Large-scale sequencing and population genomic analyses reveal frequent transmission, a highly admixed global population structure and evidence of pervasive negative selection in Haemophilus influenzae...

Hypervirulent Klebsiella pneumoniae (HVKp) express a thick mucoid capsular polysaccharide which is essential for virulence and survival in the bloodstream but inhibits epithelial adhesion and invasion...

Understanding how complex, multi-gene systems evolve and function across genetic backgrounds is a central question in molecular evolution. While such systems often impose costs through epistatic inter...

Neonatal antibiotic use is shown to reduce immune response to infant vaccines, accompanied by reduced abundance of Bifidobacteria in the gut microbiota, with experiments in mice indicating that probio...

Research Assistant - Godlee Group (Fixed Term) in the Department of Biochemistry at the University of Cambridge.

InducTn-seq, a method for inducible mutagenesis followed by transposon insertion site sequencing, enables temporal control of transposition to bypass population bottlenecks and enable the quantificati...

Nature Communications - Acute systemic immune activation may affect gut-luminal colonisation dynamics. Here, the authors show that LPS exposure in mice elevates gut-luminal oxygen species levels,...

Stochastic, reversible switches in the expression of Salmonella flagella variants were first described by Andrewes in 1922. Termed phase variation (PV), subsequent research found that this phenomenon ...

Phagocytosed bacteria can serve as an alternative nutrient source for macrophages, influencing their metabolic and immune responses through the recycling of microbial components, with the process regulated by nutrient-sensing mechanisms and bacterial viability.

Despite being heavily infiltrated by immune cells, tuberculosis (TB) granulomas often subvert the host response to Mycobacterium tuberculosis (Mtb) infection and support bacterial persistence. We prev...

Signaling from pathogen sensing to effector activation is a fundamental principle of cellular immunity. While cyclic (oligo)nucleotides have emerged as key signaling molecules, the existence of other ...

Diabetic infections are a reservoir for the emergence and proliferation of antibiotic resistance in Staphylococcus aureus.

Surface polysaccharides are common antigens in priority pathogens and therefore attractive targets for novel control strategies such as vaccines, monoclonal antibody and phage therapies. Distinct serotypes correspond to diverse polysaccharide structures that are encoded by distinct biosynthesis gene clusters, e.g. the Klebsiella pneumoniae species complex (KpSC) K- and O- loci encode the synthesis machinery for the capsule (K) and outer-lipopolysaccharides (O), respectively. We previously presented Kaptive and Kaptive 2, programs to identify K and O-loci directly from KpSC genome assemblies (later adapted for Acinetobacter baumannii), enabling sero-epidemiological analyses to guide vaccine and phage therapy development. However, for some KpSC genome collections, Kaptive (v≤2) was unable to type a high proportion of K-loci. Here we identify the cause of this issue as assembly fragmentation, and present a new version of Kaptive (v3) to circumvent this problem, reduce processing times and simplify output interpretation. We compared the performance of Kaptive v2 and Kaptive v3 for typing genome assemblies generated from subsampled Illumina read sets (decrements of 10x depth), for which a corresponding high quality completed genome was also available to determine the 'true' loci (n=549 KpSC, n=198 A. baumannii). Both versions of Kaptive showed high rates of agreement to the matched true locus among 'typeable' locus calls (≥96% for ≥20x read depth), but Kaptive v3 was more sensitive, particularly for low depth assemblies (at <40x depth, v3 ranged 0.85-1 vs v2 0.09-0.94) and/or typing KpSC K-loci (e.g. 0.97 vs 0.82 for non-subsampled assemblies). Overall, Kaptive v3 was also associated with a higher rate of optimal outcomes i.e. loci matching those in the reference database were correctly typed and genuine novel loci were reported as untypeable (73-98% for v3 vs 7-77% for v2 for KpSC K-loci). Kaptive v3 was >1 order of magnitude faster than Kaptive v2 making it easy to analyse thousands of assemblies on a desktop computer, facilitating broadly accessible in silico serotyping that is both accurate and sensitive. The Kaptive v3 source code is freely available on GitHub (https://github.com/klebgenomics/Kaptive), and has been implemented in Kaptive Web (https://kaptive-web.erc.monash.edu). ### Competing Interest Statement The authors have declared no competing interest.

Vasodilation is a crucial protective response to inflammation and infection. Endothelial cells control vasodilation through the bioavailability of eNOS-produced nitric oxide (NO), and the generation o...