Research Overview

By developing and exploiting large-scale, high throughput experimental genetic screening tools, combined with the development and implementation of bioinformatic and computational (e.g., machine learning) approaches, the van Opijnen aims to understand a microbe and the phenotypes it generates in interaction with drugs and/or its host as a complete system. Approaches explored are thereby geared towards determining the relationship between a microbe’s genotype and its (potential) phenotype(s). To accomplish this the lab broadly focuses on three areas:

  • Phenotypic Perturbation Screening
    By developing tailored genetic screening tools based on for instance (single cell)Tn-Seq, CRISPRi and RNA-Seq, the van Opijnen Lab untangles phenotypes that can range from simple one-to-one, to highly complex relationships between all the individual genetic components in the genome in interaction with drugs and/or the host.
  • Data Integration and Analysis
    Genomic data storage, integration and analyses are key to gain new biological insights that will lead to next generation diagnostics and treatment strategies. The van Opijnen Lab is developing a suite of cloud-based services that bestows any scientist with the power of analyses and interpretation.
  • Network building to develop new strategies
    By combining the experimental, screening and computational tools the lab develops and implements, it aims to enable rapid and comprehensive multidimensional profile building for any bacterium or infectious disease. These profiles and networks are subsequently mined to predict the emergence of drug and/or immune escape, develop new potential treatment strategies including drug and antibody approaches, and identify potent vaccine targets.

Research Background

Dr. van Opijnen received his BA from the University of Amsterdam as well as his MS in evolutionary genetics, for which he performed research at the University of Amsterdam and the University of Rochester in New York. He received his PhD from the University of Amsterdam Medical School for his work on the evolution and genomics of the Human Immunodeficiency Virus.

As a postdoctoral fellow in the lab of Dr. Andrew Camilli at Tufts University and the Howard Hughes Medical Institute he developed Tn-Seq and worked on the systems biology of bacterial pathogens. He is the author of several popular science books, and previously was an Associate Professor of Microbial Systems Biology at Boston College, and the Director of the Microbial Innovation lab at the Broad Institute of MIT and Harvard.
 

Publications

  1. Identification of determinants that allow maintenance of high-level fluoroquinolone resistance in Acinetobacter baumannii. mBio. 2025 Jan 08; 16(1):e0322124. View Abstract
  2. Diclofenac sensitizes multi-drug resistant Acinetobacter baumannii to colistin. PLoS Pathog. 2024 Nov; 20(11):e1012705. View Abstract
  3. Identification of Determinants that Allow Maintenance of High-Level Fluoroquinolone Resistance in Acinetobacter baumannii. bioRxiv. 2024 Oct 16. View Abstract
  4. CRISPRi-TnSeq maps genome-wide interactions between essential and non-essential genes in bacteria. Nat Microbiol. 2024 Sep; 9(9):2395-2409. View Abstract
  5. Graphene Multiplexed Sensor for Point-of-Need Viral Wastewater-Based Epidemiology. ACS Appl Bio Mater. 2024 07 15; 7(7):4622-4632. View Abstract
  6. Directed Evolution of a Bacterial Leucyl tRNA in Mammalian Cells for Enhanced Noncanonical Amino Acid Mutagenesis. ACS Synth Biol. 2024 Jul 19; 13(7):2141-2149. View Abstract
  7. Covalent Inhibition of a Host-Pathogen Protein-Protein Interaction Reduces the Infectivity of Streptococcus pneumoniae. JACS Au. 2024 Jul 22; 4(7):2484-2491. View Abstract
  8. Diclofenac sensitizes multi-drug resistant Acinetobacter baumannii to colistin. bioRxiv. 2024 May 17. View Abstract
  9. RNA cis-regulators are important for Streptococcus pneumoniae in vivo success. PLoS Genet. 2024 Mar; 20(3):e1011188. View Abstract
  10. Dual membrane-spanning anti-sigma factors regulate vesiculation in Bacteroides thetaiotaomicron. Proc Natl Acad Sci U S A. 2024 Mar 05; 121(10):e2321910121. View Abstract
  11. Enhanced Directed Evolution in Mammalian Cells Yields a Hyperefficient Pyrrolysyl tRNA for Noncanonical Amino Acid Mutagenesis. Angew Chem Int Ed Engl. 2024 02 26; 63(9):e202316428. View Abstract
  12. Streptococcus pneumoniae favors tolerance via metabolic adaptation over resistance to circumvent fluoroquinolones. mBio. 2024 Feb 14; 15(2):e0282823. View Abstract
  13. LptD depletion disrupts morphological homeostasis and upregulates carbohydrate metabolism in Escherichia coli. FEMS Microbes. 2023; 4:xtad013. View Abstract
  14. Droplet Tn-Seq identifies the primary secretion mechanism for yersiniabactin in Yersinia pestis. EMBO Rep. 2023 10 09; 24(10):e57369. View Abstract
  15. Dual Membrane-spanning Anti-Sigma Factors Regulate Vesiculation in Gut Bacteroidota. bioRxiv. 2023 Jul 13. View Abstract
  16. Genome-wide phage susceptibility analysis in Acinetobacter baumannii reveals capsule modulation strategies that determine phage infectivity. PLoS Pathog. 2023 Jun; 19(6):e1010928. View Abstract
  17. CRISPRi-TnSeq: A genome-wide high-throughput tool for bacterial essential-nonessential genetic interaction mapping. bioRxiv. 2023 Jun 01. View Abstract
  18. Virus-assisted directed evolution of enhanced suppressor tRNAs in mammalian cells. Nat Methods. 2023 01; 20(1):95-103. View Abstract
  19. Interspecies recombination, not de novo mutation, maintains virulence after ß-lactam resistance acquisition in Streptococcus pneumoniae. Cell Rep. 2022 12 13; 41(11):111835. View Abstract
  20. A bacterial pan-genome makes gene essentiality strain-dependent and evolvable. Nat Microbiol. 2022 10; 7(10):1580-1592. View Abstract
  21. A genome-wide atlas of antibiotic susceptibility targets and pathways to tolerance. Nat Commun. 2022 06 07; 13(1):3165. View Abstract
  22. Immunosuppression broadens evolutionary pathways to drug resistance and treatment failure during Acinetobacter baumannii pneumonia in mice. Nat Microbiol. 2022 06; 7(6):796-809. View Abstract
  23. Yersinia pseudotuberculosis doxycycline tolerance strategies include modulating expression of genes involved in cell permeability and tRNA modifications. PLoS Pathog. 2022 05; 18(5):e1010556. View Abstract
  24. The Phenylacetic Acid Catabolic Pathway Regulates Antibiotic and Oxidative Stress Responses in Acinetobacter. mBio. 2022 06 28; 13(3):e0186321. View Abstract
  25. Targeted control of pneumolysin production by a mobile genetic element in Streptococcus pneumoniae. Microb Genom. 2022 04; 8(4). View Abstract
  26. Rapid, Multianalyte Detection of Opioid Metabolites in Wastewater. ACS Nano. 2022 03 22; 16(3):3704-3714. View Abstract
  27. Host-informed therapies for the treatment of pneumococcal pneumonia. Trends Mol Med. 2021 10; 27(10):971-989. View Abstract
  28. Dynamic Pneumococcal Genetic Adaptations Support Bacterial Growth and Inflammation during Coinfection with Influenza. Infect Immun. 2021 06 16; 89(7):e0002321. View Abstract
  29. Essential Gene Analysis in Acinetobacter baumannii by High-Density Transposon Mutagenesis and CRISPR Interference. J Bacteriol. 2021 05 20; 203(12):e0056520. View Abstract
  30. Author Correction: Antibiotic susceptibility signatures identify potential antimicrobial targets in the Acinetobacter baumannii cell envelope. Nat Commun. 2020 Nov 24; 11(1):6107. View Abstract
  31. Antibiotic susceptibility signatures identify potential antimicrobial targets in the Acinetobacter baumannii cell envelope. Nat Commun. 2020 09 09; 11(1):4522. View Abstract
  32. Transposon Insertion Sequencing, a Global Measure of Gene Function. Annu Rev Genet. 2020 11 23; 54:337-365. View Abstract
  33. Entropy of a bacterial stress response is a generalizable predictor for fitness and antibiotic sensitivity. Nat Commun. 2020 08 31; 11(1):4365. View Abstract
  34. Peptide Probes of Colistin Resistance Discovered via Chemically Enhanced Phage Display. ACS Infect Dis. 2020 09 11; 6(9):2410-2418. View Abstract
  35. Topologically correct synthetic reconstruction of pathogen social behavior found during Yersinia growth in deep tissue sites. Elife. 2020 06 16; 9. View Abstract
  36. A decade of advances in transposon-insertion sequencing. Nat Rev Genet. 2020 09; 21(9):526-540. View Abstract
  37. Dielectrophoresis assisted rapid, selective and single cell detection of antibiotic resistant bacteria with G-FETs. Biosens Bioelectron. 2020 May 15; 156:112123. View Abstract
  38. ShinyOmics: collaborative exploration of omics-data. BMC Bioinformatics. 2020 Jan 17; 21(1):22. View Abstract
  39. Droplet Tn-Seq combines microfluidics with Tn-Seq for identifying complex single-cell phenotypes. Nat Commun. 2019 12 16; 10(1):5729. View Abstract
  40. The Landscape of Phenotypic and Transcriptional Responses to Ciprofloxacin in Acinetobacter baumannii: Acquired Resistance Alleles Modulate Drug-Induced SOS Response and Prophage Replication. mBio. 2019 06 11; 10(3). View Abstract
  41. Bacterial Factors Required for Transmission of Streptococcus pneumoniae in Mammalian Hosts. Cell Host Microbe. 2019 06 12; 25(6):884-891.e6. View Abstract
  42. The Transcriptional landscape of Streptococcus pneumoniae TIGR4 reveals a complex operon architecture and abundant riboregulation critical for growth and virulence. PLoS Pathog. 2018 12; 14(12):e1007461. View Abstract
  43. Phage Display of Dynamic Covalent Binding Motifs Enables Facile Development of Targeted Antibiotics. J Am Chem Soc. 2018 05 16; 140(19):6137-6145. View Abstract
  44. MAGenTA: a Galaxy implemented tool for complete Tn-Seq analysis and data visualization. Bioinformatics. 2017 Sep 01; 33(17):2781-2783. View Abstract
  45. Antibiotics Disrupt Coordination between Transcriptional and Phenotypic Stress Responses in Pathogenic Bacteria. Cell Rep. 2017 08 15; 20(7):1705-1716. View Abstract
  46. Strain Dependent Genetic Networks for Antibiotic-Sensitivity in a Bacterial Pathogen with a Large Pan-Genome. PLoS Pathog. 2016 09; 12(9):e1005869. View Abstract
  47. Genome-Wide Fitness and Genetic Interactions Determined by Tn-seq, a High-Throughput Massively Parallel Sequencing Method for Microorganisms. Curr Protoc Microbiol. 2015 Feb 02; 36:1E.3.1-1E.3.24. View Abstract
  48. Genomic analyses of pneumococci from children with sickle cell disease expose host-specific bacterial adaptations and deficits in current interventions. Cell Host Microbe. 2014 May 14; 15(5):587-599. View Abstract
  49. Genome-Wide Fitness and Genetic Interactions Determined by Tn-seq, a High-Throughput Massively Parallel Sequencing Method for Microorganisms. Curr Protoc Mol Biol. 2014 Apr 14; 106:7.16.1-7.16.24. View Abstract
  50. Transposon insertion sequencing: a new tool for systems-level analysis of microorganisms. Nat Rev Microbiol. 2013 07; 11(7):435-42. View Abstract
  51. A fine scale phenotype-genotype virulence map of a bacterial pathogen. Genome Res. 2012 Dec; 22(12):2541-51. View Abstract
  52. Control of virulence by small RNAs in Streptococcus pneumoniae. PLoS Pathog. 2012; 8(7):e1002788. View Abstract
  53. Genome-wide fitness and genetic interactions determined by Tn-seq, a high-throughput massively parallel sequencing method for microorganisms. Curr Protoc Microbiol. 2010 Nov; Chapter 1:Unit1E.3. View Abstract
  54. Tn-seq: high-throughput parallel sequencing for fitness and genetic interaction studies in microorganisms. Nat Methods. 2009 Oct; 6(10):767-72. View Abstract
  55. Adaptation of HIV-1 depends on the host-cell environment. PLoS One. 2007 Mar 07; 2(3):e271. View Abstract
  56. Effects of random mutations in the human immunodeficiency virus type 1 transcriptional promoter on viral fitness in different host cell environments. J Virol. 2006 Jul; 80(13):6678-85. View Abstract
  57. The host environment drives HIV-1 fitness. Rev Med Virol. 2005 Jul-Aug; 15(4):219-33. View Abstract
  58. T-cell activation leads to poor activation of the HIV-1 clade E long terminal repeat and weak association of nuclear factor-kappaB and NFAT with its enhancer region. J Biol Chem. 2004 Dec 17; 279(51):52949-60. View Abstract
  59. The human immunodeficiency virus type 1 promoter contains a CATA box instead of a TATA box for optimal transcription and replication. J Virol. 2004 Jul; 78(13):6883-90. View Abstract
  60. Human immunodeficiency virus type 1 subtypes have a distinct long terminal repeat that determines the replication rate in a host-cell-specific manner. J Virol. 2004 Apr; 78(7):3675-83. View Abstract
  61. Genetic conflicts over sex ratio: mite-endosymbiont interactions. Am Nat. 2003 Feb; 161(2):254-66. View Abstract
  62. AFLP fingerprinting for assessing intraspecific variation and genome mapping in mites. Exp Appl Acarol. 2000; 24(10-11):775-93. View Abstract
  63. High temperatures eliminate Wolbachia, a cytoplasmic incompatibility inducing endosymbiont, from the two-spotted spider mite. Exp Appl Acarol. 1999 Nov; 23(11):871-81. View Abstract

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