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Klebsiella pneumoniae is a major cause of opportunistic healthcare-associated infections, which are increasingly complicated by the presence of extended-spectrum beta-lactamases (ESBLs) and carbapenem resistance. We conducted a year-long prospective surveillance study of K. pneumoniae clinical isolates in hospital patients. Whole-genome sequence (WGS) data reveals a diverse pathogen population, including other species within the K. pneumoniae species complex (18%). Several infections were caused by K. variicola/K. pneumoniae hybrids, one of which shows evidence of nosocomial transmission. A wide range of antimicrobial resistance (AMR) phenotypes are observed, and diverse genetic mechanisms identified (mainly plasmid-borne genes). ESBLs are correlated with presence of other acquired AMR genes (median n  = 10). Bacterial genomic features associated with nosocomial onset are ESBLs (OR 2.34, p  = 0.015) and rhamnose-positive capsules (OR 3.12, p  < 0.001). Virulence plasmid-encoded features (aerobactin, hypermucoidy) are observed at low-prevalence (<3%), mostly in community-onset cases. WGS-confirmed nosocomial transmission is implicated in just 10% of cases, but strongly associated with ESBLs (OR 21, p  < 1 × 10 −11 ). We estimate 28% risk of onward nosocomial transmission for ESBL-positive strains vs 1.7% for ESBL-negative strains. These data indicate that K. pneumoniae infections in hospitalised patients are due largely to opportunistic infections with diverse strains, with an additional burden from nosocomially-transmitted AMR strains and community-acquired hypervirulent strains. Klebsiella pneumoniae is an opportunistic pathogen of increasing public health concern due to the prevalence of antimicrobial resistance. Here, the authors provide insight into the resistance profiles, bacterial genome features and virulence genes, in a year-long prospective study of K. pneumoniae clinical isolates.

BackgroundPredictive markers for the outcomes of fecal microbiota transplantation (FMT) in ulcerative colitis (UC) are poorly defined. Existing microbial analyses of FMT efficacy are based on time-consuming and costly sequencing methods, thereby limiting their practical application in clinical settings.Therefore, we focused on four common siderophores found in Gram-negative pathogens. By analyzing the changes in the total copy number of siderophore genes before and after FMT, we aimed to explore their association with FMT efficacy and evaluate their potential as non-invasive biomarkers for predicting FMT responsiveness.MethodsWe enrolled patients with active UC (Mayo score ≥ 3) who underwent two FMT procedures. Fecal samples were collected before and 8 weeks after each FMT session and determined the total copy number of eight siderophore genes, including enterobactin (entF, fepA), salmochelin (iroB, iroN), aerobactin (iucA, iutA), and yersiniabactin (irp1, fyuA). Patients were classified into responder and non-responder groups based on their Mayo scores. The relationship between the total siderophore genes copy number and FMT efficacy was examined.ResultsSeventy-two patients with UC underwent FMT. The UC clinical response and remission rates were 62.5% and 19.4% after the first FMT, which increased to 71.7% and 43.4%, respectively, after the second FMT. Compared with the baseline, the total siderophore genes copy number significantly decreased in the responder group, from 1557.32 copies/ng to 251.90 copies/ng after the second FMT. In the non-responder group, the total copy number of siderophore genes showed an increasing trend after the second FMT, from 65.46 copies/ng to 330.78 copies/ng. The total baseline copy number was significantly higher in responders than in non-responders (P < 0.01). A baseline total copy number cutoff value of 289.63 copies/ng showed 85.5% sensitivity and 88.2% specificity in predicting FMT responsiveness.ConclusionsThe total copy number of fecal siderophore genes in patients with UC correlates with FMT treatment response, providing a promising biomarker for predicting FMT responsiveness.

Klebsiella pneumoniae has been classified into two types, classical K. pneumoniae (cKP) and hypervirulent K. pneumoniae (hvKP). cKP isolates are highly diverse and important causes of nosocomial infections; they include globally disseminated antibiotic-resistant clones. hvKP isolates are sensitive to most antibiotics but are highly virulent, causing community-acquired infections in healthy individuals. The virulence phenotype of hvKP is associated with pathogenicity loci responsible for siderophore and hypermucoid capsule production. Recently, convergent strains of K. pneumoniae , which possess features of both cKP and hvKP, have emerged and are cause of much concern. Here, we screen the genomes of 2,608 multidrug-resistant K. pneumoniae isolates from the United States and identify 47 convergent isolates. We perform phenotypic and genomic characterization of 12 representative isolates. These 12 convergent isolates contain a variety of antimicrobial resistance plasmids and virulence plasmids. Most convergent isolates contain aerobactin biosynthesis genes and produce more siderophores than cKP isolates but not more capsule. Unexpectedly, only 1 of the 12 tested convergent isolates has a level of virulence consistent with hvKP isolates in a murine pneumonia model. These findings suggest that additional studies should be performed to clarify whether convergent strains are indeed more virulent than cKP in mouse and human infections. Convergent strains, those containing characteristics of both multidrug-resistant & hypervirulent Klebsiella pneumoniae , are a global threat to public health. In this work, authors analyse convergent isolates from the United States and reveal unexpectantly low virulence.

BackgroundAnkylosing spondylitis (AS) is a common disease with unclear etiology and pathogenesis. The relationship between disease activity and biomarkers in AS requires further exploration. Abnormal activation of the ‘gut-joint axis’ may be a key factor in the pathogenesis of AS. Some studies suggest that Klebsiella pneumoniae detected in the feces of AS patients correlates with disease activity and that increased bacterial siderophores of Klebsiella pneumoniae increase its virulence. There is a lack of studies on whether bacterial siderophores in the gut are associated with AS. This study investigates the relationship between intestinal siderophores and AS, providing new evidence for the research on the gut-joint axis, etiology, pathogenesis, and treatment of AS.MethodsThe study involved 48 confirmed AS patients and 30 healthy controls (HCs) to explore the potential relationship between fecal bacterial siderophores and AS. Fecal samples were collected, and polymerase chain reaction (PCR) and quantitative real-time PCR (qPCR) analyzed eight siderophore genes: enterobactin (entF, fepA), salmochelin (iroB, iroN), aerobactin (iucA, iutA), and yersiniabactin (irp1, fyuA). The positivity rate and gene copy number were compared between AS patients and HCs.ResultsIn this study, the qualitative results indicated that the positivity rate of siderophore genes in fecal samples from patients with AS was higher than that in the HCs. This was particularly evident for the iroB gene (64.58% vs. 13.33%, P<0.05) and the iroN gene (72.92% vs. 10.00%, P<0.05) associated with salmochelin, as well as the yersiniabactin (IDDF2025-ABS-0136 figure 1. Positivity rate of siderophore genes in fecal samples of AS patients and healthy controls). Quantitative results revealed that the copy number of siderophore genes in fecal samples from AS patients was greater than that in HCs, with the total copy number of all siderophore genes in AS patients significantly exceeding that in HCs (517.64 vs. 83.34 copies/ng DNA, P<0.05) (IDDF2025-ABS-0136 figure 2. Quantitative analysis of siderophore gene copy numbers in fecal samples). The receiver operating characteristic (ROC) curve analysis differentiated AS from HCs with a cutoff at 189.61 copies/ng DNA, achieving 62.5% sensitivity and 90.0% specificity (AUC = 0.759, P<0.001) (IDDF2025-ABS-0136 figure 3. ROC curve for discriminating AS from HCs based on the total copy number of fecal siderophore genes).Abstract IDDF2025-ABS-0136 Figure 1Positivity rate of siderophore genes in fecal samples of AS patients and healthy controls[Figure omitted. See PDF]Abstract IDDF2025-ABS-0136 Figure 2Quantitative analysis of siderophore gene copy numbers in fecal samples[Figure omitted. See PDF]Abstract IDDF2025-ABS-0136 Figure 3ROC curve for discriminating AS from HCs based on the total copy number of fecal siderophore genes[Figure omitted. See PDF]ConclusionsDetecting fecal bacterial siderophore genes may be a novel potential biomarker for AS, offering new possibilities for assessing disease activity and related studies.

BackgroundNon-invasive biomarkers are currently recommended for assessing ulcerative colitis (UC) disease activity. Gut microbiome-related biomarkers are used as direct indicators of the intestinal microbiota and have considerable potential for disease assessment and therapeutic guidance in UC. This study aims to explore the relationship between fecal siderophore genes and UC activity and their potential value as a non-invasive biomarker to evaluate UC activity.MethodsWe included 166 patients with active UC (37 mild, 83 moderate, and 46 severe cases) and 165 healthy controls (HCs). Quantitative real-time PCR were used for the detection of eight siderophore genes, including enterobactin (entF, fepA), salmochelin (iroB, iroN), aerobactin (iucA, iutA), and yersiniabactin (irp1, fyuA).ResultsPatients with UC showed higher siderophore gene total copy number than HCs (1182.49 vs. 176.44 copies/ng, P<0.01). A threshold of 2877.68 copies/ng distinguished patients with active UC from HCs, with 90.3% specificity and 33.1% sensitivity.Based on clinical disease activity, the total copy number of siderophore genes was significantly higher in patients with severe active UC than in those with moderate (3111.03 vs 1183.54 copies/ng, P<0.05) and mild (3111.03 vs 672.60 copies/ng, P<0.01) active UC. Moreover, patients with severe endoscopic activity exhibited an increased total copy number of fecal siderophore genes, higher than that in patients with mild-to-moderate endoscopic activity (1318.02 vs. 723.10 copies/ng, P<0.05). A threshold of 10 298.63 copies/ng achieved 92.5% specificity and 43.5% sensitivity in identifying severe active UC, and 94% specificity and 22.5% sensitivity in identifying endoscopic severe active UC.In parallel test with serum C-reactive protein, the sensitivity and specificity increased to 89.1% and 75.8% for the clinical severe active stage and 55.2% and 88.0% for the endoscopic severe active stage, respectively.ConclusionsTotal siderophore gene copy number was positively correlated with both clinical and endoscopic disease activity in UC. The high prevalence and total copy number of bacterial siderophore genes indicated that they potentially serve as a novel non-invasive biomarker for UC activity.

Background Klebsiella pneumoniae is a leading cause of bloodstream infection (BSI). Strains producing extended-spectrum beta-lactamases (ESBLs) or carbapenemases are considered global priority pathogens for which new treatment and prevention strategies are urgently required, due to severely limited therapeutic options. South and Southeast Asia are major hubs for antimicrobial-resistant (AMR) K. pneumoniae and also for the characteristically antimicrobial-sensitive, community-acquired “hypervirulent” strains. The emergence of hypervirulent AMR strains and lack of data on exopolysaccharide diversity pose a challenge for K. pneumoniae BSI control strategies worldwide. Methods We conducted a retrospective genomic epidemiology study of 365 BSI K. pneumoniae from seven major healthcare facilities across South and Southeast Asia, extracting clinically relevant information (AMR, virulence, K and O antigen loci) using Kleborate , a K. pneumoniae -specific genomic typing tool. Results K. pneumoniae BSI isolates were highly diverse, comprising 120 multi-locus sequence types (STs) and 63 K-loci. ESBL and carbapenemase gene frequencies were 47% and 17%, respectively. The aerobactin synthesis locus ( iuc ), associated with hypervirulence, was detected in 28% of isolates. Importantly, 7% of isolates harboured iuc plus ESBL and/or carbapenemase genes. The latter represent genotypic AMR-virulence convergence, which is generally considered a rare phenomenon but was particularly common among South Asian BSI (17%). Of greatest concern, we identified seven novel plasmids carrying both iuc and AMR genes, raising the prospect of co-transfer of these phenotypes among K. pneumoniae . Conclusions K. pneumoniae BSI in South and Southeast Asia are caused by different STs from those predominating in other regions, and with higher frequency of acquired virulence determinants. K. pneumoniae carrying both iuc and AMR genes were also detected at higher rates than have been reported elsewhere. The study demonstrates how genomics-based surveillance—reporting full molecular profiles including STs, AMR, virulence and serotype locus information—can help standardise comparisons between sites and identify regional differences in pathogen populations.

Background Klebsiella pneumoniae is a recognised agent of multidrug-resistant (MDR) healthcare-associated infections; however, individual strains vary in their virulence potential due to the presence of mobile accessory genes. In particular, gene clusters encoding the biosynthesis of siderophores aerobactin ( iuc ) and salmochelin ( iro ) are associated with invasive disease and are common amongst hypervirulent K . pneumoniae clones that cause severe community-associated infections such as liver abscess and pneumonia. Concerningly, iuc has also been reported in MDR strains in the hospital setting, where it was associated with increased mortality, highlighting the need to understand, detect and track the mobility of these virulence loci in the K . pneumoniae population. Methods Here, we examined the genetic diversity, distribution and mobilisation of iuc and iro loci amongst 2503 K . pneumoniae genomes using comparative genomics approaches and developed tools for tracking them via genomic surveillance. Results Iro and iuc were detected at low prevalence (< 10%). Considerable genetic diversity was observed, resolving into five iro and six iuc lineages that show distinct patterns of mobilisation and dissemination in the K . pneumoniae population. The major burden of iuc and iro amongst the genomes analysed was due to two linked lineages ( iuc1 / iro1 74% and iuc2 / iro2 14%), each carried by a distinct non-self-transmissible IncFIB K virulence plasmid type that we designate KpVP-1 and KpVP-2. These dominant types also carry hypermucoidy ( rmpA ) determinants and include all previously described virulence plasmids of K . pneumoniae . The other iuc and iro lineages were associated with diverse plasmids, including some carrying IncFII conjugative transfer regions and some imported from Escherichia coli ; the exceptions were iro3 (mobilised by ICE Kp1 ) and iuc4 (fixed in the chromosome of K . pneumoniae subspecies rhinoscleromatis ). Iro / iuc mobile genetic elements (MGEs) appear to be stably maintained at high frequency within known hypervirulent strains (ST23, ST86, etc.) but were also detected at low prevalence in others such as MDR strain ST258. Conclusions Iuc and iro are mobilised in K . pneumoniae via a limited number of MGEs. This study provides a framework for identifying and tracking these important virulence loci, which will be important for genomic surveillance efforts including monitoring for the emergence of hypervirulent MDR K . pneumoniae strains.

Highly invasive, community-acquired Klebsiella pneumoniae infections have recently emerged, resulting in pyogenic liver abscesses. These infections are caused by hypervirulent K. pneumoniae (hvKP) isolates primarily of capsule serotype K1 or K2. Hypervirulent K1 isolates belong to clonal complex 23 (CC23), indicating that this clonal lineage has a specific genetic background conferring hypervirulence. Here, we apply whole-genome sequencing to a collection of K. pneumoniae isolates to characterize the phylogenetic background of hvKP isolates with an emphasis on CC23. Most of the hvKP isolates belonged to CC23 and grouped into a distinct monophyletic clade, revealing that CC23 is a unique clonal lineage, clearly distinct from nonhypervirulent strains. Separate phylogenetic analyses of the CC23 isolates indicated that the CC23 lineage evolved recently by clonal expansion from a single common ancestor. Limited grouping according to geographical origin was observed, suggesting that CC23 has spread globally through multiple international transmissions. Conversely, hypervirulent K2 strains clustered in genetically unrelated groups. Strikingly, homologues of a large virulence plasmid were detected in all hvKP clonal lineages, indicating a key role in K. pneumoniae hypervirulence. The plasmid encodes two siderophores, aerobactin and salmochelin, and RmpA (regulator of the mucoid phenotype); all these factors were found to be restricted to hvKP isolates. Genomic comparisons revealed additional factors specifically associated with CC23. These included a distinct variant of a genomic island encoding yersiniabactin, colibactin, and microcin E492. Furthermore, additional novel genomic regions unique to CC23 were revealed which may also be involved in the increased virulence of this important clonal lineage. IMPORTANCE During the last 3 decades, hypervirulent Klebsiella pneumoniae (hvKP) isolates have emerged, causing severe community-acquired infections primarily in the form of pyogenic liver abscesses. This syndrome has so far primarily been found in Southeast Asia, but increasing numbers of cases are being reported worldwide, indicating that the syndrome is turning into a globally emerging disease. We applied whole-genome sequencing to a collection of K. pneumoniae clinical isolates to reveal the phylogenetic background of hvKP and to identify genetic factors associated with the increased virulence. The hvKP isolates primarily belonged to clonal complex 23 (CC23), and this clonal lineage was revealed to be clearly distinct from nonhypervirulent strains. A specific virulence plasmid was found to be associated with hypervirulence, and novel genetic determinants uniquely associated with CC23 were identified. Our findings extend the understanding of the genetic background of the emergence of hvKP clones. During the last 3 decades, hypervirulent Klebsiella pneumoniae (hvKP) isolates have emerged, causing severe community-acquired infections primarily in the form of pyogenic liver abscesses. This syndrome has so far primarily been found in Southeast Asia, but increasing numbers of cases are being reported worldwide, indicating that the syndrome is turning into a globally emerging disease. We applied whole-genome sequencing to a collection of K. pneumoniae clinical isolates to reveal the phylogenetic background of hvKP and to identify genetic factors associated with the increased virulence. The hvKP isolates primarily belonged to clonal complex 23 (CC23), and this clonal lineage was revealed to be clearly distinct from nonhypervirulent strains. A specific virulence plasmid was found to be associated with hypervirulence, and novel genetic determinants uniquely associated with CC23 were identified. Our findings extend the understanding of the genetic background of the emergence of hvKP clones.

Background The degree to which the chromosomal mediated iron acquisition system contributes to virulence of many bacterial pathogens is well defined. However, the functional roles of plasmid encoded iron acquisition systems, specifically Sit and aerobactin, have yet to be determined for Salmonella spp. In a recent study, Salmonella enterica strains isolated from different food sources were sequenced on the Illumina MiSeq platform and found to harbor the incompatibility group (Inc) FIB plasmid. In this study, we examined sequence diversity and the contribution of factors encoded on the IncFIB plasmid to the virulence of S . enterica . Results Whole genome sequences of seven S . enterica isolates were compared to genomes of serovars of S . enterica isolated from food, animal, and human sources. SeqSero analysis predicted that six strains were serovar Typhimurium and one was Heidelberg. Among the S. Typhimurium strains, single nucleotide polymorphism (SNP)-based phylogenetic analyses revealed that five of the isolates clustered as a single monophyletic S . Typhimurium subclade, while one of the other strains branched with S . Typhimurium from a bovine source. DNA sequence based phylogenetic diversity analyses showed that the IncFIB plasmid-encoded Sit and aerobactin iron acquisition systems are conserved among bacterial species including S. enterica . The IncFIB plasmid was transferred to an IncFIB plasmid deficient strain of S . enterica by conjugation. The transconjugant SE819::IncFIB persisted in human intestinal epithelial (Caco-2) cells at a higher rate than the recipient SE819. Genes of the Sit and aerobactin operons in the IncFIB plasmid were differentially expressed in iron-rich and iron-depleted growth media. Conclusions Minimal sequence diversity was detected in the Sit and aerobactin operons in the IncFIB plasmids present among different bacterial species, including foodborne Salmonella strains. IncFIB plasmid encoded factors play a role during infection under low-iron conditions in host cells.

A number of converging strands of research suggest that the intestinal Enterobacteriaceae plays a crucial role in the development and progression of inflammatory bowel disease (IBD), however, the changes in the abundance of Enterobacteriaceae species and their related metabolic pathways in Crohn's disease (CD) and ulcerative colitis (UC) compared to healthy people are not fully explained by comprehensive comparative metagenomics analysis. In the current study, we investigated the alternations of the Enterobacterales population in the gut microbiome of patients with CD and UC compared to healthy subjects. Metagenomic datasets were selected from the Integrative Human Microbiome Project (HMP2) through the Inflammatory Bowel Disease Multi'omics Database (IBDMDB). We performed metagenome-wide association studies on fecal samples from 191 CD patients, 132 UC patients, and 125 healthy controls (HCs). We used the metagenomics dataset to study bacterial community structure, relative abundance, differentially abundant bacteria, functional analysis, and Enterobacteriaceae-related biosynthetic pathways. Compared to the gut microbiome of HCs, six Enterobacteriaceae species were significantly elevated in both CD and UC patients, including , , , , , , and , while , , and were uniquely differentially abundant and enriched in the CD cohort. Four species were uniquely differentially abundant and enriched in the UC cohort, including , , , and . Our analysis also showed a dramatically increased abundance of in their intestinal bacterial community. Biosynthetic pathways of aerobactin siderophore, LPS, enterobacterial common antigen, nitrogen metabolism, and sulfur relay systems encoded by were significantly elevated in the CD samples compared to the HCs. Menaquinol biosynthetic pathways were associated with UC that belonged to strains. In conclusion, compared with healthy people, the taxonomic and functional composition of intestinal bacteria in CD and UC patients was significantly shifted to Enterobacteriaceae species, mainly and species.