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Barbara Kazmierczak, PhD, MD

Gustavus and Louise Pfeiffer Research Foundation M.D.-Ph.D. Program Director and Professor of Medicine (Infectious Diseases) and of Microbial Pathogenesis; Professor, Microbial Pathogenesis; Director, MD-PhD Program, Yale University

Contact Information

Barbara Kazmierczak, PhD, MD

Lab Location

Office Location

Mailing Address

  • Infectious Diseases

    PO Box 208056, 333 Cedar Street

    New Haven, CT 06520-8056

    United States

Yale Medicine

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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. Recent projects also address strategies to discover new and re-purpose old antibiotics against this MDR pathogen.

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.

Specialized Terms: Pseudomonas aeruginosa; Innate immunity; Host-pathogen interactions; Mucosal immunity

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. Regulation 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. Single-cell analysis of Type 3 secretion system expression: how is phenotypic heterogeneity generated within a clonal population, and how does it affect fitness of a pathogen in the host?
  5. Novel approaches to understanding intrinsic antibiotic resistance and developing new antimicrobials.
  6. Acquisition of gut and airway microbiome populations in infants with Cystic Fibrosis and healthy controls: consequences for disease progression and development of inflammation.

Coauthors

Research Interests

Bacterial Infections; Education, Medical, Graduate; Immunity, Innate; Microbiology; Pseudomonas; Biomedical Research; Host-Pathogen Interactions; Infectious Disease Medicine

Research Image

Heterogeneous expression of virulence in Pseudomonas aeruginosa

A Type 3 secretion system transcriptional reporter driving sfGFP expression reveals variation among genetically identical bacteria exposed to conditions that induce this virulence system.

Selected Publications

  • A Primed Subpopulation of Bacteria Enables Rapid Expression of the Type 3 Secretion System in Pseudomonas aeruginosa.Lin CK, Lee DSW, McKeithen-Mead S, Emonet T, Kazmierczak B. A Primed Subpopulation of Bacteria Enables Rapid Expression of the Type 3 Secretion System in Pseudomonas aeruginosa. MBio 2021, 12: e0083121 PubMed ID: 34154400, PMCID: PMC8262847, DOI: 10.1128/mBio.00831-21.
  • A Screen for Antibiotic Resistance Determinants Reveals a Fitness Cost of the Flagellum in Pseudomonas aeruginosa.Rundell EA, Commodore N, Goodman AL, Kazmierczak BI. A Screen for Antibiotic Resistance Determinants Reveals a Fitness Cost of the Flagellum in Pseudomonas aeruginosa. Journal Of Bacteriology 2020, 202 PubMed ID: 31871033, PMCID: PMC7043666, DOI: 10.1128/JB.00682-19.
  • Global chemical effects of the microbiome include new bile-acid conjugations.Quinn RA, Melnik AV, Vrbanac A, Fu T, Patras KA, Christy MP, Bodai Z, Belda-Ferre P, Tripathi A, Chung LK, Downes M, Welch RD, Quinn M, Humphrey G, Panitchpakdi M, Weldon KC, Aksenov A, da Silva R, Avila-Pacheco J, Clish C, Bae S, Mallick H, Franzosa EA, Lloyd-Price J, Bussell R, Thron T, Nelson AT, Wang M, Leszczynski E, Vargas F, Gauglitz JM, Meehan MJ, Gentry E, Arthur TD, Komor AC, Poulsen O, Boland BS, Chang JT, Sandborn WJ, Lim M, Garg N, Lumeng JC, Xavier RJ, Kazmierczak BI, Jain R, Egan M, Rhee KE, Ferguson D, Raffatellu M, Vlamakis H, Haddad GG, Siegel D, Huttenhower C, Mazmanian SK, Evans RM, Nizet V, Knight R, Dorrestein PC. Global chemical effects of the microbiome include new bile-acid conjugations. Nature 2020, 579: 123-129 PubMed ID: 32103176, PMCID: PMC7252668, DOI: 10.1038/s41586-020-2047-9.
  • The Enemy of my Enemy: Bacterial Competition in the Cystic Fibrosis Lung.Kazmierczak BI. The Enemy of my Enemy: Bacterial Competition in the Cystic Fibrosis Lung. Cell Host & Microbe 2020, 28: 502-504 PubMed ID: 33031766, DOI: 10.1016/j.chom.2020.09.009.
  • In Situ Structures of Polar and Lateral Flagella Revealed by Cryo-Electron Tomography.Zhu S, Schniederberend M, Zhitnitsky D, Jain R, Galán JE, Kazmierczak BI, Liu J. In Situ Structures of Polar and Lateral Flagella Revealed by Cryo-Electron Tomography. Journal Of Bacteriology 2019, 201 PubMed ID: 31010901, PMCID: PMC6560136, DOI: 10.1128/JB.00117-19.
  • Modulation of flagellar rotation in surface-attached bacteria: A pathway for rapid surface-sensing after flagellar attachment.Schniederberend M, Williams JF, Shine E, Shen C, Jain R, Emonet T, Kazmierczak BI. Modulation of flagellar rotation in surface-attached bacteria: A pathway for rapid surface-sensing after flagellar attachment. PLoS Pathogens 2019, 15: e1008149 PubMed ID: 31682637, PMCID: PMC6855561, DOI: 10.1371/journal.ppat.1008149.
  • Interaction of the cyclic-di-GMP binding protein FimX and the Type 4 pilus assembly ATPase promotes pilus assembly.Jain R, Sliusarenko O, Kazmierczak BI. Interaction of the cyclic-di-GMP binding protein FimX and the Type 4 pilus assembly ATPase promotes pilus assembly. PLoS Pathogens 2017, 13: e1006594 PubMed ID: 28854278, PMCID: PMC5595344, DOI: 10.1371/journal.ppat.1006594.
  • Inflammation: A Double-Edged Sword in the Response to Pseudomonas aeruginosa Infection.Lin CK, Kazmierczak BI. Inflammation: A Double-Edged Sword in the Response to Pseudomonas aeruginosa Infection. Journal Of Innate Immunity 2017, 9: 250-261 PubMed ID: 28222444, PMCID: PMC5469373, DOI: 10.1159/000455857.
  • Rampant Cheating by Pathogens?Rundell EA, McKeithen-Mead SA, Kazmierczak BI. Rampant Cheating by Pathogens? PLoS Pathogens 2016, 12: e1005792 PubMed ID: 27606630, PMCID: PMC5015830, DOI: 10.1371/journal.ppat.1005792.
  • NAIP proteins are required for cytosolic detection of specific bacterial ligands in vivo.Rauch I, Tenthorey JL, Nichols RD, Al Moussawi K, Kang JJ, Kang C, Kazmierczak BI, Vance RE. NAIP proteins are required for cytosolic detection of specific bacterial ligands in vivo. The Journal Of Experimental Medicine 2016, 213: 657-65 PubMed ID: 27045008, PMCID: PMC4854734, DOI: 10.1084/jem.20151809.
  • Cross-regulation of Pseudomonas motility systems: the intimate relationship between flagella, pili and virulence.Kazmierczak BI, Schniederberend M, Jain R. Cross-regulation of Pseudomonas motility systems: the intimate relationship between flagella, pili and virulence. Current Opinion In Microbiology 2015, 28: 78-82 PubMed ID: 26476804, PMCID: PMC4688086, DOI: 10.1016/j.mib.2015.07.017.
  • Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation.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. Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation. Nature Genetics 2014, 46: 1135-1139 PubMed ID: 25217960, PMCID: PMC4177367, DOI: 10.1038/ng.3066.
  • Distinct contributions of interleukin-1α (IL-1α) and IL-1β to innate immune recognition of Pseudomonas aeruginosa in the lung.Al Moussawi K, Kazmierczak BI. Distinct contributions of interleukin-1α (IL-1α) and IL-1β to innate immune recognition of Pseudomonas aeruginosa in the lung. Infection And Immunity 2014, 82: 4204-11 PubMed ID: 25069982, PMCID: PMC4187872, DOI: 10.1128/IAI.02218-14.
  • Cheating by type 3 secretion system-negative Pseudomonas aeruginosa during pulmonary infection.Czechowska K, McKeithen-Mead S, Al Moussawi K, Kazmierczak BI. Cheating by type 3 secretion system-negative Pseudomonas aeruginosa during pulmonary infection. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 7801-6 PubMed ID: 24821799, PMCID: PMC4040582, DOI: 10.1073/pnas.1400782111.
  • The GTPase activity of FlhF is dispensable for flagellar localization, but not motility, in Pseudomonas aeruginosa.Schniederberend M, Abdurachim K, Murray TS, Kazmierczak BI. The GTPase activity of FlhF is dispensable for flagellar localization, but not motility, in Pseudomonas aeruginosa. Journal Of Bacteriology 2013, 195: 1051-60 PubMed ID: 23264582, PMCID: PMC3571332, DOI: 10.1128/JB.02013-12.
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