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Microorganisms Jun 2024Numerous studies have reported a correlation between gut microbiota and influenza A virus (IAV) infection and disease severity. However, the causal relationship between...
Numerous studies have reported a correlation between gut microbiota and influenza A virus (IAV) infection and disease severity. However, the causal relationship between these factors remains inadequately explored. This investigation aimed to assess the influence of gut microbiota on susceptibility to human infection with H7N9 avian IAV and the severity of influenza A (H1N1)pdm09 infection. A two-sample Mendelian randomization analysis was conducted, integrating our in-house genome-wide association study (GWAS) on H7N9 susceptibility and H1N1pdm09 severity with a metagenomics GWAS dataset from a Chinese population. Twelve and fifteen gut microbiotas were causally associated with H7N9 susceptibility or H1N1pdm09 severity, separately. Notably, and were negative associated with H7N9 susceptibility and H1N1pdm09 severity, respectively. Moreover, and were associated with H7N9 susceptibility, while and were correlated with H1N1pdm09 severity. These results provide novel insights into the interplay between gut microbiota and IAV pathogenesis as well as new clues for mechanism research regarding therapeutic interventions or IAV infections. Future studies should concentrate on clarifying the regulatory mechanisms of gut microbiota and developing efficacious approaches to reduce the incidence of IAV infections, which could improve strategy for preventing and treating IAV infection worldwide.
PubMed: 38930552
DOI: 10.3390/microorganisms12061170 -
Veterinary Research Jun 2024Bacteria utilize intercellular communication to orchestrate essential cellular processes, adapt to environmental changes, develop antibiotic tolerance, and enhance...
Bacteria utilize intercellular communication to orchestrate essential cellular processes, adapt to environmental changes, develop antibiotic tolerance, and enhance virulence. This communication, known as quorum sensing (QS), is mediated by the exchange of small signalling molecules called autoinducers. AI-2 QS, regulated by the metabolic enzyme LuxS (S-ribosylhomocysteine lyase), acts as a universal intercellular communication mechanism across gram-positive and gram-negative bacteria and is crucial for diverse bacterial processes. In this study, we demonstrated that in Streptococcus suis (S. suis), a notable zoonotic pathogen, AI-2 QS enhances galactose utilization, upregulates the Leloir pathway for capsular polysaccharide (CPS) precursor production, and boosts CPS synthesis, leading to increased resistance to macrophage phagocytosis. Additionally, our molecular docking and dynamics simulations suggest that, similar to S. pneumoniae, FruA, a fructose-specific phosphoenolpyruvate phosphotransferase system prevalent in gram-positive pathogens, may also function as an AI-2 membrane surface receptor in S. suis. In conclusion, our study demonstrated the significance of AI-2 in the synthesis of galactose metabolism-dependent CPS in S. suis. Additionally, we conducted a preliminary analysis of the potential role of FruA as a membrane surface receptor for S. suis AI-2.
Topics: Streptococcus suis; Galactose; Quorum Sensing; Virulence; Animals; Bacterial Capsules; Lactones; Streptococcal Infections; Homoserine; Polysaccharides, Bacterial
PubMed: 38886823
DOI: 10.1186/s13567-024-01335-5 -
Frontiers in Public Health 2024is one of the porcine pathogens that have recently emerged as a pathogen capable of causing zoonoses in some humans. Patients infected with can present with sepsis,...
INTRODUCTION
is one of the porcine pathogens that have recently emerged as a pathogen capable of causing zoonoses in some humans. Patients infected with can present with sepsis, meningitis, or arthritis. Compared to common pathogens, such as , , and , infections in humans have been reported only rarely.
METHODS
This case report described a 57-year-old man who presented with impaired consciousness and fever following several days of backache. He was a butcher who worked in an abattoir and had wounded his hands 2 weeks prior. The patient was dependent on alcohol for almost 40 years. was detected in the cerebrospinal fluid by metagenomic next-generation sequencing. Although he received adequate meropenem and low-dose steroid therapy, the patient suffered from bilateral sudden deafness after 5 days of the infection. The final diagnosis was meningitis and sepsis.
RESULTS
The patient survived with hearing loss in both ears and dizziness at the 60-day follow-up.
DISCUSSION
We reported a case of infection manifested as purulent meningitis and sepsis. Based on literature published worldwide, human meningitis shows an acute onset and rapid progression in the nervous system. Similar to bacterial meningitis, effective antibiotics, and low-dose steroids play important roles in the treatment of human meningitis.
Topics: Humans; Streptococcus suis; Male; Middle Aged; Streptococcal Infections; China; Meningitis, Bacterial; Anti-Bacterial Agents; Sepsis; Hearing Loss, Sudden
PubMed: 38808002
DOI: 10.3389/fpubh.2024.1369703 -
Vaccines May 2024() is a Gram-positive bacterium that causes substantial disease in pigs. is also an emerging zoonoses in humans, primarily in Asia, through the consumption of...
() is a Gram-positive bacterium that causes substantial disease in pigs. is also an emerging zoonoses in humans, primarily in Asia, through the consumption of undercooked pork and the handling of infected pig meat as well as carcasses. The complexity of epidemiology, characterized by the presence of multiple bacterial serotypes and strains with diverse sequence types, identifies a critical need for a universal vaccine with the ability to confer cross-protective immunity. Highly conserved immunogenic proteins are generally considered good candidate antigens for subunit universal vaccines. In this study, the cross-protection of the sugar ABC transporter substrate-binding protein (S-ABC), a surface-associated immunogenic protein of , was examined in mice for evaluation as a universal vaccine candidate. S-ABC was shown to be highly conserved, with 97% amino acid sequence identity across 31 strains deposited in GenBank. Recombinantly expressed S-ABC (rS-ABC) was recognized via rabbit sera specific to serotype 2. The immunization of mice with rS-ABC induced antigen-specific antibody responses, as well as IFN-γ and IL-4, in multiple organs, including the lungs. rS-ABC immunization conferred high (87.5% and 100%) protection against challenges with serotypes 2 and 9, demonstrating high cross-protection against these serotypes. Protection, albeit lower (50%), was also observed in mice challenged with serotype 7. These data identify S-ABC as a promising antigenic target within a universal subunit vaccine against .
PubMed: 38793795
DOI: 10.3390/vaccines12050544 -
Microorganisms Apr 2024() is a zoonotic pathogen capable of causing severe diseases in humans and pigs, including meningitis, sepsis, polyserositis, arthritis, and endocarditis. This study...
() is a zoonotic pathogen capable of causing severe diseases in humans and pigs, including meningitis, sepsis, polyserositis, arthritis, and endocarditis. This study aimed to investigate the biological characteristics of 19 strains of isolated from diseased pigs in Hubei Province between 2021 and 2023. Through bioinformatics analysis, we investigated the serotype, MLST, pan-genome characteristics, SNP, AMR, and ICE of the 19 isolates. Among the 19 strains, ten serotypes were identified, and serotype 9 was the most prevalent (21.05%). Ten new alleles and nine new sequence types (STs) were discovered, with ST28 and ST243 emerging as the predominant STs. The results of the pan-genomic analysis of indicate that there are 943 core genes, 2259 shell genes, and 5663 cloud genes. Through SNP evolutionary analysis, we identified a strong genetic similarity between SS31 and the reference genome P1/7. The analysis of antibiotic resistance genes revealed widespread presence of (B) and (O) genes among 19 strains of . This association may be linked to the high resistance of to lincosamides, macrolides, and tetracyclines. Integrative and conjugative elements (ICEs) and integrative and mobilizable elements (IMEs) were identified in 16 strains, with a carriage rate of 84.21%, and resistance genes were identified within the ICE/IME elements of 8 strains. Antimicrobial susceptibility testing revealed that all strains showed sensitivity to vancomycin and lincomycin but resistance to tilmicosin, tiamulin, amoxicillin, and doxycycline. This study contributes to our understanding of the genomic diversity of in Hubei Province of China, providing essential data for the comprehensive prevention and control of infections in China.
PubMed: 38792744
DOI: 10.3390/microorganisms12050917 -
Frontiers in Immunology 2024In response to the global threat posed by bacterial pathogens, which are the second leading cause of death worldwide, vaccine development is challenged by the diversity...
In response to the global threat posed by bacterial pathogens, which are the second leading cause of death worldwide, vaccine development is challenged by the diversity of bacterial serotypes and the lack of immunoprotection across serotypes. To address this, we introduce BacScan, a novel genome-wide technology for the rapid discovery of conserved highly immunogenic proteins (HIPs) across serotypes. Using bacterial-specific serum, BacScan combines phage display, immunoprecipitation, and next-generation sequencing to comprehensively identify all the HIPs in a single assay, thereby paving the way for the development of universally protective vaccines. Our validation of this technique with , a major pathogenic threat, led to the identification of 19 HIPs, eight of which conferred 20-100% protection against challenge in animal models. Remarkably, HIP 8455 induced complete immunity, making it an exemplary vaccine target. BacScan's adaptability to any bacterial pathogen positions it as a revolutionary tool that can expedite the development of vaccines with broad efficacy, thus playing a critical role in curbing bacterial transmission and slowing the march of antimicrobial resistance.
Topics: Animals; Mice; Bacterial Proteins; Streptococcal Infections; Streptococcus suis; Genome, Bacterial; High-Throughput Nucleotide Sequencing; Female; Antigens, Bacterial; Humans; Bacterial Vaccines
PubMed: 38779673
DOI: 10.3389/fimmu.2024.1392456 -
Animals : An Open Access Journal From... Apr 2024() is a zoonotic pathogen with a global distribution, which causes serious diseases in both humans and animals and economic losses in the swine industry. As antibiotic...
() is a zoonotic pathogen with a global distribution, which causes serious diseases in both humans and animals and economic losses in the swine industry. As antibiotic resistance increases, there is an urgent imperative to explore novel antibacterial alternatives. In the present study, we selected the anticancer drug 5-fluorouracil (5-FU) approved by the Food and Drug Administration (FDA) as a candidate drug to treat infections. The results showed that various pathogens, especially , are more sensitive to 5-FU. Moreover, the cytotoxicity of 5-FU is relatively low. Extensive in vitro assays demonstrated the pronounced bacteriostatic and bactericidal efficacy of 5-FU against susceptible and multidrug-resistant strains. Its mechanisms of action include damage to the bacterial cell walls and membranes, resulting in the leakage of intracellular components, and the inhibition of thymidylate synthase (TS), leading to a depletion of deoxythymidine triphosphate (dTTP) pools, ultimately causing thymine-less death and lethal DNA damage in bacteria. Gene-knockout experiments further showed that 5-FU played a role by inhibiting the gene-encoding thymidine synthase. Finally, we determined that infections can be alleviated by 5-FU in the mouse infection model. This study emphasizes the antibacterial potential of 5-FU against and provides evidence for its targeting of bacterial membrane damage and DNA damage. In summary, 5-FU can control infection and is expected to become a new alternative to antibiotics.
PubMed: 38731290
DOI: 10.3390/ani14091286 -
Journal of Infection in Developing... Apr 2024Streptococcus suis (S. suis) disease is a zoonotic infection caused by invasive S. suis and can lead to meningitis, septic shock, arthritis, and endocarditis. Early...
INTRODUCTION
Streptococcus suis (S. suis) disease is a zoonotic infection caused by invasive S. suis and can lead to meningitis, septic shock, arthritis, and endocarditis. Early treatment is the key to reducing mortality. However, clinical manifestations of most cases are atypical, severely limiting rapid diagnosis and treatment.
CASE REPORT
Here, we report a 74-year-old female patient diagnosed with S. suis infection. The main symptoms were hearing loss, lumbago, and scattered ecchymosis of the lower extremities and trunk. Blood non-specific infection indexes were significantly increased and platelets were significantly decreased; however, no pathogens were obtained from routine blood culture. Finally, the S. suis infection was confirmed by metagenomic next-generation sequencing (mNGS) of blood and cerebrospinal fluid. After antibiotic treatment, the limb and trunk scattered ecchymosis and lumbago symptoms were significantly relieved, but the hearing did not recover.
CONCLUSIONS
Human infection with S. suis is rare in central cities, and it is easy to misdiagnose, especially in cases with atypical early symptoms. mNGS technology, combined with clinical observation, is helpful to clarify the direction of diagnosis and treatment, which is conducive to patient recovery.
Topics: Humans; Streptococcus suis; Female; Aged; Streptococcal Infections; High-Throughput Nucleotide Sequencing; Metagenomics; Anti-Bacterial Agents
PubMed: 38728637
DOI: 10.3855/jidc.18805 -
Veterinary Research May 2024Streptococcus suis is a bacterial pathogen that causes important economic losses to the swine industry worldwide. Since there are no current commercial vaccines, the use...
Streptococcus suis is a bacterial pathogen that causes important economic losses to the swine industry worldwide. Since there are no current commercial vaccines, the use of autogenous vaccines applied to gilts/sows to enhance transfer of passive immunity is an attractive alternative to protect weaned piglets. However, there is no universal standardization in the production of autogenous vaccines and the vaccine formulation may be highly different among licenced manufacturing laboratories. In the present study, an autogenous vaccine that included S. suis serotypes 2, 1/2, 5, 7 and 14 was prepared by a licensed laboratory and administrated to gilts using a three-dose program prior to farrowing. The antibody response in gilts as well as the passive transfer of antibodies to piglets was then evaluated. In divergence with previously published data with an autogenous vaccine produced by a different company, the increased response seen in gilts was sufficient to improve maternal antibody transfer to piglets up to 5 weeks of age. However, piglets would still remain susceptible to S. suis disease which often appears during the second part of the nursery period. Vaccination did not affect the shedding of S. suis (as well as that of the specific S. suis serotypes included in the vaccine) by either gilts or piglets. Although all antibiotic treatments were absent during the trial, the clinical protective effect of the vaccination program with the autogenous vaccine could not be evaluated, since limited S. suis cases were present during the trial, confirming the need for a complete evaluation of the clinical protection that must include laboratory confirmation of the aetiological agent involved in the presence of S. suis-associated clinical signs. Further studies to evaluate the usefulness of gilt/sow vaccination with autogenous vaccines to protect nursery piglets should be done.
Topics: Animals; Streptococcus suis; Swine; Swine Diseases; Streptococcal Infections; Female; Autovaccines; Immunity, Maternally-Acquired; Streptococcal Vaccines; Serogroup; Vaccination
PubMed: 38715138
DOI: 10.1186/s13567-024-01313-x -
Emerging Microbes & Infections Dec 2024is a major bacterial pathogen in pigs and an emerging zoonotic pathogen. Different serotypes exhibit diverse characteristics in population structure and pathogenicity....
is a major bacterial pathogen in pigs and an emerging zoonotic pathogen. Different serotypes exhibit diverse characteristics in population structure and pathogenicity. Surveillance data highlight the significance of serotype 4 (SS4) in swine streptococcusis, a pathotype causing human infections. However, except for a few epidemiologic studies, the information on SS4 remains limited. In this study, we investigated the population structure, pathogenicity, and antimicrobial characteristics of SS4 based on 126 isolates, including one from a patient with septicemia. We discovered significant diversities within this population, clustering into six minimum core genome (MCG) groups (1, 2, 3, 4, 7-2, and 7-3) and five lineages. Two main clonal complexes (CCs), CC17 and CC94, belong to MCG groups 1 and 3, respectively. Numerous important putative virulence-associated genes are present in these two MCG groups, and 35.00% (7/20) of pig isolates from CC17, CC94, and CC839 (also belonging to MCG group 3) were highly virulent (mortality rate ≥ 80%) in zebrafish and mice, similar to the human isolate ID36054. Cytotoxicity assays showed that the human and pig isolates of SS4 strains exhibit significant cytotoxicity to human cells. Antimicrobial susceptibility testing showed that 95.83% of strains isolated from our labs were classified as multidrug-resistant. Prophages were identified as the primary vehicle for antibiotic resistance genes. Our study demonstrates the public health threat posed by SS4, expanding the understanding of SS4 population structure and pathogenicity characteristics and providing valuable information for its surveillance and prevention.
Topics: Streptococcus suis; Animals; Swine; Humans; Streptococcal Infections; Serogroup; Swine Diseases; Virulence; Mice; Genome, Bacterial; Zebrafish; Anti-Bacterial Agents; Phylogeny; Microbial Sensitivity Tests; Virulence Factors
PubMed: 38703011
DOI: 10.1080/22221751.2024.2352435