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Capsular polysaccharides are critical virulence factors of Klebsiella pneumoniae, enabling the bacterium to evade host immune recognition and exacerbate infection. Phage-derived depolymerases, which specifically degrade these capsular polysaccharides, are increasingly recognized as a highly promising strategy for the treatment of bacterial infections. In the present study, we isolated and characterized a lytic Klebsiella pneumoniae phage, named phiTH1, and sequenced its genome. The K30-type capsular polysaccharide was identified as the receptor for phiTH1 infection. A tail fiber protein with a pectate lyase domain, Dop5, was then recognized as a potential K30-type depolymerase. Therefore, the recombinant protein Dop5 was expressed in Escherichia coli and purified, and its in vitro capsular depolymerase activity was demonstrated. Further, by using a murine aspiration pneumonia model induced by K30-type Klebsiella pneumoniae TH1, we found that Dop5 protected 80% of mice from lethal challenge with Klebsiella pneumoniae. After Dop5 treatment, the pathological damage in multiple organs of mice was alleviated, the bacterial load was reduced, and serum levels of inflammatory cytokines and complement C3 decreased, along with a significant reduction in the pathological score of the lungs. Hence, this study revealed the potential of the depolymerase Dop5 for the treatment of Klebsiella pneumoniae infections.

Background Klebsiella aerogenes can cause ventilator-associated pneumonia by forming biofilms, and it is frequently associated with multidrug resistance. Phages are good antibiotic alternatives with unique advantages. There has been a lack of phage therapeutic explorations, kinetic studies, and interaction mechanism research targeting K. aerogenes . Methods Plaque assay, transmission electron microscopy and whole-genome sequencing were used to determine the biology, morphology, and genomic characteristics of the phage. A mouse pneumonia model was constructed by intratracheal/endobronchial delivery of K. aerogenes to assess the therapeutic effect of phage in vivo. Bioinformatics analysis and a prokaryotic protein expression system were used to predict and identify a novel capsule depolymerase. Confocal laser scanning microscopy, Galleria mellonella larvae infection models and other experiments were performed to clarify the function of the capsule depolymerase. Results A novel lytic phage (pK4-26) was isolated from hospital sewage. It was typical of the Podoviridae family and exhibited serotype specificity, high lytic activity, and high environmental adaptability. The whole genome is 40,234 bp in length and contains 49 coding domain sequences. Genomic data show that the phage does not carry antibiotic resistance, virulence, or lysogenic genes. The phage effectively lysed K. aerogenes in vivo, reducing mortality and alleviating pneumonia without promoting obvious side effects. A novel phage-derived depolymerase was predicted and proven to be able to digest the capsule, remove biofilms, reduce bacterial virulence, and sensitize the bacteria to serum killing. Conclusions The phage pK4-26 is a good antibiotic alternative and can effectively relieve pneumonia caused by multidrug-resistant K. aerogenes . It carries a depolymerase that removes biofilms, reduces virulence, and improves intrinsic immune sensitivity.

Bacterial infections caused by multidrug-resistant (MDR) gram-negative strains carrying the mobile colistin resistance gene mcr-1 are serious threats to world public health due to the lack of effective treatments. Inhibition of the ATP synthase makes bacteria such as Staphylococcus aureus and Klebsiella pneumoniae more sensitive to polymyxin. This provides new strategies for treating infections caused by polymyxins-resistant bacteria carrying mcr-1 . Six mcr-1 -positive strains were isolated from clinical samples, and all were identified as Escherichia coli . Here we investigated several ATP synthase inhibitors, N , N ’-dicyclohexylcarbodiimide (DCCD), resveratrol, and piceatannol, for their antibacterial effects against the mcr-1 -positive strains combined with polymyxin B (POL). Checkerboard assay, time-kill assay, biofilm inhibition and eradication assay indicated the significant synergistic effect of ATP synthase inhibitors/POL combination in vitro. Meanwhile, mouse infection model experiment was also performed, showing a 5 log 10 reduction of the pathogen after treatment with the resveratrol/POL combination. Moreover, adding adenosine disodium triphosphate (Na 2 ATP) could inhibit the antibacterial effect of the ATP synthase inhibitors/POL combination. In conclusion, our study confirmed that inhibition of ATP production could increase the susceptibility of bacteria carrying mcr-1 to polymyxins. This provides a new strategy against polymyxins-resistant bacteria infection.

Staphylococcus aureus is an opportunistic human pathogen that is often involved in severe infections such as pneumonia and sepsis in which bacterial virulence factors play a key role. Infections caused by S. aureus are often difficult to eradicate, particularly when they are associated with biofilm. The physiological roles of the Crp/Fnr family regulator ArcR are elusive in S. aureus. In this study, it was found that the deletion of arcR increased the hemolytic ability and biofilm formation in S. aureus. Differential gene expression analysis by RNA-seq and real-time quantitative reverse transcription PCR showed that genes associated with hemolytic ability (hla and hlb) and biofilm formation (icaA, icaB, icaC and icaD) were significantly upregulated compared with those in the wild-type strain. The results revealed that ArcR regulated the expression of the hla and ica operon by binding to their promoter regions, respectively. This study provided new insights into the functional importance of ArcR in regulating the virulence and biofilm of S. aureus.

Veillonella spp. are Gram-negative opportunistic pathogens present in the respiratory, digestive, and reproductive tracts of mammals. An abnormal increase in Veillonella relative abundance in the body is closely associated with periodontitis, inflammatory bowel disease, urinary tract infections, and many other diseases. We designed a pair of primers and a probe based on the 16S rRNA gene sequences of Veillonella and conducted real-time quantitative PCR (qPCR) and droplet digital PCR (ddPCR) to quantify the abundance of Veillonella in fecal samples. These two methods were tested for specificity and sensitivity using simulated clinical samples. The sensitivity of qPCR was 100 copies/μL, allowing for the accurate detection of a wide range of Veillonella concentrations from 10 3 to 10 8 CFU/mL. The sensitivity of ddPCR was 11.3 copies/μL, only allowing for the accurate detection of Veillonella concentrations from 10 1 to 10 4 CFU/mL because of the limited number of droplets generated by ddPCR. ddPCR is therefore more suitable for the detection of low-abundance Veillonella samples. To characterize the validity of the assay system, clinical samples from children with inflammatory bowel disease were collected and analyzed, and the results were verified using isolation methods. We conclude that molecular assays targeting the 16S rRNA gene provides an important tool for the rapid diagnosis of chronic and infectious diseases caused by Veillonella and also supports the isolation and identification of Veillonella for research purposes. Key points • With suitable primer sets, the qPCR has a wider detection range than ddPCR. • ddPCR is suitable for the detection of low-abundance samples. • Methods successfully guided the isolation of Veillonella in clinical sample.

Staphylococcus aureus is an opportunistic human pathogen that is often involved in severe infections such as pneumonia and sepsis in which bacterial virulence factors play a key role. Infections caused by S. aureus are often difficult to eradicate, particularly when they are associated with biofilm. The physiological roles of the Crp/Fnr family regulator ArcR are elusive in S. aureus. In this study, it was found that the deletion of arcR increased the hemolytic ability and biofilm formation in S. aureus. Differential gene expression analysis by RNA-seq and real-time quantitative reverse transcription PCR showed that genes associated with hemolytic ability (hla and hlb) and biofilm formation (icaA, icaB, icaC and icaD) were significantly upregulated compared with those in the wild-type strain. The results revealed that ArcR regulated the expression of the hla and ica operon by binding to their promoter regions, respectively. This study provided new insights into the functional importance of ArcR in regulating the virulence and biofilm of S. aureus.

Reactive oxygen species (ROS) play an essential role in the regulation of seed dormancy, germination, and deterioration in plants. The low level of ROS as signaling particles promotes dormancy release and triggers seed germination. Excessive ROS accumulation causes seed deterioration during seed storage. Maintaining ROS homeostasis plays a central role in the regulation of seed dormancy, germination, and deterioration in crops. This study highlights the current advances in the regulation of ROS homeostasis in dry and hydrated seeds of crops. The research progress in the crosstalk between ROS and hormones involved in the regulation of seed dormancy and germination in crops is mainly summarized. The current understandings of ROS-induced seed deterioration are reviewed. These understandings of ROS-dependent regulation on seed dormancy, germination, and deterioration contribute to the improvement of seed quality of crops in the future.

Seed vigor affects seed germination and seedling emergence, and therefore is an important agronomic trait in rice. Small auxin-up RNAs (SAURs) function in a range of developmental processes, but their role in seed vigor remains unclear. Here, we observed that disruption of OsSAUR33 resulted in reduced germination rates and low seed uniformity in early germination. Expression of OsSAUR33 was higher in mature grains and early germinating seeds. RNA-seq analysis revealed that OsSAUR33 modulated seed vigor by affecting the mobilization of stored reserves during germination. Disruption of OsSAUR33 increased the soluble sugar content in dry mature grains and seeds during early germination. OsSAUR33 interacted with the sucrose non-fermenting-1-related protein kinase OsSnRK1A, a regulator of the sugar signaling pathway, which influences the expression of sugar signaling-related genes during germination. Disruption of OsSAUR33 increased sugar-sensitive phenotypes in early germination, suggesting OsSAUR33 likely affects seed vigor through the sugar pathway. One elite haplotype of OsSAUR33 associated with higher seed vigor was identified mainly in indica accessions. This study provides insight into the effects of OsSAUR33 on seed vigor in rice.

The role of the tropical Pacific Ocean and its linkages to the southern hemisphere during the last deglacial warming remain highly controversial. Here we explore the evolution of Pacific horizontal and vertical thermal gradients over the past 30 kyr by compiling 340 sea surface and 7 subsurface temperature records, as well as one new ocean heat content record. Our records reveal that La Niña-like conditions dominated during the deglaciation as a result of the more intense warming in the western Pacific warm pool. Both the subsurface temperature and ocean heat content in the warm pool rose earlier than the sea surface temperature, and in phase with South Pacific subsurface temperature and orbital precession, implying that heat exchange between the tropical upper water column and the extratropical Southern Ocean facilitated faster warming in the western Pacific. Our study underscores the key role of the thermal coupling between the warm pool and the Southern Ocean and its relevance for future global warming. The mechanism of the last deglacial global warming is key for future climate. Here, the authors shed light on the pivotal role of the thermal coupling between the western Pacific warm pool and the Southern Ocean.

Introduction Observational studies have indicated that individuals with hypertension (HTN) and diabetes mellitus (DM) tend to exhibit elevated plasma atherogenic index of plasma (AIP), defined as log (triglyceride [TG]/high-density lipoprotein cholesterol (HDL-C)). However, the precise relationship between these factors remains unclear. This study aimed to examine the correlations among HTN, DM, and AIP. Methods Data from the National Health and Nutrition Examination Survey (NHANES; 2011–2016), a nationally representative sample, were analyzed to assess the relationship between AIP and the coexistence of HTN and DM in United States (US) adults. AIP served as the exposure variable, adjusted for 28 covariates. Baseline characteristics, correlation analysis, stratified analysis, and non-linear modeling were employed to elucidate these associations. The Extreme Gradient Boosting (XGBoost) machine learning algorithm was utilized to evaluate the predictive value of various variables for the presence of HTN and DM. Receiver operating characteristic (ROC) curve analysis was performed to assess AIP’s diagnostic accuracy for detecting HTN and DM. Results Baseline characteristics revealed that individuals with HTN and DM had higher mean AIP values (0.39). Participants with alcohol use, obesity, or metabolic syndrome were more likely to present with both conditions. A significant positive correlation between AIP and the coexistence of HTN and DM was found (model 1: odds ratio [OR] = 5.93, 95% confidence interval [CI] = 3.84–9.16, P  < 0.001; model 2: OR = 6.78, 95% CI = 4.14–11.1, P  < 0.001; model 3: OR = 3.95, 95% CI = 1.66–9.39, P  = 0.005), as confirmed by stratified analysis and smoothing curve analysis. The XGBoost algorithm identified AIP as an important predictor of HTN and DM. ROC curve analysis demonstrated AIP’s relatively high accuracy in predicting these conditions. Smoothing curve analysis further supported the positive associations among AIP, HTN, and DM. Conclusion This cross-sectional study highlights AIP was significantly associated with HTN combined with DM, underscoring its potential as a diagnostic tool. These findings provide valuable insights for future preventive and therapeutic approaches.