The Leptospira interrogans proteome's response to zinc highlights the potential involvement of this metal in translational-machinery and virulence

Author(s)

Hecktheuer, Amanda Silva ; Santos, Cassia Moreira ; Ferreira, Fabienne Antunes ; Barbosa, Angela Silva ; Isaac, Lourdes ; Marques, Marilis Valle ; Mazzon, Ricardo Ruiz

• Document type: Journal article
• Source: BIOMETALS; v. N/A, p. 22-pg., 2024-09-21.

Abstract

Leptospires, as motile Gram-negative bacteria, employ sophisticated strategies for efficient invasion and dissemination within their hosts. In response, hosts counteract pathogens through nutritional immunity, a concept involving the deprivation of essential metals such as zinc. Zinc, pivotal in modulating pathogen-host interactions, influences proteins structural, catalytic, and regulatory functions. A comprehensive understanding of how leptospires regulate intracellular zinc availability is crucial for deciphering their survival mechanisms. This study explores the proteomic profile of Leptospira interrogans sv. Copenhageni str. 10A cultivated in Ellinghausen-McCullough-Johnson-Harris medium supplemented with the zinc chelator TPA or ZnCl2. Among the 2161 proteins identified, 488 were subjected to scrutiny, revealing 102 less abundant and 81 more abundant in response to TPA. Of these 488 proteins, 164 were exclusive to the presence of TPA and 141 were exclusive to the zinc-enriched conditions. Differentially expressed proteins were classified into clusters of orthologous groups (COGs) with a distribution in metabolic functions (37.8%), information storage/processing (21.08%), cellular processes/signaling (28.04%), and poorly characterized proteins (10.65%). Differentially expressed proteins are putatively involved in processes like 1-carbon compound metabolism, folate biosynthesis, and amino acid/nucleotide synthesis. Zinc availability significantly impacted key processes putatively related to leptospires' interactions with their host, such as motility, biofilm formation, and immune escape. Under conditions of higher zinc concentration, ribosomal proteins, chaperones and components of transport systems were observed, highlighting interactions between regulatory networks responsive to zinc and iron in L. interrogans. This study not only revealed hypothetical proteins potentially related to zinc homeostasis, but also identified possible virulence mechanisms and pathogen-host adaptation strategies influenced by the availability of this metal. There is an urgent need, based on these data, for further in-depth studies aimed at detailing the role of zinc in these pathways and mechanisms, which may ultimately determine more effective therapeutic approaches to combat Leptospira infections. (AU)

• FAPESP's process: 17/12924-3 - Etiopathogenesis of Leptospirosis: contribution of the complement system for the control of infection in vivo and in vitro and inflammatory response: identification of gene polymorphisms of the complement system in Leptospirosis patients
• Grantee: Lourdes Isaac
• Support Opportunities: Research Projects - Thematic Grants