Unique Posttranslational Modification Sites of Acetylation, Citrullination, Glutarylation, and Phosphorylation Are Found to Be Specific to the Proteins Partitioned in the Triton X-114 Fractions of Leptospira

Abstract

Posttranslational modifications (PTMs) are decisive factors in the structure, function, and localization of proteins in prokaryotic and eukaryotic organisms. However, prokaryotic organisms lack subcellular organelles, and protein localization based on subcellular locations like cytoplasm, inner membrane, periplasm, and outer membrane can be accounted for functional characterization. We have identified 131 acetylated, 1182 citrullinated, 72 glutarylated, 5 palmitoylated, and 139 phosphorylated proteins from Triton X-114 fractionated proteins of Leptospira , the pathogen of re-emerging zoonotic disease leptospirosis. In total, 74.7% of proteins were found exclusively in different Triton X-114 fractions. Additionally, 21.9% of proteins in multiple fractions had one or more PTM specific to different Triton X-114 fractions. Altogether, 96.6% of proteins showed exclusiveness to different Triton X-114 fractions either due to the presence of the entire protein or with a specific PTM type or position. Further, the PTM distribution within Triton X-114 fractions showed higher acetylation in aqueous, glutarylation in detergent, phosphorylation in pellet, and citrullination in wash fractions representing cytoplasmic, outer membrane, inner membrane, and extracellular locations, respectively. Identification of PTMs in proteins with respect to the subcellular localization will help to characterize candidate proteins before developing novel drugs and vaccines rationally to combat leptospirosis.

Physiological Temperature and Osmotic Changes Drive Dynamic Proteome Alterations in the Leptospiral Outer Membrane and Enhance Protein Export Systems

“…Leptospirosis, a zoonosis, is caused by several pathogenic species of Leptospira for which mammalian hosts, primarily rodents, act as a reservoir, and humans get infected accidentally through their skin, wounds, and damaged mucosa exposed to the water contaminated with the urine of these animals. − Despite being a neglected disease, leptospirosis is a reemerging public health problem, with a worldwide burden of 500,000 per year and a fatality rate of 25%. , Urban slums are experiencing an influx of residents, and climate change in tropical and subtropical countries is leading to more frequent heavy rainfall and floods. Consequently, water contaminated with Leptospira has become widespread, and human exposure to the pathogen has increased the incidence of leptospirosis. , Although many patients recover from this disease with a mild febrile illness, it can cause severe damage to vital organs, including hemorrhagic manifestations, leading to multiorgan failure and death. , Furthermore, symptoms of leptospirosis are similar to the common febrile illnesses, leading to delays in diagnosis and medical management . There are many gaps in understanding the pathophysiology of leptospirosis and the host immunity, which hinders taking necessary steps to combat the disease in terms of developing a potential vaccine, precise diagnostic tools, and potential biomarkers to predict disease severity …”

“…Consequently, water contaminated with Leptospira has become widespread, and human exposure to the pathogen has increased the incidence of leptospirosis. 6,7 Although many patients recover from this disease with a mild febrile illness, it can cause severe damage to vital organs, including hemorrhagic manifestations, leading to multiorgan failure and death. 8,9 Furthermore, symptoms of leptospirosis are similar to the common febrile illnesses, leading to delays in diagnosis and medical management.…”