Functional Validation of the Proteome-Identified LIC_13056 Putative Lipoprotein of Leptospira interrogans and the Potential Role in Pathogenesis

TL;DR

This study identifies a Leptospira protein that may help the bacteria infect and evade the immune system.

Contribution

The functional validation of LIC_13056 as a lipoprotein involved in Leptospira pathogenesis is novel.

Findings

LIC_13056 binds to α8 integrin subunit, potentially aiding kidney colonization.

LIC_13056 binds plasminogen and activates it to plasmin.

LIC_13056 interacts with complement components and inhibits C9 polymerization.

Abstract

Leptospirosis is a widespread zoonosis of human and veterinary concern. The etiological agent of the disease is the pathogenic bacteria of the genus Leptospira. Transmission typically occurs through mucosal contact and/or injured skin with the urine of infected animals or contaminated environmental sources. Understanding the biology and pathogenesis of leptospires is the main focus of our study. In this work, we characterized a novel protein encoded by the LIC_13056 gene from L. interrogans serovar Copenhageni, having an OmpA-like domain. We show that this coding sequence (CDS), previously assigned as a hypothetical protein with an unknown function, is capable of binding to the cellular receptor α8 integrin subunit, potentially contributing to kidney colonization. Additionally, the protein bound to both purified and normal human serum (NHS) plasminogen (PLG). In both conditions, PLG bound to protein was able to generate plasmin (PLA). Furthermore, rLIC_13056 interacted with the complement system components C4b, C4BP, C8 and C9. The interaction of recombinant protein to the C9 had a negative impact on C9 polymerization. Taken together, the protein LIC_13056, having an OmpA-like domain, appears to be involved in leptospiral pathogenesis via different stages of the infection process; PLA generation together with the inhibition of the membrane attack complex (MAC) may contribute to the immune evasion mechanism of Leptospira, thus facilitating the infection.

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