Serum profiling of leptospirosis patients to investigate proteomic alterations

Abstract

Leptospirosis is a zoonotic infectious disease of tropical, subtropical and temperate zones, which is caused by the pathogenic spirochetes of genus Leptospira. Although this zoonosis is generally not considered as fatal, the pathogen can eventually cause severe infection with septic shock, multi-organ failure and lethal pulmonary hemorrhages leading to mortality. In this study, we have performed a proteomic analysis of serum samples from leptospirosis patients (n=6), febrile controls (falciparum malaria) (n=8) and healthy subjects (n=18) to obtain an insight about disease pathogenesis and host immune responses in leptospiral infections. 2DE and 2D-DIGE analysis in combination with MALDI-TOF/TOF MS revealed differential expression of 22 serum proteins in leptospirosis patients compared to the healthy controls. Among the identified differentially expressed proteins, 8 candidates exhibited different trends compared to the febrile controls. Functional analysis suggested the involvement of differentially expressed proteins in vital physiological pathways, including acute phase response, complement and coagulation cascades and hemostasis. This is the first report of analysis of human serum proteome alterations in leptospirosis patients, which revealed several differentially expressed proteins, including α-1-antitrypsin, vitronectin, ceruloplasmin, G-protein signaling regulator, apolipoprotein A-IV, which have not been reported in context of leptospirosis previously. This study will enhance our understanding about leptospirosis pathogenesis and provide a glimpse of host immunological responses. Additionally, a few differentially expressed proteins identified in this study may further be investigated as diagnostic or prognostic serum biomarkers for leptospirosis. This article is part of a Special Issue entitled: Integrated omics.

Leptospiral LruA Is Required for Virulence and Modulates an Interaction with Mammalian Apolipoprotein AI

“…Moreover, a recent study showed that levels of ApoA-I precursor were reduced up to 3-fold in the sera of human leptospirosis patients (45). All of these findings are consistent with our in vitro results suggesting that binding of ApoA-I to leptospires may be the cause of reduced circulating HDL.…”

Comparative proteomics of inhaled silver nanoparticles in healthy and allergen provoked mice

“…The tryptic peptides were analyzed with a Q Exactive mass spectrometer (Thermo Fisher Scientific) coupled with a Dionex UltiMate ® 3000 Rapid Separation LC system (Thermo Fisher Scientific 20,21 The UniProt accession database was used to access the 19 overlapping BALF proteins (between Group 1 vs Group 3 and Group 2 vs Group 4) identified in this study. These proteins were uploaded and mapped against the Mus musculus reference dataset to extract and summarize the functional annotation associated with individual genes/proteins or groups of genes/proteins and to identify the gene ontology terms, biological processes, functional classification, and important pathways for each dataset.…”

Proteomic analysis of Plasmodium falciparum induced alterations in humans from different endemic regions of India to decipher malaria pathogenesis and identify surrogate markers of severity

“…other clinically related illnesses. To this end, in our earlier reports, we have demonstrated that a panel of serum/plasma proteins consisting of six candidates (serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein 4 and apolipoprotein A-I) can distinguish malaria from the other infectious diseases with overlapping clinical manifestations (dengue fever and leptospirosis)[13,40,41].…”