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International Journal of Molecular... Apr 2024Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in cattle raised in North America. At the feedlot, cattle are subject to metaphylactic...
Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in cattle raised in North America. At the feedlot, cattle are subject to metaphylactic treatment with macrolides to prevent BRD, a practice that may promote antimicrobial resistance and has resulted in an urgent need for novel strategies. is one of the major bacterial agents of BRD. The inhibitory effects of two amphipathic, α-helical (PRW4, WRL3) and one β-sheet (WK2) antimicrobial peptides were evaluated against multidrug-resistant (MDR) isolated from Alberta feedlots. WK2 was not cytotoxic against bovine turbinate (BT) cells by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. All three peptides inhibited , with WK2 being the most efficacious against multiple isolates. At 8-16 µg/mL, WK2 was bactericidal against Mh 330 in broth, and at 32 µg/mL in the presence of BT cells, it reduced the population by 3 logs CFU/mL without causing cytotoxic effects. The membrane integrity of Mh 330 was examined using NPN (1-N-phenylnaphthylamine) and ONPG (o-Nitrophenyl β-D-galactopyranoside), with both the inner and outer membranes being compromised. Thus, WK2 may be a viable alternative to the use of macrolides as part of BRD prevention and treatment strategies.
Topics: Animals; Cattle; Anti-Bacterial Agents; Antimicrobial Peptides; Bovine Respiratory Disease Complex; Mannheimia haemolytica; Microbial Sensitivity Tests; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand
PubMed: 38673750
DOI: 10.3390/ijms25084164 -
American Journal of Otolaryngology 2024
Topics: Humans; Risk Factors; Haemophilus Infections; Haemophilus influenzae; Male; Female; Child, Preschool; Hearing Loss; Child; Infant; Otitis Media; Retrospective Studies
PubMed: 38669813
DOI: 10.1016/j.amjoto.2024.104290 -
Journal of Medical Microbiology Apr 2024, a member of the Pasteurellaceae family, is known for its highly infectious nature and is the primary causative agent of infectious pleuropneumonia in pigs. This...
, a member of the Pasteurellaceae family, is known for its highly infectious nature and is the primary causative agent of infectious pleuropneumonia in pigs. This disease poses a considerable threat to the global pig industry and leads to substantial economic losses due to reduced productivity, increased mortality rates, and the need for extensive veterinary care and treatment. Due to the emergence of multi-drug-resistant strains, Chinese herbal medicine is considered one of the best alternatives to antibiotics due to its unique mechanism of action and other properties. As a type of Chinese herbal medicine, Rhein has the advantages of a wide antibacterial spectrum and is less likely to develop drug resistance, which can perfectly solve the limitations of current antibacterial treatments. The killing effect of Rhein on was detected by fluorescence quantification of differential expression changes of key genes, and scanning electron microscopy was used to observe the changes in status after Rhein treatment. Establishing a mouse model to observe the treatment of Rhein after infection. Here, in this study, we found that Rhein had a good killing effect on and that the MIC was 25 µg ml. After 3 h of action, Rhein (4×MIC) completely kills and Rhein has good stability. In addition, the treatment with Rhein (1×MIC) significantly reduced the formation of bacterial biofilms. Therapeutic evaluation in a murine model showed that Rhein protects mice from and relieves lung inflammation. Quantitative RT-PCR (Quantitative reverse transcription polymerase chain reaction is a molecular biology technique that combines both reverse transcription and polymerase chain reaction methods to quantitatively detect the amount of a specific RNA molecule) results showed that Rhein treatment significantly downregulated the expression of the IL-18 (Interleukin refers to a class of cytokines produced by white blood cells), TNF-α, p65 and p38 genes. Along with the downregulation of genes such as IL-18, it means that Rhein has an inhibitory effect on the expression of these genes, thereby reducing the activation of inflammatory cells and the production of inflammatory mediators. This helps reduce inflammation and protects tissue from further damage. This study reports the activity of Rhein against and its mechanism, and reveals the ability of Rhein to treat infection in mice, laying the foundation for the development of new drugs for bacterial infections.
Topics: Animals; Anthraquinones; Actinobacillus pleuropneumoniae; Anti-Bacterial Agents; Mice; Actinobacillus Infections; Swine; Disease Models, Animal; Female; Drugs, Chinese Herbal; Lung; Swine Diseases
PubMed: 38668646
DOI: 10.1099/jmm.0.001826 -
American Journal of Otolaryngology 2024
Topics: Humans; Haemophilus Infections; Haemophilus influenzae; Child; Hearing Loss; Child, Preschool
PubMed: 38657535
DOI: 10.1016/j.amjoto.2024.104291 -
Human Vaccines & Immunotherapeutics Dec 2024Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory illness in older adults. A major cause of COPD-related morbidity and mortality is acute... (Clinical Trial)
Clinical Trial
Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory illness in older adults. A major cause of COPD-related morbidity and mortality is acute exacerbation of COPD (AECOPD). Bacteria in the lungs play a role in exacerbation development, and the most common pathogen is non-typeable (NTHi). A vaccine to prevent AECOPD containing NTHi surface antigens was tested in a clinical trial. This study measured IgG and IgA against NTHi vaccine antigens in sputum. Sputum samples from 40 COPD patients vaccinated with the NTHi vaccine were collected at baseline and 30 days after the second dose. IgG and IgA antibodies against the target antigens and albumin were analyzed in the sputum. We compared antibody signals before and after vaccination, analyzed correlation with disease severity and between sputum and serum samples, and assessed transudation. Antigen-specific IgG were absent before vaccination and present with high titers after vaccination. Antigen-specific IgA before and after vaccination were low but significantly different for two antigens. IgG correlated between sputum and serum, and between sputum and disease severity. Sputum albumin was higher in patients with severe COPD than in those with moderate COPD, suggesting changes in transudation played a role. We demonstrated that immunization with the NTHi vaccine induces antigen-specific antibodies in sputum. The correlation between IgG from sputum and serum and the presence of albumin in the sputum of severe COPD patients suggested transudation of antibodies from the serum to the lungs, although local IgG production could not be excluded.: NCT02075541.
Topics: Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Antibodies, Bacterial; Antigens, Bacterial; Haemophilus Infections; Haemophilus influenzae; Haemophilus Vaccines; Immunity, Mucosal; Immunoglobulin A; Immunoglobulin G; Lung; Pulmonary Disease, Chronic Obstructive; Sputum
PubMed: 38655676
DOI: 10.1080/21645515.2024.2343544 -
TheScientificWorldJournal 2024species are frequently encountered as serious diseases in small ruminants. It is the main cause of respiratory pasteurellosis in sheep and goats of all age groups.
BACKGROUND
species are frequently encountered as serious diseases in small ruminants. It is the main cause of respiratory pasteurellosis in sheep and goats of all age groups.
METHODS
The cross-sectional study was conducted from December 2022 to April 2023 in Haramaya district, eastern Ethiopia, to isolate and identify and and estimate their prevalence, associated risk factors, and antimicrobial sensitivity of isolates in small ruminants using a purposive sampling method. A total of 384 samples (156 nasal swabs from clinic cases and 228 lung swabs from abattoir cases) were collected. STATA 14 software was used to analyze the data. In addition, multivariable logistic regression analysis was performed to assess an association of risk factors.
RESULTS
Out of the 384 samples examined, 164 were positive for pasteurellosis, resulting in a 42.70% prevalence. Similarly, 63 (38.4%) of the 164 positive results were from nasal swabs, while 101 (61.6%) came from lung samples. accounted for 126 (76.82%) of the isolates, while accounted for 38 (23.17%). Of the 63 nasal swab isolates, 33 (37%) were from goats and 30 (42.8%) were from sheep. And 17 (10.89%) and 46 (29.58%), respectively, were and . Of the 46 (40%) of the 101 (44.3%) isolates of the pneumonic lung, samples were from goats, while 55 (48.47%) were from sheep. In this study, the risk factors (species, age, and body condition score) were found to be significant ( < 0.05). isolates evaluated for antibiotic susceptibility were highly resistant to oxacillin (90.90%), followed by gentamycin (72.72%), and penicillin (63.63%). However, the isolates were highly sensitive to chloramphenicol (90.90%), followed by tetracycline (63.63%), and ampicillin (54.54%).
CONCLUSION
This study showed that and are the common causes of mannheimiosis and pasteurellosis in small ruminants, respectively, and isolates were resistant to commonly used antibiotics in the study area. Thus, an integrated vaccination strategy, antimicrobial resistance monitoring, and avoidance of stress-inducing factors are recommended.
Topics: Animals; Pasteurella multocida; Mannheimia haemolytica; Ethiopia; Sheep; Goats; Anti-Bacterial Agents; Cross-Sectional Studies; Microbial Sensitivity Tests; Sheep Diseases; Goat Diseases; Prevalence; Risk Factors; Pasteurella Infections
PubMed: 38655561
DOI: 10.1155/2024/5605552 -
Poultry Science Jun 2024Infectious coryza (IC) is an acute infectious respiratory disease in chickens that is caused by Avibacterium paragallinarum (A. paragallinarum). A. paragallinarum poses...
Infectious coryza (IC) is an acute infectious respiratory disease in chickens that is caused by Avibacterium paragallinarum (A. paragallinarum). A. paragallinarum poses a significant threat to poultry health due to its virulence and multidrug resistance. This study isolated and identified 21 A. paragallinarum isolates from Guangdong between 2022 and 2023. Biochemical tests showed that 100% of A. paragallinarum isolates fermented glucose but did not ferment alginate and galactose, and only YZ18 was nicotinamide adenine dinucleotide independent. To determine the genetic relatedness between these isolates and NCBI reference strains, whole-genome-based phylogenetic analysis was employed. In addition, analysis of the 2,000 bp-length hmtp210 gene showed that the hmtp210 gene was strongly associated with A. paragallinarum serotypes. Meanwhile, a PCR assay for serotyping A. paragallinarum was developed based on the hmtp210 gene, this assay has high sensitivity and specificity. The antimicrobial susceptibility of isolates was assessed using the disk diffusion method. The antibiotic resistance genes of isolates were analyzed using the genomic method. Phenotypic resistance to ampicillin (95.2%), streptomycin (95.2%), methotrexate-sulfamethoxazole (90.5%), and tetracycline (85.7%) was most frequent among the isolates. All of the isolates exhibited resistance to multiple drugs, and furthermore, the isolates possessed a collective total of 14 genes associated with antibiotic resistance. This study will contribute to advancing our knowledge of A. paragallinarum antibiotic resistance and provide a scientific basis for the prophylaxis and treatment of IC, and the subsequent rational design of potential clinical therapeutics.
Topics: Poultry Diseases; Animals; China; Chickens; Anti-Bacterial Agents; Prevalence; Haemophilus Infections; Pasteurellaceae; Drug Resistance, Bacterial; Phylogeny; Haemophilus paragallinarum; Genome, Bacterial
PubMed: 38652951
DOI: 10.1016/j.psj.2024.103751 -
Journal of Korean Medical Science Apr 2024is a frequently encountered pathogen responsible for respiratory tract infections in children. Following the detection of ceftriaxone-resistant at our institution, we...
BACKGROUND
is a frequently encountered pathogen responsible for respiratory tract infections in children. Following the detection of ceftriaxone-resistant at our institution, we aimed to investigate the resistance mechanisms of ceftriaxone in , with a particular focus on alterations in penicillin-binding protein 3 (PBP3) and β-lactamase production.
METHODS
Among isolates collected at Asan Medical Center Children's Hospital from March 2014 to April 2019, ceftriaxone-resistant strains by the disk-diffusion test were included. Ceftriaxone minimum inhibitory concentrations (MICs) were determined using the E-test according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. The presence of β-lactamase was assessed through cefinase test and TEM-1/ROB-1 polymerase chain reaction (PCR). PBP3 alterations were explored via gene sequencing.
RESULTS
Out of the 68 collected strains, 21 exhibited resistance to ceftriaxone in disk diffusion tests. Two strains were excluded due to failed subculture. Among 19 ceftriaxone-resistant isolates, eighteen were non-typeable and twelve were positive for TEM-1 PCR. Isolates were classified into groups II (harboring only N526K, n = 3), III (N526K+S385T, n = 2), III+ (S385T+L389F+N526K, n = 11), and III-like+ (S385T+L389F+R517H, n = 3) according to the PBP3 alteration pattern. With a median ceftriaxone MIC of 0.190 mg/L (range, 0.008-0.750), the median ceftriaxone MIC was the highest in group III-like+ (0.250 mg/L), followed by groups III+ (0.190 mg/L), III (0.158 mg/L), and II (0.012 mg/L). All three strains belonging to group II, which did not harbor the S385T substitution, had ceftriaxone MICs of ≤ 0.125 mg/L.
CONCLUSION
The emergence of ceftriaxone-resistant with ceftriaxone MIC values of up to 0.75 mg/L was observed even in children in South Korea, with most associated with S385T and L389F substitutions. The N526K mutation alone does not significantly impact ceftriaxone resistance. Further large-scale studies are essential to investigate changes in antibiotic resistance patterns and factors influencing antibiotic resistance in isolated from pediatric patients in Korea.
Topics: Ceftriaxone; Haemophilus influenzae; Humans; Anti-Bacterial Agents; Microbial Sensitivity Tests; Republic of Korea; beta-Lactamases; Child; Haemophilus Infections; Penicillin-Binding Proteins; Child, Preschool; Drug Resistance, Bacterial; Infant; Female; Male; Bacterial Proteins
PubMed: 38651222
DOI: 10.3346/jkms.2024.39.e136 -
Physical Chemistry Chemical Physics :... May 2024Soluble -glycosyltransferase from (ApNGT) catalyzes the glycosylation of asparagine residues, and represents one of the most encouraging biocatalysts for -glycoprotein...
Soluble -glycosyltransferase from (ApNGT) catalyzes the glycosylation of asparagine residues, and represents one of the most encouraging biocatalysts for -glycoprotein production. Since the sugar tolerance of ApNGT is restricted to limited monosaccharides (, Glc, GlcN, Gal, Xyl, and Man), tremendous efforts are devoted to expanding the substrate scope of ApNGT enzyme engineering. However, rational design of novel NGT variants suffers from an elusive understanding of the substrate-binding process from a dynamic point of view. Here, by employing extensive all-atom molecular dynamics (MD) simulations integrated with a kinetic model, we reveal, at the atomic level, the complete donor-substrate binding process from the bulk solvent to the ApNGT active-site, and the key intermediate states of UDP-Glc during its loading dynamics. We are able to determine the critical transition event that limits the overall binding rate, which guides us to pinpoint the key ApNGT residues dictating the donor-substrate entry. The functional roles of several identified gating residues were evaluated through site-directed mutagenesis and enzymatic assays. Two single-point mutations, N471A and S496A, could profoundly enhance the catalytic activity of ApNGT. Our work provides deep mechanistic insights into the structural dynamics of the donor-substrate loading process for ApNGT, which sets a rational basis for design of novel NGT variants with desired substrate specificity.
Topics: Actinobacillus pleuropneumoniae; Kinetics; Molecular Dynamics Simulation; Substrate Specificity; Glycosyltransferases; Mutagenesis, Site-Directed; Catalytic Domain
PubMed: 38647259
DOI: 10.1039/d3cp06034a -
BMC Veterinary Research Apr 2024Gamithromycin is an effective therapy for bovine and swine respiratory diseases but not utilized for rabbits. Given its potent activity against respiratory pathogens, we...
BACKGROUND
Gamithromycin is an effective therapy for bovine and swine respiratory diseases but not utilized for rabbits. Given its potent activity against respiratory pathogens, we sought to determine the pharmacokinetic profiles, antimicrobial activity and target pharmacokinetic/pharmacodynamic (PK/PD) exposures associated with therapeutic effect of gamithromycin against Pasteurella multocida in rabbits.
RESULTS
Gamithromycin showed favorable PK properties in rabbits, including high subcutaneous bioavailability (86.7 ± 10.7%) and low plasma protein binding (18.5-31.9%). PK analysis identified a mean plasma peak concentration (C) of 1.64 ± 0.86 mg/L and terminal half-life (T) of 31.5 ± 5.74 h after subcutaneous injection. For P. multocida, short post-antibiotic effects (PAE) (1.1-5.3 h) and post-antibiotic sub-inhibitory concentration effects (PA-SME) (6.6-9.1 h) were observed after exposure to gamithromycin at 1 to 4× minimal inhibitory concentration (MIC). Gamithromycin demonstrated concentration-dependent bactericidal activity and the PK/PD index area under the concentration-time curve over 24 h (AUC)/MIC correlated well with efficacy (R > 0.99). The plasma AUC/MIC ratios of gamithromycin associated with the bacteriostatic, bactericidal and bacterial eradication against P. multocida were 15.4, 24.9 and 27.8 h in rabbits, respectively.
CONCLUSIONS
Subcutaneous administration of 6 mg/kg gamithromycin reached therapeutic concentrations in rabbit plasma against P. multocida. The PK/PD ratios determined herein in combination with ex vivo activity and favorable rabbit PK indicate that gamithromycin may be used for the treatment of rabbit pasteurellosis.
Topics: Rabbits; Animals; Cattle; Swine; Anti-Bacterial Agents; Pasteurella Infections; Macrolides; Pasteurella multocida; Lagomorpha; Microbial Sensitivity Tests; Cattle Diseases; Swine Diseases
PubMed: 38643185
DOI: 10.1186/s12917-024-03988-y