About

Victor Nizet, M.D., is a Distinguished Professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences, and also serves as Professor, Division Chief, and Vice Chair of the Department of Pediatrics at the School of Medicine. His laboratory focuses on understanding the fundamental mechanisms of bacterial pathogenesis and the innate immune system, with a special emphasis on invasive and antibiotic-resistant pathogens. His research involves discovering and characterizing bacterial virulence factors related to cytotoxicity, adherence, invasion, inflammation, molecular mimicry, and resistance to immunologic clearance. Additionally, he investigates host factors such as antimicrobial peptides, leukocyte surface receptors, signal transduction pathways, and transcription factors involved in defense against invasive bacterial infections. His work has led to the development of novel treatment strategies, including targeted neutralization of bacterial virulence phenotypes, pharmacologic boosting of innate immune cell function, drug repurposing, and innovative nano therapeutic and vaccine approaches. Dr. Nizet has made significant contributions to elucidating the genetic basis and mechanisms of virulence factors in human bacterial pathogens and the functions of the mammalian innate immune system, highlighting strategies for enhancing phagocytic defenses against drug-resistant pathogens.

Research topics

• Biology
• Microbiology
• Medicine
• Immunology
• Computational biology
• Genetics
• Chemistry
• Internal medicine
• Bioinformatics
• Physiology
• Intensive care medicine
• Nanotechnology
• Biotechnology
• Virology
• Materials science
• Neuroscience
• Cell biology
• Biochemistry

Selected publications

• Group B Streptococci lyse endothelial cells to infect the brain in a zebrafish meningitis model

  PLoS Biology · 2025-07-03 · 5 citations

  articleOpen access

  To cause meningitis, bacteria move from the bloodstream to the brain, crossing the endothelial cells of the blood-brain barrier. Most studies on how bacteria cross the blood-brain barrier have been performed in vitro using cultured endothelial cells, due to a paucity of animal models. Group B Streptococcus (GBS) is the leading cause of bacterial meningitis in neonates and is primarily thought to cross the blood-brain barrier by transcytosis through endothelial cells. To test this hypothesis in vivo, we used optically transparent zebrafish larvae. Time-lapse confocal microscopy revealed that GBS forms extracellular microcolonies in brain blood vessels and causes perforation and lysis of blood-brain barrier endothelial cells, which promotes bacterial entry into the brain. Vessels infected with GBS microcolonies were distorted and contained thrombi. Inhibition of clotting worsened brain invasion, suggesting a host-protective role for thrombi. The GBS lysin cylE, implicated in brain invasion in vitro, was found dispensable in vivo. Instead, pro-inflammatory mediators associated with endothelial cell damage and blood-brain barrier breakdown were specifically upregulated in the zebrafish head upon GBS entry into the brain. Therefore, GBS crosses the blood-brain barrier in vivo not by transcytosis, but by endothelial cell lysis and death. Given that we observe the same invasion route for a meningitis-associated strain of Streptococcus pneumoniae, our findings suggest that streptococcal infection of brain blood vessels triggers endothelial cell inflammation and lysis, thereby facilitating brain invasion.

  PublisherDOI

• The Central Importance of Vaccines to Mitigate the Threat of Antibiotic-Resistant Bacterial Pathogens

  Vaccines · 2025-08-23 · 2 citations

  reviewOpen accessSenior authorCorresponding

  Antibiotics have dramatically reduced the burden of infectious diseases since their discovery, but the accelerating rise in antimicrobial resistance (AMR) now threatens these gains. AMR was responsible for nearly 5 million deaths in 2023 and continues to undermine the efficacy of existing treatments, particularly in low- and middle-income countries. While efforts to address AMR have focused heavily on antibiotic stewardship and new drug development, vaccines represent a powerful yet underutilized tool for prevention. By reducing the incidence of bacterial infections, vaccines lower antibiotic consumption, interrupt transmission of resistant strains, and minimize the selective pressures that drive resistance. Unlike antibiotics, vaccines offer long-lasting protection, rarely induce resistance, and confer indirect protection through herd immunity. This review examines the global burden and drivers of AMR, highlights the unique advantages of vaccines over antibiotics in mitigating AMR, and surveys the current development pipeline of vaccines targeting key multidrug-resistant bacterial pathogens.

  PublisherOA PDFDOI

• Effect of Perinatal Ampicillin or Amoxicillin/Clavulanate Exposure on Maternal and Infant Gut Microbiome, Metabolome, and Infant Responses to the 20-valent Pneumococcal Conjugate Vaccine

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-08

  articleOpen access

  SUMMARY Emerging studies suggest that antibiotics can disrupt the gut microbiome and alter vaccine-induced immune responses, but the specific consequences of early-life exposure on neonatal immune development remains poorly understood. Here, we examined how two antibiotics frequently used in perinatal care, broad-spectrum ampicillin (AMP) and the extended-spectrum combination amoxicillin/clavulanate (AMOX/CLAV), administered during gestation and lactation, influence neonatal gut microbiome composition, fecal metabolome profiles, and responses to the 20-valent pneumococcal conjugate vaccine (PCV20). Maternal treatment with AMOX/CLAV, but not AMP, significantly reduced PCV-specific IgG titers at 4-and 6-weeks post-prime immunization compared to untreated controls. Exclusive exposure to AMOX/CLAV also impaired neutrophil-mediated opsonophagocytic killing, indicating diminished antibody functionality. These effects were transient, with immune parameters normalizing by week 8 post-prime immunization. Metabolomic and microbiome profiling revealed that maternal AMP and AMOX/CLAV differentially perturbed specific metabolite classes including bile acids, N -acyl lipids, and indole-derivatives, as well as key commensal taxa including Bacteroidales and Coriobacteriales within the gut microbiota. Together, these findings reveal a previously underappreciated maternal-offspring route of antibiotic influence that transiently disrupts neonatal vaccine responsiveness through microbiome and metabolome alterations. These results highlight maternal antibiotic exposure as a modifiable factor shaping early-life immunity.

  PublisherDOI

• Epigenetic silencing of interleukin-10 by host-derived oxidized phospholipids supports a lethal inflammatory response to infections

  Immunity · 2025-07-17 · 5 citations

  articleOpen access
  PublisherOA PDFDOI

• How to Utilize a Genome-Scale Metabolic Model and iModulon in the Research of Streptococcus pyogenes M1 Serotype

  2025-08-06

  articleOpen accessSenior author

  <i>Streptococcus pyogenes</i> can cause a wide variety of acute infections throughout the body of its human host [...]

  PublisherOA PDFDOI

• Antimicrobial resistance is widespread among intestinal and extra-intestinal <i>Bacteroides fragilis</i> strains

  Infection and Immunity · 2025-11-24

  articleOpen access

  ABSTRACT Bacteroides fragilis is an important member of the human gut microbiota, where it contributes to immune modulation, intestinal barrier integrity, and colonization resistance. Despite its beneficial roles as a symbiont in the gut, B. fragilis is also the most commonly isolated anaerobe in clinical infections, implicated in intra-abdominal abscesses, bloodstream infections, and soft tissue infections. Antimicrobial resistance (AMR) is increasingly recognized as a major factor in its transition from symbiont to opportunist; however, the relationship between resistance and anatomical site of isolation remains poorly defined. Here, we compared AMR phenotypes and genotypes between intestinal and extra-intestinal B. fragilis isolates to assess whether clinical strains are enriched for resistance determinants. Surprisingly, we found comparable susceptibility profiles and AMR gene content between the two groups. Minimal inhibitory concentrations (MICs) were broadly similar, and β-lactamase activity was detected in ~70% of the isolates regardless of the isolation site. We found that resistance genes were similarly distributed across both intestinal and clinical strains. A microbial genome-wide association study (mGWAS) confirmed the known resistance markers, such as ermF , aadS , and tetQ, and identified novel associations with conjugative transposons, efflux transporters, regulatory genes, and previously uncharacterized loci. These findings suggest that intestinal strains serve as a reservoir of clinically relevant resistance determinants that may be mobilized under selective pressure. Although prior work has largely focused on clinical isolates, our findings highlight the need to surveil AMR within the gut microbiota, where widespread resistance in commensal bacteria has the potential to complicate treatment of extra-intestinal infections.

  PublisherDOI

• Extended-Spectrum β-Lactamase-Producing Escherichia coli and Pediatric UTIs: A Review of the Literature and Selected Experimental Observations

  Antibiotics · 2025-12-18

  articleOpen access

  (UPEC). An increasing proportion of these strains produce extended-spectrum β-lactamases (ESBLs), which render β-lactam antibiotics ineffective. Interestingly, some patients with ESBL-producing UTIs improve clinically following treatment with antibiotics like cephalexin, despite demonstrated in vitro resistance. Working alongside and at times synergistically with antibiotics, host immune factors, such as the antimicrobial peptide cathelicidin (LL-37), contribute to bacterial clearance through direct killing and inhibition of biofilm formation. In this review, we summarize the current understanding of pediatric ESBL-producing UPEC infections and present selected in vitro and in vivo experimental data evaluating the combined effects of LL-37 and cephalexin on clinical isolates. Although no synergy was observed, ESBL-producing isolates demonstrated reduced bacterial burden in vivo compared to a non-ESBL UPEC strain. These findings suggest that host immune factors and environmental conditions may influence the fitness and virulence of drug-resistant UTI pathogens, warranting further investigation.

  PublisherOA PDFDOI

• Amoxicillin and metronidazole resistance of bacteria isolated from dental implants with peri-implant diseases: A pilot cross-sectional study

  2025-10-13

  preprintOpen accessSenior author

  Background. Peri-implant mucositis is a reversible inflammatory lesion of the mucosa surrounding a dental implant, caused by the accumulation of bacterial plaque and biofilm formation, without bone loss. If peri-implant mucositis is not addressed, it can progress to peri-implantitis, characterized by significant inflammation and infection of the peri-implant mucosa accompanied by the loss of supporting bone. Clinical evidence suggests that the management of peri-implant infections consist of mechanical debridement of implant, surgical intervention, and the administration of antibiotics. However, limited information is available regarding antibiotic resistance in bacteria causing peri-implant diseases. This study is focused to assess the antibiotic resistance of bacteria isolated from explanted dental implants with peri-implant infections, to amoxicillin, clindamycin and metronidazole. Methods. Biofilms were recovered using titanium curettes from dental implants of 10 patients with peri-implant infections: patients with peri-implant mucositis (n=4) exhibited redness, swelling or bleeding and absence of bone loss; patients with peri-implantitis (n=6) were diagnosed based on probing depth ≥6 mm and presence of bone loss. Antibiotic sensitivity was assessed using the Kirby-Bauer disk diffusion method in accordance with the Clinical and Laboratory Standards Institute at 10 μg per disk of amoxicillin, 30 μg per disk of clindamycin, and metronidazole at a concentration of 50 μg per disk. The results were expressed as the diameters of inhibition zones for each antibiotic. Two peri-implant bacteria were identified by sequencing of their 16s rRNA. Results. Cultivation of microorganisms revealed predominant facultative anaerobic bacteria. Peri-implant bacteria showed resistance to amoxicillin and metronidazole at 100% (10 out of 10). All isolates from dental implants with peri-implant infections (10 out of 10) were sensitive to clindamycin. Two isolates, M29 and P30 strains were identified as Streptococcus salivarius by 16s rRNA sequencing. Conclusion. Our findings reveal emerging resistance to amoxicillin and metronidazole in clinical isolates from implants with peri-implant infections, yet bacterial susceptibility to clindamycin remains.

  PublisherDOI

• STING-adjuvanted outer membrane vesicle nanoparticle vaccine against Pseudomonas aeruginosa

  JCI Insight · 2025-07-24 · 4 citations

  articleOpen accessSenior authorCorresponding

  Multidrug-resistant (MDR) bacterial pneumonia poses a critical threat to global public health. The opportunistic Gram-negative pathogen Pseudomonas aeruginosa is a leading cause of nosocomial-associated pneumonia, and an effective vaccine could protect vulnerable populations, including the elderly, immunocompromised, and those with chronic respiratory diseases. Highly heterogeneous outer membrane vesicles (OMVs), shed from Gram-negative bacteria, are studded with immunogenic lipids, proteins, and virulence factors. To overcome limitations in OMV stability and consistency, we described what we believe to be a novel vaccine platform that combines immunogenic OMVs with precision nanotechnology - creating a bacterial cellular nanoparticle (CNP) vaccine candidate, termed Pa-STING CNP, which incorporates an adjuvanted core that activates the STING (stimulator of interferon genes) pathway. In this design, OMVs are coated onto the surface of self-adjuvanted STING nanocores. Pa-STING CNP vaccination induced substantial antigen presenting cell recruitment and activation in draining lymph nodes, robust anti-Pseudomonas antibody responses, and provided protection against lethal challenge with the hypervirulent clinical P. aeruginosa isolate PA14. Antibody responses mediated this protection and provided passive immunity against the heterologous P. aeruginosa strain PA01. These findings provided evidence that nanotechnology can be used to create a highly efficacious vaccine platform against high priority MDR pathogens such as P. aeruginosa.

  PublisherOA PDFDOI

• Natural Macrophage Membrane-Coated Nanoparticles as a Multifaceted Sepsis Therapeutic to Sequester Inflammatory and Toxic Mediators

  ACS Nano · 2025-11-11 · 4 citations

  articleSenior authorCorresponding

  Bacterial sepsis is a life-threatening immune dysregulation triggered by bacterial infection and propagated by a dysfunctional host response, culminating in systemic tissue damage and multiorgan failure. In the United States, sepsis results in the hospitalization of more than one million patients annually and accounts for nearly one in three hospital deaths. Despite decades of efforts to develop immunoregulatory sepsis therapies, no clinically approved treatments exist. Recent advances in nanotechnology have introduced innovative approaches, including cellular nanodecoys synthesized from natural macrophage membranes coated onto polymeric nanoparticle cores. Here we introduce a human macrophage membrane-derived drug candidate, CTI-111, capable of sequestering soluble microbial toxins, drivers of inflammation, and pro-inflammatory cytokines from multiple sources. Therapeutic administration of CTI-111 reduces inflammation and improves survival in multiple murine sepsis models. We further demonstrate that CTI-111 can bind multiple sepsis-associated human cytokines in the complex environment of septic serum ex vivo. Together, these findings highlight the potential of CTI-111 as a multifaceted therapy for sepsis.

  PublisherDOI

Recent grants

• NIH Grant R01AI052453

  NIH · $5.3M · 2018

• NIH Grant R01AI096837

  NIH · $2.7M · 2017

• GAS Switch from Colonizing Bacterium to Invasive Pathogen

  NIH · $3.8M · 2008–2020

• NIH Grant R56AI090863

  NIH · $704k · 2011

• Broad recognition of group A Streptococcus M proteins

  NIH · $426k · 2018–2020

Frequent coauthors

• Jason N. Cole

  Cidara Therapeutics (United States)

  119 shared

• George Sakoulas

  University of California, San Diego

  103 shared

• Samira Dahesh

  102 shared

• Mary E. Hensler

  University of California, San Diego

  95 shared

• Satoshi Uchiyama

  National Cancer Center Hospital East

  86 shared

• Richard L. Gallo

  University of California, San Diego

  85 shared

• Joshua Olson

  University of Detroit Mercy

  81 shared

• Maren von Köckritz‐Blickwede

  University of Veterinary Medicine Hannover, Foundation

  81 shared

Education

• Pediatric Infectious Diseases Fellowship

  Seattle Children's Hospital & University of Washington

  1997

• Pediatric Residency & Chief Residency

  Boston Children's Hospital & Harvard University

  1993

• M.D.

  Stanford University School of Medicine

  1989

• B.S., Biology

  Reed College

  1984

Awards & honors

• American Lung Associate Career Investigator Award (2004)
• American Heart Association Established Investigator Award (2…
• American Society for Clinical Investigation (2006)
• E. Mead Johnson Award for Research in Pediatrics (2008)
• American Asthma Foundation Senior Investigator Award (2008)