Barbara Kazmierczak, MD, PhD
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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.
- Regulation 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.
- 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?
- Novel approaches to understanding intrinsic antibiotic resistance and developing new antimicrobials.
- 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
Selected Publications
- Identification of Efflux Substrates Using a Riboswitch-Based Reporter in Pseudomonas aeruginosaUrdaneta-Páez V, Hamchand R, Anthony K, Crawford J, Sutherland A, Kazmierczak B. Identification of Efflux Substrates Using a Riboswitch-Based Reporter in Pseudomonas aeruginosa. MSphere 2023, 8: e00069-23. PMID: 36946743, PMCID: PMC10117056, DOI: 10.1128/msphere.00069-23.
- Assessment of polymicrobial interactions in bacterial isolates from transfused platelet units associated with sepsisKerantzas CA, Merwede J, Snyder EL, Hendrickson JE, Tormey CA, Kazmierczak BI, Peaper DR. Assessment of polymicrobial interactions in bacterial isolates from transfused platelet units associated with sepsis. Transfusion 2022, 62: 2458-2463. PMID: 36178430, DOI: 10.1111/trf.17136.
- Pearls of wisdom for aspiring physician-scientist residency applicants and program directorsGallagher EJ, Rockey DC, Kontos CD, Vyas JM, Brass LF, Hu PJ, Isales CM, Ajijola OA, Rathmell WK, Conlin PR, Baiocchi RA, Kazmierczak BI, Akabas MH, Williams CS. Pearls of wisdom for aspiring physician-scientist residency applicants and program directors. JCI Insight 2022, 7: e158467. PMID: 35315364, PMCID: PMC8986063, DOI: 10.1172/jci.insight.158467.
- A Primed Subpopulation of Bacteria Enables Rapid Expression of the Type 3 Secretion System in Pseudomonas aeruginosaLin 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: e00831-21. PMID: 34154400, PMCID: PMC8262847, DOI: 10.1128/mbio.00831-21.
- Co-Culture of Acinetobacter calcoaceticus-baumannii complex and Staphylococcus saprophyticus Supports Simple Point Contamination Model in Recent Cases of Transfusion-Related SepsisKerantzas C, Merwede J, Snyder E, Hendrickson J, Tormey C, Kazmierczak B, Peaper D. Co-Culture of Acinetobacter calcoaceticus-baumannii complex and Staphylococcus saprophyticus Supports Simple Point Contamination Model in Recent Cases of Transfusion-Related Sepsis. American Journal Of Clinical Pathology 2020, 154: s14-s14. DOI: 10.1093/ajcp/aqaa137.025.
- The Enemy of my Enemy: Bacterial Competition in the Cystic Fibrosis LungKazmierczak BI. The Enemy of my Enemy: Bacterial Competition in the Cystic Fibrosis Lung. Cell Host & Microbe 2020, 28: 502-504. PMID: 33031766, DOI: 10.1016/j.chom.2020.09.009.
- Global chemical effects of the microbiome include new bile-acid conjugationsQuinn 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. PMID: 32103176, PMCID: PMC7252668, DOI: 10.1038/s41586-020-2047-9.
- 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 PMID: 31871033, PMCID: PMC7043666, DOI: 10.1128/jb.00682-19.
- Modulation of flagellar rotation in surface-attached bacteria: A pathway for rapid surface-sensing after flagellar attachmentSchniederberend 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. PMID: 31682637, PMCID: PMC6855561, DOI: 10.1371/journal.ppat.1008149.
- 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 PMID: 31010901, PMCID: PMC6560136, DOI: 10.1128/jb.00117-19.
- Interaction of the cyclic-di-GMP binding protein FimX and the Type 4 pilus assembly ATPase promotes pilus assemblyJain 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. PMID: 28854278, PMCID: PMC5595344, DOI: 10.1371/journal.ppat.1006594.
- Inflammation: A Double-Edged Sword in the Response to Pseudomonas aeruginosa InfectionLin CK, Kazmierczak BI. Inflammation: A Double-Edged Sword in the Response to Pseudomonas aeruginosa Infection. Journal Of Innate Immunity 2017, 9: 250-261. PMID: 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. PMID: 27606630, PMCID: PMC5015830, DOI: 10.1371/journal.ppat.1005792.
- NAIP proteins are required for cytosolic detection of specific bacterial ligands in vivoRauch I, Tenthorey JL, Nichols RD, Moussawi K, Kang JJ, Kang C, Kazmierczak BI, Vance RE. NAIP proteins are required for cytosolic detection of specific bacterial ligands in vivo. Journal Of Experimental Medicine 2016, 213: 657-665. PMID: 27045008, PMCID: PMC4854734, DOI: 10.1084/jem.20151809.
- Cross-regulation of Pseudomonas motility systems: the intimate relationship between flagella, pili and virulenceKazmierczak 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. PMID: 26476804, PMCID: PMC4688086, DOI: 10.1016/j.mib.2015.07.017.
- Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammationRomberg 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. PMID: 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 LungMoussawi 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: 4204-4211. PMID: 25069982, PMCID: PMC4187872, DOI: 10.1128/iai.02218-14.
- Cheating by type 3 secretion system-negative Pseudomonas aeruginosa during pulmonary infectionCzechowska K, McKeithen-Mead S, 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: 7801-7806. PMID: 24821799, PMCID: PMC4040582, DOI: 10.1073/pnas.1400782111.
- The GTPase Activity of FlhF Is Dispensable for Flagellar Localization, but Not Motility, in Pseudomonas aeruginosaSchniederberend 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 2012, 195: 1051-1060. PMID: 23264582, PMCID: PMC3571332, DOI: 10.1128/jb.02013-12.
- Chronic versus Acute Pseudomonas aeruginosa Infection StatesKazmierczak B, Murray T. Chronic versus Acute Pseudomonas aeruginosa Infection States. 2012, 21-39. DOI: 10.1128/9781555818524.ch2.
- Correction to A Biosynthetic Strategy for Re-engineering the Staphylococcus aureus Cell Wall with Non-native Small MoleculesNelson J, Chamessian A, McEnaney P, Murelli R, Kazmierczak B, Spiegel D. Correction to A Biosynthetic Strategy for Re-engineering the Staphylococcus aureus Cell Wall with Non-native Small Molecules. ACS Chemical Biology 2011, 6: 971-971. PMCID: PMC3262475, DOI: 10.1021/cb200283s.
- Pseudomonas aeruginosa ExoT Acts In Vivo as a GTPase-Activating Protein for RhoA, Rac1, and Cdc42Kazmierczak B, Engel J. Pseudomonas aeruginosa ExoT Acts In Vivo as a GTPase-Activating Protein for RhoA, Rac1, and Cdc42. Infection And Immunity 2002, 70: 2198-2205. PMID: 11895987, PMCID: PMC127837, DOI: 10.1128/iai.70.4.2198-2205.2002.
- INTERACTION OF BACTERIAL PATHOGENS WITH POLARIZED EPITHELIUMKazmierczak B, Mostov K, Engel J. INTERACTION OF BACTERIAL PATHOGENS WITH POLARIZED EPITHELIUM. Annual Review Of Microbiology 2001, 55: 407-435. PMID: 11544362, DOI: 10.1146/annurev.micro.55.1.407.
- Pseudomonas aeruginosa ExoT inhibits in vitro lung epithelial wound repairGeiser T, Kazmierczak B, Garrity‐Ryan L, Matthay M, Engel J. Pseudomonas aeruginosa ExoT inhibits in vitro lung epithelial wound repair. Cellular Microbiology 2001, 3: 223-236. PMID: 11298646, DOI: 10.1046/j.1462-5822.2001.00107.x.
- Rho GTPase activity modulates Pseudomonas aeruginosa internalization by epithelial cellsKazmierczak B, Jou T, Mostov K, Engel J. Rho GTPase activity modulates Pseudomonas aeruginosa internalization by epithelial cells. Cellular Microbiology 2001, 3: 85-98. PMID: 11207623, DOI: 10.1046/j.1462-5822.2001.00091.x.
- The Arginine Finger Domain of ExoT Contributes to Actin Cytoskeleton Disruption and Inhibition of Internalization ofPseudomonas aeruginosa by Epithelial Cells and MacrophagesGarrity-Ryan L, Kazmierczak B, Kowal R, Comolli J, Hauser A, Engel J. The Arginine Finger Domain of ExoT Contributes to Actin Cytoskeleton Disruption and Inhibition of Internalization ofPseudomonas aeruginosa by Epithelial Cells and Macrophages. Infection And Immunity 2000, 68: 7100-7113. PMID: 11083836, PMCID: PMC97821, DOI: 10.1128/iai.68.12.7100-7113.2000.
- pIV, a Filamentous Phage Protein that Mediates Phage Export Across the Bacterial Cell Envelope, Forms a MultimerKazmierczak B, Mielke D, Russel M, Model P. pIV, a Filamentous Phage Protein that Mediates Phage Export Across the Bacterial Cell Envelope, Forms a Multimer. Journal Of Molecular Biology 1994, 238: 187-198. PMID: 8158648, DOI: 10.1006/jmbi.1994.1280.
- Analysis of the structure and subcellular location of filamentous phage pIV.Russel M, Kaźmierczak B. Analysis of the structure and subcellular location of filamentous phage pIV. Journal Of Bacteriology 1993, 175: 3998-4007. PMID: 8320216, PMCID: PMC204828, DOI: 10.1128/jb.175.13.3998-4007.1993.
- Neuromodulator‐Mediated Phosphorylation of Specific Proteins in a Neurotumor Hybrid Cell Line (NCB‐20)Berry‐Kravis E, Kazmierczak B, Derechin V, Dawson G. Neuromodulator‐Mediated Phosphorylation of Specific Proteins in a Neurotumor Hybrid Cell Line (NCB‐20). Journal Of Neurochemistry 1988, 50: 1287-1296. PMID: 2450174, DOI: 10.1111/j.1471-4159.1988.tb10606.x.