Bulitta Research Lab

Combating bacterial ‘superbugs’ via latest experimental and computational approaches

Bacterial ‘superbugs’ which are resistant to most, or all antibiotics, present one of the three most serious threats to human health in the US and worldwide. This has been highlighted by the World Health Organization, the US President’s Office, the European Union, and numerous national and international organizations. If bacterial resistance to antibiotics is not tackled successfully, a tremendous financial loss (>$1 trillion till 2050), widespread human suffering and an increased mortality from bacterial infections have all been predicted. Without effective antibiotic therapy, care of premature neonates, transplants, cancer chemotherapy and many other achievements of modern medicine will no longer be possible without significant risk. Therefore, society is on a path of reverting back to the pre-antibiotic era.

To combat this substantial global health crisis, the dynamic antimicrobial research team at Lake Nona is developing innovative antibiotic combination therapies which can successfully treat infections by these ‘superbugs’. This team is headed by Dr. Jürgen Bulitta who is an internationally recognized expert in antimicrobial pharmacology, latest in vitro infection models, and translational mechanistic modeling. His team is greatly enhanced by multiple fruitful collaborations with the UF Institute for Therapeutic Innovation located in the same building at Lake Nona, as well as a strategic network of national and international collaborators.

Dr. Bulitta has a long-standing interest in beta-lactam antibiotics, which are the largest and most commonly used group of antibiotics. These drugs can be used safely in patients of all ages. However, there are substantial gaps in our understanding of how beta-lactam antibiotics can be used optimally, which gives rise to innovative combination therapies to combat ‘superbugs.’ This particularly applies to the use of two beta-lactams simultaneously. Such combinations can inactivate an optimal set of different target receptors (i.e. different penicillin-binding proteins, PBPs). Additionally, our team is developing novel approaches of how to enhance the penetration of antibiotics to their bacterial target sites. This research involves the development of innovative combination therapies which include beta-lactam, aminoglycoside, polymyxin and other antibiotics, as well as a beta-lactamase inhibitor.

The second research stream by Dr. Bulitta’s group focuses on human pharmacokinetics, pharmacodynamics and toxicodynamics. This includes advanced models of oral and inhaled drug absorption and greatly benefits from Dr. Yuanyuan Jiao’s expertise in clinical pharmacy. The latter research includes a fruitful collaboration with Dr. Guenther Hochhaus (COP, UF) in a stream of FDA-funded clinical studies. The latter assess important properties of inhaled corticosteroid formulations. This research is highly important for the development of the much-needed generic formulations for inhaled drugs.

Dr. Bulitta is continuously developing a free, open-source facilitator tool (SADAPT-TRAN) which greatly supports Quantitative and Systems Pharmacology (QSP) modeling in the S-ADAPT software package. This tool greatly enhances the capabilities and efficiency of researchers worldwide to perform translational, mechanistic modeling and optimally dose patients. These approaches and concepts are taught in Dr. Bulitta’s new course on “Translational Clinical Pharmacology” (PHA6133).

Ongoing Projects

Translational Antimicrobial Pharmacology

NIH/NIAID 1P01AI179409 Drusano GL (contact) / Bulitta JB  Role: Co-Equal PD / PI
Translational development of new agents alone and in combination to combat Gram-negative pathogens important in Ventilator- Associated Bacterial Pneumonia: Leveraging the Gram-negative toolbox that is ready for prime time

NIH/NIAID R01 AI148560 Tsuji BT (contact) / Bulitta JB  Role: PI
Novel Strategies for Antibiotic Combinations to Combat Gram-negative Superbugs

NIH/NIAID SBIR 2R44AI136213-04 Roemer T (PI) Role: Co-I
Development of a PO-administered beta-lactam-tarocin combination agent to treat methicillin susceptible and methicillin resistant Staphylococci

NIH R01 R01 AI173064 Bulman Z (PI)  Role: Co-I
Precise Combination Strategies Targeting Carbapenem-Resistant Klebsiella pneumoniae

NIH R01 AI173238 Drusano G (PI) Role: Co-I
Optimizing Multi-drug Mycobacterium tuberculosis Therapy for Rapid Sterilization and Resistance Suppression

Inhaled Corticosteroids

FDA 75F40122C00182 Cristofoletti (PI) Role: Co-I
Advancing In Vitro and (Patho) Physiology-Based Pharmacokinetics Models to Understand and Predict Pulmonary Absorption and Tissue Retention of Inhaled Drugs

FDA U01 FD007936 Bulitta JB (contact) / Hochhaus G Role: PI
Feasibility of predicting regional lung exposure from systemic pharmacokinetic data of generic OIDPs via population pharmacokinetic modeling and non-compartmental approaches

Completed Projects

1. NIH/NIAID R01 AI136803 Bulitta JB (PI) Role: PI
   Combating resistant superbugs by understanding the molecular determinants of target site penetration and binding
2. NIH/NIAID R01 AI130185 Bulitta JB (PI) Role: PI
   Next-generation combination dosing strategies to combat resistant Acinetobacter baumannii
3. FDA HHSF223201710199C Luna BM (PI) Role: Subaward-PI
   A Preclinical Mouse Model of Acinetobacter baumannii Infection For Antibacterial Development
4. NIH/NIAID HHSN2722017000201 Miesel L (PI) Role: Subaward-PI
   New Strain Testing and PK-PD Studies for Therapeutics in Murine Models of Bacterial Thigh Infections
5. FDA 75F40119C10154 Hochhaus G (PI) Role: Co-PI
   Systematic Evaluation of the Ex-Throat Plume Properties of MDI Formulations
   Collaborator: Emmace Consulting AB, Sweden www.emmace.se. Led by Dr. Mårten Svensson
6. FDA U01 FD004943 Hochhaus G (PI) Role: Co-PI
   Comprehensive Evaluation of Formulation Effects on Metered Dose Inhaler Performance, Food and Drug Administration
7. FDA HHSF223201310220C Hochhaus G / Bulitta J (PD/PI) Role: PD/PI
   Study to investigate the sensitivity of pharmacokinetics in detecting differences in physicochemical properties of the active in suspension nasal products for local action
8. FDA HHSF223201610099C Bulitta JB (PI) Role: PI
   Pharmacokinetic Comparison of Locally Acting Orally Inhaled Drug Products
9. NIH/NIAID R01 AI111990 Tsuji B / Li J (PD/PI) Role: Co-I
   Novel PK/PD Strategies for Polymyxin Combinations against Gram-negative Superbugs
10. State of Florida 7ZK30 Brown AN (PI) Role: Co-I
    Identification of antiviral therapies for the treatment of Zika virus using existing drugs
11. NHMRC APP1101553 Project Landersdorfer CB (PI) Role: Co-I
    Targeting hypermutable ‘superbugs’ in chronic respiratory infections by optimised antibiotic combination dosage regimens

Current Members

Professor of Pharmacotherapy and Translational Research; Preeminence Position

Jurgen Bulitta, Ph.D.

Antimicrobial Pharmacology, Chemistry

Research Assistant Professor

Yinzhi Lang, Ph.D.

Bioanalytics, Mass Spec., Glycoproteomics

Research Assistant Professor

Alaa Ropy Sayed, Ph.D.

Molecular Biology

Postdoctoral Research Associate

Xindi Shan, Ph.D.

Biochemistry, Glycobiology

Postdoctoral Research Associate

Yongzhen Zhang, Ph.D.

Medicinal Chemistry, Biosynthesis

Research Technician

Yanan Zang, M.Sc.

Bioanalytics, Proteomics, Metabolomics

Research Technician

Abeer Elsayed, M.Sc.

Biochemistry

Research Technician

Rossie Jimenez, B.Sc.

Biotechnology, PK/PD

Research Technician

Keisha Cadet, B.Sc.

Microbiology, Biotech, PK/PD

Research Coordinator II

Ann Ross Wlodarski, MHA

Past Members

Bartolomé Moyá Cañellas, Ph.D.

Assistant Professor, Fundació Institut d’Investigació Sanitària Illes Balears – IdISBa, Spain

Tae Hwan Kim, Ph.D.

Assistant Professor, College of Pharmacy, Daegu Catholic University, Korea

Mong-Jen Chen, Ph.D.

Senior Scientist, Clinical Pharmacology, AbbVie, Chicago USA

Hongmei Xu, Ph.D.

Sr. Director, Clinical Pharmacology, Karyopharm, Boston USA

Rajbharan Yadav, Ph.D.

Scientist, Translational PK/PD, Genentech Inc., San Francisco USA

Xun Tao, Ph.D.

Scientist, Translational PK/PD, Genentech Inc., San Francisco USA

Dhruvitkumar S. Sutaria, Ph.D.

Associate Scientist, Genentech Inc., San Francisco USA

Yuanyuan Jiao, Ph.D.

Clinical Pharmacologist, Peking University Cancer Hospital

Nirav Shah, Ph.D.

PK/PD Scientist, Biologics Development Sciences, Janssen R&D, J&J

Brett Fleisher Ph.D.

Associate Scientist, PTPK Genentech

Stefanie Drescher, Ph.D.

Pharmacist, QSP Modeling, Inhaled corticosteroids with Dr. Hochhaus

Eunjeong (Elena) Shin, PhD.

Postodoctoral Fellow, Case Western Reserve University

Carolin Werkman, Ph.D.

Scientist, Alnylam Pharmaceuticals

Jieqiang Zhou, Ph.D.

Senior Scientist, Clinical Pharmacometrics, AstraZeneca