Profiles

Abby Kroken, PhD

Degrees

Ph.D.  Medical College of Wisconsin

Research Interests

Major Research Interests: Host-pathogen interaction at the ocular surface leading to bacterial keratitis.

Kroken Laboratory

The corneal surface of the eye is highly antimicrobial. Few live bacteria can be detected on the corneas of people, and healthy animal models can eliminate pathogenic bacteria from the ocular surface within hours. Both injury and contact lens wear allow microbes to attach to and invade corneal tissue, potentially leading to vision-threatening keratitis. The environmental bacterium Pseudomonas aeruginosa is responsible for the majority of soft contact lens-related infections, and is also a significant threat following eye injuries.

Not all bacteria within a population behave identically. Only a subset of P. aeruginosa express virulence factors with known roles in causing disease (a phenomenon termed bistability). Related, not all bacteria occupy the same subcellular niches while invading host tissue. Though P. aeruginosa is often appreciated as an effective extracellular pathogen toward innate immune cells, some bacteria can be internalized by epithelial cells, and either occupy vacuolar compartments or escape and replicate in host cell cytoplasm. Intracellular bacteria typically trigger specific host inflammatory responses, such as inflammasome activation and lysis of the invaded cell. We are investigating how P. aeruginosa mitigates this host defense to maintain its intracellular niche in epithelial cells, as well as the relative importance of intracellular bacteria in early colonization of host tissue.  

One of our primary strategies is using imaging to study host-microbe interactions at the single cell level. The cornea, a clear and accessible tissue, is uniquely amenable to visualizing fluorescent markers and reporters of both host and microbe. In addition, primary epithelial cells and cell lines grown as multilayers at an air-liquid interface replicate aspects of cornea architecture and allow time-lapse imaging to track the outcome of host cells harboring intracellular bacteria. We expect that knowing the proportion and position of bacteria that produce virulence factors will guide antimicrobial and antivirulence therapeutic interventions.

Selected Publications

Peer-reviewed publications as of Feb 2021: ¹co-first author

Szczotka-Flynn L, Shovlin J, Schnider C, Caffery B, Alfonso E , Carnt N, Chalmers R, Collier S, Jacobs D, Joslin C, Kroken A, Lakkis C, Pearlman E, Schein O, Stapleton F, Tu E, Willcox M. American Academy of Optometry Microbial Keratitis Think Tank. Optometry and Vision Science. In press, accepted Dec 31, 2020

Fleiszig SMJ, Kroken AR, Nieto V, Grosser MR, Wan SJ, Metruccio MME, Evans DJ. Contact lens-related corneal infection: Intrinsic resistance and its compromise. 2019. Progress in Retina and Eye Research Nov 20; 100804. PMID: 31756497

Nieto V, Kroken AR, Grosser MR, Smith BE, Metruccio MME, Hagan P, Hallsten ME, Evans DJ, Fleiszig, SMJ. A novel form of intracellular bacterial motility performed by Pseudomonas aeruginosa. 2019. MBio, Aug 20;10(4). pii: e02880-18. PMID: 31431558

Metruccio MME, Wan SJ, Horneman H, Kroken AR, Sullivan AB, Truong TN, Mun JJ, Tam CKP, Frith R, Welsh L, George MD, Morris CA, Evans DJ, Fleiszig SMJ. A novel murine model for contact lens wear reveals clandestine IL-1R dependent corneal parainflammation and susceptibility to microbial keratitis upon inoculation with Pseudomonas aeruginosa. 2018. The Ocular Surface, 17 (1), 119-133. PMID: 30439473

Kroken AR, Chen CK,  Evans DJ, Yahr, TL, Fleiszig SMJ. The impact of ExoS on Pseudomonas aeruginosa internalization by epithelial cells is independent of fleQ and correlates with bistability of type three secretion system gene expression. 2018. MBio, May 1;9(3). pii: e00668-18. PMID: 29717012

Kroken AR, Blum FC, Zuverink M, Barbieri JT. Entry of Botulinum neurotoxin subtype A variants into neurons. 2016. Infection and Immunity, 85(1), e00795-16. PMID: 27795365

Przedpelski A, Tepp W,  Kroken AR, Fu Z, Kim JJ, Johnson EA, Barbieri JT. Enhancing the Protective Immune Response against Botulism. 2013. Infection and immunity 81 (7), 2638-2644. PMID: 23670557

Blum FC, Chen C, Kroken AR, Barbieri JT. Tetanus Toxin and Botulinum Toxin A utilize unique mechanisms to enter neurons of the central nervous system. 2012. Infection and immunity 80 (5), 1662-1669. PMID: 22392932

Kroken AR, Karalewitz AP, Fu Z, Kim JJ, Barbieri JT. Novel Ganglioside-mediated Entry of Botulinum Neurotoxin Serotype D into Neurons. 2011. Journal of Biological Chemistry 286 (30), 26828-26837. PMID: 21632541

Kroken AR, Karalewitz AP, Fu Z, Baldwin MR, Kim JJ, Barbieri JT. Unique ganglioside binding by Botulinum Neurotoxins C and D-SA. 2011. FEBS Journal 278 (23), 4486-4496. PMID: 21554541

Karalewitz AP¹, Kroken AR¹, Fu Z, Baldwin MR, Kim JJ, Barbieri JT. Identification of a Unique Ganglioside Binding Loop within Botulinum Neurotoxins C and D-SA. 2010. Biochemistry 49 (37), 8117-8126. PMID: 20731382