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Thoracic Cancer Apr 2024The causal relationship between breast cancer (BC) and the oral microbiome remains unclear. In this case-control study, using two-sample Mendelian randomization (MR), we...
BACKGROUND
The causal relationship between breast cancer (BC) and the oral microbiome remains unclear. In this case-control study, using two-sample Mendelian randomization (MR), we thoroughly explored the relationship between the oral microbiome and BC in the East Asian population.
METHODS
Genetic summary data related to oral microbiota and BC were collected from genome-wide association studies involving participants of East Asian descent. MR estimates were generated by conducting various analyses. Sequencing data from a case-control study were used to verify the validity of these findings.
RESULTS
MR analysis revealed that 30 tongue and 37 salivary bacterial species were significantly associated with BC. Interestingly, in both tongue and salivary microbiomes, we observed the causal effect of six genera, namely, Aggregatibacter, Streptococcus, Prevotella, Haemophilus, Lachnospiraceae, Oribacterium, and Solobacterium, on BC. Our case-control study findings suggest differences in specific bacteria between patients with BC and healthy controls. Moreover, sequencing data confirmed the MR analysis results, demonstrating that compared with the healthy control group, the BC group had a higher relative abundance of Pasteurellaceae and Streptococcaceae but a lower relative abundance of Bacteroidaceae.
CONCLUSIONS
Our MR analysis suggests that the oral microbiome exerts a causative effect on BC risk, supported by the sequencing data of a case-control study. In the future, studies should be undertaken to comprehensively understand the complex interaction mechanisms between the oral microbiota and BC.
Topics: Female; Humans; Breast Neoplasms; Case-Control Studies; East Asian People; Genome-Wide Association Study; Mendelian Randomization Analysis; Microbiota; Mouth
PubMed: 38485288
DOI: 10.1111/1759-7714.15280 -
Access Microbiology 2024() was long known as an easy-to-treat bacterium, but increasing resistance against beta-lactams and other critically important antibiotics is now a growing concern. We...
INTRODUCTION
() was long known as an easy-to-treat bacterium, but increasing resistance against beta-lactams and other critically important antibiotics is now a growing concern. We describe here the whole-genome sequencing (WGS) analysis of three non-typeable isolates received in 2018-2019 by the Belgian National Reference Centre (NRC) for , as they presented an unusual multi-resistant profile.
METHODS
All three isolates were sequenced by WGS and mapped to the reference isolate Rd KW20. Shorten uptake signal sequences (USSs) known to be associated with homologous recombination were sought in and genes, and inner partial sequences were compared against the blast nucleotide database to look for similarity with other species. Their antimicrobial resistance (AMR) genotype was studied. Core-genome multilocus sequence typing (MLST) was performed on the NTHi database pubMLST to place our isolates in the actual worldwide epidemiology.
RESULTS
The isolates also harboured interspecies recombination patterns in the region involved in cell wall synthesis. The three isolates were multidrug resistant and two of them were also resistant to amoxicillin-clavulanic acid and showed a reduced susceptibility to meropenem. All three isolates belonged to the MLST clonal complex (CC) 422, and WGS revealed that the three were very similar. They harboured mobile genetic elements (carrying , and genes associated with resistance), mutations in and linked to fluoroquinolone resistance as well as remodelling events in that might be related to lower carbapenem susceptibility.
CONCLUSION
The evolution towards antimicrobial multiresistance (AMR) is a complex and poorly understood phenomenon, although probably linked to a large degree to the presence of USSs and exchange within the family . To better understand the respective roles of clonal expansion, horizontal gene transfers, spontaneous mutations and interspecies genetic rearrangements in shaping AMR, both analysis of communities over time within individuals and worldwide monitoring of non-typeable causing infections should be conducted.
PubMed: 38482359
DOI: 10.1099/acmi.0.000649.v3 -
International Journal of Medical... Mar 2024Nontypeable Haemophilus influenzae (NTHi) is the dominant pathogen in several infectious diseases. Currently the use of antibiotics is the main intervention to prevent...
Nontypeable Haemophilus influenzae (NTHi) is the dominant pathogen in several infectious diseases. Currently the use of antibiotics is the main intervention to prevent NTHi infections, however with the emergence of drug resistant strains, it has compromised the treatment of respiratory infections with antibiotics. Therefore there is an urgent need to develop a safe and effective vaccine to prevent NTHi infections. We investigate the potential of C-HapS-P6 fusion protein as a vaccine for treating NTHi in murine models. PGEX-6P2/C-HapS-P6 fusion gene was constructed using overlap extension polymerase chain reaction. The recombined plasmid was transformed into Escherichia coli for protein expression. The mice were subjected to intraperitoneal immunization using purified antigens. Immunoglobulin (Ig) G in serum samples and IgA in nasal and lung lavage fluids were analyzed using enzyme-linked immunosorbent assay. Cytokine release and proliferation capacity of splenic lymphocytes in response to antigens were measured in vitro. The protective effect of the C-HapS-P6 protein against NTHi infection was evaluated by NTHi count and histological examination. The data showed that the C-HapS-P6 fusion protein increased significantly the levels of serum IgG and nasal and lung IgA, and promoted the release of interleukin (IL)-2, interferon-ϒ, IL-4, IL-5, and IL-17 and the proliferation of splenic lymphocytes compared with C-HapS or P6 protein treatment alone. Moreover, C-HapS-P6 effectively reduced the NTHi colonization in the nasopharynx and lungs of mice. In conclusion, our results demonstrated that the C-HapS-P6 fusion protein vaccine can significantly enhance humoral and cell immune responses and effectively prevent against NTHi infection in the respiratory tract in murine models.
Topics: Mice; Animals; Haemophilus influenzae; Bacterial Outer Membrane Proteins; Vaccines; Immunoglobulin G; Immunoglobulin A; Anti-Bacterial Agents; Haemophilus Infections; Antibodies, Bacterial; Mice, Inbred BALB C
PubMed: 38461565
DOI: 10.1016/j.ijmm.2024.151616 -
BMC Veterinary Research Mar 2024Pasteurella multocida type A (PmA) mainly causes respiratory diseases such as pneumonia in bovines, leading to great economic losses to the breeding industry. At...
Pasteurella multocida type A (PmA) mainly causes respiratory diseases such as pneumonia in bovines, leading to great economic losses to the breeding industry. At present, there is still no effective commercial vaccine against PmA infection. In this study, a mutant strain (PmCQ2Δ4555-4580) with brand-new phenotypes was obtained after serially passaging at 42 °C. Whole genome resequencing and PCR analysis showed that PmCQ2Δ4555-4580 missed six genes, including PmCQ2_004555, PmCQ2_004560, PmCQ2_004565, PmCQ2_004570, PmCQ2_004575, and PmCQ2_004580. Importantly, the virulence of PmCQ2Δ4555-4580 was reduced by approximately 2.8 × 10 times in mice. Notably, live PmCQ2Δ4555-4580 could provide 100%, 100% and 40% protection against PmA, PmB and PmF, respectively; and inactivated PmCQ2Δ4555-4580 could provide 100% and 87.5% protection against PmA and PmB. Interestingly, immune protection-related proteins were significantly upregulated in PmCQ2Δ4555-4580 based on RNA-seq and bioinformatics analysis. Meaningfully, by in vitro expression, purification and in vivo immunization, 12 proteins had different degrees of immune protective effects. Among them, PmCQ2_008205, PmCQ2_010435, PmCQ2_008190, and PmCQ2_004170 had the best protective effect, the protection rates against PmA were 50%, 40%, 30%, and 30%, respectively, and the protective rates against PmB were 62.5%, 42.9%, 37.5%, and 28.6%, respectively. Collectively, PmCQ2Δ4555-4580 is a potential vaccine candidate for the prevention of Pasteurellosis involving in high expression of immune protective related proteins.
Topics: Animals; Mice; Cattle; Pasteurella multocida; Vaccines, Attenuated; Pasteurella Infections; Immunization; Vaccination; Bacterial Vaccines; Cattle Diseases; Rodent Diseases
PubMed: 38461234
DOI: 10.1186/s12917-024-03948-6 -
Frontiers in Immunology 2024Influenza A viruses (IAVs) infect the respiratory tract of mainly humans, poultry, and pigs. Co-infections with pathogenic lung bacteria are a common event and...
INTRODUCTION
Influenza A viruses (IAVs) infect the respiratory tract of mainly humans, poultry, and pigs. Co-infections with pathogenic lung bacteria are a common event and contribute to the severity of disease progression. Neutrophils are a major cell type of the innate immune system and are rapidly recruited to the site of infection. They have several effector functions to fight invading pathogens such as the secretion of reactive oxygen species (ROS) or the release of neutrophil extracellular traps (NETs). NETs are known to promote the growth of bacteria, especially if degraded by nucleases.
METHODS
In this study, bronchoalveolar lavage fluid (BALF) from 45 field-infected pigs was analyzed for 1) NET markers, 2) influence on growth of lung bacteria, and 3) impact on neutrophil functions. BALF samples from 21 IAV-positive pigs and 24 lung diseased but IAV-negative pigs were compared.
RESULTS
Here, we show that neutrophils in the lungs of IAV-positive pigs release vesicular NETs. Several NET markers were increased in the BALF of IAV-positive pigs compared with the BALF from IAV-negative pigs. The amount of NET markers positively correlated with the viral load of the IAV infection. Interestingly, the BALF of IAV-positive pigs enhanced the growth of bacteria belonging to the family of Pasteurellaceae as potential coinfecting bacteria. These effects were weaker with the BALF derived from IAV-negative pigs with other lung infections. The intensity of oxidative burst in neutrophils was significantly decreased by BALF from IAVpositive pigs, indicating impaired antimicrobial activity of neutrophils. Finally, the lung milieu reflected by IAV-positive BALF does not enable neutrophils to kill but rather enhances its growth.
DISCUSSION
In summary, our data show that an IAV infection is affecting neutrophil functions, in particular the release of NETs and ROS. Furthermore, IAV infection seems to provide growth-enhancing factors for especially coinfecting Pasteurellaceae and reduces the killing efficiency of neutrophils.
Topics: Humans; Animals; Swine; Neutrophils; Reactive Oxygen Species; Bronchoalveolar Lavage; Bacteria; Dimercaprol; Influenza A virus
PubMed: 38449874
DOI: 10.3389/fimmu.2024.1325269 -
Veterinary Pathology Jul 2024-associated abomasitis has been clinically described as a cause of sudden death in lambs, but it is poorly characterized. We describe the pathological features of a...
-associated abomasitis has been clinically described as a cause of sudden death in lambs, but it is poorly characterized. We describe the pathological features of a severe fibrinonecrotizing abomasitis in 3 lambs that died suddenly. All 3 abomasums had a thickened submucosa due to edema and necrotic areas delimited by bands of degenerate neutrophils with slender nuclei (oat cells) and angiocentric distributions. The overlying mucosa was congested. Myriads of gram-negative coccobacilli were observed within the oat cell bands. was isolated from the abomasum in all 3 animals and was serotyped as A2 in one of them. Pericarditis and pleuritis were observed in 2 of the lambs. spp. were isolated in 1 lamb and detected by immunohistochemistry in the 3 animals, suggesting clostridial co-infection. should be considered among the differential diagnoses of necrotizing abomasitis in lambs.
Topics: Animals; Mannheimia haemolytica; Sheep Diseases; Sheep; Abomasum; Pasteurellaceae Infections; Necrosis; Stomach Diseases; Male; Female; Immunohistochemistry
PubMed: 38440930
DOI: 10.1177/03009858241235393 -
Microbiology Spectrum Apr 2024is an upper respiratory tract commensal in several mammal and bird species but can also cause severe disease in humans and in production animals such as poultry,...
is an upper respiratory tract commensal in several mammal and bird species but can also cause severe disease in humans and in production animals such as poultry, cattle, and pigs. In this study, we performed whole-genome sequencing of isolates recovered from a range of human infections, from the mouths of cats, and from wounds on dogs. Together with publicly available genome sequences, we performed phylogenetic and comparative genomic analyses. While isolates from cats and dogs were spread across the phylogenetic tree, human infections were caused almost exclusively by subsp. strains. Most of the human isolates were capsule type A and LPS type L1 and L3; however, some strains lacked a capsule biosynthesis locus, and some strains contained a novel LPS outer-core locus, distinct from the eight LPS loci that can currently be identified using an LPS multiplex PCR. In addition, the strains isolated from human infections contained novel mobile genetic elements. We compiled a curated database of known virulence factor and antibiotic resistance genes (PastyVRDB) allowing for detailed characterization of isolates. The majority of human isolates encoded a reduced range of iron receptors and contained only one filamentous hemagglutinin gene. Finally, gene-trait analysis identified a putative L-fucose uptake and utilization pathway that was over-represented in subsp. strains and may represent a novel host predilection mechanism in this subspecies. Together, these analyses have identified pathogenic mechanisms likely important for zoonotic infections.IMPORTANCE can cause serious infections in humans, including skin and wound infections, pneumonia, peritonitis, meningitis, and bacteraemia. Cats and dogs are known vectors of human pasteurellosis, transmitting via bite wounds or contact with animal saliva. The mechanisms that underpin human predilection and pathogenesis are poorly understood. With increasing identification of antibiotic-resistant strains, understanding these mechanisms is vital for developing novel treatments and control strategies to combat human infection. Here, we show that a narrow range of strains cause disease in humans, while cats and dogs, common vectors for zoonotic infections, can harbor a wide range of strains. We also present a curated -specific database, allowing quick and detailed characterization of newly sequenced isolates.
Topics: Humans; Cats; Cattle; Animals; Swine; Dogs; Pasteurella multocida; Phylogeny; Lipopolysaccharides; Pasteurella Infections; Anti-Bacterial Agents; Zoonoses; Mammals
PubMed: 38426766
DOI: 10.1128/spectrum.03805-23 -
Diagnostic Microbiology and Infectious... May 2024Haemophilus influenzae is an important pathogen able to cause various forms of respiratory and invasive disease. To provide high sensitivity for detection, culture media...
Haemophilus influenzae is an important pathogen able to cause various forms of respiratory and invasive disease. To provide high sensitivity for detection, culture media must inhibit growth of residential flora from the respiratory tract. This study aimed to identify and compare the diagnostic and economic advantages of using bacitracin containing selective agar (SEL) or oleandomycin disk supplemented chocolate agar (CHOC). Growth and semi-quantitative abundance of H. influenzae and growth suppression of residential flora was prospectively assessed in a 28-week period. H. influenzae was identified in 164 (5 %) of all included samples: CHOC and SEL, CHOC only, and SEL only were positive in 95, 24, and 45 cases. Diagnostic superiority of SEL was primarily attributable to the results of throat swabs. However, on average, € 200 had to be spent for the detection of each additional isolate that was recovered only because of additional incubation on SEL.
Topics: Humans; Agar; Bacitracin; Haemophilus influenzae; Oleandomycin; Chocolate; Culture Media
PubMed: 38422664
DOI: 10.1016/j.diagmicrobio.2024.116203 -
Brazilian Journal of Biology = Revista... 2024The paper describes data from the study of cultural, morphological, and biochemical properties and the pathogenicity and virulence of epizootic isolates of Pasteurella...
The paper describes data from the study of cultural, morphological, and biochemical properties and the pathogenicity and virulence of epizootic isolates of Pasteurella multocida obtained from cattle and saigas. The study aimed to investigate the properties of P. multocida isolated from saigas and cattle during their seasonal migration, with a focus on its role in the epizootic process and potential transmission to farm animals. The research was conducted in a laboratory setting at the West Kazakhstan Agrarian-Technical University. White mice, saigas, and cattle were examined, and pathological and bacteriological analyses were performed on tissues and secretions. Pathogenicity, virulence, and toxigenicity of the isolated Pasteurella cultures were determined through biological tests on white mice. The morphological, cultural, and biochemical properties of the isolates were studied using standard microbiological methods. The study found that P. multocida isolates from both saigas and cattle exhibited high pathogenicity and virulence when tested on white mice. The isolates from sick and dead animals displayed 65.3 and 83.3% pathogenicity, respectively. The isolates were toxic to white mice, with filtrate dilutions showing 100% toxigenicity. Comparative analysis showed morphological and cultural similarities between Pasteurella isolates from saigas and cattle, confirming their identity. This research demonstrates that P. multocida, isolated from both saigas and cattle, contributes to the epizootic process and poses a threat to farm animals. Saigas, in particular, play a role in disease transmission during seasonal migrations. Understanding the ecological interactions between wild and farm animals is crucial for implementing preventive measures to control the spread of infectious diseases, emphasizing the need for comprehensive monitoring and intervention strategies.
Topics: Humans; Mice; Animals; Cattle; Pasteurella multocida; Pasteurella Infections; Seasons; Virulence; Virulence Factors
PubMed: 38422302
DOI: 10.1590/1519-6984.280780 -
Applied Microbiology and Biotechnology Feb 2024Pasteurella multocida is an important bacterial pathogen that can cause diseases in both animals and humans. Its elevated morbidity and mortality rates in animals result...
Pasteurella multocida is an important bacterial pathogen that can cause diseases in both animals and humans. Its elevated morbidity and mortality rates in animals result in substantial economic repercussions within the livestock industry. The prevention of diseases caused by P. multocida through immunization is impeded by the absence of a safe and effective vaccine. Outer membrane vesicles (OMVs) secreted from the outer membrane of Gram-negative bacteria are spherical vesicular structures that encompass an array of periplasmic components in conjunction with a diverse assortment of lipids and proteins. These vesicles can induce antibacterial immune responses within the host. P. multocida has been shown to produce OMVs. Nonetheless, the precise characteristics and immunomodulatory functions of P. multocida OMVs have not been fully elucidated. In this study, OMVs were isolated from P. multocida using an ultrafiltration concentration technique, and their morphology, protein constitution, and immunomodulatory properties in RAW264.7 cells were studied. Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) revealed that the OMVs exhibited typical spherical and bilayered lipid vesicular architecture, exhibiting an average diameter of approximately 147.5 nm. The yield of OMVs was 2.6 × 10 particles/mL. Proteomic analysis revealed a high abundance of membrane-associated proteins within P. multocida OMVs, with the capability to instigate the host's immune response. Furthermore, OMVs stimulated the proliferation and cellular uptake of macrophages and triggered the secretion of cytokines, such as TNF-ɑ, IL-1β, IL-6, IL-10, and TGF-β1. Consequently, our results indicated that OMVs from P. multocida could directly interact with macrophages and regulate their immune function in vitro. These results supported the prospective applicability of P. multocida OMVs as a platform in the context of vaccine development. KEY POINTS: • Preparation and characterization of P. multocida OMVs. • P. multocida OMVs possess a range of antigens and lipoproteins associated with the activation of the immune system. • P. multocida OMVs can activate the proliferation, internalization, and cytokine secretion of macrophages in vitro.
Topics: Animals; Humans; Pasteurella multocida; Prospective Studies; Proteomics; Macrophages; Periplasm
PubMed: 38407600
DOI: 10.1007/s00253-024-13060-2