The Lancet Microbe

Shigellosis is a gastrointestinal illness caused by bacteria belonging to one of four species of Shigella. Sexually transmissible shigellosis was first reported in 1974, but recently there has been a global increase in the transmission of extensively drug-resistant strains. Here, we sought to characterise the natural history of sexually transmissible shigellosis through literature review and genomic epidemiological analysis of early outbreaks. The literature review revealed a significant gap in ...

BackgroundSince June 2022, there has been a rise in the number of ceftriaxone resistant Neisseria gonorrhoeae cases detected in England (n = 15), of which one third were extensively-drug resistant (XDR). We describe the demographic and clinical details of the recent cases and investigate the phenotypic and molecular characteristics of the isolates. For a comprehensive overview, we also reviewed 16 ceftriaxone-resistant cases previously identified in England since December 2015 and performed a gl...

BackgroundMelioidosis is a grossly neglected but often-fatal tropical disease. The disease is named "a great mimicker" after its broad clinical manifestations, which makes disease diagnosis challenging and time-consuming. To improve diagnosis, we developed and evaluated the performance of the CRISPR-Cas12a system called "CRISPR-BP34" to detect Burkholderia pseudomallei DNA across clinical specimens from patients suspected to have melioidosis. MethodsWe documented time taken for diagnosis, antib...

Candida auris emerged in Chicago, IL, USA in 2016 and has since become endemic. We used whole genome sequencing (WGS) of 494 isolates, epidemiologic metadata, and patient transfer data to describe the transmission of C. auris among Chicago healthcare facilities between 2016 - 2021. 99% of isolates formed a single clade IV phylogenetic lineage, suggesting a single introduction. Isolates were grouped into genomic clusters based on phylogenetic clustering and relatedness. Isolates from 14 facilitie...

Post-exposure prophylaxis with doxycycline (doxyPEP) is being introduced to prevent bacterial sexually transmitted infections (STIs). Pre-existing tetracycline resistance in Neisseria gonorrhoeae limits doxyPEP effectiveness against gonorrhea, and selection for tetracycline resistant lineages may influence prevalence of resistance to other antimicrobials via selection for multi-drug resistant strains. Using genomic and antimicrobial susceptibility data from 5,644 clinical isolates of N. gonorrho...

The antimicrobial resistance crisis has persisted despite broad attempts at intervention. Detailed studies of the population dynamics that lead to resistance could identify additional intervention points. An important driver of resistance in the most concerning antibiotic resistant pathogens can be selection imposed on bacterial populations that are not the intended target of antimicrobial therapy. Here we focus on the important nosocomial pathogen Enterococcus faecium in a hospital system where...

BackgroundKlebsiella pneumoniae is a common opportunistic pathogen known for having virulent and antimicrobial resistance (AMR) phenotypes. In addition to accumulating AMR and virulence genes, K. pneumoniae serves as a vehicle for broadly disseminating these elements into other species. Here, we applied genomic surveillance in a one-health framework to assess the impact of the human-animal-environment interface on AMR transmission. MethodsWe sequenced representative genomes of Klebsiella pneumo...

The diarrhoeal disease, shigellosis, can be sustained as a sexually transmissible enteric illness among gay, bisexual, and other men who have sex with men (GBMSM). Multiple extensively drug-resistant strains of Shigella have been detected through genomic surveillance, which have typically been associated with plasmids carrying the gene variant blaCTX-M-27. We report an increase in likely sexually transmissible cases of Shigella carrying blaCTX-M-15, which was previously associated with travel. I...

BackgroundStudying within-host genetic diversity of Mycobacterium tuberculosis (Mtb) in patients during treatment may identify adaptations to antibiotic and immune pressure. Understanding the significance of genetic heteroresistance, and more specifically heterozygous resistance-associated variants (RAVs), is clinically important given increasing use of rapid molecular tests and whole genome sequencing (WGS). MethodsWe analyse data from six studies in KwaZulu-Natal, South Africa. Most patients ...

Candida auris, initially identified in 2009, has rapidly become a critical concern due to its antifungal resistance and significant mortality rates in healthcare-associated outbreaks. To date, whole-genome sequencing (WGS) has identified five unique clades of C. auris, with some strains displaying resistance to all primary antifungal drug classes. In this study, we presented the first WGS analysis of C. auris from Bangladesh, describing its origins, transmission dynamics, and antifungal suscepti...

The MtrCDE efflux pump of Neisseria gonorrhoeae exports a wide range of antimicrobial compounds that the gonococcus encounters at mucosal surfaces during colonization and infection. Here, we evaluate the role of this efflux pump system in strain FA1090 in human male urethral infection with a Controlled Human Infection Model. Using the strategy of competitive multi-strain infection with wild-type FA1090 and an isogenic mutant strain that does not contain a functional MtrCDE pump, we found that th...

BackgroundExtended spectrum beta-lactamases-producing (ESBL-P) and/or carbapenem-resistant (CR) Klebsiella pneumoniae have severely restricted available treatment options in healthcare settings in Vietnam. Understanding the diversity and transmission mechanisms of ESBL- and carbapenemase-encoding K. pneumoniae is important in both hospital and community settings for patient management. MethodsWe conducted a 6-month prospective cohort study of 69 Intensive care unit (ICU) patients from two hospi...

Bacteria have the potential to migrate between sites in the human body, but the dynamics and consequences of within-host translocation remain poorly understood. Here we investigate the link between gut and lung Pseudomonas aeruginosa populations in an intensively sampled ICU patient using a combination of genomics, isolate phenotyping, host immunity profiling, and clinical data. Crucially, we show that lung colonization was driven by the repeated translocation of bacterial clones from the gut. M...

Drug-resistant infections caused by spores of the mould Aspergillus fumigatus pose a major challenge in managing chronic respiratory disease. Evidence shows that a substantial burden of aspergillosis is caused by strains that have evolved resistance to azole antifungal chemicals in the environment, however the contribution of local exposures to the colonisation of patients remains unclear. To investigate routes of acquisition, we whole-genome sequenced A. fumigatus isolates from individuals with...

Clinical trials of SARS-CoV-2 therapeutics often include virological secondary endpoints to compare viral clearance and viral load reduction between treatment and placebo arms. This is typically achieved using RT-qPCR, which cannot differentiate replicant competent virus from non-viable virus or free RNA, limiting its utility as an endpoint. Culture based methods for SARS-CoV-2 exist; however, these are often insensitive and poorly standardised for use as clinical trial endpoints. We report opt...

BackgroundAntimicrobial resistance (AMR) poses a significant global health challenge, resulting in over 1.27 million deaths in 2019 and projected to cause up to 10 million deaths annually in the future. To address this issue, the healthcare sector requires rapid and accurate bacterial identification, which is currently not readily available for effective antimicrobial stewardship. In a UK national first, we implemented 16S ribosomal RNA (rRNA) sequencing using Oxford Nanopore Technology (ONT) in...

BackgroundAmong patients colonized with carbapenem-resistant Klebsiella pneumoniae (CRKP), only a subset develop clinical infection. While patient characteristics may influence risk for infection, it remains unclear if the genetic background of CRKP strains contributes to this risk. We applied machine learning to quantify the capacity of patient characteristics and microbial genotypes to discriminate infection and colonization, and identified patient and microbial features associated with infect...

Acinetobacter baumannii (Ab) disease in the U.S. is commonly attributed to outbreaks of one or two monophyletic carbapenem resistance (CR) Ab lineages that vary by region. However, there is limited knowledge regarding Ab epidemiology and population structure in the U.S. Deep South, and few studies compare contemporary CR and carbapenem-susceptible (Cs) Ab, despite prevalence of the latter. We performed a 12-year time series analysis of Ab cases in a large hospital in Birmingham, AL, and 89 isola...

Despite the high level of morbidity and mortality worldwide, there is increasing evidence for asymptomatic carriers of the novel coronavirus SARS-CoV-2. We analyzed blood specimens from 1,559 healthy blood donors, collected in the greater New York metropolitan area between the months of March and July 2020 for antibodies to SARS-CoV-2 virus. Using our proprietary technology, SERA (Serum Epitope Repertoire Analysis), we observed a significant increase in SARS-CoV-2 seropositivity rates over the f...

Plasmids carry genes conferring antimicrobial resistance (AMR), and other clinically important traits; their ability to move within and between species may provide the machinery for rapid dissemination of such genes. Existing studies using complete plasmid assemblies, which are essential for reliable inference, have been small and/or limited to those carrying particularly antimicrobial resistance genes (ARGs). In this study, we sequenced 1,880 complete plasmids from 738 isolates from bloodstream...