Leptospira interrogans Binds to Human Cell Surface Receptors Including Proteoglycans

Abstract

Leptospirosis is a global public health problem, primarily in the tropical developing world. The pathogenic mechanisms of the causative agents, several members of the genus Leptospira, have been underinvestigated. The exception to this trend has been the demonstration of the binding of pathogenic leptospires to the extracellular matrix (ECM) and its components. In this work, interactions of Leptospira interrogans bacteria with mammalian cells, rather than the ECM, were examined. The bacteria bound more efficiently to the cells than to the ECM, and a portion of this cell-binding activity was attributable to attachment to glycosaminoglycan (GAG) chains of proteoglycans (PGs). Chondroitin sulfate B PGs appeared to be the primary targets of L. interrogans attachment, while heparan sulfate PGs were much less important. Inhibition of GAG/PGmediated attachment resulted in partial inhibition of bacterial attachment, suggesting that additional receptors for L. interrogans await identification. GAG binding may participate in the pathogenesis of leptospirosis within the host animal. In addition, because GAGs are expressed on the luminal aspects of epithelial cells in the proximal tubules of the kidneys, this activity may play a role in targeting the bacteria to this critical site.

Pathogenic Leptospira Species Acquire Factor H and Vitronectin via the Surface Protein LcpA

“…Pathogenic Leptospira strains have been shown to bind the soluble complement-regulatory proteins FH, FHL-1, FHR-1, and C4BP (4-7) and several ECM and plasma molecules, including laminin, collagens, fibronectin, elastin, tropoelastin, proteoglycans, fibrinogen, and plasminogen (20,21,27,28). Here we demonstrate that this spirochete also interacts with human vitronectin.…”

“…Immunohistochemical studies allowed detection of vitronectin in a variety of normal human tissues, including the liver, lungs, kidneys, and blood vessel walls (15,18). Previous reports have demonstrated that leptospires bind several extracellular matrix components (20,21), but interaction of these particular spirochetes with vitronectin has never been evaluated.…”

Calcium Binding to Leptospira Outer Membrane Antigen LipL32 Is Not Necessary for Its Interaction with Plasma Fibronectin, Collagen Type IV, and Plasminogen

“…Accordingly, leptospires employ surface-exposed proteins to bind to a wide range of host ligands, including laminin, collagen, cellular and plasma fibronectin, elastin, proteoglycans, fibrinogen, and plasminogen (13,30,31,36,37). LipL32 binds to plasma fibronectin, collagen types I, IV, and V, laminin, and plasminogen (11)(12)(13).…”

Interação de proteínas de membrana de Leptospira com os reguladores Fator H e C4BP do sistema complemento humano.

“…Treponema denticola também expressa uma proteína que interage com FH (FhbB) e assim escapa da morte pela ativação da via alternativa do complemento (Miller et al, 2012). As leptospiras patogênicas interagem com diversos componentes de matriz extracelular como laminina, colágeno tipo I e IV, fibronectina, elastina e proteoglicanos (Breiner et al, 2009;Ito, Yanagawa,1987;. Cabe ressaltar que leptospiras patogênicas são micro-organismos altamente invasivos, capazes de aderir e invadir células hospedeiras mais eficientemente do que as estirpes não patogênicas e saprófitas (Fraga et al, 2011;Liu, 2007).…”