Microbial Genomics

Linezolid is a critical last-resort antimicrobial for multidrug-resistant Enterococcus faecium, particularly against vancomycin-resistant lineages where therapeutic options are severely limited. While resistance has historically arisen through de novo chromosomal mutations, the global emergence of transferable resistance mechanisms threatens to render more infections untreatable. Here, we characterise a recent (2023-2024) hospital-associated outbreak of linezolid-resistant E. faecium in Queensla...

BackgroundKlebsiella pneumoniae is a common cause of neonatal sepsis in Africa, and is frequently hospital acquired. We recently reported an outbreak of multidrug-resistant K. pneumoniae sepsis amongst neonates at a rural hospital in The Gambia, West Africa, involving 57 cases and case fatality of 60%. Here we undertook a retrospective pathogen genomic epidemiology study of clinical and environmental K. pneumoniae isolated during the outbreak, to identify the outbreak strain, refine the epidemic...

BackgroundClostridium perfringens can cause life-threatening extraintestinal infections in immunocompromised patients, an area in which we have little information regarding strain factors that impact patient risks and outcomes. MethodsWe conducted genomic-epidemiologic analyses on C. perfringens isolates from 70 patients seen at Brigham and Womens Hospital over 2021-2024. Genomic analyses evaluated strain profiles within a broader context of 2,321 C. perfringens genomes from foodborne, veterina...

BackgroundThe never-ending emergence of superbugs casts a shadow over the victorious age of antibiotics. In fact, the triumph of antibiotics was previously viewed in retrospection as our final victory over bacteria. Bacteria like Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli are now raising an alarming number of infections across hospitals and communities around the globe. The objective was to evaluate the implications for antimicrobial stewardship based on identifying the...

IntroductionSequence-based typing (SBT) has been the standard molecular typing method for understanding Legionella pneumophila genetic relationships. However, genome-scale typing approaches, namely core-genome (cg) or whole-genome (wg) multilocus sequence typing (MLST), provide higher discriminatory power. To advance these capabilities, the Legionella International Typing (LIT) workgroup was established to develop, evaluate, and disseminate a novel cgMLST schema with enhanced wgMLST resolution f...

Bacterial infections are a major cause of morbidity and mortality among children under five in low- and middle-income countries (LMICs). Children in LMICs are exposed to and colonized by a range of pathogenic bacteria, yet patterns of bacterial exchange between humans are not well known, in part because culturing and sequencing single bacterial isolates is labor-intensive. Here, we apply a machine learning strain tracking approach to metagenomic data from 511 stool samples from children and moth...

Understanding host susceptibility to Mycobacterium tuberculosis (Mtb) is critical for the development of new vaccines. Certain individuals "resist" becoming infected with Mtb despite intensive exposure; however, it is unknown whether there is a genetic basis for "resistance" to Mtb infection across populations. Here we conducted a genome-wide association study (GWAS) of resistance to Mtb infection by carefully characterizing exposure to TB patients among 4,058 close contacts in India, Brazil, an...

ObjectivesTo quantify how urine sample type and polymicrobial context impact antimicrobial resistance (AMR) in urinary tract infections (UTIs), using routine diagnostics at scale. MethodsIn this retrospective, single-centre study, we analysed 188,687 urine cultures from the Institute of Medical Microbiology, University of Zurich, Switzerland (January 2015 to May 2023). We compared midstream urine (MU), indwelling catheter (IDC), and intermittent catheter (IMC) samples. Samples were classified a...

BackgroundThe role of the gut microbiome and specific enteric bacteria in influencing the development of colorectal cancer (CRC) remains incompletely understood. Recently, it was shown that human CRC-derived strains of Clostridioides difficile were capable of inducing colonic tumorigenesis in a susceptible mouse model. We hypothesized that C. difficile contributes to the pathogenesis of human CRC and would be enriched in CRC tumors compared to paired normal tissues from the same individual. Met...

Accurate identification of unknown pathogens is critical for medicine and public health, yet current metagenomic workflows remain heavily dependent on specialized bioinformatics expertise and manual interpretation, creating substantial bottlenecks in time-sensitive diagnostic settings1. The key challenges lie in achieving precise species identification amidst high background noise and translating complex microbial data into clinically actionable insights2,3. Here we present the Global Pathogen A...

Influenza A(H3N2) subclade K virus was detected in Canada early in the 2025/26 influenza season, bearing an antigenic transition in the hemagglutinin (HA) glycoprotein. Analysis of 396 HA sequences from Canada showed antigenic divergence from 2025/26 influenza vaccine strains, consistent with partial mismatch. Phylodynamic analysis revealed sustained pre-vaccine transmission without clear post-vaccine expansion. Phylogenetic and phylogeographic analyses indicated interprovincial mixing within a ...

Antimicrobial resistance (AMR) is a growing problem, with annual deaths set to pass 10 million by 2050 if current trends continue. Wastewater surveillance has been proposed as a strategy to understand population-level resistance, and water reclamation facilities (WRFs) have been identified as a control point for environmental dissemination of resistant bacteria. Understanding dynamics of AMR across WRFs requires advanced molecular tools that elucidate host bacteria, especially for mobile resista...

Strengthening in-country sequencing capacity generated 28 Lassa virus genomes from human clinical cases, expanding our knowledge of Lassa fever in Guinea. Phylogeographic analysis revealed cross-border exchange between Liberia and the NZerekore region, and a Sierra Leone introduction into the Gueckedou area. Enhanced genomic surveillance is crucial to guide future public health actions.

Measles outbreaks have surged globally in recent years, but current surveillance systems have limited capacity to monitor measles virus (MeV) transmission and evolution at population scale. Although MeV can be detected in wastewater, the public health potential of wastewater genomic surveillance for MeV remains largely unexplored. Here, we deploy sensitive, low-cost MeV wastewater genomic surveillance combining virus concentration, whole-genome amplicon sequencing, and bioinformatic analysis alo...

BackgroundElimination of Plasmodium vivax is challenging due to its dormant liver stages (hypnozoites), which can reactivate weeks or months after the primary infection, causing relapses and ongoing transmission of the parasite. Despite these challenges, P. vivax clinical case numbers have declined over the past decade in Cambodia. We used parasite genotyping to assess whether the decline in case numbers was reflected in parasite diversity and relatedness as a proxy to transmission. MethodsGeno...

Genomic surveillance of influenza viruses informs vaccine strain selection and evolutionary forecasting. Sequencing efforts vary widely across U.S. states, which raises concerns about spatial sampling bias. We evaluated how well 10,958 influenza virus genomes sampled by our group in Michigan captured the genetic diversity in 34,743 genomes circulating nationally from the 2021/22 through 2024/25 seasons. We defined seasonal hemagglutinin haplotypes and tracked their detection across states. A sma...

Mycobacterium tuberculosis (MTB) disease is a major global health threat with most tuberculosis (TB) cases occurring in low-and middle-income countries (LMIC) with limited healthcare infrastructure. Near-point-of-care testing which can be deployed at peripheral clinical settings is needed to start treatment earlier and thereby improve treatment outcomes. Here we report the development and preliminary characterization of an MTB detection assay that utilizes tongue swab or sputum specimens for The...

From 2021 to 2025, MRSA emerged as a major multidrug-resistant pathogen in the study area. Among 545 S. aureus isolates, 67.2% were MRSA, disproportionately affecting children under five (26.5%) and males (55.5%). Case incidence more than doubled by 2025, suggesting rising transmission or resistance. Most isolates were hospital-associated (85.2%), predominantly from outpatients (88.5%), with middle ear discharge as the main source (67%). Gentamicin showed the highest susceptibility (72.1%), whil...

ObjectivesDiagnosis of community-acquired Legionnaires disease (CALD) relies on microbiological testing. Routine testing in hospitalised CAP patients has low positivity rates. We externally validated a Legionella prediction score, assessed its applicability in routine care, and explored potential updates. MethodsWe analysed data from 196 CALD patients from 20 Swiss hospitals and 196 Legionella-negative CAP controls matched by date of diagnosis ({+/-}14 days; August 2022-March 2024). We assessed...

Microbial keratitis is a sight-threatening corneal infection with varying etiological agents, primarily bacteria and fungi. Assessing and contrasting the virulence factors of microorganisms isolated from a non-contact lens-associated keratitis (NCLAK) and contact lens-associated keratitis (CLAK) is the goal of the current investigation. Samples were collected from over 60 patients and analysed using standard microbiological techniques, including culture, Gram staining, KOH mount, biochemical tes...