Alvaro Toledo

EDr. Alvaro Toledomail: at922@sebs.rutgers.edu

 

Abstract

Epidemics of vector-borne pathogens have dramatically changed in recent years, as we have witnessed the introduction of Zika and West Nile viruses in the US, Crimean-Congo hemorrhagic fever in south-western Europe, and the continuous emergence of Lyme disease throughout the Northeast of the USA and central Europe. Ticks are the most important vectors for infectious diseases in the northern hemisphere and second after mosquitoes worldwide. As a result, there is an increasing public health interest in tick-borne pathogens.

My research focuses on the study of ticks and tick-borne pathogens with a special emphasis on Borrelia burgdorferi, the agent of Lyme disease. B. burgdorferi has a complex life cycle that involves two very distinct milieus, the tick mid gut and the vertebrate host. In order to survive, Borrelia tightly regulates the expression of outer surface proteins (Osps), most notably OspA and OspB in the tick mid gut, and OspC in the mammalian host. Nonetheless, little is known about the sensing mechanisms by which the spirochete accomplishes this adaptation. Important to note, B. burgdorferi requires cholesterol to grow but cannot synthetize it. The spirochete uptakes cholesterol from the host to makeup cholesterol glycolipids (CGal and ACGal), which are major lipid components of the spirochete membrane. Notably, cholesterol glycolipids sort themselves out in the membrane to form cholesterol-rich microdomains. These domains, known as lipid rafts, have a subset of specific proteins involved in important biological processes including sensing, signaling and protein trafficking. As a microbiologist I am interested in three fundamental questions: 1) whether cholesterol is a comorbidity factor in Lyme disease? 2) The role of lipid rafts as sensing platforms; 3) the mechanisms by which Borrelia uptakes, transports and metabolizes cholesterol.

In addition, as a public health entomologist by training I am interested in vector-borne diseases, surveillance, prevention and control. Tick-borne pathogens not only face a harsh environment in the tick (i.e., lack of nutrients, tick immune system) but also likely compete with members of the tick midgut flora and other pathogens. Little is known about these interactions and how they may shape the ability of the tick to transmit and acquire pathogens. In this context there are two fundamental questions that need to be addressed. 1) The role of the microbiome in the transmission and acquisition of pathogens by the tick. 2) The ecological relationships of tick-borne pathogens in the tick.

Research Projects

  • Hypercholesterolemia and Lyme disease
  • Characterization of lipid rafts in Borrelia burgdoferi
  • Uptage and use of cholesterol by Borrelia burgdoferi
  • Tick microbiome and tick borne pathogens.

Recent Publications (Last 5 years)

    1. JL Coleman, A Toledo, JL Benach  HtrA of Borrelia burgdorferi Leads to Decreased Swarm Motility and Decreased Production of Pyruvate mBio 9 (4), e01136-18 2018
    2. A Toledo, Z Huang, JL Coleman, E London, JL Benach Lipid rafts can form in the inner and outer membranes of Borrelia burgdorferi and have different properties and associated proteins. Molecular Microbiology 108 (1), 63-76, 2, 2018
    3. A Toledo, Z Huang, JL Benach, E London Analysis of Lipids and Lipid Rafts in Borrelia. Borrelia burgdorferi, 69-82, 2018
    4. Z Huang, AM Toledo, JL Benach, E London Ordered Membrane Domain-Forming Properties of the Lipids of Borrelia burgdorferi. Biophysical journal 111 (12), 2666-2675 2, 2016
    5. Z Huang, E London, JL Benach, A Toledo How Lipid Composition Controls Ordered Membrane Domain (“Raft”) Formation in Membranes of Pathogenic Bacteria. Biophysical Journal 110 (3), 583a-584a 2016
    6. A Toledo, IL de Carvalho, , CL Carvalho, JF Barandika, LB Respicio-Kingry C Garcia-Amil, AL García-Pérez, AS Olmeda, L Zé-Zé, JM Petersen, P Anda, MS Núncio, R Escudero. Francisella species in ticks and animals, Iberian Peninsula. Ticks and tick-borne diseases 7 (1), 159-165 9, 2016
    7. JL Coleman, A Toledo, JL Benach Borrelia burgdorferi HtrA: evidence for twofold proteolysis of outer membrane protein p66Molecular microbiology 99 (1), 135-150 8, 2016
    8. A Toledo, JL Benach Hijacking and use of host lipids by intracellular pathogens. Microbiology spectrum 3 (6) 5, 2015
    9. A Toledo, A Pérez, JL Coleman, JL Benach The lipid raft proteome of Borrelia burgdorferi. Proteomics 15 (21), 3662-3675       14, 2015
    10. A Toledo, JD Monzón, JL Coleman, JC Garcia-Monco, JL Benach Hypercholesterolemia and ApoE deficiency result in severe infection with Lyme disease and relapsing-fever Borrelia. Proceedings of the National Academy of Sciences, 201502561 11, 2015
    11. AM Farnoud, AM Toledo, JB Konopka, M Del Poeta, E London Raft-like membrane domains in pathogenic microorganisms. Current topics in membranes 75, 233-268 23, 2015
    12. A Toledo, JT Crowley, JL Coleman, TJ LaRocca, S Chiantia, E London, JL Benach Selective association of outer surface lipoproteins with the lipid rafts of Borrelia burgdorferi. MBio 5 (2), e00899-14 16, 2014
    13. TJ LaRocca, P Pathak, S Chiantia, A Toledo, JR Silvius, JL Benach, E London Proving lipid rafts exist: membrane domains in the prokaryote Borrelia burgdorferi have the same properties as eukaryotic lipid rafts. PLoS pathogens 9 (5), e1003353 63, 2013
    14. JL Coleman, JT Crowley, AM Toledo, JL Benach The HtrA protease of Borrelia burgdorferi degrades outer membrane protein BmpD and chemotaxis phosphatase CheX. Molecular microbiology 88 (3), 619-633, 32, 2013
    15. JT Crowley, AM Toledo, TJ LaRocca, JL Coleman, E London, JL Benach Lipid exchange between Borrelia burgdorferi and host cells. PLoS pathogens 9 (1), e1003109, 56, 2013

Grants

Northeast Biodefense Center Career Development and Training Program from the National Institute of Allergy and Infectious Diseases (NIAID). Grant number 7(GG006382). 2012-2014

Comorbidity of hypercholesterolemia and Lyme disease. Award 436,813. National Institute of Allergy and Infectious Diseases (NIAID) Grant number 1R21AI125806-01A1 (1/15/2017-12/31/2018).