Population genomics, resistome and plasmidome of invasive Klebsiella pneumoniae isolates in adults hospitalised in Johannesburg, South Africa

Population genomics, resistome and plasmidome of invasive Klebsiella pneumoniae isolates in adults hospitalised in Johannesburg, South Africa | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Population genomics, resistome and plasmidome of invasive Klebsiella pneumoniae isolates in adults hospitalised in Johannesburg, South Africa Denasha L. Reddy, Courtney P. Olwagen, Shama Khan, Nicholas J. Dean, and 14 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8967609/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Klebsiella pneumoniae (KPn) is a leading cause of healthcare-associated infections in adults in low- and middle-income countries. We conducted laboratory-based surveillance between 2023 and 2024 in Johannesburg, South Africa, and analysed 508 KPn whole genomes isolated from blood and cerebrospinal fluid cultures of hospitalised adults. We investigated the key antimicrobial resistance (AMR) profiles in invasive KPn isolates, and plasmid-mediated AMR. Overall, 79.1% of the KPn isolates harboured genes conferring a multidrug-resistant (MDR) phenotype. The prevalence of genotypic AMR compared to phenotypic AMR was higher for aminoglycosides and carbapenems, similar for third generation cephalosporins, and lower for colistin, respectively. Three plasmid types, IncX3, IncFII and IncFIB, were most frequently associated with harbouring beta-lactamase genes bla CTX, bla TEM, bla NDM, and bla OXA . On multiple regression modelling, ST2497 was associated with increased risk of death. Overall, our findings contribute to the genomic characterisation of drug-resistant KPn invasive disease in the WHO African Region. Klebsiella pneumoniae (KPn) has emerged as a leading cause of community-associated infections (CAIs) and healthcare-associated infections (HAIs) in adults, 1, 2 with the highest burden of disease in low- and middle-income countries (LMICs). 3 According to a predictive statistical modelling study on the global burden of bacterial antimicrobial resistance (AMR) in 2019, KPn invasive disease (KPn-ID) accounted for 50,000 deaths attributable to AMR in Africa. 3 Due to the rising global public health crisis of bacterial AMR, third-generation-cephalosporin (3GC)- and carbapenem-resistant strains of KPn have been included in the critical group of the World Health Organisation (WHO) Bacterial Priority Pathogens List since 2017, 4 underscoring the need for novel therapeutic agents and preventive strategies. Notably, carbapenem-resistant KPn (CRKp) rose from fifth in 2017 to become the top WHO priority pathogen in 2024, due to limited treatment options, high associated mortality, and rapidly increasing AMR rates across the majority of WHO regions. 4 In a recent meta-analysis, the estimated global prevalence of hospital-acquired CRKp was 28.7% (95% CI, 26.5%–30.9%), with rates exceeding 50.0% in some regions. 5 In addition to AMR, convergence of AMR with hypervirulence genes has been reported in KPn, and poses a new diagnostic and therapeutic challenge. 6 Genomic-based surveillance of KPn, with a particular focus on accurately identifying CRKp and hypervirulent (hvKp) strains, integrated with clinical data, is needed to accurately determine the burden of KPn disease and guide targeted public health interventions aimed at reducing KPn-associated morbidity and mortality in vulnerable populations. 2, 7 Key interventions include the implementation of robust infection prevention and control (IPC) measures, development of novel antimicrobial therapies, and advancement of preventive strategies such as vaccination. 8-10 Despite the growing global threat posed by CRKp and hvKp, molecular surveillance in the WHO African region remains limited, resulting in underestimation of the disease burden and delays in timely, evidence-based responses to emerging threats. 6, 7 We previously reported on the clinical and microbiological epidemiology of KPn-ID in African adults, 11 and now we add to that the detailed genomic epidemiology of KPn infections in hospitalised adults in Johannesburg, South Africa to address the knowledge gap of key AMR and virulence profiles in invasive KPn isolates. Health sciences/Diseases Health sciences/Medical research Biological sciences/Microbiology Klebsiella pneumoniae molecular epidemiology antimicrobial resistance virulence plasmids Full Text Additional Declarations No competing interests reported. Supplementary Files 3.KPIDWGScasesSupplementarymaterialnpjAntimicrobialsandResistance.pdf 4.SupplementaryfileS1.xlsx 5.Supplementary.BioSampleObjectsAccessionnumbersCasesKPID508.pdf Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 18 May, 2026 Reviews received at journal 09 May, 2026 Reviewers agreed at journal 15 Apr, 2026 Reviewers agreed at journal 10 Apr, 2026 Reviewers invited by journal 30 Mar, 2026 Editor assigned by journal 12 Mar, 2026 Submission checks completed at journal 12 Mar, 2026 First submitted to journal 25 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8967609","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":605076753,"identity":"411e8c63-7c42-4f9d-a781-67acab0498ed","order_by":0,"name":"Denasha L. 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We conducted laboratory-based surveillance between 2023 and 2024 in Johannesburg, South Africa, and analysed 508 KPn whole genomes isolated from blood and cerebrospinal fluid cultures of hospitalised adults. We investigated the key antimicrobial resistance (AMR) profiles in invasive KPn isolates, and plasmid-mediated AMR. Overall, 79.1% of the KPn isolates harboured genes conferring a multidrug-resistant (MDR) phenotype. The prevalence of genotypic AMR compared to phenotypic AMR was higher for aminoglycosides and carbapenems, similar for third generation cephalosporins, and lower for colistin, respectively. Three plasmid types, IncX3, IncFII and IncFIB, were most frequently associated with harbouring beta-lactamase genes bla\u003csub\u003eCTX, \u003c/sub\u003ebla\u003csub\u003eTEM,\u003c/sub\u003e bla\u003csub\u003eNDM, \u003c/sub\u003eand bla\u003csub\u003eOXA\u003c/sub\u003e. On multiple regression modelling, ST2497 was associated with increased risk of death. Overall, our findings contribute to the genomic characterisation of drug-resistant KPn invasive disease in the WHO African Region.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eKlebsiella pneumoniae \u003c/em\u003e(KPn) has emerged as a leading cause of community-associated infections (CAIs) and healthcare-associated infections (HAIs) in adults,\u003csup\u003e1, 2\u003c/sup\u003e with the highest burden of disease in low- and middle-income countries (LMICs).\u003csup\u003e3\u003c/sup\u003e According to a predictive statistical modelling study on the global burden of bacterial antimicrobial resistance (AMR) in 2019, \u0026nbsp;KPn\u003cem\u003e \u003c/em\u003einvasive\u003cem\u003e \u003c/em\u003edisease (KPn-ID)\u003cem\u003e \u003c/em\u003eaccounted for 50,000 deaths attributable to AMR in Africa.\u003csup\u003e3\u003c/sup\u003e Due to the rising global public health crisis of bacterial AMR, third-generation-cephalosporin (3GC)- and carbapenem-resistant strains of KPn have been included in the critical group of the World Health Organisation (WHO) Bacterial Priority Pathogens List since 2017,\u003csup\u003e4\u003c/sup\u003e underscoring the need for novel therapeutic agents and preventive strategies. Notably, carbapenem-resistant KPn\u003cem\u003e \u003c/em\u003e(CRKp) rose from fifth in 2017 to become the top WHO priority pathogen in 2024, due to limited treatment options, high associated mortality, and rapidly increasing AMR rates across the majority of WHO regions.\u003csup\u003e4\u003c/sup\u003e In a recent meta-analysis, the estimated global prevalence of hospital-acquired CRKp was 28.7% (95% CI, 26.5%–30.9%), with rates exceeding 50.0% in some regions.\u003csup\u003e5\u003c/sup\u003e In addition to AMR, convergence of AMR with hypervirulence genes has been reported in KPn, and poses a new diagnostic and therapeutic challenge.\u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eGenomic-based surveillance of KPn, with a particular focus on accurately identifying CRKp and hypervirulent (hvKp) strains, integrated with clinical data, is needed to accurately determine the burden of KPn disease and guide targeted public health interventions aimed at reducing KPn-associated morbidity and mortality in vulnerable populations.\u003csup\u003e2, 7\u003c/sup\u003e Key interventions include the implementation of robust infection prevention and control (IPC) measures, development of novel antimicrobial therapies, and advancement of preventive strategies such as vaccination.\u003csup\u003e8-10\u003c/sup\u003e Despite the growing global threat posed by CRKp and hvKp, molecular surveillance in the WHO African region remains limited, resulting in underestimation of the disease burden and delays in timely, evidence-based responses to emerging threats.\u003csup\u003e6, 7\u003c/sup\u003e We previously reported on the clinical and microbiological epidemiology of KPn-ID in African adults,\u003csup\u003e11\u003c/sup\u003e and now we add to that the detailed genomic epidemiology of KPn infections in hospitalised adults in Johannesburg, South Africa to address the knowledge gap of key AMR and virulence profiles in invasive KPn isolates.\u003c/p\u003e","manuscriptTitle":"Population genomics, resistome and plasmidome of invasive Klebsiella pneumoniae isolates in adults hospitalised in Johannesburg, South Africa","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-13 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