About

Erol Fikrig, MD, is the Waldemar Von Zedtwitz Professor of Medicine (Infectious Diseases), Professor of Epidemiology (Microbial Diseases), and of Microbial Pathogenesis at Yale School of Medicine. He serves as the Section Chief of Infectious Diseases within the Department of Internal Medicine and is an affiliated faculty member at the Yale Institute for Global Health. His research focuses on infectious diseases, exploring microbial pathogenesis and the mechanisms of infectious agents. Dr. Fikrig's work contributes to understanding the biology of infectious pathogens and developing strategies for prevention and treatment.

Research topics

• Biology
• Virology
• Immunology
• Computer Science
• Evolutionary biology
• Microbiology
• Bioinformatics
• Zoology
• Biochemistry
• Medicine
• Ecology
• Genetics

Selected publications

• Ixodes scapularis STING promotes Powassan virus infection in ticks

  Research Square · 2026-01-28

  preprintOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Borrelia Burgdorferi binds Serum Amyloid A and Modulates Subcutaneous Adipose Tissue Immune Signaling

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-02

  articleOpen access

  Abstract Borrelia burgdorferi causes over 470,000 infections annually [1]. Following a tick bite, Borrelia spirochetes replicate in human skin and disseminate through tissues, including subcutaneous adipose tissue. Adipose tissue is a complex organ containing non-immune and immune cells that play a significant role in the immune response [2], yet little is known about adipose tissue signaling after Borrelia infection. We investigated the landscape of immune signaling within adipose tissue-resident cells during Borrelia infection in human tissue (skin and adipose tissue) ex vivo . Immune pathways overall were downregulated in adipose tissue during Borrelia infection. Despite this, adipose stem/progenitor cells exhibited increased pro-inflammatory and extracellular matrix (ECM)-related signaling (IL-6, MIF, collagen, laminin, fibronectin), positioning them as key hubs of intercellular communication during infection. Myeloid lineage cells showed cluster-specific upregulation of immune genes such as IL1B and TNF . Network analyses highlighted laminin, and strong outgoing MIF signals in all adipose-resident cell clusters. Among the identified genes modulated after Borrelia infection, we observed reduced expression levels of serum amyloid A in adipose tissue-resident cells, a marker typically elevated in Lyme disease patient serum during acute infection. Here, we show that human serum amyloid A1 and serum amyloid A2 directly bind B. burgdorferi spirochetes, using flow cytometry. Functionally, serum amyloid A2 reduces spirochete viability in vitro in a dose-dependent manner and enhances opsonization and phagocytosis by macrophages. Together, these findings show that adipose tissue is a site of active immune signaling in the setting of Borrelia infection and identifies SAA as a host defense factor against Borrelia .

  PublisherOA PDFDOI

• CCL17 Influences <i>Borrelia burgdorferi</i> Infection in the Heart

  The Journal of Infectious Diseases · 2025-01-03

  articleOpen accessSenior author

  Lyme disease, caused by Borrelia burgdorferi, is transmitted to humans by Ixodes ticks. CCL17 is a potent chemokine that plays important roles in diverse illnesses, including autoimmune and infectious diseases. CCL17 knockout mice, infected with B. burgdorferi, had a reduced pathogen load in the heart compared to control animals. Mice lacking CCL17 also showed signs of immune alteration upon B. burgdorferi infection, including diverse serum levels of proinflammatory cytokines and less monocytes and macrophages infiltration. CCL17 also interacts directly with B. burgdorferi, the first demonstration that this chemokine has an affinity for a vector-borne pathogen.

  PublisherOA PDFDOI

• Structural and functional significance of <i>Aedes aegypti</i> AgBR1 flavivirus immunomodulator

  Journal of Virology · 2025-04-24 · 1 citations

  articleOpen access

  salivary gland protein, has gained attention for its immunomodulatory potential, along with another protein, called NeSt1. We have determined the crystal structure of AgBR1 at 1.2 Å resolution. Despite its chitinase-like fold, we demonstrated that AgBR1 does not bind to chitobiose or chitinhexaose, while a key mutation in the catalytic site abrogates enzymatic activity, suggesting that the protein's function has been repurposed. Our study also shows that AgBR1 and NeSt1, when presented to murine primary macrophages, alter cellular pathways related to virus entry by endocytosis, immune response, and cell proliferation. AgBR1 (and NeSt1) do not directly bind to the Zika virus or modulate its replication. We propose that their immunomodulatory effects on Zika virus transmission are through regulation of host-cell response, a consequence of evolutionary cross talk and virus opportunism. These structural and functional insights are prerequisites for developing strategies to halt the spread of mosquito-borne disease.IMPORTANCEOur study informs on the structural and functional significance of a mosquito salivary gland protein, AgBR1 (along with another protein called NeSt1), in the transmission of the Zika virus (ZIKV), a mosquito-borne virus that has caused global health concerns. By analyzing AgBR1's three-dimensional structure in combination with cellular and interaction studies, we discovered that AgBR1 does not function like typical proteins in its family-it does not degrade sugars. However, we show that it primes immune cells in a way that could help the virus enter cells more easily but not by interacting with the virus or altering viral replication. This finding is significant because it reveals how mosquito proteins, repurposed by evolution, can influence virus transmission without the virus's direct presence. Understanding how proteins like AgBR1 work could guide the development of new strategies to prevent Zika virus spread, with potential relevance for other mosquito-borne viruses.

  PublisherDOI

• Secretory leukocyte protease inhibitor influences periarticular joint inflammation in Borrelia burgdorferi-infected mice

  eLife · 2025-05-20

  articleOpen accessSenior author

  Lyme disease, caused by Borrelia burgdorferi , is the most common tick-borne infection in the United States. Arthritis is a major clinical manifestation of infection, and synovial tissue damage has been attributed to the excessive pro-inflammatory responses. The secretory leukocyte protease inhibitor (SLPI) promotes tissue repair and exerts anti-inflammatory effects. The role of SLPI in the development of Lyme arthritis in C57BL/6 mice, which can be infected with B. burgdorferi but only develop mild joint inflammation, was therefore examined. Slpi -deficient C57BL/6 mice challenged with B. burgdorferi had a higher infection load in the tibiotarsal joints and marked periarticular swelling compared to infected wild-type control mice. The ankle joint tissues of B. burgdorferi- infected Slpi -deficient mice contained significantly higher percentages of infiltrating neutrophils and macrophages. B. burgdorferi -infected Slpi -deficient mice also exhibited elevated serum levels of IL-6, neutrophil elastase, and MMP-8. Moreover, using a recently developed BASEHIT ( BA cterial S election to E lucidate H ost-microbe I nteractions in high T hroughput) library, we found that SLPI directly interacts with B. burgdorferi . These data demonstrate the importance of SLPI in suppressing periarticular joint inflammation in Lyme disease.

  PublisherDOI

• Author response: Secretory leukocyte protease inhibitor influences periarticular joint inflammation in B. burgdorferi-infected mice

  2025-04-28

  peer-reviewOpen accessSenior author

  Lyme disease, caused by Borrelia burgdorferi, is the most common tick-borne infection in the United States. Arthritis is a major clinical manifestation of infection, and synovial tissue damage has been attributed to the excessive pro-inflammatory responses. The secretory leukocyte protease inhibitor (SLPI) promotes tissue repair and exerts anti-inflammatory effects. The role of SLPI in the development of Lyme arthritis in C57BL/6 mice, which can be infected with B. burgdorferi, but only develop mild joint inflammation, was therefore examined. SLPI-deficient C57BL/6 mice challenged with B. burgdorferi had a higher infection load in the tibiotarsal joints and marked periarticular swelling, compared to infected wild type control mice. The ankle joint tissues of B. burgdorferi-infected SLPI-deficient mice contained significantly higher percentages of infiltrating neutrophils and macrophages. B. burgdorferi-infected SLPI-deficient mice also exhibited elevated serum levels of IL-6, neutrophil elastase, and MMP-8. Moreover, using a recently developed BASEHIT (BActerial Selection to Elucidate Host-microbe Interactions in high Throughput) library, we found that SLPI directly interacts with B. burgdorferi. These data demonstrate the importance of SLPI in suppressing periarticular joint inflammation in Lyme disease.

  PublisherDOI

• Antibody responses to SG6, AgSAP, and SAMSP1 following Anopheline salivary exposure

  medRxiv · 2025-07-15 · 1 citations

  preprintOpen access

  ABSTRACT Background Current methods to determine exposure to malaria-infected mosquitoes via entomologic investigations are technically challenging and can be inaccurate in low transmission settings. Antibody responses to mosquito salivary antigens (MSA) like gSG6-P1 have been used as biomarkers of exposure to Anopheles mosquito bites. Methods This study investigates two novel Anopheles gambiae salivary antigens, AgSAP and SAMSP1, as potential biomarkers of vector exposure. We evaluated the humoral response to gSG6-P1, SAMSP1, and AgSAP in a murine model and in malaria-exposed individuals with submicroscopic parasitemia across different malaria endemicity areas, seasons, and infection statuses in coastal Tanzania. We also analyzed antibody kinetics following direct skin feeding assays carried out using uninfected colony-reared An. gambiae . Results GSG6-P1, AgSAP, and SAMSP1 levels increased in mice at eight weeks after weekly mosquito feedings. However, human gSG6-P1 and AgSAP levels were paradoxically lower four weeks after direct skin feeding assays. SAMSP1 was the only MSA that induced a significantly higher humoral response during the rainy season, suggesting that it may be a more reliable biomarker for vector exposure in regions with multiple Anopheles species. Conclusions Mosquito salivary antigens associated with Plasmodium infection like AgSAP and SAMSP1 show promise as biomarkers of malaria vector exposure. However, the dynamics of IgG response against AgSAP and SAMSP1 after mosquito bites requires further study.

  PublisherOA PDFDOI

• Secretory leukocyte protease inhibitor influences periarticular joint inflammation in B. burgdorferi-infected mice

  eLife · 2025-01-16

  preprintOpen accessSenior author

  Abstract Lyme disease, caused by Borrelia burgdorferi, is the most common tick-borne infection in the United States. Arthritis is a major clinical manifestation of infection, and synovial tissue damage has been attributed to the excessive pro-inflammatory responses. The secretory leukocyte protease inhibitor (SLPI) promotes tissue repair and exerts anti-inflammatory effects. The role of SLPI in the development of Lyme arthritis in C57BL/6 mice, which can be infected with B. burgdorferi, but only develop mild joint inflammation, was therefore examined. SLPI-deficient C57BL/6 mice challenged with B. burgdorferi had a higher infection load in the tibiotarsal joints and marked periarticular swelling, compared to infected wild type control mice. The ankle joint tissues of B. burgdorferi-infected SLPI-deficient mice contained significantly higher percentages of infiltrating neutrophils and macrophages. B. burgdorferi-infected SLPI-deficient mice also exhibited elevated serum levels of IL-6, neutrophil elastase, and MMP-8. Moreover, using a recently developed BASEHIT (BActerial Selection to Elucidate Host-microbe Interactions in high Throughput) library, we found that SLPI directly interacts with B. burgdorferi. These data demonstrate the importance of SLPI in suppressing periarticular joint inflammation in Lyme disease.

  PublisherOA PDFDOI

• A Multivalent Peptide Vaccine Against Malaria, Targeting <i>Plasmodium</i> Circumsporozoite Protein and Mosquito AgTRIO

  The Journal of Infectious Diseases · 2025-08-12 · 1 citations

  articleOpen accessSenior author

  Malaria begins when an infected mosquito injects saliva containing Plasmodium sporozoites into the host skin. The immune response against a mosquito saliva protein, AgTRIO, reduces Plasmodium infection and can work in combination with antibody against the Plasmodium circumsporozoite protein (CSP). We have now developed a chimeric peptide, PfAg, containing regions from Plasmodium falciparum CSP (PfCSP) and AgTRIO. Mice administered PfAg generated robust humoral responses against both PfCSP and AgTRIO. After exposure to PfCSP-expressing Plasmodium berghei-infected mosquitoes, PfAg-immunized inbred C57BL/6 and outbred CD-1 mice had significantly improved survival compared with control animals. These data will aid in the development of a new malaria vaccine.

  PublisherDOI

• Author response: Secretory leukocyte protease inhibitor influences periarticular joint inflammation in B. burgdorferi-infected mice

  2025-01-16

  peer-reviewOpen accessSenior author

  Lyme disease, caused by Borrelia burgdorferi, is the most common tick-borne infection in the United States. Arthritis is a major clinical manifestation of infection, and synovial tissue damage has been attributed to the excessive pro-inflammatory responses. The secretory leukocyte protease inhibitor (SLPI) promotes tissue repair and exerts anti-inflammatory effects. The role of SLPI in the development of Lyme arthritis in C57BL/6 mice, which can be infected with B. burgdorferi, but only develop mild joint inflammation, was therefore examined. SLPI-deficient C57BL/6 mice challenged with B. burgdorferi had a higher infection load in the tibiotarsal joints and marked periarticular swelling, compared to infected wild type control mice. The ankle joint tissues of B. burgdorferi-infected SLPI-deficient mice contained significantly higher percentages of infiltrating neutrophils and macrophages. B. burgdorferi-infected SLPI-deficient mice also exhibited elevated serum levels of IL-6, neutrophil elastase, and MMP-8. Moreover, using a recently developed BASEHIT (BActerial Selection to Elucidate Host-microbe Interactions in high Throughput) library, we found that SLPI directly interacts with B. burgdorferi. These data demonstrate the importance of SLPI in suppressing periarticular joint inflammation in Lyme disease.

  PublisherDOI

Recent grants

• NIH Grant R01AI032947

  NIH · $5.7M · 2013

• The role of NLRP6 and DHX15 in control of infection by RNA viruses

  NIH · $2.1M · 2018–2023

• NIH Grant R56AI041440

  NIH · $414k · 2010

• NIH Grant R01AI041440

  NIH · $5.5M · 2015

• NIH Grant P01AI030548

  NIH · $12.1M · 2001

Frequent coauthors

• Richard A. Flavell

  Howard Hughes Medical Institute

  174 shared

• Sukanya Narasimhan

  Yale University

  146 shared

• Joppe W. Hovius

  Amsterdam University Medical Centers

  98 shared

• Kathleen DePonte

  Yale University

  84 shared

• Stephen W. Barthold

  University of California, Davis

  79 shared

• Durland Fish

  Yale University

  77 shared

• John F. Anderson

  75 shared

• Jacob W. IJdo

  Gold Coast Hospital

  75 shared

Labs

• Fikrig LabPI

Education

• M.D., Medicine

  Yale University School of Medicine

  1989

• B.S., Microbiology

  University of California, Los Angeles

  1984