Comparative proteomic analysis of lung tissue from guinea pigs with Leptospiral Pulmonary Haemorrhage Syndrome (LPHS) reveals a decrease in abundance of host proteins involved in cytoskeletal and cellular organization

Authors: SCHULLER, S - University College Dublin; SERGEANT, K - Centre De Recherche Public - Gabriel Lippmann; RENAUT, J - Centre De Recherche Public - Gabriel Lippmann; CALLANAN, J - University College Dublin; SCAIFE, C - University College Dublin; Nally, Jarlath

Submitted to: Journal of Proteomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/8/2015
Publication Date: 6/3/2015
Citation: Schuller, S., Sergeant, K., Renaut, J., Callanan, J.J., Scaife, C., Nally, J.E. 2015. Comparative proteomic analysis of lung tissue from guinea pigs with Leptospiral Pulmonary Haemorrhage Syndrome (LPHS) reveals a decrease in abundance of host proteins involved in cytoskeletal and cellular organization. Journal of Proteomics. 122:55-72. DOI: 10.1016/j.jprot.2015.03.021.

Interpretive Summary: Leptospiral pulmonary hemorrhage syndrome (LPHS) is a severe form of acute leptospirosis which is increasingly recognized in both humans and animals. Patients with LPHS develop pulmonary hemorrhage which is associated with high mortality rates. The pathogenic mechanisms of LPHS are not understood and likely multifactorial in that host, as well as pathogen-related factors, play a role. In order to further understand mechanisms of LPHS, which in turn will facilitate the development of effective treatment strategies, the protein content of infected lung tissue was compared to that of non-infected lung tissue. Results indicate that during LPHS, there is an increased abundance of acute phase proteins whilst there is a concomitant decrease in proteins involved in cell structure. These results highlight the role of the host response to infection and indicate that the observed hemorrhage is facilitated in part by a breakdown in cell wall structure.

Technical Abstract: The recent completion of the complete genome sequence of the guinea pig (Cavia porcellus) provides innovative opportunities to apply proteomic technologies to an important animal model of disease. In this study, a 2-D guinea pig proteome lung map was used to investigate the pathogenic mechanisms of a particularly severe form of leptospirosis, the Leptospiral Pulmonary Haemorrhage Syndrome (LPHS). LPHS is increasingly recognized in both humans and animals and is characterized by rapidly progressive intra-alveolar haemorrhage leading to high mortality. The pathogenic mechanisms of LPHS are poorly understood which hampers the application of effective treatment regimes. Comparison of lung proteomes from infected and non-infected guinea pigs via differential in-gel electrophoresis revealed highly significant differences in abundance of proteins contained in 130 spots. After exclusion of spots containing co-migrating proteins, 55 proteins with increased and 32 proteins with decreased abundance in LPHS lung tissue were identified via mass spectrometry. These proteins were mapped to functional groups and canonical pathways using Ingenuity Pathway Analysis®. Acute phase proteins were the largest functional group amongst proteins with increased abundance in LPHS lung tissue, and likely reflect a local and/or systemic host response to infection. The observed decrease in abundance of proteins involved in cytoskeletal and cellular organization in LPHS lung tissue further suggests that infection with pathogenic Leptospira induces changes in the abundance of host proteins involved in cellular architecture and adhesion leading to the dramatically increased alveolar septal wall permeability seen in LPHS. A 2-D guinea pig lung proteome map containing 486 protein IDs and their respective post translational modifications are publically available to facilitate future pulmonary proteomics in the guinea pig (http://proteomics-54 portal.ucd.ie/ and ftp://PASS00619:[e-mail]/).