Harnessing genomics in the battle against antimicrobial resistance and neglected tropical diseases

Melioidosis is a severe and frequently fatal disease caused by an environmental bacterium, Burkholderia pseudomallei, that widespread throughout the tropics. It estimated to affect approximately 165,000 people every year kill 89,000 of them [[1]Limmathurotsakul D. Golding N. Dance D.A.B. et al.Predicted global distribution pseudomallei burden melioidosis.Nature Microbiol. 2016; 1: 15008Crossref Scopus (426) Google Scholar]. Despite this, it remains little known, even in countries which endemic, infection significantly underestimated national surveillance systems [[2]Chansrichavala P. Wongsuwan Suddee S. al.Public awareness melioidosis Thailand potential use video clips as educational tools.PLoS ONE [Electronic Resource]. 2015; 10e0121311Crossref PubMed (13) Scholar,[3]Hantrakun V. Kongyu Klaytong al.Clinical epidemiology 7126 patients implications for notifiable diseases system.Open forum Infect. 2019; 6: ofz498Crossref (9) so neglected does not feature official lists Neglected Tropical Diseases (NTD) though believed cause loss more disability-adjusted life years than many formally recognised NTDs [[4]Birnie E. Virk H.S. Savelkoel J. al.Global 2015: systematic review data synthesis.Lancet Infect Dis. 19: 892-902Summary Full Text PDF (29) In this issue EBioMedicine, Madden colleagues report development tool, they call ARDaP, detecting antimicrobial resistance (AMR) determinants next generation sequencing (NGS) B. having found shortcomings with existing tools purpose [[5]Madden D.E. Webb J.R. Steinig E.J. Currie B.J. Price E.P. Sarovich D.S Taking next-gen step: comprehensive detection from pseudomallei.EBioMedicine. 2021; 63: 103152https://doi.org/10.1016/j.ebiom.2020.103152Summary (2) They ARDaP accurately detected all previously described SNP, indel, CNV, inversion, gene AMR isolates studied, predicted three undescribed determinants. comparison, other commonly-used such CARD, ResFinder AMRFinderPlus failed find any clinically-relevant variants only intrinsic genes present strains. ways, was strange choice organism study, reflecting prior research interests authors. Although species intrinsically resistant antibiotics has large highly plastic genome organised two chromosomes, exhibits frequent horizontal acquisition [[6]Holden M.T. Titball R.W. Peacock S.J. al.Genomic plasticity causative agent melioidosis, pseudomallei.PNAS. 2004; 101: 14240-14245Crossref (541) Scholar], probably its need adapt competition within niche, acquired major problem amongst being treated infections [[7]Wuthiekanun Amornchai Saiprom al.Survey clinical over decades Northeast Thailand.Antimicrob Agents Chemother. 2011; 55: 5388-5391Crossref (56) The reason two-fold. First, although occur minority during treatment, always result chromosomal mutations, plasmid-mediated transferrable resistance, occurs Enterobacterales example, never been reported [[8]Schweizer H.P. Mechanisms antibiotic pseudomallei: treatment melioidosis.Future 2012; 7: 1389-1399Crossref (123) Secondly, person-to-person spread rarely if ever seen, when develop evolutionary dead end. addition, whilst may be extremely efficient way unlikely applicable majority laboratories serve poor, rural populations developing world are most likely suffer at least foreseeable future. fact, important aspect study al. approach adapted bacterial which, like included datasets used test tools. There determining [[9]Su M. Satola S.W. Read T.D Genome-based prediction resistance.J Clin 57: e01405-e01418Crossref (79) but demonstrates suitable mechanisms pathogens where wide spectrum mutations. able identify minor allele variants, enabling samples single colony cannot obtained, flag unknown further investigation, useful addition knowledge incomplete. While components bioinformatic pipeline individually available, combines open-source package produces user-friendly report, will invaluable non-specialist bioinformaticians. However, accurate required custom database species. To extend require substantial effort curate catalogues species-specific make those available scientific community, done widely databases [[10]Feldgarden Brover Haft D.H. al.Validating AMRFinder tool using genotype-phenotype correlations collection isolates.Antimicrob 63 (e00483-19)Crossref (185) A barrier adoption NGS predominantly identified resource-limited settings these can number phenotypically-characterised strains permits. Detailed phenotyping routinely performed settings, seen limited despite high disease. limitations, represents step towards incorporating into routine practice authors confirm sole responsibility conception preparation invited Commentary. Dr. reports personal fees InBios, outside submitted work; Batty nothing disclose. have both funded Wellcome grant ( 106698 ) Major Overseas Programme. Comprehensive pseudomalleiExisting software packages inadequate due inability detect conferred CNVs, inversions, functional loss. overcomes shortcomings. Further, enables mixed sequence down 5% allelic frequency, differentiate natural genetic variation constructed microbial interest detection. Full-Text Open Access