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Japanese Journal of Infectious Diseases Jun 2024Campylobacter jejuni is one of the major bacteria that causes diarrhea in humans. It has been associated with many cases of food poisoning in Japan caused by eating raw...
Campylobacter jejuni is one of the major bacteria that causes diarrhea in humans. It has been associated with many cases of food poisoning in Japan caused by eating raw or undercooked chicken meat, chicken liver, and grilled chicken (Yakitori). Campylobacter jejuni is also known as the preceding infection pathogen of Guillain-Barré syndrome (GBS), which causes considerable health impact on humans. In January 2022, in a case of C. jejuni food poisoning that occurred at a restaurant in Tokyo, one of four patients with diarrhea developed GBS. The poisoning is presumed to have been caused by undercooked chicken dishes. Recently, it was one of the common cases in Japan. Moreover, C. jejuni isolates from three patients, including the patient with GBS, had the same genotype (ST22, HS19, and LOS A). This genotype was frequently detected from patients with GBS in our past surveys. Our findings confirmed that the patient developed GBS via food poisoning after consuming undercooked chicken dish.
PubMed: 38945857
DOI: 10.7883/yoken.JJID.2024.108 -
Two-year investigation of spore-formers through the production chain at two cheese plants in Norway.Food Research International (Ottawa,... Aug 2024Spore-forming bacteria are the most complex group of microbes to eliminate from the dairy production line due to their ability to withstand heat treatment usually used...
Spore-forming bacteria are the most complex group of microbes to eliminate from the dairy production line due to their ability to withstand heat treatment usually used in dairy processing. These ubiquitous microorganisms have ample opportunity for multiple points of entry into the milk chain, creating issues for food quality and safety. Certain spore-formers, namely bacilli and clostridia, are more problematic to the dairy industry due to their possible pathogenicity, growth, and production of metabolites and spoilage enzymes. This research investigated the spore-forming population from raw milk reception at two Norwegian dairy plants through the cheesemaking stages until ripening. Samples were collected over two years and examined by amplicon sequencing in a culture independent manner and after an anaerobic spore-former enrichment step. In addition, a total of 608 isolates from the enriched samples were identified at the genus or species level using MALDI-TOF analysis. Most spore-forming isolates belong to the genera Bacillus or Clostridium, with the latter dominating the enriched MPN tubes of raw milk and bactofugate. Results showed a great variation among the clostridia and bacilli detected in the enriched MPN tubes. However, B. licheniformis and C. tyrobutyricum were identified in all sample types from both plants throughout the 2-year study. In conclusion, our results shed light on the fate of different spore-formers at different processing stages in the cheese production chain, which could facilitate targeted actions to reduce quality problems.
Topics: Norway; Cheese; Food Microbiology; Spores, Bacterial; Milk; Clostridium; Animals; Bacillus; Food Handling; Dairying
PubMed: 38945575
DOI: 10.1016/j.foodres.2024.114610 -
Antiviral Research Jun 2024The WHO declared the official end of the SARS-CoV-2 caused public health emergency on May 5, 2023, after two years in which the virus infected approximately 750 Mio...
The WHO declared the official end of the SARS-CoV-2 caused public health emergency on May 5, 2023, after two years in which the virus infected approximately 750 Mio individuals causing estimated up to 7 Mio deaths. Likely, the virus will continue to evolve in the human population as a seasonal respiratory pathogen. To now prevent severe infection outcomes in vulnerable individuals, effective antivirals are urgently needed to complement the protection provided by vaccines. SARS-CoV-2 enters its host cell via ACE2 mediated membrane fusion, either at the plasma membrane, if the protease TMPRSS2 is present or via the endosome, in a cathepsin dependent fashion. A small number of positive regulators of viral uptake were described in the literature, which are potentially useful targets for host directed antiviral therapy or biomarkers indicating increased or diminished susceptibility to infection. We identified here by cell surface proximity ligation novel proteins, required for efficient virion uptake. Importantly, chemical inhibition of one of these factors, SLC3A2, resulted in robust reduction of viral replication, to that achieved with a TMPRSS2 inhibitor. Our screen identified new host dependency factors for SARS-CoV-2 entry, which could be targeted by novel antiviral therapies.
PubMed: 38945485
DOI: 10.1016/j.antiviral.2024.105951 -
Free Radical Biology & Medicine Jun 2024To date, Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver disease associated with clinical complications. Dietary fatty acids have been...
BACKGROUND
To date, Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver disease associated with clinical complications. Dietary fatty acids have been suggested to be involved in preventing or reversing the accumulation of hepatic fat. However, contradicting roles of monounsaturated fatty acids to the liver have been implicated in various human and murine models, mainly due to the insolubility nature of fatty acids.
METHODS
High pressure homogenization methods were used to fabricate oleic acid embedded lipid nanoparticles (OALNs). The in vitro and in vivo models were used to validate the physiological effect of this OALNs via various cellular and molecular approaches including cell viability essay, fluorescent staining, electron microscope, RNAseq, qPCR, Western blots, and IHC staining.
RESULTS
We successfully fabricated OALNs with enhanced stability and solubility. More importantly, lipid accumulation was successfully induced in hepatocytes via the application of OALNs in a dose-dependent manner. Overload of OALNs resulted in ROS accumulation and apoptosis of hepatocytes dose-dependently. With the help of transcriptome sequencing and traditional experimental approaches, we demonstrated that the lipotoxic effect induced by OALNs was exerted via the DDIT3/BCL2/BAX/Caspases signaling. Moreover, we also verified that OALNs induced steatosis and subsequent apoptosis in the liver of mice via the activation of DDIT3 in vivo.
CONCLUSIONS
In all, our results established a potential pathogenic model of NAFLD for further studies and indicated the possible involvement of DDIT3 signaling in abnormal steatosis process of the liver.
PubMed: 38945456
DOI: 10.1016/j.freeradbiomed.2024.06.024 -
The Journal of Biological Chemistry Jun 2024The development of safe and effective broad-spectrum antivirals that target the replication machinery of respiratory viruses is of high priority in pandemic preparedness...
The development of safe and effective broad-spectrum antivirals that target the replication machinery of respiratory viruses is of high priority in pandemic preparedness programs. Here, we studied the mechanism of action of a newly discovered nucleotide analog against diverse RNA-dependent RNA polymerases (RdRp) of prototypic respiratory viruses. GS-646939 is the active 5'-triphosphate (TP) metabolite of a 4'-cyano modified C-adenosine analog phosphoramidate prodrug GS-7682. Enzyme kinetics show that the RdRps of human rhinovirus type 16 (HRV-16) and enterovirus 71 (EV-71) incorporate GS-646939 with unprecedented selectivity; GS-646939 is incorporated 20-50-fold more efficiently than its natural ATP counterpart. The RdRp complex of respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) incorporate GS-646939 and ATP with similar efficiency. In contrast, influenza B RdRp shows a clear preference for ATP and human mitochondrial RNA polymerase (h-mtRNAP) does not show significant incorporation of GS-646939. Once incorporated into the nascent RNA strand, GS-646939 acts as a chain-terminator although higher NTP concentrations can partially overcome inhibition for some polymerases. Modeling and biochemical data suggest that the 4'-modification inhibits RdRp translocation. Comparative studies with GS-443902, the active triphosphate form of the 1'-cyano modified prodrugs remdesivir and obeldesivir, reveal not only different mechanisms of inhibition, but also differences in the spectrum of inhibition of viral polymerases. In conclusion, 1'-cyano and 4'-cyano modifications of nucleotide analogs provide complementary strategies to target the polymerase of several families of respiratory RNA viruses.
PubMed: 38945449
DOI: 10.1016/j.jbc.2024.107514 -
International Journal of Infectious... Jun 2024Hospitalised neonates are vulnerable to infection and have high rates of antibiotic utilisation.
Prospective antimicrobial stewardship interventions by multidisciplinary teams to reduce neonatal antibiotic use in South Africa: the Neonatal Antimicrobial Stewardship (NeoAMS) study.
BACKGROUND
Hospitalised neonates are vulnerable to infection and have high rates of antibiotic utilisation.
METHODS
Fourteen South African neonatal units (seven public, seven private sector) assembled multidisciplinary teams involving neonatologists, microbiologists, pharmacists, and nurses to implement prospective audit and feedback neonatal antimicrobial stewardship (NeoAMS) interventions. The teams attended seven online training sessions. Pharmacists conducted weekday antibiotic prescription reviews in the neonatal intensive care unit and/or neonatal wards providing feedback to the clinical teams. Anonymised demographic and NeoAMS interventions data were aggregated for descriptive purposes and statistical analysis.
FINDINGS
During the 20-week NeoAMS intervention in 2022, 565 neonates were enrolled. Pharmacists evaluated seven hundred antibiotic prescription episodes; rule-out sepsis (180; 26%) and culture-negative sepsis (138; 20%) were the most frequent indications for antibiotic prescription. For infection episodes with an identified pathogen, only 51% (116/229) of empiric treatments provided adequate antimicrobial coverage. Pharmacists recommended 437 NeoAMS interventions (0·6 per antibiotic prescription episode), with antibiotic discontinuation (42%), therapeutic drug monitoring (17%), and dosing (15%) recommendations most frequent. Neonatal clinicians' acceptance rates for AMS recommendations were high (338; 77%). Mean antibiotic length of therapy decreased by 24% from 9·1 to 6·9 days (0·1 day decrease per intervention week; p=0·001), with the greatest decline in length of therapy for culture-negative sepsis (8·2 days (95%CI 5·7-11·7) to 5·9 days (95% CI 4·6-7·5); p=0·032).
INTERPRETATION
This neonatal AMS programme was successfully implemented in heterogenous and resource-limited settings. Pharmacist-recommended AMS interventions had high rates of clinician acceptance. The NeoAMS intervention significantly reduced neonatal antibiotic use, particularly for culture-negative sepsis.
FUNDING
A grant from Merck provided partial support.
PubMed: 38945432
DOI: 10.1016/j.ijid.2024.107158 -
Infection, Genetics and Evolution :... Jun 2024Chronic leg ulcers are hard to treat and can be a burden, particularly in resource-limited settings where diagnosis is a challenge. Staphylococcus aureus is among the...
BACKGROUND
Chronic leg ulcers are hard to treat and can be a burden, particularly in resource-limited settings where diagnosis is a challenge. Staphylococcus aureus is among the common bacteria isolated from chronic wounds with a great impact on wound healing, particularly in patients with co-morbidities. Antimicrobial resistance genes and virulence factors in Staphylococcus aureus isolates were assessed to support healthcare professionals to make better therapeutic choices, and importantly to curb the development and spread of antibiotic resistance.
METHODS
A cross-sectional study involved both inpatients and outpatients with chronic leg ulcers was conducted from August 2022 to April 2023 in 2 health facilities in Kilimanjaro region in Tanzania. Antimicrobial susceptibility testing was done using the disc diffusion method. Further, whole genome sequencing was performed to study the genotypic characteristics of the isolates.
RESULTS
A total of 92 participants were recruited in which 9 participants were only positive for 10 Staphylococcus aureus isolates upon culture. Five STs among 9 isolates were identified. Most of them belonged to ST8 (44%), with 1 isolate does not belong to any ST. Additionally, 50% of the isolates were methicillin-resistant Staphylococcus aureus (MRSA). All S. aureus isolates had almost similar virulence factors such as hemolysin, proteases and evasions that promote toxin production, protease production and host immune evasion respectively. Moreover, all mecA positive S. aureus isolates were phenotypically susceptible to cefoxitin.
CONCLUSION
Presence of mecA positive S. aureus isolates which are also phenotypically susceptible to cefoxitin implies the possibility of classifying MRSA as MSSA. This may result in the possible emergence of highly cefoxitin - resistant strains in health care and community settings when subsequently exposed to beta-lactam agents. Therefore, combination of whole genome sequencing and conventional methods is important in assessing bacterial resistance and virulence to improve management of patients.
PubMed: 38945421
DOI: 10.1016/j.meegid.2024.105631 -
Virologica Sinica Jun 2024Hand, foot and mouth disease (HFMD), mainly caused by enterovirus 71 (EV71), have frequently occurred in the Asia-Pacific region, posing a significant threat to the...
Hand, foot and mouth disease (HFMD), mainly caused by enterovirus 71 (EV71), have frequently occurred in the Asia-Pacific region, posing a significant threat to the health of infants and young children. Therefore, research on the infection mechanism and pathogenicity of enteroviruses is increasingly becoming important. The 3D polymerase, as the most critical RNA-dependent RNA polymerase (RdRp) for EV71 replication, is widely targeted to inhibit EV71 infection. In this study, we identified a novel host protein, AIMP2, capable of binding to 3D polymerase and inhibiting EV71 infection. Subsequent investigations revealed that AIMP2 recruits the E3 ligase SMURF2, which mediates the polyubiquitination and degradation of 3D polymerase. Furthermore, the antiviral effect of AIMP2 extended to the CVA16 and CVB1 serotypes. Our research uncovered the dynamic regulatory function of AIMP2 during EV71 infection, revealing a novel antiviral mechanism and providing new insights for the development of antienteroviral therapeutic strategies.
PubMed: 38945214
DOI: 10.1016/j.virs.2024.06.009 -
Virologica Sinica Jun 2024Bats are the natural reservoir hosts for SARS-related coronavirus (SARSr-CoV) and other highly pathogenic microorganisms. Therefore, it is conceivable that an individual...
Bats are the natural reservoir hosts for SARS-related coronavirus (SARSr-CoV) and other highly pathogenic microorganisms. Therefore, it is conceivable that an individual bat may harbor multiple microbes. However, there is limited knowledge on the overall co-circulation of microorganisms in bats. Here, we conducted a 16-year monitoring of bat viruses in south and central China and identified 238 SARSr-CoV positive samples across nine bat species from ten provinces or administrative districts. Among these, 76 individual samples were selected for further metagenomics analysis. We found a complex microenvironment characterized by the general co-circulation of microbes from two different sources: mammal-associated viruses or environment-associated microbes. The later includes commensal bacteria, enterobacteria-related phages, and insect or fungal viruses of food origin. Results showed that 25% (19/76) of the samples contained at least one another mammal-associated virus, notably alphacoronaviruses (13/76) such as AlphaCoV/YN2012, HKU2-related CoV and AlphaCoV/Rf-HuB2013, along with viruses from other families. Notably, we observed three viruses co-circulating within a single bat, comprising two coronavirus species and one picornavirus. Our analysis also revealed the potential presence of pathogenic bacteria or fungi in bats. Furthermore, we obtained 25 viral genomes from the 76 bat SARSr-CoV positive samples, some of which formed new evolutionary lineages. Collectively, our study reveals the complex microenvironment of bat microbiome, facilitating deeper investigations into their pathogenic potential and the likelihood of cross-species transmission.
PubMed: 38945213
DOI: 10.1016/j.virs.2024.06.008 -
Molecular Genetics and Metabolism Jun 2024The malate aspartate shuttle (MAS) plays a pivotal role in transporting cytosolic reducing equivalents - electrons - into the mitochondria for energy conversion at the... (Review)
Review
The malate aspartate shuttle (MAS) plays a pivotal role in transporting cytosolic reducing equivalents - electrons - into the mitochondria for energy conversion at the electron transport chain (ETC) and in the process of oxidative phosphorylation. The MAS consists of two pairs of cytosolic and mitochondrial isoenzymes (malate dehydrogenases 1 and 2; and glutamate oxaloacetate transaminases 1 and 2) and two transporters (malate-2-oxoglutarate carrier and aspartate glutamate carrier (AGC), the latter of which has two tissue-dependent isoforms AGC1 and AGC2). While the inner mitochondrial membrane is impermeable to NADH, the MAS forms one of the main routes for mitochondrial electron uptake by promoting uptake of malate. Inherited bi-allelic pathogenic variants in five of the seven components of the MAS have been described hitherto and cause a wide spectrum of symptoms including early-onset epileptic encephalopathy. This review provides an overview of reported patients suffering from MAS deficiencies. In addition, we give an overview of diagnostic procedures and research performed on patient-derived cellular models and tissues. Current cellular models are briefly discussed and novel ways to achieve a better understanding of MAS deficiencies are highlighted.
PubMed: 38945121
DOI: 10.1016/j.ymgme.2024.108520