Bacterial Pathogenesis and Antimicrobial Resistance Unit
John P. Dekker, M.D., Ph.D.
Lasker Clinical Research Scholar
Chief, Bacterial Pathogenesis and Antimicrobial Resistance Unit
Director, Genomics Section, Microbiology Service, Department of Laboratory Medicine, NIH Clinical Center
Specialty(s): Pathology, Clinical, Pathology, Medical Microbiology
Major Areas of Research
- Studies of the mechanisms by which antimicrobial resistance emerges in the natural context of human infection
- Genomic sequencing of historical clinical bacterial isolates in combination with in vitro models of adaptive evolution to characterize evolutionary pathways by which present day resistance to specific antimicrobial drug classes has evolved
- Study of the pathogenesis of gram-negative bacterial infections in patients with primary immunodeficiency diseases
- Application of population genomics approaches to study in vivo adaptive evolution of bacterial infections in the context of acute and chronic infection
- Biochemical studies of bacterial metabolic adaptations that occur during infection
The emergence of antimicrobial resistance (AMR) in bacteria has been recognized as a critical threat to public health. Many important classes of bacterial AMR undergo selection and evolution in the natural context of antibiotic treatment in a human host, though important features of host context are not commonly included in studies of AMR. A main area of focus within the Bacterial Pathogenesis and Antimicrobial Resistance Unit is the application of systems biology approaches to study the evolutionary mechanisms by which resistance emerges in this natural context. The approaches applied include genomic sequencing of current and historical clinical bacterial isolates, transcriptome analysis with RNA-seq, proteomics, metabolomics, and in vitro adaptive evolution.
Another linked area of focus within the unit is the study of bacterial pathoadaptation in the immunocompromised host. Within this context, bacterial pathogens may undergo rapid and dramatic evolution, facilitating host adaptation and the development of antibiotic resistance. In some cases, elevated mutation rates due to evolved mismatch repair and proofreading deficiencies have been shown to accelerate this evolution. An important insight from studies of within-host adaptation has been that genetic modifications occurring during chronic infection may parallel those that underlie the emergence of human-restricted pathogens from broad-host range generalists over longer evolutionary periods. In the BPARU, we apply a systems biology approach to study selection dynamics and host-pathogen interactions in the context of defined genetic immunodeficiency diseases. This approach integrates genomics, transcriptomics (RNA-seq), and metabolomic methods to identify and characterize specializations that occur during within-host adaptation. Population genomics approaches are applied in combination with molecular genetic analysis to understand selection dynamics and host-pathogen interactions in the context of defined genetic immunodeficiency diseases.
Recent progress in characterizing molecular mechanisms of antimicrobial resistance has also made possible the development of new approaches to the detection of AMR based on proteomics and sequencing. The Bacterial Pathogenesis and Antimicrobial Resistance Unit has developed novel approaches to rapid AMR diagnostics based on mass spectrometry and nanopore sequencing.
M.D., Harvard Medical School
Ph.D., Harvard University
Dr. Dekker received his M.D. from Harvard Medical School and Ph.D. from Harvard University through the NIH Medical Scientist Training Program. He completed pathology residency and fellowship training in medical microbiology at Massachusetts General Hospital and is board-certified in clinical pathology and medical microbiology through the American Board of Pathology. In 2013, he joined the NIH Clinical Center as a senior staff member of the Microbiology Service in the Department of Laboratory Medicine. In this role, he co-directed the Bacteriology, Specimen Processing, Parasitology, and Molecular Epidemiology sections of the laboratory before serving as acting chief of the Microbiology Service in 2018. In 2018, Dr. Dekker was named as a Lasker Clinical Research Scholar and recruited as a tenure-track investigator within the NIAID intramural research program, where he established the Bacterial Pathogenesis and Antimicrobial Resistance Unit within the Laboratory for Clinical Immunology and Microbiology. In addition, he continues to oversee the Genomics Section within the Microbiology Service, which focuses on development of next-generation sequencing-based approaches with applications in epidemiology and infectious diseases.
Dr. Dekker has served on FDA anti-infective drug advisory committees and is an editor for the Journal of Clinical Microbiology. In 2016, Dr. Dekker received the Beckman-Coulter Young Investigator award from the American Society for Microbiology, and he received an NIH Clinical Center CEO Award in 2017 for developing diagnostic methods using next-generation sequencing for improved rapid infectious disease and antibiotic resistance diagnosis. In 2020, he was recognized with the Young Physician-Scientist Award by the American Society for Clinical Investigation.
Tisza MJ, Smith DDN, Clark AE, Youn JH; NISC Comparative Sequencing Program; Khil PP, Dekker JP. Roving methyltransferases generate a mosaic epigenetic landscape and influence evolution in Bacteroides fragilis group. Nat Commun. 2023 Jul 10;14(1):4082.
Dulanto Chiang A, Patil PP, Beka L, Youn JH, Launay A, Bonomo RA, Khil PP, Dekker JP. Hypermutator strains of Pseudomonas aeruginosa reveal novel pathways of resistance to combinations of cephalosporin antibiotics and beta-lactamase inhibitors. PLoS Biol. 2022 Nov 18;20(11):e3001878.
Launay A, Wu CJ, Dulanto Chiang A, Youn JH, Khil PP, Dekker JP. In vivo evolution of an emerging zoonotic bacterial pathogen in an immunocompromised human host. Nat Commun. 2021 Jul 23;12(1):4495.
Wang H, Cissé OH, Bolig T, Drake SK, Chen Y, Strich JR, Youn JH, Okoro U, Rosenberg AZ, Sun J, LiPuma JJ, Suffredini AF, Dekker JP. A Phylogeny-Informed Proteomics Approach for Species Identification within the Burkholderia cepacia Complex. J Clin Microbiol. 2020 Oct 21;58(11):e01741-20.
Khil PP, Dulanto Chiang A, Ho J, Youn JH, Lemon JK, Gea-Banacloche J, Frank KM, Parta M, Bonomo RA, Dekker JP. Dynamic Emergence of Mismatch Repair Deficiency Facilitates Rapid Evolution of Ceftazidime-Avibactam Resistance in Pseudomonas aeruginosa Acute Infection. mBio. 2019 Sep 17;10(5):e01822-19.
Lemon JK, Khil PP, Frank KM, Dekker JP. Rapid Nanopore Sequencing of Plasmids and Resistance Gene Detection in Clinical Isolates. J Clin Microbiol. 2017 Dec;55(12):3530-3543.
Information for Prospective Laboratory Trainees
If you wish to inquire about postdoctoral or other positions in the Bacterial Pathogenesis and Antimicrobial Resistance Unit, contact Dr. Dekker.
In the BPARU, we apply a systems biology approach to understand selection dynamics and host-pathogen interactions in the context of defined genetic immunodeficiency diseases. This approach integrates genomics, transcriptomics (RNA-seq), and metabolomic methods to identify and characterize specializations that occur during within-host adaptation.