Colistin represents one of the few available drugs for treating infections caused by carbapenem-resistant Enterobacteriaceae. As such, the recent plasmid-mediated spread of the colistin resistance gene mcr-1 poses a significant public health threat, requiring global monitoring and surveillance. Here, we characterize the global distribution of mcr-1 using a data set of 457 mcr-1-positive sequenced isolates. We find mcr-1 in various plasmid types but identify an immediate background common to all mcr-1 sequences. Our analyses establish that all mcr-1 elements in circulation descend from the same initial mobilization of mcr-1 by an ISApl1 transposon in the mid 2000s (2002–2008; 95% highest posterior density), followed by a marked demographic expansion, which led to its current global distribution. Our results provide the first systematic phylogenetic analysis of the origin and spread of mcr-1, and emphasize the importance of understanding the movement of antibiotic resistance genes across multiple levels of genomic organization.

Hypervirulent Klebsiella pneumoniae (hvKP) is traditionally defined by hypermucoviscosity, but data based on genetic background are limited. Antimicrobial-resistant hvKP has been increasingly reported but has not yet been systematically studied. K. pneumoniae isolates from bloodstream infections, hospital-acquired pneumonia, and intra-abdominal infections were collected from 10 cities in China during February to July 2013. Clinical data were collected from medical records. All K. pneumoniae isolates were investigated by antimicrobial susceptibility testing, string test, extended-spectrum ␤-lactamase (ESBL) gene detection, capsular serotypes, virulence gene profiles, and multilocus sequence typing. hvKP was defined by aerobactin detection. Of 230 K. pneumoniae isolates, 37.8% were hvKP. The prevalence of hvKP varied among different cities, with the highest rate in Wuhan (73.9%) and the lowest in Zhejiang (8.3%). Hypermucoviscosity and the presence of K1, K2, K20, and rmpA genes were strongly associated with hvKP (P < 0.001). A significantly higher incidence of liver abscess (P ‫؍‬ 0.026), sepsis (P ‫؍‬ 0.038), and invasive infections (P ‫؍‬ 0.043) was caused by hvKP. Cancer (odds ratio [OR], 2.285) and diabetes mellitus (OR, 2.256) appeared to be independent variables associated with hvKP infections by multivariate analysis. Importantly, 12.6% of hvKP isolates produced ESBLs, and most of them carried bla CTX-M genes. Patients with neutropenia (37.5% versus 5.6%; P ‫؍‬ 0.020), history of systemic steroid therapy (37.5% versus 5.6%; P ‫؍‬ 0.020), and combination therapy (62.5% versus 16.7%; P ‫؍‬ 0.009) were more likely to be infected with ESBL-producing hvKP. The prevalence of hvKP is high in China and has a varied geographic distribution. ESBLproducing hvKP is emerging, suggesting an urgent need to enhance clinical awareness, especially for immunocompromised patients receiving combination therapy. Over the past few decades, increasing rates of hypervirulent Klebsiella pneumoniae (hvKP) infection have been reported worldwide (1-4). Such strains are notorious for their capacity to cause serious and metastatic infections in young and healthy individuals, such as pyogenic liver abscesses and endophthalmitis (5). Hypermucoviscosity is an important in vitro parameter for identification of hvKP (6, 7). However, several controversies have arisen regarding the association of hypermucoviscosity phenotype and virulence (8, 9). Hypermucoviscosity-negative strains are more prone to cause severe infections and have a higher mortality rate in diabetic mice than hypermucoviscous K. pneumoniae (8). Our previous study also demonstrated that one of the five hypermucoviscous K. pneumoniae isolates showed high virulence in both in vitro and in vivo assays (9). Therefore, it is apparent that hvKP cannot be defined by string test alone (10). Aerobactin accounts for increased siderophore production and is a major virulence determinant and new defining trait for hvKP based on genetic background (11). Some advances have been made recently...

ZIF-67, a MOF with N-coordinated Co atoms, can assist the formation of active sites in oxygen reduction catalysts by pyrolysis and acid leaching.

Compared to extensively studied oxygen reduction reaction (ORR) catalysis in alkaline media, development of highly active and stable nonprecious metal catalysts (NPMCs) to replace Pt in acidic electrolytes remains grand challenges. Among currently studied catalysts, the Fe-N-C formulation holds the greatest promise for the ORR in acid. Here, we report a new highly active and stable Fe-N-C catalyst featured with well-dispersed atomic Fe in porous carbon matrix, which was prepared through one single thermal conversion from Fe-doped ZIF-8, a metal-organic framework (MOF) containing Zn 2+ and well-defined Fe-N4 coordination. Unlike other Fe-N-C catalyst preparation, no additional tedious post-treatments such as acid leaching and the second heating treatment are required in this work. Notably, an O2-free environment for preparing the Fedoped ZIF-8 precursor is found to be crucial for yielding uniform Fe distribution into highly porous N-doped carbon matrix. The resulting new Fe-N-C catalyst exhibited exceptionally improved ORR

With the advent of HIV and the widespread emergence of drug-resistant strains of Mycobacterium tuberculosis, newer control strategies in the form of a better vaccine could decrease the global incidence of tuberculosis. A desirable trait in an effective live attenuated vaccine strain is an ability to persist within the host in a limited fashion in order to produce important protective antigens in vivo. Attenuated M. tuberculosis vaccine candidates have been constructed by deleting genes required for growth in mice. These candidate vaccines did not elicit adequate protective immunity in animal models, due to their inability to persist sufficiently long within the host tissues. Here we report that an auxotrophic mutant of M. tuberculosis defective in the de novo biosynthesis of pantothenic acid (vitamin B5) is highly attenuated in immunocompromised SCID mice and in immunocompetent BALB/c mice. SCID mice infected with the pantothenate auxotroph survived significantly longer (250 days) than mice infected with either bacille Calmette-Guerin (BCG) vaccine or virulent M. tuberculosis (77 and 35 days, respectively). Subcutaneous immunization with this auxotroph conferred protection in C57BL/6J mice against an aerosol challenge with virulent M. tuberculosis, which was comparable with that afforded by BCG vaccination. Our findings highlight the importance of de novo pantothenate biosynthesis in limiting the intracellular survival and pathogenesis of M. tuberculosis without reducing its immunogenicity in vaccinated mice.

In human being’s history, both the Iron Age and Silicon Age thrived after a matured massive processing technology was developed. Graphene is the most recent superior material which could potentially initialize another new material Age. However, while being exploited to its full extent, conventional processing methods fail to provide a link to today’s personalization tide. New technology should be ushered in. Three-dimensional (3D) printing fills the missing linkage between graphene materials and the digital mainstream. Their alliance could generate additional stream to push the graphene revolution into a new phase. Here we demonstrate for the first time, a graphene composite, with a graphene loading up to 5.6 wt%, can be 3D printable into computer-designed models. The composite’s linear thermal coefficient is below 75 ppm·°C−1 from room temperature to its glass transition temperature (Tg), which is crucial to build minute thermal stress during the printing process.

No abstract

Acute leukemia characterized by chromosomal rearrangements requires additional molecular disruptions to develop into full-blown malignancy1,2, yet the cooperative mechanisms remain elusive. Using whole-genome sequencing of a pair of monozygotic twins discordant for MLL (also called KMT2A) gene-rearranged leukemia, we identified a transforming MLL-NRIP3 fusion gene3 and biallelic mutations in SETD2 (encoding a histone H3K36 methyltransferase)4. Moreover, loss-of-function point mutations in SETD2 were recurrent (6.2%) in 241 patients with acute leukemia and were associated with multiple major chromosomal aberrations. We observed a global loss of H3K36 trimethylation (H3K36me3) in leukemic blasts with mutations in SETD2. In the presence of a genetic lesion, downregulation of SETD2 contributed to both initiation and progression during leukemia development by promoting the self-renewal potential of leukemia stem cells. Therefore, our study provides compelling evidence for SETD2 as a new tumor suppressor. Disruption of the SETD2-H3K36me3 pathway is a distinct epigenetic mechanism for leukemia development.