About

Vladimir Emiliano Diaz-Ochoa is a researcher with a focus on microbiology, immunology, and host-pathogen interactions. His work involves understanding the molecular mechanisms underlying microbial virulence, immune responses, and the role of metal ions in mucosal immunity and microbial pathogenesis. Throughout his career, he has contributed to the scientific understanding of how pathogens evade immune defenses and how host factors influence infection outcomes. He has received numerous honors and awards, including fellowships from the Howard Hughes Medical Institute, UC Davis, and UC Irvine, as well as recognition for excellence in microbiology and host-microbe interaction research. His research has been published in various scientific journals, highlighting his contributions to the fields of microbiology, immunology, and infectious disease. Diaz-Ochoa's work is characterized by a detailed investigation into the signaling pathways and molecular responses involved in host defense and microbial survival strategies.

Research topics

• Biology
• Microbiology
• Cell biology
• Immunology
• Internal medicine
• Medicine
• Chemistry
• Biochemistry
• Genetics
• Pathology

Selected publications

• Glucose uptake is essential for <i>Brucella abortus</i> growth in the extracellular space of the murine placenta

  Infection and Immunity · 2025-03-12

  articleOpen access

  ABSTRACT Brucella abortus infects the placenta of its natural bovine host, which results in abortion and transmission of infection to other cattle and to humans. While the metabolism of B. abortus during chronic infection of the mononuclear phagocyte system has been studied, the nutrients fueling growth of B. abortus in the placenta are unknown. We found that in mice, glucose is an important carbon source for B. abortus in the placenta. A gluP mutant lacking a major facilitator superfamily protein required for glucose uptake had diminished growth in the placenta of pregnant mice and caused reduced inflammatory pathology and fetal demise. The gluP mutant was able to replicate intracellularly in a trophoblast cellular model and to cause trophoblast cell death in infected placentas. Attenuated growth of the gluP mutant was maintained in mice conditionally deficient for peroxisome proliferator-activated receptor γ in macrophages, suggesting that M2-like macrophages were not the major site for glucose-dependent growth of B. abortus in the placenta. Our results show that the infected placenta contains multiple distinct nutrient niches and that glucose utilization within the interstitial space of the placenta is an important process contributing to bacterial growth and fetal demise during placental B. abortus infection.

  PublisherDOI

• Vitamin A deficiency impairs neutrophil-mediated control of Salmonella via SLC11A1 in mice

  Nature Microbiology · 2024-02-19 · 15 citations

  articleOpen access

  Abstract In sub-Saharan Africa, multidrug-resistant non-typhoidal Salmonella serovars are a common cause of fatal bloodstream infection. Malnutrition is a predisposing factor, but the underlying mechanisms are unknown. Here we show that vitamin A deficiency, one of the most prevalent micronutrient deficits afflicting African children, increases susceptibility to disseminated non-typhoidal Salmonella disease in mice and impairs terminal neutrophil maturation. Immature neutrophils had reduced expression of Slc11a1 , a gene that encodes a metal ion transporter generally thought to restrict pathogen growth in macrophages. Adoptive transfer of SLC11A1-proficient neutrophils, but not SLC11A1-deficient neutrophils, reduced systemic Salmonella burden in Slc11a1 −/− mice or mice with vitamin A deficiency. Loss of terminal granulopoiesis regulator CCAAT/enhancer-binding protein ϵ (C/EBPϵ) also decreased neutrophil-mediated control of Salmonella , but not that mediated by peritoneal macrophages. Susceptibility to infection increased in Cebpe −/− Slc11a1 +/+ mice compared with wild-type controls, in an Slc11a1 -expression-dependent manner. These data suggest that SLC11A1 deficiency impairs Salmonella control in part by blunting neutrophil-mediated defence.

  PublisherOA PDFDOI

• The IRE1α-XBP1 signaling axis promotes glycolytic reprogramming in response to inflammatory stimuli

  bioRxiv (Cold Spring Harbor Laboratory) · 2022-10-21

  preprintOpen access

  ABSTRACT Immune cells must be able to adjust their metabolic programs to effectively carry out their effector functions. Here, we show that the ER stress sensor IRE1α and its downstream transcription factor XBP1 enhance the upregulation of glycolysis in classically activated macrophages (CAM). The IRE1α-XBP1 signaling axis supports this glycolytic switch in macrophages when activated by LPS stimulation or infection with the intracellular bacterial pathogen Brucella abortus . Importantly, these different inflammatory stimuli have distinct mechanisms of IRE1α activation; while TLR4 supports glycolysis under both conditions, TLR4 is required for activation of IRE1α in response to LPS treatment but not B. abortus infection. Though IRE1α and XBP1 are necessary for maximal induction of glycolysis in CAM, activation of this pathway is not sufficient to increase the glycolytic rate of macrophages, indicating that the cellular context in which this pathway is activated ultimately dictates the cell’s metabolic response and that IRE1α activation may be a way to fine-tune metabolic reprogramming. IMPORTANCE The immune system must be able to tailor its response to different types of pathogens in order to eliminate them and protect the host. When confronted with bacterial pathogens, macrophages, frontline defenders in the immune system, switch to a glycolysis-driven metabolism to carry out their antibacterial functions. Here, we show that IRE1α, a sensor of ER stress, and its downstream transcription factor XBP1 support glycolysis in macrophages during infection with Brucella abortus or challenge with Salmonella LPS. Interestingly, these stimuli activate IRE1α by independent mechanisms. While the IRE1α-XBP1 signaling axis promotes the glycolytic switch, activation of this pathway is not sufficient to increase glycolysis in macrophages. This study furthers our understanding of the pathways that drive macrophage immunometabolism and highlights a new role for IRE1α and XBP1 in innate immunity.

  PublisherOA PDFDOI

• The IRE1α-XBP1 Signaling Axis Promotes Glycolytic Reprogramming in Response to Inflammatory Stimuli

  mBio · 2022 · 11 citations

  • Cell biology
  • Biology
  • Microbiology

  The immune system must be able to tailor its response to different types of pathogens in order to eliminate them and protect the host. When confronted with bacterial pathogens, macrophages, frontline defenders in the immune system, switch to a glycolysis-driven metabolism to carry out their antibacterial functions. Here, we show that IRE1α, a sensor of ER stress, and its downstream transcription factor XBP1 support glycolysis in macrophages during infection with Brucella abortus or challenge with Salmonella LPS. Interestingly, these stimuli activate IRE1α by independent mechanisms. While the IRE1α-XBP1 signaling axis promotes the glycolytic switch, activation of this pathway is not sufficient to increase glycolysis in macrophages. This study furthers our understanding of the pathways that drive macrophage immunometabolism and highlights a new role for IRE1α and XBP1 in innate immunity.

  PublisherDOI

• Virulence factors perforate the pathogen-containing vacuole to signal efferocytosis

  Cell Host & Microbe · 2021 · 41 citations

  • Biology
  • Microbiology
  • Cell biology

  Intracellular pathogens commonly reside within macrophages to find shelter from humoral defenses, but host cell death can expose them to the extracellular milieu. We find intracellular pathogens solve this dilemma by using virulence factors to generate a complement-dependent find-me signal that initiates uptake by a new phagocyte through efferocytosis. During macrophage death, Salmonella uses a type III secretion system to perforate the membrane of the pathogen-containing vacuole (PCV), thereby triggering complement deposition on bacteria entrapped in pore-induced intracellular traps (PITs). In turn, complement activation signals neutrophil efferocytosis, a process that shelters intracellular bacteria from the respiratory burst. Similarly, Brucella employs its type IV secretion system to perforate the PCV membrane, which induces complement deposition on bacteria entrapped in PITs. Collectively, this work identifies virulence factor-induced perforation of the PCV as a strategy of intracellular pathogens to generate a find-me signal for efferocytosis.

  PublisherOA PDFDOI

• Vitamin A supplementation boosts control of antibiotic-resistant Salmonella infection in malnourished mice

  PLoS neglected tropical diseases · 2020 · 4 citations

  • Medicine
  • Immunology
  • Internal medicine

  Disseminated disease from non-typhoidal Salmonella enterica strains results in >20% mortality globally. Barriers to effective treatment include emerging multidrug resistance, antibiotic treatment failure, and risk factors such as malnutrition and related micronutrient deficiencies. Individuals in sub-Saharan Africa are disproportionately affected by non-typhoidal S. enterica bloodstream infections. To inform a clinical trial in people, we investigated vitamin A as a treatment in the context of antibiotic treatment failure in a mouse model of vitamin A deficiency. Vitamin A-deficient (VAD) mice exhibited higher systemic bacterial levels with a multidrug-resistant clinical isolate in comparison to mice on a control diet. Sex-specific differences in vitamin A deficiency and disseminated infection with S. enterica serotype Typhimurium (S. Typhimurium) were observed. VAD male mice had decreased weight gain compared to control male mice. Further, infected VAD male mice had significant weight loss and decreased survival during the course of infection. These differences were not apparent in female mice. In a model of disseminated S. Typhimurium infection and antibiotic treatment failure, we assessed the potential of two consecutive doses of vitamin A in alleviating infection in male and female mice on a VAD or control diet. We found that subtherapeutic antibiotic treatment synergized with vitamin A treatment in infected VAD male mice, significantly decreasing systemic bacterial levels, mitigating weight loss and improving survival. These results suggest that assessing vitamin A as a therapy during bacteremia in malnourished patients may lead to improved health outcomes in a subset of patients, especially in the context of antibiotic treatment failure.

  PublisherOA PDFDOI

• LysMD3 is a type II membrane protein without an role in the response to a range of pathogens

  Journal of Biological Chemistry · 2018-03-01 · 15 citations

  articleOpen access

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  PublisherOA PDFDOI

• Utilization of Host Polyamines in Alternatively Activated Macrophages Promotes Chronic Infection by Brucella abortus

  Infection and Immunity · 2017-12-04 · 22 citations

  articleOpen access

  ABSTRACT Treatment of intracellular bacterial pathogens with antibiotic therapy often requires a long course of multiple drugs. A barrier to developing strategies that enhance antibiotic efficacy against these pathogens is our poor understanding of the intracellular nutritional environment that maintains bacterial persistence. The intracellular pathogen Brucella abortus survives and replicates preferentially in alternatively activated macrophages (AAMs); however, knowledge of the metabolic adaptations promoting exploitation of this niche is limited. Here we show that one mechanism promoting enhanced survival in AAMs is a shift in macrophage arginine utilization from production of nitric oxide (NO) to biosynthesis of polyamines, induced by interleukin 4 (IL-4)/IL-13 treatment. Production of polyamines by infected AAMs promoted both intracellular survival of B. abortus and chronic infection in mice, as inhibition of macrophage polyamine synthesis or inactivation of the putative putrescine transporter encoded by potIHGF reduced both intracellular survival in AAMs and persistence in mice. These results demonstrate that increased intracellular availability of polyamines induced by arginase-1 expression in IL-4/IL-13-induced AAMs promotes chronic persistence of B. abortus within this niche and suggest that targeting of this pathway may aid in eradicating chronic infection.

  PublisherOA PDFDOI

• Salmonella Mitigates Oxidative Stress and Thrives in the Inflamed Gut by Evading Calprotectin-Mediated Manganese Sequestration

  Cell Host & Microbe · 2016-06-01 · 166 citations

  articleOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Salmonella Typhimurium Expresses Manganese Transporters to Overcome the Host Antimicrobial Response

  eScholarship (California Digital Library) · 2015-01-01

  articleOpen access1st authorCorresponding

  Salmonella enterica serovar Typhimurium (S. Typhimurium) induces a host inflammatory response that suppresses the growth of commensal bacteria. A contributing factor is the expression of proteins that starve microbes of metals. One such protein, calprotectin (CP), sequesters zinc (Zn2+) and manganese (Mn2+). While growth of commensal bacteria is suppressed, intestinal inflammation enhances S. Typhimurium growth. We tested the hypothesis that Salmonella is resistant to CP-mediated Mn2+ starvation. Using wild-type CP or CP mutants deficient in either Zn2+ or Mn2+ binding, we determined that S. Typhimurium resisted CP-mediated Mn2+ starvation and growth inhibition by expressing three Mn2+ transporters (SitABCD, MntH, and ZupT) . We also show that Salmonella mutants lacking Mn2+ transporters had a growth defect in the inflamed gut that was not rescued in CP deficient (S100a9-/-) mice. Remarkably, growth inhibition of the sitA mntH zupT mutant was reduced in Il22-/- mice, which lack a key cytokine involved in the induction of metal-binding antimicrobials, a finding that suggests the host might also deploy CP-independent mechanisms of Mn2+ sequestration.Under anaerobic conditions, CP did not inhibit sitA mntH zupT growth, suggesting that Mn2+ sequestration may enhance Salmonella susceptibility to oxidative stress. Consistent with this hypothesis, Mn2+ is a co-factor for SodA, a superoxide dismutase in Salmonella that reduces oxidative stress. We found that SodA helped S. Typhimurium overcome CP-mediated growth inhibition and contributed to Salmonella growth in the inflamed gut. Because neutrophils are the major source of oxidative stress during Salmonella induced gastroenteritis, we partially rescued the growth defect of the sitA mntH zupT and sodA mutants when we depleted neutrophils in C57BL/6 mice. We also rescued the growth defect of the sitA mntH zupT and sodA mutants in Cybb-/- mice, which have a defect in producing ROS. Moreover, the growth defect of the sitA mntH zupT mutant was less prominent in Cybb-/- S100a9-/- mice, most likely because these mice lack some ability to enhance oxidative stress through CP-mediated Mn2+ sequestration. Altogether, we demonstrate that Mn2+ transporters contribute to S. Typhimurium growth in the inflamed gut by helping Salmonella overcome Mn2+ starvation to effectively mitigate the host oxidative burst.

  Publisher

Frequent coauthors

• Renée M. Tsolis

  University of California, Davis

  7 shared

• Briana M. Young

  University of California, Davis

  3 shared

• Bevin C. English

  University of California, San Francisco

  3 shared

• Kristen L. Lokken-Toyli

  University of California Davis Medical Center

  3 shared

• Tobias Kerrinnes

  Helmholtz Institute for RNA-based Infection Research

  3 shared

• Eric P. Skaar

  Vanderbilt University Medical Center

  3 shared

• Andreas J. Bäumler

  3 shared

• Hirotaka Hiyoshi

  Nagasaki University

  2 shared

Education

• Ph.D., Biomedical Sciences, Microbiology and Molecular Genetics

  University of California, Irvine

  2015

• Bachelor of Science; Major: Biological Sciences

  University of California, Irvine

  2009

• Associates Degree in Chemistry

  Cerritos College

  2005

Awards & honors

• 2011-2012 Graduate Fellow Award, conferred by the Howard Hug…
• 2012 Oral Presentation Competition, 2nd place, UCI Immunolog…
• 2014 ASM Richard and Mary Finkelstein Travel Award and Oral…
• 2014-2015 President’s Dissertation Year Fellowship, UC Irvin…
• 2015 Keystone Symposia Scholarship to attend symposium on Gu…