ArticleBMC genomics2014
From microbial gene essentiality to novel antimicrobial drug targets.
Article in BMC genomics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 70 citations in OpenAlex.
- Proton pump inhibitor exposure modulates functional and transcriptional responses inFrontiers in cellular and infection microbiology · 2026Article
- CRISPRi-seq in Haemophilus influenzae reveals genome-wide and medium-specific growth determinants.PLoS pathogens · 2025Article
- Essential genes formSystems · 2024Article
- Unrealized targets in the discovery of antibiotics for Gram-negative bacterial infections.Nature reviews. Drug discovery · 2023Review
- Bactabolize is a tool for high-throughput generation of bacterial strain-specific metabolic models.eLife · 2023Article
- Article
- Transposon insertional mutagenesis of diverse yeast strains suggests coordinated gene essentiality polymorphisms.Nature communications · 2022Article
- Innate Host Defense against Klebsiella pneumoniae and the Outlook for Development of Immunotherapies.Journal of innate immunity · 2022Review
- In Silico Prediction and Prioritization of Novel Selective Antimicrobial Drug Targets inAntibiotics (Basel, Switzerland) · 2021Article
- Novel antimicrobial development using genome-scale metabolic model of Gram-negative pathogens: a review.The Journal of antibiotics · 2021Review
- Learning from -omics strategies applied to uncoverComputational and structural biotechnology journal · 2021Review
- Article
- Genome-wide identification of essential genes in Mycobacterium intracellulare by transposon sequencing - Implication for metabolic remodeling.Scientific reports · 2020Article
- Pharmacodynamics of Ceftiofur Selected by Genomic and Proteomic Approaches ofInternational journal of genomics · 2020Article
- Article
- The Laminin Interactome: A Multifactorial Laminin-Binding Strategy by Nontypeable Haemophilus influenzae for Effective Adherence and Colonization.The Journal of infectious diseases · 2019Article
- High-throughput analysis of Yersinia pseudotuberculosis gene essentiality in optimised in vitro conditions, and implications for the speciation of Yersinia pestis.BMC microbiology · 2018Article
- Article
- HU ofFrontiers in microbiology · 2018Article
- Comparative analysis of the Burkholderia cenocepacia K56-2 essential genome reveals cell envelope functions that are uniquely required for survival in species of the genus Burkholderia.Microbial genomics · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBacterial respiratory tract infections, mainly caused by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are among the leading causes of global mortality and morbidity. Increased resistance of these pathogens to existing antibiotics necessitates the search for novel targets to develop potent antimicrobials.
resultHere, we report a proof of concept study for the reliable identification of potential drug targets in these human respiratory pathogens by combining high-density transposon mutagenesis, high-throughput sequencing, and integrative genomics. Approximately 20% of all genes in these three species were essential for growth and viability, including 128 essential and conserved genes, part of 47 metabolic pathways. By comparing these essential genes to the human genome, and a database of genes from commensal human gut microbiota, we identified and excluded potential drug targets in respiratory tract pathogens that will have off-target effects in the host, or disrupt the natural host microbiota. We propose 249 potential drug targets, 67 of which are targets for 75 FDA-approved antimicrobials and 35 other researched small molecule inhibitors. Two out of four selected novel targets were experimentally validated, proofing the concept.
conclusionHere we have pioneered an attempt in systematically combining the power of high-density transposon mutagenesis, high-throughput sequencing, and integrative genomics to discover potential drug targets at genome-scale. By circumventing the time-consuming and expensive laboratory screens traditionally used to select potential drug targets, our approach provides an attractive alternative that could accelerate the much needed discovery of novel antimicrobials.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.