From disinfection to pathogenicity: Occurrence, resistome risks and assembly mechanism of biocide and metal resistance genes in hospital wastewaters.

Hospital wastewaters (HWWs) represent critical reservoir for the accumulation and propagation of resistance genes. However, studies on biocide and metal resistance genes (BMRGs) and their associated resistome risks and driving mechanisms in HWWs are still in their infancy. Here, metagenomic assembly was firstly used to investigate host pathogenicity and transferability profiles of BMGRs in a typical HWWs system. As a result, genes conferring resistance to Ethidium Bromide, Benzylkonium Chloride, and Cetylpyridinium Chloride dominated biocide resistance genes (BRGs), whereas Cu resistance gene was the largest contributor of metal resistance genes (MRGs). Most BMRGs experienced significant reduction from anoxic-aerobic treatment to sedimentation stages but exhibited enrichment after chlorine disinfection. Network analysis indicated intense interactions between BMRGs and virulence factors (VFs). Polar_flagella, belonging to the adherence was identified to play important role in the network. Contig-based analysis further revealed noteworthy shifts in host associations along the treatment processes, with Pseudomonadota emerging as the primary carrier, hosting 91.1% and 85.3% of the BRGs and MRGs. A total of 199 opportunistic pathogens were identified to carry 285 BMRG subtypes, which mainly included Pseudomonas alcaligenes, Pseudomonas lundensis, and Escherichia coli. Notably, ruvB conferring resistance to Cr, Cetylpyridinium Chloride, and Dodine were characterized with the highest frequency carried by pathogens. Diverse co-occurrence patterns between BMRGs and mobile genetic elements (MGEs) were found from the raw influent to final effluent. Overall, 10.5% BRGs and 8.84% MRGs were mobile and among the 4 MGEs, transposase exhibited the greatest potential for the BMRGs dissemination. Furthermore, deterministic processes played a dominant role in bacterial communities and BMRGs assembly in HWWs. Bacterial communities contributed more than MGEs in shaping the resistome. Taken together, this work demonstrated widespread BMRGs pollution throughout the HWWs treatment system, emphasizing the potential for informing resistome risk and ecological mechanism in medical practice.

Co-Fe-N@biochar anode for improvment the electricity generation performance of microbial fuel cell.

Microbial fuel cells (MFCs) can generate energy while processing organic pollutants, which has a great impact on environmental wastewater treatment applications. In this study, a gel polymer was formed by Co-Fe-N co-doping biochar (Co-Fe-N@BC), which was used as the anode material to improve the electricity generation performance of MFC. The Co-Fe-N@BC material prepared at 900℃ carbonised biomass into more graphitic carbon, and its total resistance (3.56 Ω) was significantly reduced. In the corresponding dual-chamber MFC, the current density was 2.81 A/m2, and the power density reached 1181 mW/m2 at maximum. Among the materials tested, the Co-Fe-N@BC anode MFC had the highest chemical oxygen demand removal rate and coulombic efficiency, reaching 91% and 13%, respectively. It is proved that MFC with Co-Fe-N@BC anode has the best electrochemical performance.

Corrigendum: Systems pharmacology approach to investigate the mechanism of Kai-Xin-San in Alzheimer's disease.

[This corrects the article DOI: 10.3389/fphar.2020.00381.].

Clinical characteristics of respiratory tract infection caused by Klebsiella pneumoniae in immunocompromised patients: a retrospective cohort study.

Purpose: With advancements in medical technology and the growth of an aging society, the number of immunocompromised patients has increased progressively. Klebsiella pneumoniae (K. pneumoniae) is one of the most common opportunistic pathogens, causing a severe disease burden. We aimed to further clarify the differences in respiratory tract K. pneumoniae infections between immunocompromised and immunocompetent populations. Methods: We retrospectively compared cases of respiratory tract K. pneumoniae infection in immunocompromised and immunocompetent patients admitted to Ruijin Hospital in Shanghai between January 2019 and August 2020 to clarify the differences between the two groups. Results: We enrolled 400 immunocompromised patients and 386 immunocompetent patients. Compared to the immunocompetent group, immunocompromised patients were more likely to develop bacteremia and shock and to require mechanical ventilation support during hospitalization. Immunocompromised patients also had a greater probability of polymicrobial infection and a higher rate of antibacterial resistance to carbapenem, which resulted in a higher intensive care unit admission rate, 30-day case fatality rate (CFR), and 6-month CFR. Multivariate analysis indicated that immunocompromised patients with respiratory diseases (odds ratio [OR], 2.189; 95% confidence interval [CI], 1.103-4.344; P = 0.025) and cardiovascular diseases (OR, 2.008; 95% CI, 1.055-3.822; P = 0.034), using mechanical ventilation (OR, 3.982; 95% CI, 2.053-7.722; P = 0.000), or infected with multidrug-resistant K. pneumoniae (OR, 3.870; 95%, 1.577-9.498; P = 0.003) were more likely to have a higher 30-day CFR. Conclusion: The disease burden of K. pneumoniae infection in immunocompromised patients is high. Immunocompromised patients who presented with respiratory diseases and cardiovascular diseases, used mechanical ventilation, or were infected with multidrug-resistant K. pneumoniae experienced a higher 30-day mortality rate.

Epidemiology, genetic diversity, and evolutionary dynamics of Tembusu virus.

Tembusu virus (TMUV) is an emerging pathogenic flavivirus associated with acute egg-drop and fatal encephalitis in domestic waterfowl. Since its initial identification in mosquitoes in 1955, TMUV has been confirmed to infect ducks, pigeons, sparrows, geese, and chickens, posing a significant threat to the poultry industry. Here, we sequenced two DTMUV strains isolated in 2019 and systematically investigated the possible origin, genetic relationships, evolutionary dynamics, and transmission patterns of TMUV based on complete virus genome sequences in the public database. We found that TMUV can be divided into four major clusters: TMUV, cluster 1, cluster 2, and cluster 3. Interestingly, we found that cluster 2.2 (within cluster 2) is the most commonly involved in interspecies transmission events, and subcluster 2.1.2 (within cluster 2.1) is currently the most prevalent cluster circulating in Asia. Notably, we also identified three positively selected sites in the E and NS1 proteins, which may be involved in virus replication, immune evasion, and host adaptation. Finally, phylogeographic analysis revealed that cluster dispersal originated in Southeast Asia and that short-distance transmission events have occurred frequently. Altogether, these data provide novel insights into the evolution and dispersal of TMUV, facilitating the development of rapid diagnostics, vaccines, and therapeutics against TMUV infection.

Incidence Rate, Pathogens and Economic Burden of Catheter-Related Bloodstream Infection: A Single-Center, Retrospective Case-Control Study.

Purpose: Indwelling central venous catheters (CVCs) can cause catheter related bloodstream infection (CRBSI). CRBSI occurring in intensive care unit (ICU) patients may lead to the worse outcomes and extra medical costs. The present study aimed to assess the incidence and incidence density, pathogens and economic burden of CRBSI in ICU patients. Patients and Methods: A case-control study was retrospectively carried out in six ICUs of one hospital between July 2013 and June 2018. The Department of Infection Control performed routinely surveillance for CRBSI on these different ICUs. Data of the clinical and microbiological characteristics of patients with CRBSI, the incidence and incidence density of CRBSI in ICUs, the attributable length of stay (LOS), and the costs among patients with CRBSI in ICU were collected and assessed. Results: A total of 82 ICU patients with CRBSI were included into the study. The CRBSI incidence density was 1.27 per 1000 CVC-days in all ICUs, in which the highest was 3.52 per 1000 CVC-days in hematology ICU and the lowest was 0.14 per 1000 CVC-days in Special Procurement ICU. The most common pathogen causing CRBSI was Klebsiella pneumoniae (15/82, 16.67%), in which 12 (80%) were carbapenem resistant. Fifty-one patients were successfully matched with control patients. The average costs in the CRBSI group were $ 67,923, which were significantly higher (P < 0.001) than the average costs in the control group. The total average costs attributable to CRBSI were $33, 696. Conclusion: The medical costs of ICU patients were closely related to the incidence of CRBSI. Imperative measures are needed to reduce CRBSI in ICU patients.

Chronic Splenic Melioidosis in a Patient with Fever of Unknown Origin Diagnosed by Metagenomics Next-Generation Sequencing: An Emerging Cause and Literature Review.

Introduction: Human melioidosis is an emerging infectious disease in tropical areas of China, and chronic melioidosis can be a rare cause of fever of unknown origin (FUO). Timely diagnosis may improve the prognosis of melioidosis. Case Presentation: We report a case of melioidosis with splenic abscesses caused by Burkholderia pseudomallei in a 57-year-old man, who presented with FUO. Positron emission tomography/computed tomography (PET/CT) revealed multiple hypermetabolic lesions in the spleen. The spleen biopsy was conducted and metagenomics next-generation sequencing (mNGS) of the spleen specimen identified the presence of B. pseudomallei, confirming the diagnosis of melioidosis. Antimicrobial treatment was initiated with intravenous meropenem, followed by oral faropenem. During the follow-up, the patient was in good condition except having a low-grade fever occasionally. A splenectomy was performed, and subsequent culture and mNGS of the spleen pus were both positive for B. pseudomallei. Histopathological characteristics of chronic splenic melioidosis were noted. Conclusion: Melioidosis is a serious endemic disease, and it is critical to raise awareness about this disease.

Kai-Xin-San Improves Cognitive Impairment via Wnt/ß-Catenin and IRE1/XBP1s Signalings in APP/PS1 Mice.

Alzheimer's disease (AD) is the most common type of dementia with an insidious onset and slow progression. Kai-Xin-San (KXS) has been reported to be effective in improving cognitive impairment in AD. However, the mechanism is still confused. In this study, we employed APP/PS1 mice to explore the neuroprotective mechanism of KXS. Forty-eight male APP/PS1 mice were randomly divided into model group, KXS groups (0.7, 1.4, and 2.8 g/kg/d, p.o.) and the wild-type mice were assigned to the normal control group (n = 12 in each group). Y-maze and novel object recognition tests were carried out after continuous intragastric administration for 2 months. The abilities of learning, memory, and new object recognition in the APP/PS1 mice were enhanced significantly after KXS treatment. KXS can reduce the deposition of Aß40 and Aß42 in APP/PS1 mice brain. KXS decreased the levels of serum inflammatory cytokines, tumor necrosis factor-α, interleukin-1ß, and interleukin-6. KXS increased the activities of superoxide dismutase and glutathione peroxidase significantly, whereas it inhibited the contents of reactive oxygen species and malondialdehyde significantly. In addition, we also detected Wnt/ß-catenin signaling related proteins, such as Wnt7a, ß-catenin, low-density lipoprotein receptor-related protein 6 (LRP6), glycogen synthase kinase-3ß (GSK-3ß), nuclear factor kappa-B (NF-κB), postsynaptic density 95 (PSD95), microtubule associated protein-2 (MAP-2), and endoplasmic reticulum stress (IRE1 pathway) related proteins, such as inositol-requiring enzyme 1 (IRE1), phosphorylated IRE1(p-IRE1), spliced X-box-binding protein 1 (XBP1s), immunoglobulin binding protein (BIP), and protein disulfide isomerase (PDI) in the hippocampus. Results showed that KXS decreased the expression of GSK-3ß, NF-kB, p-IRE1/IRE1 ratio, XBP1s, and BIP; increased the expression of Wnt7a, ß-catenin, LRP6, PSD95, MAP2, and PDI. In conclusion, KXS improved cognitive impairment by activating Wnt/ß-catenin signaling, inhibiting the IRE1/XBP1s pathway in APP/PS1 mice.

Relationship of environmental factors in pond water and dynamic changes of gut microbes of sea bass Lateolabrax japonicus.

The effect of structure of gut microbes on the health of host has attracted increasing attention. Sea bass Lateolabrax japonicus is an important farmed fish in China. The relationship of the dynamic changes of intestinal bacterial communities in L. japonicus and the cultural water environment is very important for healthy culture. Here, the diversity and abundance of the gut microbial communities of L. japonicus were evaluated during the culture using 16S rRNA Illumina sequencing. Both the opportunistic pathogens Aeromonas (1.68%), Vibrio (1.59%), and Acinetobacter (1.22%); and the potential probiotics Lactobacillus (2.27%), Bacillus (1.16%), and Lactococcus (0.37%) were distributed in the gut of L. japonicus. The increasing concentration of nitrogen of water environments with the increase of culture time significantly correlated with shifts in the microbial community structure: 40.04% of gut microbial changes due to nitrogen concentration. Higher concentrations of nitrogen showed a significantly negative correlation with intestinal probiotics in L. japonicus. The results indicate that the abundance of intestinal bacteria of L. japonicus is mainly driven by the changes of environmental factors (e.g., nitrogen), and it's very important that the linking environmental parameters with bacterial data of guts could be used as an early warning indicator in L. japonicus heath culture.

The 20 years transition of clinical characteristics and metabolic risk factors in primary liver cancer patients from China.

Background: The clinical characteristics of primary liver cancer (PLC) patients are changing, maybe due to hepatitis viral vaccination and lifestyle changes, etc. The linkage between these changes and outcomes among these PLCs has not yet been fully elucidated. Methods: It was identified total of 1691 PLC cases diagnosed between 2000 ~ 2020. Cox proportional hazards models were utilized to determine the connections between the clinical presentations and their close risk factor(s) from PLC patients. Results: The average age of PLC patients increased gradually from 52.74 ± 0.5 years in 2000 ~ 2004 to 58.63 ± 0.44 years in 2017 ~ 2020, accompanied by an increased proportion of females from 11.11% to 22.46%, and non-viral hepatitis-related PLC was raised from 1.5% to 22.35%. 840 (49.67%) PLC patients with alpha-fetoprotein (AFP) < 20ng/mL (AFP-negative). The mortality was 285 (16.85%) or 532 (31.46%) PLC patients with alanine transaminase (ALT) between 40 ~ 60 IU/L or ALT > 60 IU/L. The PLC patients with pre-diabetes/diabetes or dyslipidemia also increased from 4.29% or 11.1% in 2000 ~ 2004 to 22.34% or 46.83% in 2017 ~ 2020. The survival period of the PLC patients with normoglycemia or normolipidemic was 2.18 or 3.14 folds longer than those patients with pre-diabetes/diabetes or hyperlipidemia (P<0.05). Conclusions: It was gradually increased that age, the proportion of females, non-viral hepatitis-related causes, AFP-negative, and abnormal glucose/lipids among PLC patients. Proper control of glucose/lipids or ALT may improve the prognosis of PLCs.

Impact of age group on bloodstream infection risk evaluation in immunosuppressed patients: a retrospective, single-centre, 5-year cohort study.

INTRODUCTION: Elderly patients in immunosuppressive status may have an increased occurrence of illness and risk of poor prognosis. It is a generally overlooked population that we should pay more attention to their risk factors of sickness and mortality. METHODS: Eight hundred and nine patients who were diagnosed with bloodstream infection in immunosuppressive states during accepting treatment in our hospital were selected from 2015 to 2019.The demographic data, underlying diseases, comorbidity, inducement, complications, pathogen sources, etiologies, and the antibiotics therapy were analyzed between ages > 65 years groups and ages < 65 years groups. RESULTS: The clinical characteristics of totally 809 immunosuppressed people diagnosed with bloodstream infection were analyzed, and among those people about 371 were ages > 65 years. By univariate logistic regression analysis and multivariate logistic regression analysis, we found that hypertension (OR: 2.864, 95% CI 2.024-4.051, P < 0.0001), cerebral Infarction (OR: 4.687, 95% CI 2.056-10.686, P < 0.0001), coronary heart disease (OR: 1.942, 95% CI 1.168-3.230, P = 0.011), acute pancreatitis (OR: 3.964, 95% CI 2.059-7.632, P < 0.0001), infective endocarditis (OR: 6.846, 95% CI 1.828-25.644, P = 0.004), aortic dissection (OR: 9.131, 95% CI 3.190-26.085, P < 0.0001), chemotherapy (OR: 3.462, 95% CI 1.815-6.603, P < 0.0001), transplant status (OR: 20.031, 95% CI 4.193-95.697, P < 0.0001), and respiratory tract infection (OR: 2.096, 95% CI 1.269-3.461, P = 0.004) were significantly different between ages > 65 years groups and ages < 65 years groups. CONCLUSION: Hypertension, cerebral Infarction, coronary heart disease, acute pancreatitis, infective endocarditis, aortic dissection, chemotherapy, transplant status, and pathogen source of respiratory tract were the independent risk factors of ages > 65 years in immunosuppressed patients, which would have the benefit to discriminate the prognostic factors in immunosuppressive elderly people with bloodstream infection.

Prognostic Risk Factors of Carbapenem-Resistant Gram-Negative Bacteria Bloodstream Infection in Immunosuppressed Patients: A 7-Year Retrospective Cohort Study.

Purpose: Carbapenem-resistant Gram-negative bacteria bloodstream infection (CRGNB-BSI) has gradually become a major threat worldwide due to its treatment difficulty and high mortality. This study aimed to determine the risk factors for CRGNB-BSI in immunosuppressed patients. Patients and Methods: A total of 427 immunosuppressed patients with CRGNB-BSI were retrospectively investigated from 2015 to 2021. Both univariate and multivariate logistic regression analyses were applied to evaluate independent risk factors for CRGNB-BSI. Results: The most common etiology was Klebsiella Pneumoniae (50.59%; 216/427), while the Acinetobacillus baumannii infection was associated with the highest mortality (58.25%) among all etiologies. The 60-day mortality of immunosuppressed patients with CRGNB-BSI was 52.48% (224/427). Procalcitonin (PCT) > 0.5 µg/L (OR = 2.32, 95% CI: 1.28-4.19, P = 0.005) and age > 55 years (OR = 2.06, 95% CI: 1.17-3.64, P = 0.012) were found to be predictors of 60-day mortality of CRGNB-BSI, and tigecycline regimen (OR = 3.20, 95% CI: 1.81-5.67, P < 0.001) was associated with higher mortality. Multivariate analysis also revealed that patients who developed acute kidney injury (AKI) (OR = 2.19, 95% CI: 1.11-4.30, P = 0.023), gastrointestinal bleeding (OR = 3.18, 95% CI: 1.10-9.16, P = 0.032), multiple organ dysfunction syndrome (MODS) (OR = 12.11, 95% CI: 2.61-56.19, P = 0.001), and septic shock (OR = 3.24, 95% CI: 1.77-5.94, P < 0.001) showed worse outcomes. The risk factors were also significantly associated with mortality in the different subgroups. Conclusion: This study demonstrated that PCT > 0.5 µg/L, age > 55 years, and the tigecycline regimen were significantly associated with higher 60-day mortality among immunosuppressed patients with CRGNB- BSI. Patients developing MODS, septic shock, or AKI had worse clinical outcomes. .

Nuclear localization of human MEIOB requires its NLS in the OB domain and interaction with SPATA22.

MEIOB is a vital protein in meiotic homologous recombination and plays an indispensable role in human gametogenesis. In mammals, MEIOB and its partner SPATA22 form a heterodimer, ensuring their effective localization on single-strand DNA (ssDNA) and proper synapsis processes. Mutations in human MEIOB (hMEIOB) cause human infertility attributed to the failure of its interaction with human SPATA22 (hSPATA22) and ssDNA binding. However, the detailed mechanism is still unclear. In our study, truncated or full-length hMEIOB and hSPATA22 are traced by fused expression with fluorescent proteins (i.e., copGFP or mCherry), and the live cell imaging system is used to observe the expression and localization of the proteins. When transfected alone, hMEIOB accumulates in the cytoplasm. Interestingly, a covered NLS in the OB domain of hMEIOB is identified, which can be exposed by hSPATA22 and is necessary for the nuclear localization of hMEIOB. When hSPATA22 loses its hMEIOB interacting domain or NLS, the nuclear localization of hMEIOB is aborted. Collectively, our results prove that the NLS in the OB domain of hMEIOB and interaction with hSPATA22 are required for hMEIOB nuclear localization.

Loss of Cep72 affects the morphology of spermatozoa in mice.

The centrosome regulates mammalian meiosis by affecting recombination, synapsis, chromosome segregation, and spermiogenesis. Cep72 is one of the critical components of the centrosome. However, the physiological role of Cep72 in spermatogenesis and fertility remains unclear. In this study, we identify Cep72 as a testis-specific expression protein. Although Cep72 knockout mice were viable and fertile, their sperms were morphologically abnormal with incomplete flagellum structures. Transcriptome analysis reveals significant differences in six genes (Gm49527, Hbb-bt, Hba-a2, Rps27a-ps2, Gm29647, and Gm8430), which were not previously associated with spermatogenesis. Overall, these results indicate that Cep72 participates in regulating sperm morphology and yet is dispensable for fertility in mice.

Identification and characterization of lncRNAs and the interaction of lncRNA-mRNA in Epinephelus coioides induced with Singapore grouper iridovirus infection.

Singapore grouper iridovirus (SGIV) is a highly pathogenic double-stranded DNA virus, and the fatality rate of SGIV-infected grouper is more than 90%. Up to now, there is no effective methods to control the disease. Long non-coding RNAs (lncRNAs) might play an important role in individual growth and development, immune regulation and other life processes. In this study, lncRNAs were identified in Epinephelus coioides, an important economic aquaculture marine fish in China and Southeast Asia, and the regulatory relationships of lncRNAs and mRNA response to SGIV infection were analyzed. A total of 11,678 lncRNAs were identified and classified from the spleen and GS (grouper spleen) cells. 105 differentially expressed lncRNAs (DElncRNAs) were detected during SGIV infection. The lncRNAs and the regulated mRNAs were analyzed using co-expression network, lncRNA target gene annotation and GO enrichment. At 24 and 48 h after SGIV infection, 118 and 339 lncRNA-mRNA pairs in GS cells were detected, and 728 and 688 differentially expressed lncRNA-mRNA pairs in spleen were obtained, respectively. GO and KEGG were used to predict the DE lncRNAs' target genes, and deduce the DE lncRNAs-affected signaling pathways. In GS cells, lncRNAs might participate in cell part, binding and catalytic activity; and lncRNAs might be involved in immune system process and transcription factor activity in spleen. These data demonstrated that lncRNAs could regulate the expression of immune-related genes response to viral infection, and providing a new insight into understanding the complexity of immune regulatory networks mediated by lncRNAs during viral infection in teleost fish.

Heating Rate during Shell Egg Thermal Treatment Elicits Stress Responses and Alters Virulence of Salmonella enterica Serovar Enteritidis; Implications for Shell Egg Pasteurization.

Thermal pasteurization of shell eggs, at various time-temperature combinations, has been proposed previously and implemented industrially. This study was conducted to determine if shell egg heating rate, which varies with different pasteurization implementations, alters the Salmonella enterica serovar Enteritidis response to different stresses or expression of virulence. Shell eggs, containing Salmonella Enteritidis in yolk, were subjected to a low (2.4°C/min) or a high (3.5°C/min) heating rate during treatments that mimicked the pasteurization temperature come-up stage. The low heating rate protected Salmonella from the following processes: (i) lethal heat at the holding stage, (ii) loss of viability during 8-h cooling after heating, and (iii) sequential antimicrobial ozone treatment. Transcriptional analysis using Salmonella reporter strains revealed that the heat stress response gene grpE was transcribed at 3-fold-higher levels (P = 0.0009) at the low than at the high heating rate. Slow heating also significantly increased the transcription of the Salmonella virulence-related genes sopB (P = 0.0012) and sseA (P = 0.0006) in comparison to fast heating. Salmonella virulence was determined experimentally as 50% lethal dose (LD50) values in an in vivo model. The slow heat treatment mildly increased Salmonella Enteritidis virulence in mice (LD50 of 3.3 log CFU), compared to that in nontreated yolk (LD50 of 3.9 log CFU). However, when ozone application followed the slow heat treatment, Salmonella virulence decreased (LD50 of 4.2 log CFU) compared to that for heat-treated or nontreated yolk. In conclusion, heating shell eggs at a low rate can trigger hazardous responses that may compromise the safety of the final pasteurized products but following the thermal treatment with ozone application may help alleviate these concerns. IMPORTANCE Pasteurization of shell eggs is an important technology designed to protect consumers against Salmonella Enteritidis that contaminates this commodity. A low heating rate is preferred over a high rate during shell egg thermal pasteurization due to product quality concern. However, it is not known whether raising the temperature at different rates, during pasteurizing, would potentially affect product safety determinants. The current study demonstrated that slow heating during the pasteurization come-up stage increased the following risks: (i) resistance of Salmonella to pasteurization holding stage or to subsequent ozone treatment, (ii) recovery of Salmonella during the cooling that followed pasteurization, and (iii) Salmonella's ability to cause disease (i.e., virulence). Our findings inform food processors about potential safety risks to consumers resulting from improper use of processing parameters during shell egg pasteurization. Additionally, treating shell eggs with ozone after heat treatment could alleviate these hazards and protect consumers from natural Salmonella Enteritidis contaminants in shell eggs.

Circulating (1 → 3)-ß-D-Glucan as an immune activation marker decreased after ART in people living with HIV.

Background: Plasma level of polysaccharide (1 → 3)-ß-D-Glucan (ßDG), as a diagnostic marker of invasive fungal infection has been reported to be elevated in people living with HIV (PLWH). We assessed the association of circulating ßDG to inflammation and systemic immune activation and the effect of antiretroviral therapy (ART) on ßDG in PLWH. Method: Plasma and peripheral blood monocular cell samples from 120 PLWH naive to ART and after 1 year's ART were collected. Plasma levels of ßDG, markers of bacterial translocation, gut damage, and cellular immune activation were quantified. Result: The plasma ßDG levels were negatively correlated with CD4+ T cells count (r = -0.25, p = 0.005) and positively with HIV viral load (r = 0.28, p = 0.002) before ART. It was also positively correlated with immune activation markers, including PD-1 expression on CD4+ T cell (r = 0.40, p = 0.01) and CD8+ T cell (r = 0.47, p = 0.002), as well as HLADR+CD38+ co-expression on CD8+ T cell (r = 0.56, p = 0.0002), but not with the plasma levels of LPS (r = 0.02, p = 0.84), LPS binding protein (LBP, r = 0.11, p = 0.36), soluble LPS receptor sCD14 (r = 0.04, p = 0.68), intestinal fatty acid binding protein (IFABP, r = -0.12, p = 0.18), and regenerating islet-derived protein 3α (REG3α, r = 0.18, p = 0.06). After 1 year's ART, the levels of ßDG were significantly decreased compared to that in pre-ART (1.31 ± 0.24 Log10 pg/ml vs. 1.39 ± 0.18 Log10 pg/ml, p < 0.001). Conclusion: The level of plasma ßDG was associated with cellular immune activation and decreased after ART in PLWH, suggesting it could serve as a biomarker of immune activation and efficacy monitoring.

Clinical and Microbiological Characteristics of Klebsiella pneumoniae Bloodstream Infection in a Chinese Hospital: Hypervirulent and Multiclonal.

Purpose: Hypervirulent Klebsiella pneumoniae (hvKP) is emerging globally and can cause various infections. This study aimed to investigate the clinical and microbiological characteristics of bloodstream infection (BSI) caused by hvKP. Patients and Methods: The clinical data of hospitalized patients with K. pneumoniae BSI were retrospectively analyzed. The K. pneumoniae strains were collected and re-identified, and antimicrobial susceptibility testing was performed using the broth microdilution method. Capsular serotypes and virulence genes were detected using polymerase chain reaction, and hvKP was defined as aerobactin positive. Molecular typing was done by multilocus sequence typing. The hvKP and classic K. pneumoniae (cKP) subgroups were compared. Results: Of the 66 nonrepetitive BSI K. pneumoniae strains included, 29 (43.9%) were hvKP. In these BSI hvKP strains, salmochelin and yersiniabactin accounted for 86.2% and 72.4%, respectively. The prevalence of rmpA, iroBCD cluster, ybtS, clbA, and allS was 89.7%, 86.2%, 72.4%, 51.7%, and 41.4%, respectively, which were all significantly different between the hvKP and cKP subgroups. Serotypes K1 and K2 were strongly associated with hypervirulence (P < 0.05). Nineteen sequence types were scattered in the 29 hvKP strains, and the most common was ST23 (24.1%). None of the hvKP strains were carbapenem resistant. Compared with cKP, hvKP was more capable of developing a liver abscess. However, the 30-day mortality rate was lower (13.8% vs 21.6%) in the hvKP subgroup than in the cKP subgroup. Conclusion: This study demonstrated a high proportion of hvKP in BSI K. pneumoniae, most of which were RmpA and siderophore producing, and of multiclonal origin.

The Role of Egg Yolk in Modulating the Virulence of Salmonella Enterica Serovar Enteritidis.

Contribution of food vehicles to pathogenicity of disease-causing microorganisms is an important but overlooked research field. The current study was initiated to reveal the relationship between virulence of Salmonella enterica serovar Enteritidis and egg yolk as a hosting medium. Mice were orally challenged with Salmonella Enteritidis cultured in egg yolk or tryptic soy broth (TSB). Additionally, mice were challenged with Salmonella Enteritidis cultured in TSB, followed by administration of sterile egg yolk, to discern the difference between pre-growth of the pathogen and its mere presence in egg yolk during infection. The pathogen's Lethal dose 50 (LD50) was the lowest when grown in yolk (2.8×102 CFU), compared to 1.1×103 CFU in TSB, and 4.6×103 CFU in TSB followed by administration of sterile yolk. Additionally, mice that orally received Salmonella Enteritidis grown in egg yolk expressed a high death rate. These findings were supported by transcriptional analysis results. Expression of promoters of virulence-related genes (sopB and sseA) in genetically modified Salmonella Enteritidis reporter strains was significantly higher (p < 0.05) when the bacterium was grown in the yolk, compared to that grown in TSB. Sequencing of RNA (RNA-seq) revealed 204 differentially transcribed genes in Salmonella Enteritidis grown in yolk vs. TSB. Yolk-grown Salmonella Enteritidis exhibited upregulated virulence pathways, including type III secretion systems, epithelial cell invasion, and infection processes; these observations were confirmed by RT-qPCR results. The transcriptomic analysis suggested that upregulation of virulence machinery of Salmonella Enteritidis grown in egg yolk was related to increased iron uptake, biotin utilization, flagellar biosynthesis, and export of virulence proteins encoded on Salmonella pathogenicity island 1, 2, 4, and 5. These biological responses may have acted in concert to increase the virulence of Salmonella infection in mice. In conclusion, growth in egg yolk enhanced Salmonella Enteritidis virulence, indicating the significance of this food vehicle to the risk assessment of salmonellosis.