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Biomolecules Jun 2024() causes serious inflammation and meningitis in piglets. Quercetin has anti-inflammatory and anti-bacterial activities; however, whether quercetin can alleviate brain...
() causes serious inflammation and meningitis in piglets. Quercetin has anti-inflammatory and anti-bacterial activities; however, whether quercetin can alleviate brain inflammation and provide protective effects during infection has not been studied. Here, we established a mouse model of infection in vivo and in vitro to investigate transcriptome changes in the mouse cerebrum and determine the protective effects of quercetin on brain inflammation and blood-brain barrier (BBB) integrity during infection. The results showed that induced brain inflammation, destroyed BBB integrity, and suppressed PI3K/Akt/Erk signaling-pathway activation in mice. Quercetin decreased the expression of inflammatory cytokines (, , , and ) and BBB-permeability marker genes (, , , and ), increased the expression of angiogenetic genes ( and ), reduced -induced tight junction disruption, and reactivated -induced suppression of the PI3K/Akt/Erk signaling pathway in vitro. Thus, we concluded that quercetin may protect BBB integrity via the PI3K/Akt/Erk signaling pathway during infection. This was the first attempt to explore the protective effects of quercetin on brain inflammation and BBB integrity in a -infected mouse model. Our findings indicated that quercetin is a promising natural agent for the prevention and treatment of infection.
Topics: Animals; Blood-Brain Barrier; Quercetin; Mice; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Disease Models, Animal; MAP Kinase Signaling System; Meningitis; Haemophilus Infections; Signal Transduction; Haemophilus parasuis; Cytokines; Swine
PubMed: 38927100
DOI: 10.3390/biom14060696 -
PloS One 2024Pleural empyema is a serious complication of pneumonia in children. Negative bacterial cultures commonly impede optimal antibiotic therapy. To improve bacterial... (Observational Study)
Observational Study
Pleural empyema is a serious complication of pneumonia in children. Negative bacterial cultures commonly impede optimal antibiotic therapy. To improve bacterial identification, we developed a molecular assay and evaluated its performance compared with bacterial culture. Our multiplex-quantitative PCR to detect Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus and Haemophilus influenzae was assessed using bacterial genomic DNA and laboratory-prepared samples (n = 267). To evaluate clinical performance, we conducted the Molecular Assessment of Thoracic Empyema (MATE) observational study, enrolling children hospitalised with empyema. Pleural fluids were tested by bacterial culture and multiplex-qPCR, and performance determined using a study gold standard. We determined clinical sensitivity and time-to-organism-identification to assess the potential of the multiplex-qPCR to reduce the duration of empiric untargeted antibiotic therapy. Using spiked samples, the multiplex-qPCR demonstrated 213/215 (99.1%) sensitivity and 52/52 (100%) specificity for all organisms. During May 2019-March 2023, 100 children were enrolled in the MATE study; median age was 3.9 years (IQR 2-5.6). A bacterial pathogen was identified in 90/100 (90%) specimens by multiplex-qPCR, and 24/100 (24%) by bacterial culture (P <0.001). Multiplex-qPCR identified a bacterial cause in 68/76 (90%) culture-negative specimens. S. pneumoniae was the most common pathogen, identified in 67/100 (67%) specimens. We estimate our multiplex-qPCR would have reduced the duration of untargeted antibiotic therapy in 61% of cases by a median 20 days (IQR 17.5-23, range 1-55). Multiplex-qPCR significantly increased pathogen detection compared with culture and may allow for reducing the duration of untargeted antibiotic therapy.
Topics: Humans; Child, Preschool; Empyema, Pleural; Male; Female; Multiplex Polymerase Chain Reaction; Child; Haemophilus influenzae; Staphylococcus aureus; Streptococcus pneumoniae; Streptococcus pyogenes; Infant; Hospitalization; Anti-Bacterial Agents; Sensitivity and Specificity; DNA, Bacterial
PubMed: 38917227
DOI: 10.1371/journal.pone.0304861 -
Emayella augustorita, New Member of Pasteurellaceae, Isolated from Blood Cultures of Septic Patient.Emerging Infectious Diseases Jun 2024We report discovery of a new bacterial genus and species of the family Pasteurellaceae by using phylogenetic and metabolic analysis. The bacterium, Emayella augustorita,...
We report discovery of a new bacterial genus and species of the family Pasteurellaceae by using phylogenetic and metabolic analysis. The bacterium, Emayella augustorita, was isolated from blood cultures of a patient in France diagnosed with an adenocarcinoma of the intestines and who was treated with a biliary prosthesis placement.
PubMed: 38907366
DOI: 10.3201/eid3008.231651 -
Aging Jun 2024Acute pancreatitis (AP) is a prevalent acute abdominal condition, and AP induced colonic barrier dysfunction is commonly observed. Total flavonoids of (TFC) have...
BACKGROUND
Acute pancreatitis (AP) is a prevalent acute abdominal condition, and AP induced colonic barrier dysfunction is commonly observed. Total flavonoids of (TFC) have exhibited noteworthy anti-inflammatory and anti-apoptotic properties.
METHODS
We established AP models, both in animals and cell cultures, employing Cerulein. 16S rRNA gene sequencing was performed to investigate the gut microorganisms changes.
RESULTS
, TFC demonstrated a remarkable capacity to ameliorate AP, as indicated by the inhibition of serum amylase, myeloperoxidase (MPO) levels, and the reduction in pancreatic tissue water content. Furthermore, TFC effectively curtailed the heightened inflammatory response. The dysfunction of colonic barrier induced by AP was suppressed by TFC. At the level, TFC treatment resulted in attenuation of increased cell apoptosis, and regulation of apoptosis related proteins expression in AR42J cells. The increase of , , , and by AP, and decrease of of , , by AP were both reversed by TFC treatment.
CONCLUSIONS
TFC can effectively suppress AP progression and AP induced colonic barrier dysfunction by mitigating elevated serum amylase, MPO levels, water content in pancreatic tissue, as well as curtailing inflammation, apoptosis. The findings presented herein shed light on the potential mechanisms by which TFC inhibit the development of AP progression and AP induced colonic barrier dysfunction.
Topics: Animals; Gastrointestinal Microbiome; Chrysanthemum; Pancreatitis; Flavonoids; Male; Rats; Colon; Apoptosis; Disease Models, Animal; Cell Line; Intestinal Mucosa
PubMed: 38862253
DOI: 10.18632/aging.205924 -
Frontiers in Immunology 2024is a bacterial pathogen that causes a variety of infections across diverse animal species, with one of the most devastating associated diseases being hemorrhagic...
BACKGROUND
is a bacterial pathogen that causes a variety of infections across diverse animal species, with one of the most devastating associated diseases being hemorrhagic septicemia. Outbreaks of hemorrhagic septicemia in cattle and buffaloes are marked by rapid progression and high mortality. These infections have particularly harmful socio-economic impacts on small holder farmers in Africa and Asia who are heavily reliant on a small number of animals kept as a means of subsistence for milk and draft power purposes. A novel vaccine target, PmSLP-3, has been identified on the surface of hemorrhagic septicemia-associated strains of and was previously shown to elicit robust protection in cattle against lethal challenge with a serogroup B strain.
METHODS
Here, we further investigate the protective efficacy of this surface lipoprotein, including evaluating the immunogenicity and protection upon formulation with a variety of adjuvants in both mice and cattle.
RESULTS
PmSLP-3 formulated with Montanide ISA 61 elicited the highest level of serum and mucosal IgG, elicited long-lasting serum antibodies, and was fully protective against serogroup B challenge. Studies were then performed to identify the minimum number of doses required and the needed protein quantity to maintain protection. Duration studies were performed in cattle, demonstrating sustained serum IgG titres for 3 years after two doses of vaccine and full protection against lethal serogroup B challenge at 7 months after a single vaccine dose. Finally, a serogroup E challenge study was performed, demonstrating that PmSLP-3 vaccine can provide protection against challenge by the two serogroups responsible for hemorrhagic septicemia.
CONCLUSION
Together, these data indicate that PmSLP-3 formulated with Montanide ISA 61 is an immunogenic and protective vaccine against hemorrhagic septicemia-causing strains in cattle.
Topics: Animals; Cattle; Pasteurella multocida; Hemorrhagic Septicemia; Bacterial Vaccines; Cattle Diseases; Mice; Antibodies, Bacterial; Female; Serogroup; Pasteurella Infections; Adjuvants, Immunologic; Immunoglobulin G; Mice, Inbred BALB C; Vaccination
PubMed: 38835751
DOI: 10.3389/fimmu.2024.1392681 -
BMC Veterinary Research Jun 2024Actinobacillus pleuropneumoniae is a serious pathogen in pigs. The abundant application of antibiotics has resulted in the gradual emergence of drugresistant bacteria,...
BACKGROUND
Actinobacillus pleuropneumoniae is a serious pathogen in pigs. The abundant application of antibiotics has resulted in the gradual emergence of drugresistant bacteria, which has seriously affected treatment of disease. To aid measures to prevent the emergence and spread of drug-resistant bacteria, herein, the kill rate and mutant selection window (MSW) of danofloxacin (DAN) against A. pleuropneumoniae were evaluated.
METHODS
For the kill rate study, the minimum inhibitory concentration (MIC) was tested using the micro dilution broth method and time-killing curves of DAN against A. pleuropneumoniae grown in tryptic soy broth (TSB) at a series drug concentrations (from 0 to 64 MIC) were constructed. The relationships between the kill rate and drug concentrations were analyzed using a Sigmoid E model during different time periods. For the MSW study, the MIC (the lowest concentration that inhibited the growth of the bacteria by ≥ 99%) and mutant prevention concentration (MPC) of DAN against A. pleuropneumoniae were measured using the agar plate method. Then, a peristaltic pump infection model was established to simulate the dynamic changes of DAN concentrations in pig lungs. The changes in number and sensitivity of A. pleuropneumoniae were measured. The relationships between pharmacokinetic/pharmacodynamic parameters and the antibacterial effect were analyzed using the Sigmoid E model.
RESULTS
In kill rate study, the MIC of DAN against A. pleuropneumoniae was 0.016 µg/mL. According to the kill rate, DAN exhibited concentration-dependent antibacterial activity against A. pleuropneumoniae. A bactericidal effect was observed when the DAN concentration reached 4-8 MIC. The kill rate increased constantly with the increase in DAN concentration, with a maximum value of 3.23 Log colony forming units (CFU)/mL/h during the 0-1 h period. When the drug concentration was in the middle part of the MSW, drugresistant bacteria might be induced. Therefore, the dosage should be avoided to produce a mean value of AUC/MIC (between 31.29 and 62.59 h. The values of AUC/MIC to achieve bacteriostatic, bactericidal, and eradication effects were 9.46, 25.14, and > 62.59 h, respectively.
CONCLUSION
These kill rate and MSW results will provide valuable guidance for the use of DAN to treat A. pleuropneumoniae infections.
Topics: Actinobacillus pleuropneumoniae; Microbial Sensitivity Tests; Anti-Bacterial Agents; Fluoroquinolones; Animals; Actinobacillus Infections; Swine; Drug Resistance, Bacterial; Swine Diseases; Mutation
PubMed: 38831324
DOI: 10.1186/s12917-024-04016-9 -
Scientific Reports Jun 2024The COVID-19 pandemic has altered the infection landscape for many pathogens. This retrospective study aimed to compare Haemophilus influenzae (H. influenzae) infections...
The COVID-19 pandemic has altered the infection landscape for many pathogens. This retrospective study aimed to compare Haemophilus influenzae (H. influenzae) infections in pediatric CAP patients hospitalized before (2018-2019) and during (2020-2022) the COVID-19 pandemic. We analyzed the clinical epidemiology and antimicrobial resistance (AMR) patterns of H. influenzae from a tertiary hospital in southwest China. A total of 986 pediatric CAP patients with H. influenzae-associated infections were included. Compared to 2018, the positivity rate increased in 2019 but dropped significantly in 2020. Although it rose in the following 2 years, the rate in 2022 remained significantly lower than in 2019. Patients' age during the pandemic was significantly higher than in 2018 and 2019, while gender composition remained similar across both periods. Notably, there were significant changes in co-infections with several respiratory pathogens during the pandemic. Resistance rates of H. influenzae isolates to antibiotics varied, with the highest resistance observed for ampicillin (85.9%) and the lowest for cefotaxime (0.0%). Resistance profiles to various antibiotics underwent dramatic changes during the COVID-19 pandemic. Resistance to amoxicillin-clavulanate, cefaclor, cefuroxime, trimethoprim-sulfamethoxazole, and the proportion of multi-drug resistant (MDR) isolates significantly decreased. Additionally, MDR isolates, alongside isolates resistant to specific drugs, were notably prevalent in ampicillin-resistant and β-lactamase-positive isolates. The number of pediatric CAP patients, H. influenzae infections, and isolates resistant to certain antibiotics exhibited seasonal patterns, peaking in the winter of 2018 and 2019. During the COVID-19 pandemic, sharp decreases were observed in February 2020, and there was no resurgence in December 2022. These findings indicate that the COVID-19 pandemic has significantly altered the infection spectrum of H. influenzae in pediatric CAP patients, as evidenced by shifts in positivity rate, demographic characteristics, respiratory co-infections, AMR patterns, and seasonal trends.
Topics: Humans; COVID-19; Male; Female; Haemophilus influenzae; Child; Child, Preschool; Haemophilus Infections; Retrospective Studies; Community-Acquired Infections; Infant; China; Anti-Bacterial Agents; Hospitalization; Adolescent; Pandemics; Coinfection; SARS-CoV-2; Drug Resistance, Bacterial
PubMed: 38830922
DOI: 10.1038/s41598-024-62728-2 -
PLoS Neglected Tropical Diseases May 2024Haemophilus ducreyi was historically known as the causative agent of chancroid, a sexually-transmitted disease causing painful genital ulcers endemic in many...
Haemophilus ducreyi was historically known as the causative agent of chancroid, a sexually-transmitted disease causing painful genital ulcers endemic in many low/middle-income nations. In recent years the species has been implicated as the causative agent of nongenital cutaneous ulcers affecting children of the South Pacific Islands and West African countries. Much is still unknown about the mechanism of H. ducreyi transmission in these areas, and recent studies have identified local insect species, namely flies, as potential transmission vectors. H. ducreyi DNA has been detected on the surface and in homogenates of fly species sampled from Lihir Island, Papua New Guinea. The current study develops a model system using Musca domestica, the common house fly, as a model organism to demonstrate proof of concept that flies are a potential vector for the transmission of viable H. ducreyi. Utilizing a green fluorescent protein (GFP)-tagged strain of H. ducreyi and three separate exposure methods, we detected the transmission of viable H. ducreyi by 86.11% ± 22.53% of flies sampled. Additionally, the duration of H. ducreyi viability was found to be directly related to the bacterial concentration, and transmission of H. ducreyi was largely undetectable within one hour of initial exposure. Push testing, Gram staining, and PCR were used to confirm the identity and presence of GFP colonies as H. ducreyi. This study confirms that flies are capable of mechanically transmitting viable H. ducreyi, illuminating the importance of investigating insects as vectors of cutaneous ulcerative diseases.
Topics: Animals; Houseflies; Haemophilus ducreyi; Chancroid; Papua New Guinea; Insect Vectors; Female; Male
PubMed: 38814945
DOI: 10.1371/journal.pntd.0012194 -
Virulence Dec 2024() is a bacterial pathogen responsible for a range of infections in humans and various animal hosts, causing significant economic losses in farming. Integrative and...
() is a bacterial pathogen responsible for a range of infections in humans and various animal hosts, causing significant economic losses in farming. Integrative and conjugative elements (ICEs) are important horizontal gene transfer elements, potentially enabling host bacteria to enhance adaptability by acquiring multiple functional genes. However, the understanding of ICEs in and their impact on the transmission of this pathogen remains limited. In this study, 42 poultry-sourced genomes obtained by high-throughput sequencing together with 393 publicly available genomes were used to analyse the horizontal transfer of ICEs. Eighty-two ICEs were identified in , including SXT/R391 and Tn916 subtypes, as well as three subtypes of ICE1056 family, with the latter being widely prevalent in and carrying multiple resistance genes. The correlations between insertion sequences and resistant genes in ICEs were also identified, and some ICEs introduced the carbapenem gene and the bleomycin gene to . Phylogenetic and collinearity analyses of these bioinformatics found that ICEs in were transmitted vertically and horizontally and have evolved with host specialization. These findings provide insight into the transmission and evolution mode of ICEs in and highlight the importance of understanding these elements for controlling the spread of antibiotic resistance.
Topics: Pasteurella multocida; Gene Transfer, Horizontal; Animals; Phylogeny; Pasteurella Infections; Genome, Bacterial; DNA Transposable Elements; Conjugation, Genetic; Evolution, Molecular; Poultry; Prevalence; High-Throughput Nucleotide Sequencing
PubMed: 38808732
DOI: 10.1080/21505594.2024.2359467 -
International Journal of Molecular... May 2024, a zoonotic pathogen that produces a 146-kDa modular toxin (PMT), causes progressive atrophic rhinitis with severe turbinate bone degradation in pigs. However, its...
, a zoonotic pathogen that produces a 146-kDa modular toxin (PMT), causes progressive atrophic rhinitis with severe turbinate bone degradation in pigs. However, its mechanism of cytotoxicity remains unclear. In this study, we expressed PMT, purified it in a prokaryotic expression system, and found that it killed PK15 cells. The host factor CXCL8 was significantly upregulated among the differentially expressed genes in a transcriptome sequencing analysis and qPCR verification. We constructed a CXCL8-knockout cell line with a CRISPR/Cas9 system and found that CXCL8 knockout significantly increased resistance to PMT-induced cell apoptosis. CXCL8 knockout impaired the cleavage efficiency of apoptosis-related proteins, including Caspase3, Caspase8, and PARP1, as demonstrated with Western blot. In conclusion, these findings establish that CXCL8 facilitates PMT-induced PK15 cell death, which involves apoptotic pathways; this observation documents that CXCL8 plays a key role in PMT-induced PK15 cell death.
Topics: Interleukin-8; Animals; Pasteurella multocida; Bacterial Toxins; Apoptosis; Swine; Bacterial Proteins; Cell Line; Caspase 8; Gene Knockout Techniques; CRISPR-Cas Systems
PubMed: 38791369
DOI: 10.3390/ijms25105330