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1.  Understanding the Microbiology of Root Caries in Geriatric Patients

As people age their gums often recede revealing root surfaces to bacterial colonization and caries development. In the past, a few acid-generating bacteria have been implicated in the etiology of root caries, but with modern molecular techniques the collection of bacteria shown to be associated with root caries is expanding. Using techniques of quantitative PCR and microbiome analysis on dental plaque from diseased and health root surfaces we are defining those bacteria that are more prevalent on carious root surfaces and investigating their potential contributions to root caries. Our long-term goal is to develop therapies that target root caries-causing bacteria for elimination from dental plaque.

2) Defining Pathogenic Mechanisms of the Human Pathogen Yersinia pestis, the Causative Agent of Plague

Plague is one of the most devastating diseases in human history and still exists in a number of regions in the world today. While only a few cases of plague are documented each year in the U.S., it is of concern as a potential bioterrorism threat. Our laboratory performs research to understand the mechanisms of pathogenesis of Y. pestis in hopes of finding vulnerabilities to be exploited in the design of anti-plague therapeutics. We focus on defining the mechanism of toxin delivery from Y. pestis to human cells, a step required for disease as well as understanding how Y. pestis survives in human blood during plague infection despite our normal antimicrobial killing capacity.

The Krukonis Laboratory uses Yersinia pestis, the causative agent of plague, as a model organism to study how bacterial pathogens delivery cytotoxins to host cells resulting in disruption of normal cellular functions including cytoskeletal arrangements and immune pathways. Y. pestis is shown in association with the human epithelial cell line HEp-2, where the cytoskeleton has collapsed and cells are rounded indicating cytotoxicity caused by injection of several cytotoxic proteins known as Yops.

3) Regulation of Virulence Gene Expression in Vibrio cholerae, the Causative Agent of Cholera

The disease cholera is a rapidly progressing diarrheal disease that causes >100,000 infections and thousands of deaths each year (World Health Organization data). Bacterial pathogens express different genes according to their environment so they tailor protein expression to the conditions in which they are growing. V. cholerae, senses when it is ingested by a human host by a change in temperature and other environmental signals to trigger a program of gene expression that allows for efficient colonization of the human host and expression of the key virulence factor, cholera toxin. Expression of cholera toxin results in up to 20 liters of diarrheal excretion per day in patients suffering from cholera leading to a life-threating dehydration and allowing rapid dissemination of V. cholerae back into the environment to infect additional hosts. Our laboratory studies the molecules utilized for initiating the gene expression program required to establish cholera toxin expression as well as proteins required for host colonization. Our hope is to identify chemical compounds that can inhibit this process and could be used as therapeutics during cholera outbreaks.

The Krukonis lab has a grant from NIH Institute of Allergy and Infectious Disease (NIAID)

NIH R21 AI 133570 entitled:

“Ail-mediated serum resistance in Yersinia pestis and its contribution to plague

virulence”

The Krukonis Lab has a grant from the 鲍鱼tv School of Dentistry entitled:

“Explorations in Bacterial Pathogenesis”

In addition, the Krukonis lab participates in anotherDMSOD grant entitled:   

“Isolation of bacteriophages that target and kill dental pathogens”

PUBLICATIONS

Some key publications from our laboratory are:

Krukonis, E.S. and Thomson, J.J. 2020 Complement Evasion Mechanisms of the

Systemic Pathogens Yersiniae and Salmonellae FEBS J. 594 (16) pp.2598-2620.

        Invited Review

Morgan, S.J., French, E.L., Plecha, S.C., and Krukonis, E.S. 2019 The wing of the ToxR

winged helix-turn-helix domain is required for DNA binding and activation of toxT

and ompU PLoS One 14(9) e0221936

Thomson, J.J., Plecha S.C. and Krukonis E.S. 2019 Ail provides multiple mechanisms of

serum resistance to Yersinia pestis Mol Microbiol Vol 111 (1) pp. 82-95

Davidson, T., Lewandowski, E., Smerecki, M., Stratton, H., Alhabeil, J., Wheater, M.,

Shepherd, K. and Krukonis, E.S. 2017 Taking Your Work Home With You: Potential

Risks of Contaminated Clothing and Hair in the Dental Clinic and Attitudes about Infection Control Can J Inf Cntl Vol 32 (3) pp. 137-142.

Tsang, T. M., Wiese, J. S., Alhabeil, J. A., Usselman, L. D., Thomson, J. J., Matti, R.,

      Kronshage, M., Maricic, N., Williams, S., Sleiman, N. H., Felek, S. and Krukonis, E.

2017. 2017. Defining the Ail Ligand-Binding Surface: Hydrophobic Residues in Two

      Extracellular Loops Mediate Cell and Extracellular Matrix Binding To Facilitate Yop

      Delivery. Infect Immun. Vol. 85 (4) e01047-15.

Morgan, S.J., French, E.L., Thomson, J.J., Seaborn C.P., Shively, C.A. and Krukonis,

E.S. 2015. Formation of an intramolecular periplasmic disulfide bond in TcpP protects TcpP and TcpH from degradation in Vibrio cholerae. J. Bact. Vol. 198(3) pp. 498-509.

Goss, T.J, Morgan, S.J., French, E.L. and Krukonis, E.S. 2013. ToxR recognizes a direct

repeat element in the toxT, ompU, ompT and ctxA promoters of Vibrio cholerae to

regulate transcription. Infect. Immun. Vol. 81(3) pp. 884-895.

Morgan, S.J., Felek, S., Gadwal, S., Koropatkin, N.M., Perry, W.J., Bryson, A.B., and

Krukonis, E.S. 2011. The two faces of ToxR: activator of ompU, co-regulator of

toxT in Vibrio cholerae, Mol. Micro. Vol. 81 (1) pp. 113-128.

Tsang, T. M., Felek, S. and Krukonis, E. S. 2010. Ail binding to fibronectin facilitates

        Yersinia pestis binding to host cells and Yop delivery. Infect. Immun. Vol. 78 (8)

        pp.3358-3368.

Goss, T. J., Seaborn, C. P., Gray, M. D. and Krukonis, E. S. 2010. Identification of the

        TcpP-binding site in the toxT promoter of Vibrio cholerae and the role of ToxR in

        TcpP-mediated activation. Infect. Immun. Vol. 78 (10) pp. 4122-4133.

Felek, S., Tsang, T. M.  and Krukonis, E. S. 2010. Three Yersinia pestis adhesins

        facilitate Yop delivery to eukaryotic cells and contribute to plague virulence. Infect.

        Immun. Vol. 78 (10) pp. 4134-4150.

Felek, S. and Krukonis, E.S. 2009. The Yersinia pestis Ail protein mediates binding

        and Yop delivery to host cells required for plague virulence. Infect. Immun., Vol.

        77 (2) pp.825-836.     Cover article

A Complete List of Published Works Can be Found in MyBibliography:

Current Lab Members:

Dr. Sarah Plecha

Postdoctoral Fellow

Karmen Rucker

Laboratory Technician and Lab Coordinator

Laura Young

Laboratory Technician

Dental Students:

Lucas Mathes – DS4

Michele Bhagwagar – DS3

Jay Wayntraub – DS3

Christen Thompson – DS3

Eilkay Samadi – DS3

William Vo – DS3

Nik Tasevski – DS3

Colleen O’Brien – DS3

Periodontics Residents:

Dr. Jonathan Zora

鲍鱼tv Undergraduates:

Amber Abram - BUILD Scholar

Sean Ojha - 鲍鱼tv Undergraduate

Past Lab Members:

Jamal Alhabeil, former Laboratory Technician and Lab Coordinator; currently teaching English Language in Nagahama, Japan for the Shiga Board of Education

Dr. Joshua Thomson

former Postdoctoral Fellow – currently Assistant Professor: 鲍鱼tv School of Dentistry

Dr. Emily French

former laboratory technician – currently in the La Crosse-Mayo Family Medicine Residency Program in La Crosse, WI; MD from Central Michigan University

Jeffrey Wiese

former laboratory technician – currently a Senior Medical writer at MMS Holdings

Dr. Suleyman Felek

former Postdoctoral Fellow – currently practicing Internal Medicine at Richmond University Medical Center, Waterbury Hospital and Yale-New Haven Children's Hospital 

Dr. Sarah Morgan

former PhD student – currently a Senior Postdoctoral fellow/lab manager at University of Washington in the laboratory of Dr. Pradeep Singh

Dr. Tiffany Tsang

former PhD student – currently a science contractor between the US government and private industry

Dr. Thomas Goss

former laboratory technician – currently a senior laboratory technician at the University of Michigan Medical School

Malte Kronshage MS

former Masters student from Germany

Former 鲍鱼tv Undergraduates

Christina Jones - former BUILD Scholar: currently a DDS/PhD candidate at the University

of Michigan School of Dentistry, in the laboratory of Dr. Isabelle Lombaert

Nour El Yaman – former BUILD Scholar

Lizbeth Garcia-Leon – former BUILD Scholar

Former Dental Students:

Zachary Mayer DDS

Keeton Colville DDS

Mohamed El-Shaer DDS

Elizabeth Doman DDS

Sumita Sam DDS

Lisa Park DDS

Shameel Khan DDS

Michelle Szewczyk DDS

Ayah Koleilat DDS

Malaka Saleh DDS

Jonathon Zora DDS

Chelseas Watkins DDS

Former Hygiene students:

Hina Qadir RDH

Teniece Roberts RDH

Megan Patlow RDH

Terlicia Winston RDH

Alexandra Willaeys RDH

Taylor Davidson RDH

Meghan Smerecki RDH

Halee Stratton RDH

Erica Lewandowski RDH

Sarah Charland RDH

Alyson Fryz RDH

Sara Trombly RDH

Heather VanOast RDH

Rajpreet Grover RDH

Shamaila Mirza RDH

Navneet Somal RDH

Hannah Howard RDH

Vrushi Patel RDH

Mirna Yousif RDH

Amanda Totin RDH

Former Dental Residents:

Krupa Patel DDS