we examined organ-level protein dynamics using a mouse model of systemic GAS infection. We quantified over 11,000 proteins, defining organ-specific markers for all analyzed tissues. From this analysis, an atlas of dynamically regulated proteins and pathways was constructed. Through statistical methods, we narrowed organ-specific markers of infection to 34 from the defined atlas. We show these markers are trackable in blood of infected mice, and a subset has been observed in plasma samples from GAS-infected clinical patients. This proteomics-based strategy provides insight into host defense responses, establishes potentially useful targets for therapeutic intervention, and presents biomarkers for determining affected organs during bacterial infection.

Deciphering cell–cell interactions and communication from gene expression

“…For example, a study mapped the interaction between inclusion membrane proteins secreted by Chlamydia trachomatis and cognate human proteins 145 , providing insights into the host machinery this pathogen uses to establish the intracellular niche needed for infection. Thus, even small-scale lists of interacting partners between the host and a single microorganism, instead of the whole microbiota, will open great opportunities to use CCC methods to understand infections and diseases on the basis of host–pathogen interactions 151 , 152 . Although this endeavour will require validation of putative interactions, as done for human–virus protein interactions 153 – 156 , results from such studies will have a considerable impact on biomedicine and microbiome fields.…”

Exposure of Mycobacterium abscessus to Environmental Stress and Clinically Used Antibiotics Reveals Common Proteome Response among Pathogenic Mycobacteria

“…Quantitative mass spectrometry analysis of sample lysates was performed using previously described methods [19][20][21]. Briefly, samples were subjected to probe sonication-assisted lysis in 4M urea with 50 mM HEPES, pH = 8.5 and 3% SDS lysis buffer.…”

Organ-level protein networks as a reference for the host effects of the microbiome

“…All organ proteome methods were performed as previously described (Lapek et al 2018). Snap-frozen organs (stored at −80°C beforehand) were suspended in PBS and homogenized using a Mini BeadBeater (Biospec).…”