Alvaro Toledo

Email: 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. Huang Z, ToledoAM, Benach JL London E. Ordered Membrane Domain-Forming Properties of the Lipids of Borrelia burgdorferi. Biophys J.2016 Dec 20;111(12):2666-2675.
    2. Toledo A, Lopes de Carvalho ICarvalho CLBarandika JFRespicio-Kingry LBGarcia-Amil CGarcía-Pérez ALOlmeda ASZé-Zé L, Petersen JM , Anda P, Núncio MS, Escudero R. Francisella species in ticks and animals, Iberian Peninsula. Ticks Tick Borne Dis. 2016 Feb 2.

    3. Coleman JL, Toledo A, Benach JL. Borrelia burgdorferi HtrA: evidence for two-fold proteolysis of outer membrane protein p66. Mol Microbiol Mol Microbiol.2016 Jan;99(1):135-50.

    4. Toledo A, Benach J.L. Hijacking and use of host lipids by intracellular pathogens. Microbiol Spectrum 3 (6) 2015 Dec 21

    5. Toledo A, Perez A, Coleman JL, Benach JL. The lipid raft proteome of Borrelia burgdorferi. Proteomics 2015 Nov;15(21):3662-75

    6. Toledo A, Monzon J, Coleman JL, Garcia-Monco JC, Benach JL. Hypercholesterolemia and ApoE Deficiency Result in Severe Infection with Lyme Disease and Relapsing Fever Borrelia. PNAS 2015 Apr 28;112(17):5491-6

    7. AM Farnoud, AM Toledo, JB Konopka, M Del Poeta, E London. Raft-Like Membrane Domains in Pathogenic Microorganisms. Current Topics in Membranes 2015;75:233-68

    8. Toledo A, Benach JL. Hijacking and Use of Host Lipids by Intracellular Pathogens. Virulence Mechanisms of Bacterial Pathogens, 5th Edition. ASM Edited by J. Bannantine

    9. Toledo A, Crowley JT, Coleman JL, LaRocca TJ, Chiantia S, London E, Benach JL. Selective association of outer surface lipoproteins with the lipid rafts of Borrelia burgdorferi. MBio. 2014 Mar 11;5(2):e00899-14. doi: 10.1128/mBio.00899-14.

    10. LaRocca TJ, Pathak P, Chiantia S, Toledo A, Silvius JR, Benach JL, London E. Proving Lipid Rafts Exist: Membrane Domains in the Prokaryote Borrelia burgdorferi Have the Same Properties as Eukaryotic Lipid Rafts. PLoS Pathog 2013. 9(5):e1003353. doi: 10.1371/journal.ppat.1003353. Epub 2013 May 16.

    11. Coleman JL, Crowley JT, Toledo A, Benach JL. The HtrA protease of Borrelia burgdorferi degrades outer membrane protein BmpD and chemotaxis phosphatase CheX. Mol Microbiol. 2013 Apr 9. doi: 10.1111/mmi.12213.

    12. Crowley JT, Toledo AM, LaRocca TJ, Coleman JL, London E, Benach JL. Lipid exchange between Borrelia burgdorferi and host cells. PLoS Pathog. 2013 Jan;9(1):e1003109. doi: 10.1371/journal.ppat.1003109. Epub 2013 Jan 10.

    13. Toledo A, Coleman JL, Kuhlow CJ, Crowley JT, Benach JL. The enolase of Borrelia burgdorferi is a plasminogen receptor released in outer membrane vesicles. Infect Immun. 2012 Jan;80(1):359-68.

    14. Jado I, Carranza-Rodríguez C, Barandika JF, Toledo A, García-Amil C, Serrano B, Bolaños M, Gil H, Escudero R, García-Pérez AL, Olmeda AS, Astobiza I, Lobo B, Rodríguez-Vargas M, Pérez-Arellano JL, López-Gatius F, Pascual-Velasco F, Cilla G, Rodríguez NF, Anda P. Molecular method for the characterization of Coxiella burnetii from clinical and environmental samples: variability of genotypes in Spain. BMC Microbiol. 2012 Jun 1;12(1):91

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).