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Abstract Disruption of ciliary homeostasis in vascular endothelial cells has been implicated in the development of atherosclerosis. However, the molecular basis for the regulation of endothelial cilia during atherosclerosis remains poorly understood. Herein, we provide evidence in male mice that the accumulation of lipid droplets in vascular endothelial cells induces ciliary loss and contributes to atherosclerosis. Triglyceride accumulation in vascular endothelial cells differentially affects the abundance of free fatty acid species in the cytosol, leading to stimulated lipid droplet formation and suppressed protein S-palmitoylation. Reduced S-palmitoylation of ciliary proteins, including ADP ribosylation factor like GTPase 13B, results in the loss of cilia. Restoring palmitic acid availability, either through pharmacological inhibition of stearoyl-CoA desaturase 1 or a palmitic acid-enriched diet, significantly restores endothelial cilia and mitigates the progression of atherosclerosis. These findings thus uncover a previously unrecognized role of lipid droplets in regulating ciliary homeostasis and provide a feasible intervention strategy for preventing and treating atherosclerosis.

ABSTRACT: Objectives: Recently, blaCTX-Ms have become the dominant ESBLs for E. coli strains worldwide. We aim to provide a systematic study on the relationships between sequence types (STs), clinical origins, and the blaCTX-Ms genotypes of E. coli strains. Methods: Totally, 1005 complete sequences of clinical E. coli were collected from NCBI. Multilocus sequence typing (MLST) and antibiotic resistance genes screening were performed. Results: Faeces (26.27%), urine (16.02%), and blood (8.26%) were shown to be the main sources of clinical E. coli isolates. The isolates belong to 153 STs and 26 clonal complexes (CCs). The most prevalent STs were ST2 (11.3%), ST43 (8.6%), and ST8 (5.7%). The positive rate for blaCTX-Ms was 34.7%. Different samples showed significantly different blaCTX-Ms positive rates (P

IntroductionKluyvera is a Gram-negative, flagellated, motile bacillus within the Enterobacteriaceae. The case reports of clinical infections shed light on the importance of this organism as an emerging opportunistic pathogen. The genus Phytobacter, which often be misidentified with Kluyvera, is also an important clinically relevant member of the Enterobacteriaceae. However, the identification of Kluyvera and Phytobacter is problematic, and their phylogenetic relationship remains unclear.MethodsHere, 81 strains of Kluyvera and 16 strains of Phytobacter were collected. A series of comparative genomics approaches were applied to the phylogenetic relationship reconstruction, virulence related genes profiles description, and antibiotic resistance genes prediction.ResultsUsing average nucleotide identity (ANI) and in silico DNA-DNA hybridization (isDDH), we offered reliable species designations of 97 strains, in which 40 (41.24%) strains were incorrectly labeled. A new Phytobacter genomospecies-1 were defined. Phytobacter and Kluyvera show great genome plasticity and inclusiveness, which may be related to their diverse ecological niches. An intergenomic distances threshold of 0.15875 was used for taxonomy reassignments at the phylogenomic-group level. Further principal coordinates analysis (PCoA) revealed 11 core genes of Kluyvera (pelX, mdtL, bglC, pcak-1, uhpB, ddpA-2, pdxY, oppD-1, cptA, yidZ, csbX) that could be served as potential identification targets. Meanwhile, the Phytobacter specific virulence genes clbS, csgA-C, fliS, hsiB1_vipA and hsiC1_vipB, were found to differentiate from Kluyvera. We concluded that the evolution rate of Kluyvera was 5.25E-6, approximately three times higher than that of Phytobacter. Additionally, the co-existence of ESBLs and carbapenem resistance genes were present in approximately 40% strains, suggesting the potential development of extensively drug-resistant or even fully drug-resistant strains.DiscussionThis work provided a better understanding of the differences between closely related species Kluyvera and Phytobacter. Their genomes exhibited great genome plasticity and inclusiveness. They not only possess a potential pathogenicity threat, but also a risk of multi-drug resistance. The emerging pathogens Kluyvera and Phytobacter warrant close attention.

IntroductionShewanella is an important opportunistic pathogen distributed in marine environments that has caused an increasing number of clinical infections. However, there are few reports on the distribution and characteristics of Shewanella in the diarrheal pathogen spectrum. In this study, we have systematically described the prevalence of Shewanella infections in diarrhea patients in Beijing, China 2017–2019, and genome characteristics and antimicrobial susceptibility of Shewanella isolates.MethodsStool samples were collected from diarrhea patients in a surveillance project from 2017 to 2019. Shewanella strains were isolated, and identified using VITEKR 2 COMPACT and MALDI-TOF MS. Average nucleotide identity (ANI) analysis, multi-locus sequence typing (MLST), phylogenetic analysis, virulence-associated genes and antimicrobial resistance genes analysis were used for genome characteristics description. The antibiotic susceptibility test was performed with microbroth dilution method.Results1104 fecal samples were collected, and the Shewanella detection rate was 2.36% (26/1104). The main manifestations of infection caused by Shewanella spp. were diarrhea (100%, 26/26), abdominal pain (65.38%, 17/26), and vomiting (38.46%, 10/26). The 26 isolates were classified into 3 species (S. algae (n = 18), S. indica (n = 5), and S. chilikensis (n = 3)) and 22 sequence types. Core genome single nucleotide polymorphism-based evolutionary tree identified three clone groups corresponding to three infection events in the same months in 2017 and 2019. The putative virulence-associated gene pool consisted of 56 potential virulence genes, including 19 virulence gene factors. The resistance rates of the 26 isolates to 17 antibiotics from high to low were as follows: polymyxin E (76.92%), cefotaxime (57.69%), ampicillin (50%), ampicillin-sulbactam (34.62%), nalidixic acid (15.38%), ciprofloxacin (11.54%), selectrin (3.846%,1/26), and tetracycline (3.846%, 1/26). The rate of multidrug resistance was 38.46% (10/26).DiscussionMonitoring for Shewanella spp. should be added to the routine surveillance of infectious diarrhea during the epidemic season.

IntroductionStenotrophomonas maltophilia complex (Smc) comprises opportunistic Gram-negative bacilli responsible for various nosocomial infections. Limited data exists concerning its evolutionary lineage, global prevalence and pathogenicity.MethodsWe conducted an extensive genomic analysis on 734 Smc genomes, of which 90 were newly sequenced and isolated from different patients. The species composition and evolutionary relationships of Smc were examined using core protein sequence analysis. Pathogenicity evaluation was used by assays for swimming motility, biofilm formation and identification of virulence factors. The broth microdilution method was used to evaluate the drug resistance spectrum of clinical isolates.ResultsPhylogenetic analyses delineated 24 species-level clades, dominated by S. maltophilia (42.8%), S. sepilia (13.6%) and S. geniculata (9.9%). Geographically, strains were primarily distributed in Europe (34.2%), Asia (33.7%) and North America (24.0%), with intricate global distribution patterns. Meanwhile, 154 virulence-associated genes and 46 antimicrobial resistance genes within Smc were identified. These genes encoded span various functions, including motility, adherence, toxin, RND antibiotic efflux pumps, beta-lactamases and aminoglycoside-modifying enzymes. Moreover, significant variations were indicated in swimming motility and biofilm-forming capability across the different species, with S. sepilia exhibiting superior levels of both traits. Additionally, no statistically significant discrepancy was detected among Smc species to other antibiotics, despite the fact that all S. geniculata isolates were resistant to Ceftazidime and much higher than other species.ConclusionOur findings indicate the need to pay increased attention to other mainstream species of Smc besides S. maltophilia in order to better manage Smc-related infections and tailor effective treatment strategies.