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Scientific Reports May 2024Respiratory infections are common causes of acute exacerbation of chronic obstructive lung disease (AECOPD). We explored whether the pathogens causing AECOPD and...
Respiratory infections are common causes of acute exacerbation of chronic obstructive lung disease (AECOPD). We explored whether the pathogens causing AECOPD and clinical features changed from before to after the coronavirus disease 2019 (COVID-19) outbreak. We reviewed the medical records of patients hospitalized with AECOPD at four university hospitals between January 2017 and December 2018 and between January 2021 and December. We evaluated 1180 patients with AECOPD for whom medication histories were available. After the outbreak, the number of patients hospitalized with AECOPD was almost 44% lower compared with before the outbreak. Patients hospitalized with AECOPD after the outbreak were younger (75 vs. 77 years, p = 0.003) and more often stayed at home (96.6% vs. 88.6%, p < 0.001) than patients of AECOPD before the outbreak. Hospital stay was longer after the outbreak than before the outbreak (10 vs. 8 days. p < 0.001). After the COVID-19 outbreak, the identification rates of S. pneumoniae (15.3 vs. 6.2%, p < 0.001) and Hemophilus influenzae (6.4 vs. 2.4%, p = 0.002) decreased, whereas the identification rates of P. aeruginosa (9.4 vs. 13.7%, p = 0.023), Klebsiella pneumoniae (5.3 vs. 9.8%, p = 0.004), and methicillin-resistant Staphylococcus aureus (1.0 vs. 2.8%, p = 0.023) increased. After the outbreak, the identification rate of influenza A decreased (10.4 vs. 1.0%, p = 0.023). After the outbreak, the number of patients hospitalized with AECOPD was lower and the identification rates of community-transmitted pathogens tended to decrease, whereas the rates of pathogens capable of chronic colonization tended to increase. During the period of large-scale viral outbreaks that require quarantine, patients with AECOPD might be given more consideration for treatment against strains that can colonize chronic respiratory disease rather than community acquired pathogens.
Topics: Humans; COVID-19; Pulmonary Disease, Chronic Obstructive; Aged; Male; Female; Hospitalization; Aged, 80 and over; SARS-CoV-2; Middle Aged; Pandemics; Respiratory Tract Infections; Disease Progression; Retrospective Studies; Streptococcus pneumoniae; Haemophilus influenzae
PubMed: 38714885
DOI: 10.1038/s41598-024-61360-4 -
BMC Oral Health May 2024To evaluate the antibacterial effectiveness of a combination of ε-poly-L-lysine (ε-PL), funme peptide (FP) as well as domiphen against oral pathogens, and assess the... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate the antibacterial effectiveness of a combination of ε-poly-L-lysine (ε-PL), funme peptide (FP) as well as domiphen against oral pathogens, and assess the efficacy of a BOP® mouthwash supplemented with this combination in reducing halitosis and supragingival plaque in a clinical trial.
MATERIALS AND METHODS
The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the compound against Fusobacterium nucleatum, Porphyromonas gingivalis, Streptococcus mutans, and Aggregatibacter actinomycetemcomitans were determined by the gradient dilution method. Subsequently, the CCK-8 assay was used to detect the toxicity of mouthwash on human gingival fibroblastst, and the effectiveness in reducing halitosis and supragingival plaque of the mouthwash supplemented with the combination was analyzed by a randomized, double-blind, parallel-controlled clinical trial.
RESULTS
The combination exhibited significant inhibitory effects on tested oral pathogens with the MIC < 1.56% (v/v) and the MBC < 3.13% (v/v), and the mouthwash containing this combination did not inhibit the viability of human gingival fibroblasts at the test concentrations. The clinical trial showed that the test group displayed notably lower volatile sulfur compounds (VSCs) at 0, 10, 24 h, and 7 d post-mouthwash (P < 0.05), compared with the baseline. After 7 days, the VSC levels of the and control groups were reduced by 50.27% and 32.12%, respectively, and notably cutting severe halitosis by 57.03% in the test group. Additionally, the Plaque Index (PLI) of the test and control group decreased by 54.55% and 8.38%, respectively, and there was a significant difference in PLI between the two groups after 7 days (P < 0.01).
CONCLUSIONS
The combination of ε-PL, FP and domiphen demonstrated potent inhibitory and bactericidal effects against the tested oral pathogens, and the newly formulated mouthwash added with the combination exhibited anti-dental plaque and anti-halitosis properties in a clinical trial and was safe.
TRIAL REGISTRATION
The randomized controlled clinical trial was registered on Chinese Clinical Trial Registry (No. ChiCTR2300073816, Date: 21/07/2023).
Topics: Humans; Halitosis; Mouthwashes; Dental Plaque; Double-Blind Method; Male; Female; Polylysine; Adult; Microbial Sensitivity Tests; Young Adult; Anti-Bacterial Agents; Porphyromonas gingivalis; Fusobacterium nucleatum; Fibroblasts; Peptides; Aggregatibacter actinomycetemcomitans; Streptococcus mutans
PubMed: 38702623
DOI: 10.1186/s12903-024-04255-0 -
Archives of Microbiology May 2024Aggregatibacter actinomycetemcomitans is an opportunistic Gram-negative periodontopathogen strongly associated with periodontitis and infective endocarditis. Recent... (Comparative Study)
Comparative Study
Aggregatibacter actinomycetemcomitans is an opportunistic Gram-negative periodontopathogen strongly associated with periodontitis and infective endocarditis. Recent evidence suggests that periodontopathogens can influence the initiation and progression of oral squamous cell carcinoma (OSCC). Herein we aimed to investigate the effect of A. actinomycetemcomitans-derived extracellular vesicles (EVs) on OSCC cell behavior compared with EVs from periodontopathogens known to associate with carcinogenesis. EVs were isolated from: A. actinomycetemcomitans and its mutant strains lacking the cytolethal distending toxin (CDT) or lipopolysaccharide (LPS) O-antigen; Porphyromonas gingivalis; Fusobacterium nucleatum; and Parvimonas micra. The effect of EVs on primary and metastatic OSCC cells was assessed using cell proliferation, apoptosis, migration, invasion, and tubulogenesis assays. A. actinomycetemcomitans-derived EVs reduced the metastatic cancer cell proliferation, invasion, tubulogenesis, and increased apoptosis, mostly in CDT- and LPS O-antigen-dependent manner. EVs from F. nucleatum impaired the metastatic cancer cell proliferation and induced the apoptosis rates in all OSCC cell lines. EVs enhanced cancer cell migration regardless of bacterial species. In sum, this is the first study demonstrating the influence of A. actinomycetemcomitans-derived EVs on oral cancer in comparison with other periodontopathogens. Our findings revealed a potential antitumorigenic effect of these EVs on metastatic OSCC cells, which warrants further in vivo investigations.
Topics: Aggregatibacter actinomycetemcomitans; Extracellular Vesicles; Mouth Neoplasms; Humans; Cell Line, Tumor; Apoptosis; Cell Proliferation; Cell Movement; Fusobacterium nucleatum; Carcinoma, Squamous Cell; Porphyromonas gingivalis
PubMed: 38702412
DOI: 10.1007/s00203-024-03976-8 -
Frontiers in Cellular and Infection... 2024cytolethal distending toxin (Cdt) is capable of intoxicating lymphocytes macrophages, mast cells and epithelial cells. Following Cdt binding to cholesterol, in the...
cytolethal distending toxin (Cdt) is capable of intoxicating lymphocytes macrophages, mast cells and epithelial cells. Following Cdt binding to cholesterol, in the region of membrane lipid rafts, the CdtB and CdtC subunits are internalized and traffic to intracellular compartments. These events are dependent upon, cellugyrin, a critical component of synaptic like microvesicles (SLMV). Target cells, such as Jurkat cells, rendered unable to express cellugyrin are resistant to Cdt-induced toxicity. Similar to Cdt, SARS-CoV-2 entry into host cells is initiated by binding to cell surface receptors, ACE-2, also associated with cholesterol-rich lipid rafts; this association leads to fusion and/or endocytosis of viral and host cell membranes and intracellular trafficking. The similarity in internalization pathways for both Cdt and SARS-CoV-2 led us to consider the possibility that cellugyrin was a critical component in both processes. Cellugyrin deficient Calu-3 cells (Calu-3) were prepared using Lentiviral particles containing shRNA; these cells were resistant to infection by VSV/SARS-CoV-2-spike pseudotype virus and partially resistant to VSV/VSV-G pseudotype virus. Synthetic peptides representing various regions of the cellugyrin protein were prepared and assessed for their ability to bind to Cdt subunits using surface plasmon resonance. Cdt was capable of binding to a region designated the middle outer loop (MOL) which corresponds to a region extending into the cytoplasmic surface of the SLMV. SARS-CoV-2 spike proteins were assessed for their ability to bind to cellugyrin peptides; SARS-CoV-2 full length spike protein preferentially binds to a region within the SLMV lumen, designated intraluminal loop 1A. SARS-CoV-2-spike protein domain S1, which contains the receptor binding domains, binds to cellugyrin N-terminus which extends out from the cytoplasmic surface of SLMV. Binding specificity was further analyzed using cellugyrin scrambled peptide mutants. We propose that SLMV represent a component of a common pathway that facilitates pathogen and/or pathogen-derived toxins to gain host cell entry.
Topics: Humans; Bacterial Toxins; Virus Internalization; SARS-CoV-2; Synaptogyrins; COVID-19; Jurkat Cells; Aggregatibacter actinomycetemcomitans; Angiotensin-Converting Enzyme 2; Endocytosis; Spike Glycoprotein, Coronavirus; Membrane Microdomains
PubMed: 38698905
DOI: 10.3389/fcimb.2024.1334224 -
The Veterinary Quarterly Dec 2024infection causes a high mortality rate in porcine animals. Antimicrobial resistance poses global threats to public health. The current study aimed to determine the...
infection causes a high mortality rate in porcine animals. Antimicrobial resistance poses global threats to public health. The current study aimed to determine the antimicrobial susceptibilities and probe the resistome of in Taiwan. Herein, 133 isolates were retrospectively collected; upon initial screening, 38 samples were subjected to next-generation sequencing (NGS). Over the period 2017-2022, the lowest frequencies of resistant isolates were found for ceftiofur, cephalexin, cephalothin, and enrofloxacin, while the highest frequencies of resistant isolates were found for oxytetracycline, streptomycin, doxycycline, ampicillin, amoxicillin, kanamycin, and florfenicol. Furthermore, most isolates (71.4%) showed multiple drug resistance. NGS-based resistome analysis revealed aminoglycoside- and tetracycline-related genes at the highest prevalence, followed by genes related to beta-lactam, sulfamethoxazole, florphenicol, and macrolide. A plasmid replicon (repUS47) and insertion sequences (IS10R and ISVAp11) were identified in resistant isolates. Notably, the multiple resistance roles of the insertion sequence IS10R were widely proposed in human medicine; however, this is the first time IS10R has been reported in veterinary medicine. Concordance analysis revealed a high consistency of phenotypic and genotypic susceptibility to florphenicol, tilmicosin, doxycycline, and oxytetracycline. The current study reports the antimicrobial characterization of for the first time in Taiwan using NGS.
Topics: Actinobacillus pleuropneumoniae; Taiwan; Anti-Bacterial Agents; Animals; Swine Diseases; Swine; High-Throughput Nucleotide Sequencing; Microbial Sensitivity Tests; Actinobacillus Infections; Retrospective Studies; Drug Resistance, Multiple, Bacterial; Drug Resistance, Bacterial
PubMed: 38688482
DOI: 10.1080/01652176.2024.2335947 -
Human Vaccines & Immunotherapeutics Dec 2024Since the introduction of type b (Hib) conjugate vaccines, invasive Hib disease has strongly declined worldwide, yet continued control of Hib disease remains important.... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Disparate kinetics in immune response of two different type b conjugate vaccines: Immunogenicity and safety observations from a randomized controlled phase IV study in healthy infants and toddlers using a 2+1 schedule.
Since the introduction of type b (Hib) conjugate vaccines, invasive Hib disease has strongly declined worldwide, yet continued control of Hib disease remains important. In Europe, currently three different hexavalent combination vaccines containing Hib conjugates are marketed. In this phase IV, single-blind, randomized, controlled, multi-country study (NCT04535037), we aimed to compare, in a 2 + 1 vaccination schedule, the immunogenicity and safety and show non-inferiority, as well as superiority, of DTPa-HBV-IPV/Hib (Ih group) versus DTaP5-HB-IPV-Hib (Va group) in terms of anti-polyribosylribitol phosphate (PRP) antibody geometric mean concentrations (GMCs) and proportion of participants reaching anti-PRP antibody concentrations greater than or equal to a threshold of 5 µg/mL. One month after the booster vaccination, the anti-PRP antibody GMC ratio (Ih group/Va group) was 0.917 (95% CI: 0.710-1.185), meeting the non-inferiority criteria. The difference in percentage of participants (Ih group - Va group) reaching GMCs ≥5 µg/mL was -6.3% (95% CI: -14.1% to 1.5%), not reaching the predefined non-inferiority threshold. Interestingly, a slightly higher post-booster antibody avidity was observed in the Ih group versus the Va group. Both vaccines were well tolerated, and no safety concerns were raised. This study illustrates the different kinetics of the anti-PRP antibody response post-primary and post-booster using the two vaccines containing different Hib conjugates and indicates a potential differential impact of concomitant vaccinations on the anti-PRP responses. The clinical implications of these differences should be further studied.
Topics: Humans; Haemophilus Vaccines; Antibodies, Bacterial; Infant; Immunization Schedule; Female; Male; Single-Blind Method; Vaccines, Conjugate; Haemophilus influenzae type b; Vaccines, Combined; Haemophilus Infections; Hepatitis B Vaccines; Poliovirus Vaccine, Inactivated; Diphtheria-Tetanus-Pertussis Vaccine; Child, Preschool; Immunogenicity, Vaccine; Europe; Polysaccharides
PubMed: 38687024
DOI: 10.1080/21645515.2024.2342630 -
Medicina 2024Brain abscess is a focal suppurative process produced in most cases by bacterial agents. Aggregatibacter aphrophilus is a gram-negative bacteria belonging to the HACEK...
Brain abscess is a focal suppurative process produced in most cases by bacterial agents. Aggregatibacter aphrophilus is a gram-negative bacteria belonging to the HACEK group, which causes infective endocarditis, liver abscesses, among others. Brain abscesses secondary to this germ are rare and, in most cases, it is associated with contact with pets, poor dental hygiene or dental procedures. Treatment consists of drainage of the abscess (greater than 2.5 cm) combined with antibiotic therapy, ideally beta-lactams. The case of a 64-year-old male patient with no relevant history is here presented. He was admitted to the emergency service due to headache, hemianopsia of a week's duration and later tonic-clonic seizures, in whom imaging studies and culture of a brain lesion subsequently revealed a brain abscess due to A. aphrophilus. This case aims to illustrate about the rarity of this infection, because A. aphrophilus is a normal part of the oropharyngeal flora and respiratory tract, in which it rarely causes invasive bacteremia.
Topics: Brain Abscess; Humans; Male; Aggregatibacter aphrophilus; Middle Aged; Pasteurellaceae Infections; Anti-Bacterial Agents; Drainage
PubMed: 38683524
DOI: No ID Found -
MBio Jun 2024The nasopharynx is an important reservoir of disease-associated and antimicrobial-resistant bacterial species. This proof-of-concept study assessed the utility of a...
UNLABELLED
The nasopharynx is an important reservoir of disease-associated and antimicrobial-resistant bacterial species. This proof-of-concept study assessed the utility of a combined culture, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), and targeted metagenomic sequencing workflow for the study of the pediatric nasopharyngeal bacterial microbiota. Nasopharyngeal swabs and clinical metadata were collected from Cambodian children during a hospital outpatient visit and then biweekly for 12 weeks. Swabs were cultured on chocolate and blood-gentamicin agar, and all colony morphotypes were identified by MALDI-TOF MS. Metagenomic sequencing was done on a scrape of all colonies from a chocolate agar culture and processed using the mSWEEP pipeline. One hundred one children were enrolled, yielding 620 swabs. MALDI-TOF MS identified 106 bacterial species/40 genera: 20 species accounted for 88.5% (2,190/2,474) of isolates. Colonization by (92.1% of children on ≥1 swab), (87.1%), and (83.2%) was particularly common. In -colonized children, a median of two serotypes [inter-quartile range (IQR) 1-2, range 1-4] was detected. For the 21 bacterial species included in the mSWEEP database and identifiable by MALDI-TOF, detection by culture + MALDI-TOF MS and culture + mSWEEP was highly concordant with a median species-level agreement of 96.9% (IQR 86.8%-98.8%). mSWEEP revealed highly dynamic lineage-level colonization patterns for which were quite different to those for . A combined culture, MALDI-TOF MS, targeted metagenomic sequencing approach for the exploration of the young child nasopharyngeal microbiome was technically feasible, and each component yielded complementary data.
IMPORTANCE
The human upper respiratory tract is an important source of disease-causing and antibiotic-resistant bacteria. However, understanding the interactions and stability of these bacterial populations is technically challenging. We used a combination of approaches to determine colonization patterns over a 3-month period in 101 Cambodian children. The combined approach was feasible to implement, and each component gave complementary data to enable a better understanding of the complex patterns of bacterial colonization.
Topics: Humans; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Nasopharynx; Microbiota; Child, Preschool; Bacteria; Female; Metagenomics; Child; Infant; Male; Cambodia; Haemophilus influenzae
PubMed: 38682956
DOI: 10.1128/mbio.00784-24 -
International Journal of Molecular... Apr 2024Different levels of EspP2 expression are seen in strains of with high and low pathogenicity. As a potential virulence factor for , the pathogenic mechanism of EspP2 in...
Different levels of EspP2 expression are seen in strains of with high and low pathogenicity. As a potential virulence factor for , the pathogenic mechanism of EspP2 in infection of host cells is not clear. To begin to elucidate the effect of on virulence, we used SC1401 in its wild-type form and SC1401, which was made -deficient. We demonstrated that EspP2 causes up-regulation of claudin-1 and occludin expression, thereby promoting the adhesion of to host cells; -deficiency resulted in significantly reduced adhesion of to cells. Transcriptome sequencing analysis of EspP2-treated PK15 cells revealed that the Rap1 signaling pathway is stimulated by EspP2. Blocking this pathway diminished occludin expression and adhesion. These results indicated that EspP2 regulates the adhesion of via Rap1 signaling pathway.
Topics: Signal Transduction; Animals; Haemophilus parasuis; rap1 GTP-Binding Proteins; Bacterial Adhesion; Bacterial Proteins; Occludin; Claudin-1; Cell Line; Swine
PubMed: 38674155
DOI: 10.3390/ijms25084570 -
International Journal of Molecular... Apr 2024Membrane proteins constitute about 20% of the human proteome and play crucial roles in cellular functions. However, a complete understanding of their structure and...
Membrane proteins constitute about 20% of the human proteome and play crucial roles in cellular functions. However, a complete understanding of their structure and function is limited by their hydrophobic nature, which poses significant challenges in purification and stabilization. Detergents, essential in the isolation process, risk destabilizing or altering the proteins' native conformations, thus affecting stability and functionality. This study leverages single-particle cryo-electron microscopy to elucidate the structural nuances of membrane proteins, focusing on the SLAC1 bacterial homolog from (TehA) purified with diverse detergents, including n-dodecyl β-D-maltopyranoside (DDM), glycodiosgenin (GDN), β-D-octyl-glucoside (OG), and lauryl maltose neopentyl glycol (LMNG). This research not only contributes to the understanding of membrane protein structures but also addresses detergent effects on protein purification. By showcasing that the overall structural integrity of the channel is preserved, our study underscores the intricate interplay between proteins and detergents, offering insightful implications for drug design and membrane biology.
Topics: Cryoelectron Microscopy; Haemophilus influenzae; Bacterial Proteins; Detergents; Microscopy, Electron, Transmission; Membrane Proteins
PubMed: 38674110
DOI: 10.3390/ijms25084528