Barbara Irene Kazmierczak PhD, MD
Associate Professor of Medicine (Infectious Diseases) and of Microbial Pathogenesis; Associate Director for Basic Research, MD-PhD Program, Yale University
Research Interests
Pseudomonas aeruginosa; Staphylococcus aureus; innate immunity; host-pathogen interactions; mucosal immunity
Research Summary
Our laboratory is interested in how environmental or commensal organisms--bacteria with which we come into daily contact--can become pathogens capable of causing severe, life-threatening infections. To answer this question, we study the bacterial determinants that allow the bacterium Pseudomonas aeruginosa to move between soil and water reservoirs to human patients, as well as the host immune responses that usually keep it in check. Our second pathogen of interest is Staphylococcus aureus; we are interested in the host immune factors that permit some individuals to become stable carriers of this bacterium on their skin and nares, while preventing others from acquiring this bacterium.
We are also studying how the use of antibiotics alters the composition of the bacteria that reside in the human gut-- the "gastrointestinal microbiome"--and what consequences this has for an individual's ability to mount immune responses to vaccines and to infecting pathogens.
Extensive Research Description
Dr. Kazmierczak studies opportunistic pathogens, with
a primary emphasis on Pseudomonas aeruginosa. Her group is focused on understanding
how microorganisms transition between commensal relationships with humans to
causing disease. The following research projects are active in the laboratory.
- Sensor kinase pathways that influence expression of genes involved in biofilm formation, Type 3 secretion and Type 6 secretion in Pseudomonas aeruginosa.
- Regulatory networks that control and coordinate pilus and flagellar assembly in response to environmental cues in Pseudomonas aeruginosa.
- Modulation of mammalian innate immune responses to Pseudomonas aeruginosa infection by the bacterial Type 3 secretion system apparatus and effectors.
- Measurement of bacterial virulence factor expression in predicting human disease outcome and severity.
- Human innate immune responses associated with persistent Staphylococcus aureus nasal carriage.
- Effects of broad spectrum antibiotic exposure on gut microbiome composition, and subsequent effects on host responses to vaccination and infection.
Selected Publications
- Kazmierczak BI, Murray TS. (2012) “Chronic vs. acute Pseudomonas aeruginosa infection states” in Regulation of Bacterial Virulence, ML Vasil and AJ Darwin, editors. ASM Press.
- Jain R, Behrens AJ, Kaever V, Kazmierczak BI. (2012) Type IV pilus assembly in Pseudomonas aeruginosa over a broad range of c-di-GMP concentrations. J Bacteriol in press
- Lavoie E, Wangdi T, Kazmierczak BI. (2011) Innate immune responses to Pseudomonas aeruginosa infection. Microbes Infection 13: 1133-1145.
- Mijares LA, Wangdi T, Sokol C, Homer R, Medzhitov R, Kazmierczak BI. (2011) Airway epithelial MyD88 restores control of Pseudomonas aeruginosa murine infection via an interluekin-1 dependent pathway. J Immunol 186: 7080-7088
- Wangdi T, Mijares LA, Kazmierczak BI. (2010). In vivo discrimination of T3SS-positive and –negative Pseudomonas aeruginosa via a caspase-1-dependent pathway. Infect Immun 78:4744-53
- Nelson JW, Chamessian AG, McEnaney PJ, Murelli RP, Kazmierczak BI, Spiegel DA. (2010) A biosynthetic strategy for re-engineering the S. aureus cell wall with non-native small molecules. ACS Chem Biol 5: 1147-1155.
- Murray TS, Ledizet M, Kazmierczak BI. (2010) Swarming motility, secretion of type 3 effectors and biofilm formation phenotypes exhibited within a large cohort of Pseudomonas aeruginosa clinical isolates. J Mol Microbiol 59: 511-520
- Sutterwala FS, Mijares LA, Li L, Ogura Y, Kazmierczak BI, Flavell RA. (2007) Immune recognition of Pseudomonas aeruginosa mediated by the IPAF/NLRC4 inflammasome. J Exp Med 204: 3235-3245.


