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Scientific Reports Dec 2023Bordetella bronchiseptica poses a significant challenge in the context of respiratory infections, particularly in weanling pigs. In this study, we investigated the...
Bordetella bronchiseptica poses a significant challenge in the context of respiratory infections, particularly in weanling pigs. In this study, we investigated the impact of a novel targeted bacteriophage in controlling B. bronchiseptica challenge (BBC) in an experimental design involving five distinct treatment groups: NC (no challenge), PC (BBC challenge), BF (10 pfu bacteriophage/kg diet + BBC), BN (2 × 10 pfu/day bacteriophage by nasal spray + BBC), and AT (antibiotic + BBC). The experiment was conducted for 2 weeks. The highest turbinate score was observed in the PC. The BF treatment showed higher plasma IL (interleukine)-1β and IL-6 compared with the BN and AT treatments. Plasma concentrations of IL-1β were increased in the BF pigs compared with the BN, AT, and NC. Among the BBC groups, the PC treatment exhibited a higher abundance of Staphylococcus. aureus and B. bronchiseptica in the lung. A lower S. aureus, Streptococcus. suis, and B. bronchiseptica colonization was detected in the AT compared with the BF and BN treatments. The BF showed lower plasma zonulin compared with the BN and AT. A higher plasma concentration of superoxide dismutase was observed in the BF and AT compared with PC and BN. The BN influenced the glycine, serine-threonine metabolism; glycerolipid metabolism; glyoxylate-dicarboxylate metabolism; and arachidonic acid metabolism compared with the NC. In conclusion, nasal-sprayed bacteriophage effectively controlled B. bronchiseptica infection, however, their efficiency was lower than the antibiotic.
Topics: Animals; Swine; Bordetella bronchiseptica; Swine Diseases; Bacteriophages; Staphylococcus aureus; Bordetella Infections; Microbiota; Anti-Bacterial Agents
PubMed: 38066337
DOI: 10.1038/s41598-023-49248-1 -
Veterinary Microbiology Sep 2023Bordetella bronchiseptica and Streptococcus suis are widely distributed swine pathogens. B. bronchiseptica is a primary pathogen and causes atrophic rhinitis and...
Bordetella bronchiseptica and Streptococcus suis are widely distributed swine pathogens. B. bronchiseptica is a primary pathogen and causes atrophic rhinitis and bronchopneumonia. S. suis is a contributing agent to porcine respiratory disease complex and causes systemic diseases including arthritis, meningitis, polyserositis, and septicemia. Colonization with B. bronchiseptica has been associated with increased colonization by other pathogenic bacteria and increased disease severity with viral and bacterial pathogens. It has also been reported to predispose cesarean derived, colostrum deprived (CDCD) piglets to S. suis systemic disease. Here, we evaluated the role of B. bronchiseptica colonization on S. suis colonization, dissemination, and disease in one study using conventional pigs and another using CDCD pigs. Pigs were challenged with S. suis, B. bronchiseptica, or B. bronchiseptica followed by S. suis. Incidence of S. suis disease was not increased in either study for animals pre-inoculated with B. bronchiseptica. Nasal colonization with S. suis was increased in coinfected animals, while B. bronchiseptica was similar between mono- and co-infected animals. Although increased S. suis disease was not seen in coinfected pigs, there is evidence that B. bronchiseptica can increase colonization with S. suis, which may contribute to enhanced disease when animals are stressed or immunocompromised.
Topics: Pregnancy; Female; Animals; Swine; Bordetella bronchiseptica; Streptococcus suis; Swine Diseases; Bordetella Infections; Nose; Bacteria
PubMed: 37542929
DOI: 10.1016/j.vetmic.2023.109841 -
Vaccine Jul 2023Despite a decrease in infections caused by Bordetella pertussis due to COVID-19 pandemic, booster vaccination of pregnant women is still recommended to protect newborns.... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Despite a decrease in infections caused by Bordetella pertussis due to COVID-19 pandemic, booster vaccination of pregnant women is still recommended to protect newborns. Highly immunogenic vaccines containing genetically inactivated pertussis toxin (PT) and filamentous hemagglutinin (FHA) may generate comparable anti-PT antibody concentrations, even at lower doses, to chemically inactivated acellular pertussis vaccines (Tdap) shown effective for maternal immunization.
METHODS
This phase 2 randomized, observer-blind, active-controlled non-inferiority trial was conducted in healthy Thai pregnant women randomly assigned to receive one dose of low-dose recombinant pertussis-only vaccine containing 1 µg PT and 1 µg FHA (ap1), or tetanus, reduced-dose diphtheria combined with ap1 (Tdap1), or combined with 2 µg PT and 5 µg FHA (Tdap2), or with 5 µg PT and 5 µg FHA (TdaP5, Boostagen®) or comparator containing 8 µg of chemically inactivated pertussis toxoid, 8 µg FHA, and 2.5 µg pertactin (Boostrix™, Tdap8). Blood was collected at Day 0 and Day 28 post-vaccination. The non-inferiority of the study vaccines was assessed based on anti-PT IgG antibody levels on Day 28 pooled with results from a similarly structured previous trial in non-pregnant women.
RESULTS
400 healthy pregnant women received one dose of vaccine. Combined with data from 250 non-pregnant women, all study vaccines containing PT were non-inferior to comparator vaccine (Tdap8). Both ap1 and TdaP5 vaccines could be considered to have superior immunogenicity to Tdap8. Local and systemic solicited reactions were similar among all vaccine groups.
CONCLUSIONS
Vaccine formulations containing PT were safe and immunogenic in pregnant women. The ap1 vaccine, with the lowest cost and reactogenicity, may be suitable for use in pregnant women when diphtheria and tetanus toxoids are not needed. This study is registered in the Thai Clinical Trial Registry (www.
CLINICALTRIALS
in.th), number TCTR20180725004.
Topics: Infant, Newborn; Humans; Female; Pertussis Toxin; Whooping Cough; Tetanus; Diphtheria; Pandemics; COVID-19; Pertussis Vaccine; Immunization, Secondary; Tetanus Toxoid; Vaccines, Synthetic; Antibodies, Bacterial; Diphtheria-Tetanus-acellular Pertussis Vaccines; Diphtheria-Tetanus-Pertussis Vaccine
PubMed: 37330371
DOI: 10.1016/j.vaccine.2023.06.001 -
Clinical Microbiology and Infection :... May 2024In Finland, whole cell pertussis vaccine (wP) was introduced in 1952 and was replaced by acellular pertussis vaccine (aP) without fimbrial (FIM) antigen in 2005. We...
OBJECTIVES
In Finland, whole cell pertussis vaccine (wP) was introduced in 1952 and was replaced by acellular pertussis vaccine (aP) without fimbrial (FIM) antigen in 2005. We aimed to analyse the changes in serotypes of circulating Bordetella pertussis before and after acellular vaccination and to explore the relationship between biofilm formation and serotype diversity after the introduction of aP vaccine.
METHODS
Serotyping of 1399 B. pertussis isolates collected at the Finnish National Reference Laboratory for Pertussis and Diphtheria in Turku, Finland, from 1974 to 2023 was performed by slide agglutination or indirect ELISA. Of 278 isolates collected after 2005, 53 were selected, genotyped for fim3 and fim2 alleles, and tested for biofilm formation. The selection criteria included maintaining a relatively equal distribution of isolates per time interval, ensuring approximately a 50:50 ratio of FIM2 (N = 26) and FIM3 (N = 27) serotypes. The reference strain Tohama I was used as a control.
RESULTS
During the wP era, the majority of circulating B. pertussis exhibited the FIM2 serotype. However, FIM3 strains have appeared since 1999 and become prevalent. After the implementation of aP vaccines, the distribution of serotypes has exhibited substantial variability. FIM3 isolates displayed an enhanced biofilm formation compared to FIM2 isolates (Geometric mean value (95% CI): 0.90 (0.79-1.03) vs. 0.75 (0.65-0.85); p < 0.05). Of the 27 FIM3 isolates, 8 harboured fim3-1 and 19 fim3-2 alleles. FIM3 isolates with fim3-2 allele were significantly associated with increased biofilm formation when compared to those with fim3-1 (1.07 (0.96-1.19) vs. 0.61 (0.52-0.72); p < 0.0001).
CONCLUSION
Following the implementation of aP vaccines, the distribution of serotypes in Finland has exhibited substantial variability. FIM3 isolates with the fim3-2 allele displayed an enhanced biofilm formation capability compared to FIM2 isolates.
Topics: Biofilms; Finland; Bordetella pertussis; Humans; Whooping Cough; Serogroup; Pertussis Vaccine; Vaccines, Acellular; Fimbriae Proteins; Serotyping; Genotype; Child, Preschool; Child; Infant; Vaccination; Antigens, Bacterial; Virulence Factors, Bordetella
PubMed: 38310999
DOI: 10.1016/j.cmi.2024.01.021 -
International Journal of Molecular... Oct 2023Transmembrane carriers of the Slc11 family catalyze proton (H)-dependent uptake of divalent metal ions (Me) such as manganese and iron-vital elements coveted during...
Transmembrane carriers of the Slc11 family catalyze proton (H)-dependent uptake of divalent metal ions (Me) such as manganese and iron-vital elements coveted during infection. The Slc11 mechanism of high-affinity Me cell import is selective and conserved between prokaryotic (MntH) and eukaryotic (Nramp) homologs, though processes coupling the use of the proton motive force to Me uptake evolved repeatedly. Adding bacterial piracy of genes spread in distinct environmental niches suggests selective gain of function that may benefit opportunistic pathogens. To better understand Slc11 evolution, Alphafold (AF2)/Colabfold (CF) 3D predictions for bacterial sequences from sister clades of eukaryotic descent (MCb and MCg) were compared using both native and mutant templates. AF2/CF model an array of native MCb intermediates spanning the transition from outwardly open (OO) to inwardly open (IO) carriers. In silico mutagenesis targeting (i) a set of (evolutionarily coupled) sites that may define Slc11 function (putative synapomorphy) and (ii) residues from networked communities evolving during MCb transition indicates that Slc11 synapomorphy primarily instructs a Me-selective conformation switch which unlocks carrier inner gate and contributes to Me binding site occlusion and outer gate locking. Inner gate opening apparently proceeds from interaction between transmembrane helix (h) h5, h8 and h1a. MCg1 xenologs revealed marked differences in carrier shape and plasticity, owing partly to an altered intramolecular H network. Yet, targeting Slc11 synapomorphy also converted MCg1 IO models to an OO state, apparently mobilizing the same residues to control gates. But MCg1 response to mutagenesis differed, with extensive divergence within this clade correlating with MCb-like modeling properties. Notably, MCg1 divergent epistasis marks the emergence of the genus -. Slc11 synapomorphy localizes to the 3D areas that deviate least among MCb and MCg1 models (either IO or OO) implying that it constitutes a 3D network of residues articulating a Me-selective carrier conformation switch which is maintained in fast-evolving clades at the cost of divergent epistatic interactions impacting carrier shape and dynamics.
Topics: Furylfuramide; Iron; Manganese; Biological Transport; Bacteria; Protons
PubMed: 37894758
DOI: 10.3390/ijms242015076 -
Microorganisms Sep 2023Urban rats serve as reservoirs for several zoonotic pathogens that seriously endanger public health, destroy stored food, and damage infrastructure due to their close...
Urban rats serve as reservoirs for several zoonotic pathogens that seriously endanger public health, destroy stored food, and damage infrastructure due to their close interaction with humans and domestic animals. Here, we characterize the core microbiomes of stomach, gut, and lung using 16S rRNA next-generation Illumina HiSeq sequencing. The USEARCH software (v11) assigned the dataset to operational taxonomic units (OTUs). The alpha diversity index was calculated using QIIME1, while the beta diversity index was determined using the Bray-Curtis and Euclidean distances between groups. Principal component analyses visualized variation across samples based on the OTU information using the R package. Linear discriminant analysis, effect sizes (LEfSe), and phylogenetic investigation were used to identify differentially abundant taxa among groups. We reported an abundance of microbiota in the stomach, and they shared some of them with the gut and lung microbiota. A close look at the microbial family level reveals abundant Lactobacillaceae and Bifidobacteriaceae in the stomach, whereas Lactobacillaceae and Erysipelotrichaceae were more abundant in the gut; in contrast, Alcaligenaceae were abundant in the lungs. At the species level, some beneficial bacteria, particularly and , and some potential pathogens, such as , , , , etc., were identified in stomach, gut, and lung samples. Moreover, the alpha and beta diversity indexes revealed significant differences between the groups. Further analysis revealed abundant differential taxonomic biomarkers, i.e., increased Prevotellaceae and Clostridia in the lungs, whereas Campylobacteria and Lachnospirales were richest in the stomachs. In conclusion, we identified many beneficial, opportunistic, and highly pathogenic bacteria, confirming the importance of urban rats for public health. This study recommends a routine survey program to monitor rodent distribution and the pathogens they carry and transmit to humans and other domestic mammals.
PubMed: 37764203
DOI: 10.3390/microorganisms11092359 -
Frontiers in Immunology 2023Periprosthetic joint infection (PJI) is a devastating complication of total joint arthroplasty surgery. Increased densities of activated mast cells have been predicted...
BACKGROUND
Periprosthetic joint infection (PJI) is a devastating complication of total joint arthroplasty surgery. Increased densities of activated mast cells have been predicted to be present in PJI compared to non-infectious arthroplasty failure based on analysis of transcriptomic data, but their presence in PJI-associated periprosthetic tissues has not been visually confirmed.
OBJECTIVE
This preliminary study investigated the presence and activation status of mast cells in periprosthetic tissues associated with PJI.
METHODS
Periprosthetic tissues from five PJI cases and three arthroplasty failures due to instability and one due to stiffness were immunohistochemically stained using tryptase and microscopically evaluated to enumerate mast cells and evaluate overall activation status within tissue samples. Mast cell activation was evidenced by the release of tryptase into the extracellular space surrounding mast cells.
RESULTS
Mast cells were found in all samples, with average cellular densities of 22 and 26 cells/mm tissue in PJI and uninfected samples, respectively (p, 0.6610). Apparent mast cell activation and degranulation was readily observed throughout each of the five PJI samples studied, but not in any of the uninfected samples studied.
CONCLUSION
While preliminary, these findings provide evidence for a role of mast cells in the immune response in PJI. Additional investigation of the role of mast cells during arthroplasty failure is warranted, providing a better understanding of underlying biology and informing potential diagnostic and treatment targets.
Topics: Humans; Mast Cells; Prosthesis-Related Infections; Tryptases; Antigen Presentation; Arthritis, Infectious
PubMed: 37654491
DOI: 10.3389/fimmu.2023.1183977 -
Antibiotics (Basel, Switzerland) May 2024Pertussis continues to be a highly contagious respiratory infection, especially in children, with cyclical peaks of disease spread every three to five years. Here, we...
Pertussis continues to be a highly contagious respiratory infection, especially in children, with cyclical peaks of disease spread every three to five years. Here, we report relevant cases of infection between August 2023 and January 2024, and compare them with prevalence in pediatric patients admitted to the Reference Italian Pediatric Hospital, located in Rome, from January 2015 to July 2023. A total of 5464 tests for were performed during the study period, and 6.9% were positive. At the time of the COVID-19 pandemic, there was a sharp decrease in the presence of , which reappeared only in August 2023, recording five new cases. All five children presented with paroxysmal cough 5 to 10 days before admission. Four patients had other mild respiratory symptoms and moderate DNA levels (Ct mean: 26). Only one child, with very high DNA levels (Ct: 9), presented with severe respiratory failure. The patients with mild/moderate infection achieved clinical recovery while the patient with the severe manifestation died of cardiac arrest. These observations highlight the reemergence of pertussis even in vaccinated countries and its association with morbidity and mortality especially in young children. This emphasizes the importance of rapid diagnosis to immediately implement appropriate treatment and monitoring of immune status.
PubMed: 38786192
DOI: 10.3390/antibiotics13050464 -
International Immunopharmacology Sep 2023The outer membrane vesicle (OMV) of bacteria is a bilayer membrane vesicle with a diameter of about 10-300 nm that is secreted during the growth of Gram-negative...
The outer membrane vesicle (OMV) of bacteria is a bilayer membrane vesicle with a diameter of about 10-300 nm that is secreted during the growth of Gram-negative bacteria. OMV is considered as a high-quality vaccine candidate antigen because of its natural immunogenicity and non-replicability. Although the excellent antigenicity of OMV has been widely confirmed, its instability and heterogeneity greatly affect its immune effect. Many studies have demonstrated that in combination with nanoparticles can enhance the stability of OMV. In this study, OMVs were used to coat chitosan nanoparticles (CNPs) and obtain a stable OMV vaccine. The characteristics, including morphology, hydrodynamic size, and zeta potential were evaluated. The immune protection of CNP-OMV and anti-infection efficacy were examined and compared in vivo and in vitro. The results showed that the CNP-OMV were homogenous with a size of 139 nm and a stable core-shell structure. And CNP-OMV could significantly increase the cell proliferation, phagocytosis and TNF-α, IL-6 and IL-10 secretion of RAW264.7 in vitro. In vivo, CNP-OMV could significantly increase the levels of anti-Bb and OMV IgG antibodies. Levels of blood lymphocyte, and Th1 (IFN-γ, IL-12), Th2 (IL-4, IL-5), and Th17 (IL-17, TNF-α) type cytokines in the serum were all significantly increased. At the same time, CNP-OMV could significantly reduce the bacterial invading the lungs of challenged rabbits. And CNP-OMV could largely protect the lungs from injury. The above results showed that CNP-OMV had a good immune efficacy and could resist the infection of Bordetella bronchiseptica. This study provided a scientific basis for the development of novel effective and safe vaccine against Bordetella bronchiseptica, and also provided a new idea for the development of new bacterial vaccine.
Topics: Animals; Rabbits; Bordetella bronchiseptica; Chitosan; Tumor Necrosis Factor-alpha; Bacterial Vaccines; Nanoparticles
PubMed: 37451023
DOI: 10.1016/j.intimp.2023.110612 -
MSystems Apr 2024The regulation of virulence is mediated by the two-component system BvgA/S, which activates the transcription of virulence-activated genes (s). In the avirulent phase,...
The regulation of virulence is mediated by the two-component system BvgA/S, which activates the transcription of virulence-activated genes (s). In the avirulent phase, the s are not expressed, but instead, virulence-repressed genes (s) are expressed, under the control of another two-component system, RisA/K. Here, we combined transcriptomic and chromatin immunoprecipitation sequencing (ChIPseq) data to examine the RisA/K regulon. We performed RNAseq analyses of RisA-deficient and RisA-phosphoablative mutants cultivated in virulent and avirulent conditions. We confirmed that the expression of most s is regulated by phosphorylated RisA. However, the expression of some, including those involved in flagellum biosynthesis and chemotaxis, requires RisA independently of phosphorylation. Many RisA-regulated genes encode proteins with regulatory functions, suggesting multiple RisA regulation cascades. By ChIPseq analyses, we identified 430 RisA-binding sites, 208 within promoter regions, 201 within open reading frames, and 21 in non-coding regions. RisA binding was demonstrated in the promoter regions of most s and, surprisingly, of some s, as well as for other genes not identified as s or s. Unexpectedly, many genes, including some s, like , , and , contain a BvgA-binding site and a RisA-binding site, which increases the complexity of the RisAK/BvgAS network in virulence regulation.IMPORTANCEThe expression of virulence-activated genes (s) of , the etiological agent of whooping cough, is under the transcriptional control of the two-component system BvgA/S, which allows the bacterium to switch between virulent and avirulent phases. In addition, the more recently identified two-component system RisA/K is required for the expression of genes, collectively named s, that are repressed during the virulent phase but activated during the avirulent phase. We have characterized the RisA/K regulon by combined transcriptomic and chromatin immunoprecipitation sequencing analyses. We identified more than 400 RisA-binding sites. Many of them are localized in promoter regions, especially s, but some were found within open reading frames and in non-coding regions. Surprisingly, RisA-binding sites were also found in promoter regions of some s, illustrating the previously underappreciated complexity of virulence regulation in .
Topics: Humans; Bordetella pertussis; Regulon; Transcription Factors; Whooping Cough; Bacterial Proteins; Chromatin Immunoprecipitation Sequencing; Gene Expression Profiling
PubMed: 38470037
DOI: 10.1128/msystems.00951-23