Hyphae Carbon Coupled with Gel Composite Assembly for Construction of Advanced Carbon/Sulfur Cathodes for Lithium-Sulfur Batteries.

The design and fabrication of novel carbon hosts with high conductivity, accelerated electrochemical catalytic activities, and superior physical/chemical confinement on sulfur and its reaction intermediates polysulfides are essential for the construction of high-performance C/S cathodes for lithium-sulfur batteries (LSBs). In this work, a novel biofermentation coupled gel composite assembly technology is developed to prepare cross-linked carbon composite hosts consisting of conductive Rhizopus hyphae carbon fiber (RHCF) skeleton and lamellar sodium alginate carbon (SAC) uniformly implanted with polarized nanoparticles (V2O3, Ag, Co, etc.) with diameters of several nanometers. Impressively, the RHCF/SAC/V2O3 composites exhibit enhanced physical/chemical adsorption of polysulfides due to the synergistic effect between hierarchical pore structures, heteroatoms (N, P) doping, and polar V2O3 generation. Additionally, the catalytic conversion kinetics of cathodes are effectively improved by regulating the 3D carbon structure and optimizing the V2O3 catalyst. Consequently, the LSBs assembled with RHCF/SAC/V2O3-S cathode show exceptional cycle stability (capacity retention rate of 94.0% after 200 cycles at 0.1 C) and excellent rate performance (specific capacity of 578 mA h g-1 at 5 C). This work opens a new door for the fabrication of hyphae carbon composites via fermentation for electrochemical energy storage.

Genetic diversity of siderophores and hypermucoviscosity phenotype in Klebsiella pneumoniae.

Siderophore is a group of low molecular weight compounds with high affinity for ferric iron, facilitating bacterial iron consumption, especially when competing with the host. Genetic diversity of the siderophore-encoding loci largely contributes to the intricacy of siderophore production and regulation in K. pneumoniae. We analyzed the genetic diversity of three acquired siderophores (salmochelin, yersiniabactin and aerobactin) in 272 K. pneumoniae strains from China, and revealed that hypervirulent and multidrug-resistant lineages had distinguished predominant siderophore loci. Strains producing more types of siderophores tend to present higher mucoviscosity levels, suggesting that siderophore production might synergistically interact with hypermucoviscosity phenotype.

Difference in biofilm formation between carbapenem-resistant and carbapenem-sensitive Klebsiella pneumoniae based on analysis of mrkH distribution.

OBJECT: To analyze the difference in biofilm formation between carbapenem-resistant and carbapenem-sensitive Klebsiella pneumoniae based on analysis of mrkH distribution and to further explore the function of mrkH for biofilm formation from the perspective of gene regulation. METHODS: 40 imipenem-resistant strains and 40 imipenem-sensitive strains were selected to conduct experiments. Carbapenem (imipenem) susceptibility test was performed by the agar-dilution method. blaKPC resistance gene, type 3 fimbriae-related coding genes (mrkA and mrkD) and regulation gene (mrkH) were screened by PCR. Biofilm formation assay was performed using crystal violet staining method in MHB. The relative expression of genes that critically involved in biofilm formation (mrkA, luxS, pgaA) and carbapenem resistance (ompk35, ompk36, acrB) were measured by quantitative real-time PCR (qRT-PCR). Furthermore, the mrkH cassette was cloned into pGEM-T Easy plasmid to yield pGEM:pmrkH and expressed in Escherichia coli DH5α and K. pneumoniae FK1911, and the biofilm formation assay after transformation was further tested. RESULTS: The MICs of imipenem were all more than 16 µg/mL in 40 imipenem-resistant strains and ranged from 0.125 µg/mL to 0.5 µg/mL in 40 imipenem-sensitive strains. Moreover, the blaKPC was identified in the 40 imipenem-resistant K. pneumoniae strains. All 80 K. pneumoniae strains were found to carry mrkA and mrkD genes. Interestingly, the mrkH gene was detected in 43 strains, of which 32 were carbapenem-sensitive strains. The biofilm formation capacity of strains carried mrkH cassette was significantly higher than other 37 strains in MHB media. The relative expression of mrkA in K. pneumoniae carrying mrkH gene was significantly up-regulated. Importantly, the biofilm formation ability of FK1911-pGEM:pmrkH strain was more higher than the strain of FK1911 in MHB medium. CONCLUSIONS: Our data demonstrated that MrkH played a crucial role in the regulation of biofilm formation by K. pneumoniae. In contrast to carbapenem-sensitive K. pneumoniae, carbapenem-resistant K. pneumoniae was less likely to have strong biofilm-forming capacity because it does not carry the mrkH gene.

Early predictors and screening tool developing for severe patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a declared global pandemic, causing a lot of death. How to quickly screen risk population for severe patients is essential for decreasing the mortality. Many of the predictors might not be available in all hospitals, so it is necessary to develop a simpler screening tool with predictors which can be easily obtained for wide wise. METHODS: This retrospective study included all the 813 confirmed cases diagnosed with COVID-19 before March 2nd, 2020 in a city of Hubei Province in China. Data of the COVID-19 patients including clinical and epidemiological features were collected through Chinese Disease Control and Prevention Information System. Predictors were selected by logistic regression, and then categorized to four different level risk factors. A screening tool for severe patient with COVID-19 was developed and tested by ROC curve. RESULTS: Seven early predictors for severe patients with COVID-19 were selected, including chronic kidney disease (OR 14.7), age above 60 (OR 5.6), lymphocyte count less than < 0.8 × 109 per L (OR 2.5), Neutrophil to Lymphocyte Ratio larger than 4.7 (OR 2.2), high fever with temperature ≥ 38.5℃ (OR 2.2), male (OR 2.2), cardiovascular related diseases (OR 2.0). The Area Under the ROC Curve of the screening tool developed by above seven predictors was 0.798 (95% CI 0.747-0.849), and its best cut-off value is > 4.5, with sensitivity 72.0% and specificity 75.3%. CONCLUSIONS: This newly developed screening tool can be a good choice for early prediction and alert for severe case especially in the condition of overload health service.

Effectiveness of anisodamine for the treatment of critically ill patients with septic shock: a multicentre randomized controlled trial.

BACKGROUND: Septic shock is characterized by an uncontrolled inflammatory response and microcirculatory dysfunction. There is currently no specific agent for treating septic shock. Anisodamine is an agent extracted from traditional Chinese medicine with potent anti-inflammatory effects. However, its clinical effectiveness remains largely unknown. METHODS: In a multicentre, open-label trial, we randomly assigned adults with septic shock to receive either usual care or anisodamine (0.1-0.5 mg per kilogram of body weight per hour), with the anisodamine doses adjusted by clinicians in accordance with the patients' shock status. The primary end point was death on hospital discharge. The secondary end points were ventilator-free days at 28 days, vasopressor-free days at 28 days, serum lactate and sequential organ failure assessment (SOFA) score from days 0 to 6. The differences in the primary and secondary outcomes were compared between the treatment and usual care groups with the χ2 test, Student's t test or rank-sum test, as appropriate. The false discovery rate was controlled for multiple testing. RESULTS: Of the 469 patients screened, 355 were assigned to receive the trial drug and were included in the analyses-181 patients received anisodamine, and 174 were in the usual care group. We found no difference between the usual care and anisodamine groups in hospital mortality (36% vs. 30%; p = 0.348), or ventilator-free days (median [Q1, Q3], 24.4 [5.9, 28] vs. 26.0 [8.5, 28]; p = 0.411). The serum lactate levels were significantly lower in the treated group than in the usual care group after day 3. Patients in the treated group were less likely to receive vasopressors than those in the usual care group (OR [95% CI] 0.84 [0.50, 0.93] for day 5 and 0.66 [0.37, 0.95] for day 6). CONCLUSIONS: There is no evidence that anisodamine can reduce hospital mortality among critically ill adults with septic shock treated in the intensive care unit. Trial registration ClinicalTrials.gov ( NCT02442440 ; Registered on 13 April 2015).

Core Genome Allelic Profiles of Clinical Klebsiella pneumoniae Strains Using a Random Forest Algorithm Based on Multilocus Sequence Typing Scheme for Hypervirulence Analysis.

BACKGROUND: Hypervirulent Klebsiella pneumoniae (hvKP) infections can have high morbidity and mortality rates owing to their invasiveness and virulence. However, there are no effective tools or biomarkers to discriminate between hvKP and nonhypervirulent K. pneumoniae (nhvKP) strains. We aimed to use a random forest algorithm to predict hvKP based on core-genome data. METHODS: In total, 272 K. pneumoniae strains were collected from 20 tertiary hospitals in China and divided into hvKP and nhvKP groups according to clinical criteria. Clinical data comparisons, whole-genome sequencing, virulence profile analysis, and core genome multilocus sequence typing (cgMLST) were performed. We then established a random forest predictive model based on the cgMLST scheme to prospectively identify hvKP. The random forest is an ensemble learning method that generates multiple decision trees during the training process and each decision tree will output its own prediction results corresponding to the input. The predictive ability of the model was assessed by means of area under the receiver operating characteristic curve. RESULTS: Patients in the hvKP group were younger than those in the nhvKP group (median age, 58.0 and 68.0 years, respectively; P < .001). More patients in the hvKP group had underlying diabetes mellitus (43.1% vs 20.1%; P < .001). Clinically, carbapenem-resistant K. pneumoniae was less common in the hvKP group (4.1% vs 63.8%; P < .001), whereas the K1/K2 serotype, sequence type (ST) 23, and positive string tests were significantly higher in the hvKP group. A cgMLST-based minimal spanning tree revealed that hvKP strains were scattered sporadically within nhvKP clusters. ST23 showed greater genome diversification than did ST11, according to cgMLST-based allelic differences. Primary virulence factors (rmpA, iucA, positive string test result, and the presence of virulence plasmid pLVPK) were poor predictors of the hypervirulence phenotype. The random forest model based on the core genome allelic profile presented excellent predictive power, both in the training and validating sets (area under receiver operating characteristic curve, 0.987 and 0.999 in the training and validating sets, respectively). CONCLUSIONS: A random forest algorithm predictive model based on the core genome allelic profiles of K. pneumoniae was accurate to identify the hypervirulent isolates.

Shp2 positively regulates cigarette smoke-induced epithelial mesenchymal transition by mediating MMP-9 production.

Cigarette smoke (CS) is a major risk factor for the development of lung cancer and chronic obstructive pulmonary disease (COPD). Epithelial-mesenchymal transition (EMT) commonly coexists in lung cancer and COPD. CS triggers many factors including matrix metalloproteinases (MMPs) production, contributing to EMT progression in the lungs. Here, how Shp2 signaling regulates the CS-induced MMP-9 production and EMT progression were investigated in mouse lungs and in pulmonary epithelial cell cultures (NCI-H292) found CS induced MMP-9 production, EMT progression (increased vimentin and α-SMA; decreased E-cadherin) and collagen deposition in lung tissues; cigarette smoke extract (CSE) induced MMP-9 production and EMT-related phenotypes in NCI-H292 cells, which were partially prevented by Shp2 KO/KD or Shp2 inhibition. The CSE exposure induced EMT phenotypes were suppressed by MMP-9 inhibition. Recombinant MMP-9 induced EMT, which was prevented by MMP-9 inhibition or Shp2 KD/inhibition. Mechanistically, CS and CSE exposure resulted in ERK1/2, JNK and Smad2/3 phosphorylation, which were suppressed by Shp2 KO/KD/inhibition. Consequentially, the CSE exposure-induced MMP-9 production and EMT progression were suppressed by ERK1/2, JNK and Smad2/3 inhibitors. Thus, CS induced MMP-9 production and EMT resulted from activation of Shp2/ERK1/2/JNK/Smad2/3 signaling pathways. Our study contributes to the underlying mechanisms of pulmonary epithelial structural changes in response to CS, which may provide novel therapeutic solutions for treating associated diseases, such as COPD and lung cancer.

Prevalence and characteristics of pks gene cluster harbouring Klebsiella pneumoniae from bloodstream infection in China.

Bloodstream infection (BSI), caused by Klebsiella pneumoniae, is associated with high morbidity and mortality, where the pks gene cluster plays a major role in their occurrence and prevalence. Information on the prevalence and characteristics of this gene cluster in K. pneumoniae is currently limited in mainland China. We therefore undertook a multicentre longitudinal study which revealed the prevalence, overall, community-onset and hospital-acquired BSI to be 20.5%, 28.3% and 13.0%, respectively. Compared to pks-negative, pks-positive isolates were significantly more susceptible to antimicrobial agents with a low incidence (5.1%) of multidrug-resistance and with infrequent extended-spectrum beta-lactamase (ESBL) production. Among pks-positive isolates, ST23 (78/117) and ST65 (20/117) were the dominant sequence types, and the majority harboured virulence genes. Community-onset BSI patients infected with pks-positive isolates had a higher proportion of liver abscesses and a lower proportion of biliary obstructions (P < 0.05). The pks-positive isolates were mostly sporadic in the phylogenetic tree, with a 65.8 and 47.0 average allele difference between Clade 1 and Clade 2, respectively. We concluded that although pks-positive K. pneumoniae were generally susceptible to antimicrobials, the high prevalence of such isolates in community cases and the genotoxicity, merits further investigation.

Diversity of virulence level phenotype of hypervirulent Klebsiella pneumoniae from different sequence type lineage.

BACKGROUND: Hypervirulent Klebsiella pneumoniae (hvKP) is emerging around the Asian-Pacific region and it is the major cause of the community-acquired pyogenic liver abscesses. Multidrug-resistant hypervirulent Klebsiella pneumoniae (MDR-hvKP) isolates were reported in France, China and Taiwan. However, the international-ally agreed definition for hvKP and the virulence level of hvKP are not clear. RESULTS: In this study, 56 hvKP isolates were collected from March 2008 to June 2012 and investigated by string test, capsule serotyping, multilocus sequence typing (MLST), virulence gene detection and serum resistance assay. Among the 56 K. pneumoniae isolates, 64.3% had the hypermucoviscosity phenotype, meanwhile, 64.3% were the K1 serotype and 19.6% were the K2 serotype. Within the K1 serotype, 94.4% were ST23, and within the K2 serotype, ST65, ST86 and ST375 accounted for the same percentage 27.3%. The serum resistance showed statistically normal distribution. According to the 50% lethal dose of Galleria. mellonella infection model, hvKP isolates were divided into high virulence level group and moderate virulence level group. The ability of each method evaluating the virulence level of hvKP was assessed using the area under the receiver operating characteristic curve. CONCLUSIONS: K1 ST23 K. pneumoniae was the most prevalent clone of the hvKP. However, K1 ST23 K. pneumoniae was the dominant clone in the moderate virulence level group. MLST was a relatively reliable evaluation method to discriminate the virulence level of hvKP in our study.

High prevalence of ESBL-producing Escherichia coli and Klebsiella pneumoniae in community-onset bloodstream infections in China.

OBJECTIVES: Community-onset bloodstream infections (COBSIs) caused by ESBL-producing Escherichia coli (ESBL-EC) and ESBL-producing Klebsiella pneumoniae (ESBL-KP) are increasing globally. This study aimed to investigate the epidemiology and risk factors of ESBL-EC and ESBL-KP in COBSIs in China. METHODS: A prospective, multicentre study was performed in 28 tertiary hospitals from September 2013 to November 2014. All isolates and ESBLs were microbiologically characterized. A statistical analysis of risk factors was performed using binary logistic regression. The trial was registered with ClinicalTrials.gov (NCT01961206). RESULTS: A total of 919 consecutive episodes of COBSIs were reported and 640 E. coli and 279 K. pneumoniae isolates (non-duplicate) were collected. According to the criteria, 662 (72.0%) cases were classified as having community-acquired bloodstream infections, while the remaining 257 (28.0%) were classified as having healthcare-associated bloodstream infections. The proportions of ESBL producers were 55.5% (355/640) among E. coli isolates and 16.5% (46/279) among K. pneumoniae isolates, respectively. Healthcare-associated infections, obstructive urinary tract disease, previous surgical history and use of a cephalosporin antibiotic within 3 months were independent predictors of COBSIs caused by ESBL-EC. Heart failure was the only independent risk factor for COBSIs due to ESBL-KP. Age was not independently associated with infections caused by ESBL producers. CTX-M-14 was the most common ESBL genotype and was widespread throughout the country. CONCLUSIONS: ESBL producers are highly prevalent in COBSIs in China, especially among cases caused by E. coli. For these resistant pathogens, clinicians should consider adequate empirical therapy, and different risk factors for prediction should be used in this country.

Clinical and microbiological characteristics of Klebsiella pneumoniae liver abscess in East China.

BACKGROUND: Klebsiella pneumoniae has been the dominant pathogen for liver abscesses in several Asian countries. Although the prevalence of K. pneumoniae liver abscess (KLA) in mainland China is increasing recently, the clinical and microbiological characteristics of KLA in China have not been elucidated. METHODS: Clinical and microbiology characteristics of 45 consecutive patients with KLA from a tertiary teaching hospital in China between June 2008 and June 2012 were retrospectively evaluated. RESULTS: Vast majority of the strains were susceptible to main antimicrobial agents. Most of K. pneumoniae strains from pyogenic liver abscess patients belonged to K1/K2 serotype (68.9% for K1 serotype and 20% for K2 serotype). All K. pneumoniae strains were rmpA positive, and 68.9% of these strains were magA positive. Overall, 57.8% (26/45) of K. pneumoniae strains belonged to ST23. Twenty-five of 26 ST23 K. pneumoniae isolates (96.2%) from KLA patients were magA-positive and K1 serotype. Only 28.9% (13/45) of KLA isolates exhibited hypermucoviscous phenotype, which is clinically used as the characteristic of hypervirulent K. pneumoniae (hvKP). Liver abscess sizes in patients infected with hvKP were tend to be larger than those in patients infected with cKP. There was no significant association between the microbiological and clinical characteristics including serotypes, magA and rmpA genotypes, and STs with the metastatic infection and prognosis of KLA. CONCLUSIONS: Neither the serotypes, magA and rmpA genotypes, nor the STs of K. pneumoniae were associated with the metastatic infection and prognosis of KLA. However, further studies with larger sample are needed in the future.

Delayed admission to ICU does not increase the mortality of patients post neurosurgery.

Increasing shortage of intensive care resources is a worldwide problem. While routine postoperative admission to the intensive care unit (ICU) of patients undergoing neurosurgery is a long established practice for many hospitals. Therefore, some neurosurgical patients have to be cared in post anesthesia care unit (PACU) before ICU admission during high ICU occupancy. The aim of this study was to compare the outcome of neurosurgical patients immediately admitted to the ICU post operation with those who were required to wait for ICU bed in PACU and managed by anesthesiologists before ICU admission. All adult neurosurgical patients admitted to our ICU between January 2010 and July 2013 were retrospectively analyzed. Recorded data included demographic data, surgical categories, end time of operation, operation hours, postoperative complication, hospital/ICU length of stay and cost, Glasgow coma score (GCS) on ICU discharge and ICU mortality. A total of 989 neurosurgical patients were evaluated. Nine hundred thirty-seven (94.7%) patients were immediately admitted and 52 (5.3%) patients had delayed ICU admission. Median PACU waiting hours was 4.3 h (interquartile range: 2.0-10.2 h). Delayed ICU admission post neurosurgery was highly associated with the end time of operation (p = 0.019) and high ICU occupancy (p < 0.0001). Average GCS on ICU discharge was higher in immediately admitted group (13.0 ± 3.5 vs. 11.4 ± 4.5, p = 0.012). However, delayed admission to ICU post neurosurgery was not associated with prolonged ICU length of stay, increased ICU mortality, increased postoperative complication and hospital/ICU cost (all p > 0.05). Thus, an algorithm for appropriate disposition of neurosurgical patients is warranted so as to balance the quality of care and control of scarce intensive resources.

Euglena's atypical respiratory chain adapts to the discoidal cristae and flexible metabolism.

Euglena gracilis, a model organism of the eukaryotic supergroup Discoba harbouring also clinically important parasitic species, possesses diverse metabolic strategies and an atypical electron transport chain. While structures of the electron transport chain complexes and supercomplexes of most other eukaryotic clades have been reported, no similar structure is currently available for Discoba, limiting the understandings of its core metabolism and leaving a gap in the evolutionary tree of eukaryotic bioenergetics. Here, we report high-resolution cryo-EM structures of Euglena's respirasome I + III2 + IV and supercomplex III2 + IV2. A previously unreported fatty acid synthesis domain locates on the tip of complex I's peripheral arm, providing a clear picture of its atypical subunit composition identified previously. Individual complexes are re-arranged in the respirasome to adapt to the non-uniform membrane curvature of the discoidal cristae. Furthermore, Euglena's conformationally rigid complex I is deactivated by restricting ubiquinone's access to its substrate tunnel. Our findings provide structural insights for therapeutic developments against euglenozoan parasite infections.

Simultaneous and ultrafast detection of pan-SARS-coronaviruses and influenza A/B viruses by a novel multiplex real-time RT-PCR assay.

Here we report an ultrafast quadruplex RT-qPCR assay with robust diagnostic ability to detect and distinguish pan-SARS-CoVs and influenza A/B viruses within 35 min. This quadruplex RT-qPCR assay comprised of one novel RNA-based internal control targeting human ß2-microglobulin (B2M) for process accuracy and three newly-designed primers-probe sets targeting the envelope protein (E) of pan-SARS-CoV, matrix protein (MP) of influenza A virus and non-structural (NS) region of influenza B virus. This quadruplex assay exhibited a sensitivity comparable to its singleplex counterparts and a slightly higher to that of the Centers for Disease Control and Prevention-recommended SARS-CoV-2 and influenza A/B assays. The novel assay showed no false-positive amplifications with other common respiratory viruses, and its 95 % limits of detection for pan-SARS-CoV and influenza A/B virus was 4.26-4.52 copies/reaction. Moreover, the assay was reproducible with less than 1 % coefficient of variation and adaptable testing different clinical and environmental samples. Our ultrafast quadruplex RT-qPCR assay can serve as an attractive tool for effective differentiation of influenza A/B virus and SARS-CoV-2, but more importantly prognose the reemergence/emergence of SARS and novel coronaviruses or influenza viruses from animal spillover.

Scalable and Versatile Metal Ion Solidificated Alginate Hydrogel for Skin Wound Infection Therapy.

Bacterial infections in wounds continue to be a major challenge in clinical settings worldwide and represent a significant threat to human health. This work proposes novel expandable and versatile methods for solidifying sodium alginate (SA) with metal ions (such as Fe3+, Co2+, Ni2+, Cu2+, and Zn2+) to create Metal-Alginate (M-Alg) hydrogel with adjustable morphology, composition, and microstructure. It conforms to the wound site, protects against second infection, reduces inflammation, and promotes the healing of infected wounds. Among these hydrogels, Cu-Alginate (Cu-Alg) shows excellent sterilization effect and good efficacy against both gram-positive and gram-negative bacteria, including multidrug-resistant (MDR) strains such as Methicillin-resistant Staphylococcus aureus (MRSA) and Carbapenem-resistant Klebsiella pneumoniae (CRKP) due to its dual antibacterial mechanisms: contact-killing and reactive oxygen species (ROS) burst. Importantly, it exhibits low cytotoxicity and biodegradability. This simple and cost-effective gel-based system has the potential to introduce an innovative approach to the management of wound infection and offers promising new perspectives for the advancement of wound care practice.

Awareness and use of the Canadian computed tomography head rule for mild head injury patients among Chinese emergency physicians.

OBJECTIVE: Computed tomography (CT) scan has been an increasingly essential diagnostic tool for emergency physicians (EPs) to triage emergency patients. Canadian computed tomography Head Rule (CCHR) had been established and widely used to spare patients with mild head injury from unnecessary radiation. However, the awareness of CCHR and its actual utilization among Chinese EPs were unknown. This survey was to investigate the awareness and use of CCHR and their associated characteristics among Chinese EPs. METHODS: Questionnaire was randomly sent to EPs from different Chinese hospitals. Surveyed EPs were asked how well they know about the CCHR and how often they use the CCHR to guide head CT use. Association between the awareness and utilization of CCHR and the physicians' characteristics were analyzed using repeated-measures logistic regression. RESULTS: About 41.7% of the total 247 responders noted they "very familiar" or "somewhat familiar" with CCHR while the utilization rate was 24.7%. With respect to the most important underlying barriers for the use of CCHR, approximate half (48.5%) cited "fear of malpractice" as the leading cause. "Received specific training regarding radiation dose of CT" was the significant predicting factor both for the awareness (OR 5.87; 95% CI, 3.08-11.21) and the use (OR 6.10, 95% CI, 2.91-12.80) of CCHR. CONCLUSIONS: Fear of malpractice and lack of radiation risk knowledge were two main barriers to apply CCHR in the request of CT for patients with mild head injury. Furthermore, EPs with specific training about radiation risk of CT were more likely to know and use of CCHR.

Development of a Novel Typing Scheme Based on the Genetic Diversity of Heme/Hemin Uptake System Hmu in Klebsiella pneumoniae Species Complex.

Iron is essential for the survival and reproduction of Klebsiella pneumoniae. Although K. pneumoniae employs multiple types of siderophores to scavenge iron during infections, the majority of host iron is retained within erythrocytes and carried by hemoglobin that is inaccessible to siderophores. HmuRSTUV is a bacterial hemin/hemoprotein uptake system. However, the genetic background and function of HmuRSTUV in K. pneumoniae remain unknown. We collected 2,242 K. pneumoniae genomes, of which 2,218 (98.9%) had complete hmuRSTUV loci. Based on the 2,218 complete hmuRSTUV sequences, we established a novel typing scheme of K. pneumoniae named hmST, and 446 nonrepetitive hmSTs were identified. In hypervirulent lineages, hmST was diversely distributed and hmST1 mainly existed in ST23 strains. In contrast, hmST was less diversely distributed among multidrug-resistant strains. hmST demonstrated greater genetic diversity in hypervirulent lineages and community-acquired and bloodstream-sourced strains. In vitro and in vivo experiments revealed that an intact hmuRSTUV was essential for hemin uptake, playing an important role in bloodstream infections. This study established a novel typing scheme of hmST based on hmuRSTUV providing new insights into identifying and monitoring the emergence of novel virulence evolution in K. pneumoniae. IMPORTANCE Siderophore is a group of low molecular weight compounds with high affinity for ferric iron, which could facilitate bacterial iron consumption. Similarly, hemin/heme scavenged by the hemin uptake system HmuRSTUV usually act as another critical iron source for K. pneumoniae. This study proved that Hmu system significantly promoted the growth of K. pneumoniae in the presence of hemin and played an important role in bloodstream infections. A novel typing scheme named hmST was established, and the genetic diversity of hmuRSTUV loci was analyzed based on a large number of genomes. This study provides new insights into identifying and monitoring the emergence of novel virulence evolution in K. pneumoniae.