Circadian clocks play important role in immunoregulation. We aimed to investigate cardiac circadian clock specific pathways and compare cardiac grafts procured at different timing on survival after transplantation to explore novel criteria for donor selection.In primate heart, phase set enrichment analysis (PSEA) showed rhythmic transcripts were enriched in antigen processing and presentation during activation of circadian rhythm. Digital sorting of immune cell composition and single-sample gene set enrichment analysis (ssGSEA) in unused donor transcriptomes showed the pathway, positive regulation of circadian rhythm significantly correlates with allograft rejection and antigen presentation pathways as well as with increased compositions of matured dendritic cell, CD4+ T cell, and naive B cell. Single-centre retrospective cohort of 390 adult heart transplants between 1 January 2015 and 31 December 2020 was used to generate a propensity score matching (PSM) cohort. Survival curve differed significantly showing inferior long-term survival when donor hearts were procured at activation group (12 pm to 12 am) compared to repression group (12 am to 12 pm) (6-year survival: 64.2% vs. 75.8%, P = 0.0065). Activation group was also associated with significantly higher rates of in-hospital death, cardiopulmonary resuscitation, and usage of mechanical circulatory support after heart transplantation compared to repression group. Furthermore, tendency for post-transplant free of rejection rates was higher in repression group compared to activation group (acute rejection, Gehan-Breslow P = 0.11 and 0.04; chronic rejection, Log rank P = 0.077 and 0.15, in full and PSM cohorts, respectively). Adjusted Cox regression analysis showed that activation group was associated with 2.20 times increased hazard of death (hazard ratio: 2.20; 95% confidence interval: 1.23-3.95; P = 0.008) compared to repression group.Circadian immunity may represent donor-related risk factors for cardiac allograft rejection through activating genes related to antigen presentation pathway and immune cells oscillation at specific time of day. Molecular circadian clock should be considered during retrieval of cardiac allografts in order to maximize graft durability.
Abstract There is an urgent need to understand the global epidemiological landscape of carbapenem-resistant Escherichia coli (CREC). Here we provide combined genomic and phenotypic characterization of the emergence of a CREC clone from the ST410 lineage. We show that the clone expands with a single plasmid, within which there is frequent switching of the carbapenemase gene type between bla NDM and bla OXA-181 with no impact on plasmid stability or fitness. A search for clone-specific traits identified unique alleles of genes involved in adhesion and iron acquisition, which have been imported via recombination. These recombination-derived allelic switches had no impact on virulence in a simple infection model, but decreased efficiency in binding to abiotic surfaces and greatly enhanced fitness in iron limited conditions. Together our data show a footprint for evolution of a CREC clone, whereby recombination drives new alleles into the clone which provide a competitive advantage in colonizing mammalian hosts.
Introduction The extent to which sinks are contaminated by carbapenem-resistant Acinetobacter baumannii (CRAB) in intensive care units (ICUs) and the association between these contaminated sinks and hospital-acquired CRAB infections during the non-cluster period remains largely unknown. Here, we performed a prospective multicenter study in 16 ICUs at 11 tertiary hospitals in Chengdu, China. Methods We sampled sinks, collected CRAB clinical isolates, and conducted whole-genome sequencing and analysis. Results A total of 789 swabs were collected from 158 sinks, and 16 CRAB isolates were recovered from 16 sinks, resulting in a contamination rate of 10.16%. Twenty-seven clinical isolates were collected during the study period. The majority (97.67%, 42/43) of the CRAB isolates belonged to ST2, and 36 (83.72%) of them had both bla OXA-23 and bla OXA-66 . The 43 strains belonged to 12 clones. One certain clone caused multiple contaminations of seven sinks in one GICU. Two clones of ST2 bla OXA-23 and bla OXA-66 -carrying sink strains were likely the sources of the two clusters in the two GICUs, respectively. Five ST2 bla OXA-23 -carrying isolates were found to be common clones but were recovered from two hospitals. Conclusion The contamination rate of CRAB in handwashing sinks is high in some local ICUs, and the contaminated sinks can serve as environmental reservoirs for CRAB clusters.
A novel Acinetobacter strain, WCHAc060041T, was recovered from hospital sewage at West China Hospital in Chengdu, Sichuan Province, China. The strain was Gram-negative coccobacillus, non-spore-forming, non-motile and strictly aerobic. The genomic DNA G+C content was 37.02 mol%. The 16S rRNA and rpoB gene sequences of the strain were ≤98.2 and≤89.5 % identical to the type strains of all known Acinetobacter species, respectively. The strain formed a distinct branch based on the genus-wide comparison of whole-cell mass fingerprints generated by matrix-assisted laser desorption/ionization-time-of flight mass spectrometry. Strain WCHAc060041T was subjected to whole genome sequencing. The average nucleotide identity based on blast (ANIb) and in silico DNA–DNA hybridization (isDDH) values between strain WCHAc060041T and type strains of other Acinetobacter species were ≤82.7 and ≤26.9 %, respectively. Strain WCHAc060041T could be distinguished from all known Acinetobacter species by its ability to assimilate gentisate and levulinate, but not to citrate (Simmons'). Genotypic and phenotypic characteristics from this study indicate that strain WCHAc060041T represents a novel species of the genus Acinetobacter , for which the name Acinetobacter sichuanensis sp. nov. is proposed. The type strain is WCHAc060041T (=CCTCC AB 2018118T=GDMCC 1.1383T=KCTC 62575T).
Hypervirulent Klebsiella pneumoniae strains are usually susceptible to many antimicrobial agents including colistin. Here we report the isolation and characterization of several colistin-resistant hypervirulent K. pneumoniae clinical strains. K. pneumoniae strains recovered from blood samples were collected at a university hospital in China. MICs of colistin were determined using microdilution. Colistin-resistant strains were subjected to whole genome sequencing to reveal their clonal background, antimicrobial resistance determinants and virulence factors. Virulence assays were performed with strains carrying the mucoid phenotype regulator gene rmpA using wax moth larvae. The pmrB gene encoding a P344L substitution was cloned into a colistin-susceptible K. pneumoniae strain to examine whether the substitution confers colistin resistance. Five colistin-resistant hypervirulent K. pneumoniae were recovered from blood samples of patients in China, belonging to four sequence/capsular types (ST23:K1, ST412:K57, ST660:K16, and ST700:K1) and carried the virulence factor rmpA. Three strains had the known colistin-resistant D150G substitution in PhoQ including one ST700:K1 strain also carrying mcr-1. The remaining two isolates had a P344L substitution of PmrB but cloning of pmrB encoding the substitution into a colistin-susceptible isolate did not alter MICs of colistin, suggesting that such a substitution did not confer resistance to colistin. In conclusion, the convergence of colistin resistance and hypervirulence in K. pneumoniae of multiple clonal backgrounds has emerged and may warrant further surveillance.
This study describes KPC-204, a novel variant of Klebsiella pneumoniae carbapenemase, characterized by a Lys-Asp-Asp (KDD) amino acid insertion at Ambler position 269 deviates from KPC-2. This variant was identified in an ST11-type clinical isolate of carbapenem-resistant Klebsiella pneumoniae from China. Notably, KPC-204 exhibits resistance to both ceftazidime-avibactam and carbapenems. Genetic analysis revealed that blaKPC-204 was located on a highly mobile IncFII/IncR plasmid within a complex genetic structure that facilitates its spread. Functional analysis, achieved through cloning into E. coli DH5α, validates KPC-204’s contribution to increased resistance to ceftazidime-avibactam. The kinetic parameters showed that KPC-204 exhibited similar affinity to KPC-2 toward ceftazidime and reduced sensitivity to avibactam. Docking simulations revealed a weaker interaction between KPC-204 and avibactam compared to KPC-2. Mating experiments demonstrated the resistance’s transmissibility. This investigation underscores the evolving diversity of KPC variants affecting ceftazidime-avibactam resistance, highlighting the necessity for continuous monitoring.
A novel actinomycete, designated as strain WCH-YHL-001T, was isolated from skin biopsy specimens of a patient at West China Hospital, Chengdu, Sichuan Province, PR China. The cells were Gram-positive, aerobic, heterotrophic and non-motile. They formed an extensive substrate with short aerial mycelia, whose branches fragmented into rod-shaped elements. Growth occurred at 10-40 °C, pH 5.0-12.0 and with NaCl concentrations of 0-4.0 % (w/v). The major cellular fatty acids of strain WCH-YHL-001T were C16 : 0, C18 : 1 ω9c, C18 : 0 10-methyl and summed feature 3. The predominant respiratory quinone was MK-8 (H4ω-cycl). The major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylinositol mannoside, unknown phospholipids and unidentified glycolipids. The diagnostic diamino acid of peptidoglycan was meso-diaminopimelic acid. The whole-cell sugar pattern consisted of arabinose and glucose. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain WCH-YHL-001T belonged to the genus Nocardia. The average nucleotide identity (ANI) and in silico DNA-DNA hybridization (isDDH) values between strain WCH-YHL-001T and type strains of Nocardia species were lower than the cut-offs (≥95-96 % for ANI and ≥70 % for isDDH) required to define a bacterial species. The genomic DNA G+C content was 67.8 mol%. Phylogenetic, physiological and chemotaxonomic data suggested that strain WCH-YHL-001T represented a novel species of the genus Nocardia, for which the name Nocardia huaxiensis sp. nov. is proposed, with the type strain WCH-YHL-001T (=GDMCC 4.181T=JCM 34475 T=NBRC 114973T).
The choice of surgical access for resection and reconstruction of buccal squamous cell carcinoma (BSCC) with the lip-splitting incision is controversial. Thus, this study aimed to evaluate the clinical and functional outcomes of midline lip split with lazy-S incision (MLSI) against the lateral lip-splitting incision (LLSI).
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