mBio
Top medRxiv preprints most likely to be published in this journal, ranked by match strength.
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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...
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Immune imprinting, also known as immune history, is a core aspect of adaptive immunity that influences antibody responses to future antigen exposures. Nevertheless, the impact of sequential flavivirus vaccinations on epitope targeting and antibody activity in humans remains incompletely understood. This question is particularly important in regions where the inactivated Japanese encephalitis virus (JEV) vaccines and the live-attenuated dengue virus (DENV) vaccines are used, as both have been ass...
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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...
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Background Short-chain fatty acids (SCFAs) are widely used as functional readouts of gut microbial activity in vivo. The growing adoption of decentralised study designs and self-collection protocols has amplified the need for reliable room-temperature storage and shipment strategies. However, SCFAs volatility and the persistence of post-collection microbial metabolism raise concerns regarding pre-analytical stability and the interpretability of measured concentrations. Methods We assessed the te...
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An H3N2 variant, named subclade K, continues to circulate widely during the 2025-2026 influenza season. This virus possesses a hemagglutinin (HA) protein that has eleven substitutions relative to the HA of the Northern Hemisphere 2025-2026 H3N2 vaccine strain. Many of these substitutions are in epitopes in well-characterized HA antigenic sites. Despite this, interim vaccine effectiveness studies indicate that the 2025-2026 influenza vaccine provides moderate protection against H3N2 subclade K in...
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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...
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The host response to Neisseria gonorrhoeae is variable, and understanding its systemic and local components is critical to understanding anti-gonococcal immunity for vaccine development. We used a controlled human infection model of male gonococcal urethritis in naive volunteers in combination with multiplex cytokine analyte analysis of blood and urine specimens taken before infection, at the time of acute symptoms, and after curative treatment of N. gonorrhoeae to study responses to early infec...
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Newly emerging influenza virus strains pose a constant threat as they encounter a population lacking neutralizing antibodies against the new strain. However, cross-reactive non-neutralizing antibodies (nnABs) may be present and assist in mitigating disease symptoms via various effector mechanisms, including antibody-dependent cellular cytotoxicity (ADCC). Although nnABs to influenza virus have received more attention lately, little information is available on their age-related prevalence, steady...
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Clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses continue to expand geographically and across mammalian hosts, raising concern about pandemic potential. The degree and specificity of pre-existing immunity in humans are key determinants of this risk. We analyzed hemagglutinin (HA)-and neuraminidase (NA)-specific antibody responses in 300 sera collected from adults in New York City. While HA directed binding antibodies to clade 2.3.4.4b H5 were low and hemagglutination-inhibiting a...
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AO_SCPLOWBSTRACTC_SCPLOWInfluenza A subclade K viruses caused high infection rates in the 2025/2026 Northern Hemisphere season, raising concerns about antigenic drift and reduced vaccine effectiveness. We measured antibody responses in matched human pre- and post-vaccination sera against a vaccine-like as well as subclade K isolates. Pre-existing immunity to subclade K variants was noted with seasonal influenza vaccination boosting titers two-fold against subclade K and three-fold against the va...
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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...
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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 ...
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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...
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Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common and life-threatening complication of chimeric antigen receptor (CAR) T-cell therapy, with early detection being critical for timely intervention and improved outcomes. Cytokines such as interleukin-6 (IL-6) are key mediators of the inflammatory cascade underlying ICANS pathogenesis, but prospective clinical evidence for their predictive value is limited. Here we quantify IL-6 levels in a prospective cohort of 40 CAR-T pat...
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BK polyomavirus (BKPyV) is a major complication in kidney transplant recipients (KTR), for whom no specific antiviral therapy is available. Modulation of immunosuppressive therapy results in virus clearance in most KTR with BKPyV DNAemia (controllers), but a significant minority fail to clear the virus (non-controllers). Here, we adapt LIBRA-seq, which links antibody sequence data to antigen specificity, to intact viral capsids of the four BKPyV genotypes to study and compare BKPyV-specific B-ce...
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BackgroundInfluenza vaccination and bacterial colonization both shape immunity in the respiratory tract, yet their combined impact on the human lung mucosa remains poorly understood. Secondary bacterial pneumonia following influenza infection is a leading cause of mortality, underscoring the need to define how vaccines and microbes intersect at the airway interface. MethodsUsing the Experimental Human Pneumococcal Challenge (EHPC) model, we examined how intramuscular inactivated (TIV) and nasal...
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Wastewater monitoring enables non-invasive, population-scale tracking of community infections independent of healthcare-seeking behavior and clinical diagnosis. Metagenomic sequencing extends this capability by enabling broad, pathogen-agnostic detection, genomic characterization, and identification of novel or unexpected threats. Here, we present data from CASPER (the Coalition for Agnostic Sequencing of Pathogens from Environmental Reservoirs), a U.S.-based wastewater metagenomic sequencing ne...
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Antibiotic resistance genes (ARGs) circulating among clinically relevant bacteria pose serious challenges to public health. Given the ancient and environmental bacterial origins of ARGs, a better understanding of the carriers of ARGs beyond the clinically most relevant species is urgently needed for more farsighted resistance monitoring and intervention measures. While the risks of emerging ARGs from environmental sources have been recognized, the identification bottlenecks stem from the limitat...
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Pathogenic organisms are typically thought to be constrained by a tradeoff between the rate and duration of transmission, an assumption that underpins a considerable body of evolutionary theory. Here we test for a transmission-duration tradeoff using detailed historical malaria infection data from an era prior to widespread use of antibiotics when humans were deliberately infected with malaria parasites as treatment for neurosyphilis (malariatherapy). These time series follow individual human in...
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BackgroundImmunocompromised (IC) individuals are at increased risk for persistent SARS-CoV-2 infections and can develop new viral mutations and lineages not seen in the community. In this case report, a persistent SARS-CoV-2 infection (330 days) in an IC patient is examined for viral mutations and mutations associated with cryptic lineages. Case PresentationThe patient was followed in a longitudinal study examining persistent SARS-CoV-2 in IC patients. The patient provided stool and nasal swab ...