Targeted metagenomic assessment reflects critical colonization in battlefield injuries
[1];
[1]
- Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
- Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States). Computing and Global Security Directorates
- Uniformed Services University of the Health Sciences, Bethesda, MD (United States); Henry M. Jackson Foundation for the Advancement of Military Sciences, Bethesda, MD (United States)
- Uniformed Services University of the Health Sciences, Bethesda, MD (United States); Henry M. Jackson Foundation for the Advancement of Military Sciences, Bethesda, MD (United States); Walter Reed National Military Medical Center, Bethesda, MD (United States)
- Uniformed Services University of the Health Sciences, Bethesda, MD (United States); Walter Reed National Military Medical Center, Bethesda, MD (United States)
Current diagnostics and clinical management strategies for combat wounds are based on decisions made by expert clinicians. However, even in the hands of experienced surgeons, wounds from combat injuries can exhibit failed healing and complications related to limitations in the rapid and comprehensive generation of diagnostic information. Previous studies have demonstrated the possible use of genomic sequencing approaches to detect microbial signatures involved in combat casualty care. While effective, whole metagenome sequencing is limited by the depth required to confidently detect all relevant signatures. To address this, we developed a targeted capture sequencing panel to detect microbial signatures relevant to wound healing. These targets include known microbial nosocomial pathogens, wound colonizers, and genes involved in virulence and antimicrobial resistance. A bioinformatics pipeline was built to identify genomic regions of interest and over 8,000 oligonucleotide probes were designed for capture. The panel was synthesized and validated using control reference genomes in human background and on wound-effluent samples from a cohort of combat-injured U.S. service members. Our panel was sensitive against wound-colonizing species, Acinetobacter baumannii and Pseudomonas aeruginosa, and was specific in detecting corresponding virulence and antimicrobial-resistance genes as well as other pathogenic species present in microflora mixtures. Random forest feature permutation confirmed the prevalence of Acinetobacter and Pseudomonas in critically colonized wounds and wounds that failed to heal, respectively. Our results demonstrate the capability of targeted sequencing tools and analysis platforms to profile and deliver information on pathogenic factors influencing wound progression, thereby guiding therapeutic intervention.
- Research Organization:
- Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
- Sponsoring Organization:
- USDOE National Nuclear Security Administration (NNSA); Department of Defense (DoD)
- Grant/Contract Number:
- AC52-07NA27344
- OSTI ID:
- 2283281
- Report Number(s):
- LLNL--JRNL-848599; 1073739
- Journal Information:
- Microbiology Spectrum, Journal Name: Microbiology Spectrum Journal Issue: 6 Vol. 11; ISSN 2165-0497
- Publisher:
- American Society for MicrobiologyCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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