Barbara Irene Kazmierczak PhD, MD

Associate Professor of Medicine (Infectious Diseases) and of Microbial Pathogenesis; Director, 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.

  1. Sensor kinase pathways that influence expression of genes involved in biofilm formation, Type 3 secretion and Type 6 secretion in Pseudomonas aeruginosa.
  2. Regulatory networks that control and coordinate pilus and flagellar assembly in response to environmental cues in Pseudomonas aeruginosa.
  3. Modulation of mammalian innate immune responses to Pseudomonas aeruginosa infection by the bacterial Type 3 secretion system apparatus and effectors.
  4. Measurement of bacterial virulence factor expression in predicting human disease outcome and severity.
  5. Human innate immune responses associated with persistent Staphylococcus aureus nasal carriage.
  6. Effects of broad spectrum antibiotic exposure on gut microbiome composition, and subsequent effects on host responses to vaccination and infection.

Selected Publications

  • Romberg N*, Al Moussawi K*, Nelson-Williams C, Stiegler AL, Loring E, Choi M, Overton J, Meffre E, Khokha MK, Huttner AJ, West B, Podoltsev NA, Boggon TJ, Kazmierczak BI#, Lifton RP#. (2014) Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation. Nat Genet doi:10.1038/ng.3066
  • Czechowska K, McKeithen-Mead S, Al Moussawi K, Kazmierczak BI. (2014) Cheating by Type 3 secretion system negative Pseudomonas aeruginosa during pulmonary infection. PNAS 111: 7801-7806
  • Al Moussawi K, Kazmierczak BI. (2014) Distinct contributions of Interleukin (IL)-1a and IL-1ß to innate immune recognition of Pseudomonas aeruginosa in the lung. Infect Immun 82:4204-4211.
  • Kazmierczak BI, Hendrixson DR. (2013) Spatial and numerical regulation of flagellar biosynthesis in polarly-flagellated bacteria. Mol Microbiol 88:655-63.
  • Schniederberend M, Abdurachim K, Murray TS, Kazmierczak BI (2013) The GTPase activity of FlhF is dispensable for flagellar localization, but not motility, in Pseudomonas aeruginosa. J Bacteriol 195: 1051-1060
  • 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 194:4285-4294.
  • 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

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