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Virulence Dec 2023type 2 (SS2), a major emerging/re-emerging zoonotic pathogen found in humans and pigs, can cause severe clinical infections, and pose public health issues. Our previous...
type 2 (SS2), a major emerging/re-emerging zoonotic pathogen found in humans and pigs, can cause severe clinical infections, and pose public health issues. Our previous studies recognized peptidyl-prolyl isomerase (PrsA) as a critical virulence factor promoting SS2 pathogenicity. PrsA contributed to cell death and operated as a pro-inflammatory effector. However, the molecular pathways through which PrsA contributes to cell death are poorly understood. Here in this study, we prepared the recombinant PrsA protein and found that pyroptosis and necroptosis were involved in cell death stimulated by PrsA. Specific pyroptosis and necroptosis signalling inhibitors could significantly alleviate the fatal effect. Cleaved caspase-1 and IL-1β in pyroptosis with phosphorylated MLKL proteins in necroptosis pathways, respectively, were activated after PrsA stimulation. Truncated protein fragments of enzymatic PPIase domain (PPI), N-terminal (NP), and C-terminal (PC) domains fused with PPIase, were expressed and purified. PrsA flanking - or C-terminal but not enzymatic PPIase domain was found to be critical for PrsA function in inducing cell death and inflammation. Additionally, PrsA protein could be anchored on the cell surface to interact with host cells. However, Toll-like receptor 2 (TLR2) was not implicated in cell death and recognition of PrsA. PAMPs of PrsA could not promote TLR2 activation, and no rescued phenotypes of death were shown in cells blocking of TLR2 receptor or signal-transducing adaptor of MyD88. Overall, these data, for the first time, advanced our perspective on PrsA function and elucidated that PrsA-induced cell death requires its flanking - or C-terminal domain but is dispensable for recognizing TLR2. Further efforts are still needed to explore the precise molecular mechanisms of PrsA-inducing cell death and, therefore, contribution to SS2 pathogenicity.
Topics: Animals; Humans; Cell Death; Peptidylprolyl Isomerase; Pyroptosis; Streptococcus suis; Swine; Toll-Like Receptor 2; Bacterial Proteins; Streptococcal Infections
PubMed: 37641974
DOI: 10.1080/21505594.2023.2249779 -
Translational Animal Science 2023() is an endemic zoonotic pathogen still lacking adequate prevention in pigs. The present case study looked back to the occurrence and consequences of outbreaks in our...
() is an endemic zoonotic pathogen still lacking adequate prevention in pigs. The present case study looked back to the occurrence and consequences of outbreaks in our swine research facilities in search of new metabolic and physiological insight. From a series of outbreaks, a dataset was created including 56 pigs sampled during disease detection based on clinical signs. Pigs suspected with infection were defined as diseased ( = 28) and included pigs defined as neurologically diseased ( = 20) when severe neurological signs (central nervous system dysfunctions, i.e., opisthotonos, ataxia, and generalized tremor) were observed. Another set of 28 pigs included respective pen mates from each case and were defined as control. Representative deaths were confirmed to be caused by Tonsillar swabs were collected and analyzed by quantitative polymerase chain reaction () for total bacteria, total , and serotypes () 2 (and/or 1/2) and 9. Blood and sera were analyzed to quantify blood gases, minerals, and reactive immunoglobulins against current isolates. Data collected included litter sibling associations, birth and weaning body weight (), and average daily gain () 7 d after the disease detection. In general, the disease increased pH, sO and the incidence of alkalosis, but reduced pCO, glucose, Ca, P, Mg, K, and Na in blood/serum compared to control. The SS2 (and/or SS1/2) prevalence was significantly ( < 0.05) increased in neurologically diseased pigs and its relative abundance tended ( < 0.10) to increase in tonsils. In contrast, the relative abundance of total was lower ( > 0.05) in diseased pigs than control pigs. Levels of reactive IgG2 were lower, but IgM were higher ( < 0.03) in neurologically affected pigs compared to control. Furthermore, there was an increased proportion of sibling pigs that were diseased compared to control. In conclusion, our results evidence that naturally affected pigs were associated to average performing pigs without any predisease trait to highlight but a sow/litter effect. Besides, neurologically affected pigs had increased (SS2 and/or 1/2) prevalence and relative abundance, a respiratory alkalosis profile, and mineral loss.
PubMed: 38023423
DOI: 10.1093/tas/txad126 -
Frontiers in Microbiology 2023Diseases caused by the zoonotic pathogen are an extensive economic problem as well as an animal welfare concern for the global swine industry. Previous studies have...
Diseases caused by the zoonotic pathogen are an extensive economic problem as well as an animal welfare concern for the global swine industry. Previous studies have evaluated the genomic diversity and population structure of isolates, however, the majority of these studies utilized isolates obtained from countries other than the U.S. This study applied whole genome sequencing and cgMLST-based typing to evaluate the population structure and genetic relatedness among isolates obtained within the U.S. The established high-resolution phylogenomic framework revealed extensive genomic variation and diversity among the sampled isolates, with isolates from the U.S. and from countries outside the U.S. found interspersed in the phylogeny. isolates obtained within the U.S. did not cluster by state or geographic location, however, isolates with similar serotypes, both obtained from within and outside the U.S., generally clustered together. Average nucleotide identity (ANI) values determined for the genomes were extensively broad, approaching the recommended species demarcation value, and correlated with the phylogenetic group distribution of the cgMLST-based tree. Numerous antimicrobial resistance (AMR) elements were identified among both U.S. and non-U.S. isolates with , , and genes identified as the most prevalent. The , , and genes, historically used as markers for virulence potential, were also observed in the genomes of isolates that grouped together forming a subclade of clonal complex 1 (CC1) isolates. Collectively, the data in this report provides critical information needed to address potential biosurveillance needs and insights into the genetic diversity and population structure of isolates obtained within the U.S.
PubMed: 37808309
DOI: 10.3389/fmicb.2023.1250265 -
Expert Opinion on Therapeutic Targets 2023Four different genetic families of the enzyme carbonic anhydrase (CA, EC 4.2.1.1) are present in bacteria, α-, β-, γ- and ι-CAs. They play relevant functions related... (Review)
Review
INTRODUCTION
Four different genetic families of the enzyme carbonic anhydrase (CA, EC 4.2.1.1) are present in bacteria, α-, β-, γ- and ι-CAs. They play relevant functions related to CO, HCO/H ions homeostasis, being involved in metabolic biosynthetic pathways, pH regulation, and represent virulence and survival factors for bacteria in various niches. Bacterial CAs started to be considered druggable targets in the last decade, as their inhibition impairs survival, growth, and virulence of these pathogens.
AREAS COVERED
Significant advances were registered in the last years for designing effective inhibitors of sulfonamide type for α-CA, α-CA, vacomycin-resistant enterococci (VRE) α- and γ-CAs, for which the in vivo validation has also been achieved. MIC-s in the range of 0.25-4.0 µg/mL for wild type and drug resistant strains, and of 0.007-2.0 µg/mL for VRE were observed for some 1,3,4-thiadiazole-2-sulfonamides, and acetazolamide was effective in gut decolonization from VRE.
EXPERT OPINION
Targeting bacterial CAs from other pathogens, among which , , , serovar Typhimurium, , , , , , , , , , may lead to novel antibacterials devoid of drug resistance problems.
Topics: Humans; Carbonic Anhydrase Inhibitors; Acetazolamide; Sulfonamides; Carbonic Anhydrases; Bacteria; Anti-Bacterial Agents; Sulfanilamide; Structure-Activity Relationship
PubMed: 37747071
DOI: 10.1080/14728222.2023.2263914 -
Methods in Molecular Biology (Clifton,... 2024Streptococcus suis is a swine bacterial pathogen that predominantly causes disease in weaned piglets characterized by swelling of joints, arthritis, septicemia,...
Streptococcus suis is a swine bacterial pathogen that predominantly causes disease in weaned piglets characterized by swelling of joints, arthritis, septicemia, meningitis, and sudden death. Intravenous, intramuscular, intraperitoneal, and intranasal infection models were developed to study the bacterial pathogenicity and efficacy of vaccines and various therapeutics. The selection of the appropriate infection model is a critical step in any study, as it may impact the outcomes of the study. Here we describe a method for infecting weaned piglets with S. suis using intraperitoneal route as a reliable, consistent, and reproducible animal model to evaluate vaccine protection against systemic bacterial infection.
Topics: Animals; Swine; Disease Models, Animal; Streptococcus suis; Streptococcal Infections; Swine Diseases; Injections, Intraperitoneal
PubMed: 38884914
DOI: 10.1007/978-1-0716-3898-9_9 -
Tropical Biomedicine Mar 2024Streptococcus suis is a bacterium of clinical importance in diverse animal hosts including companion animals and humans. Companion animals are closely associated in the...
Streptococcus suis is a bacterium of clinical importance in diverse animal hosts including companion animals and humans. Companion animals are closely associated in the living environment of humans and are potential reservoirs for zoonotic pathogens. Given the zoonotic potential of S. suis, it is crucial to determine whether this bacterium is present among the companion animal population. This study aimed to detect Streptococcus suis in companion animals namely cats and dogs of the central west coast of Peninsular Malaysia and further characterize the positive isolates via molecular and genomic approach. The detection of S. suis was done via bacterial isolation and polymerase chain reaction assay of gdh and recN gene from oral swabs. Characterization was done by multiplex PCR serotyping, as well as muti-locus sequence typing, AMR gene prediction, MGE identification and phylogenomic analysis on whole genome sequence acquired from Illumina and Oxford Nanopore sequencing. Among the 115 samples, PCR assay detected 2/59 of the cats were positive for S. suis serotype 8 while all screened dog samples were negative. This study further described the first complete whole genome of S. suis strain SS/UPM/MY/F001 isolated from the oral cavity of a companion cat. Genomic analysis revealed a novel strain of S. suis having a unique MLST profile and antimicrobial resistance genes of mefA, msrD, patA, patB and vanY. Mobile genetic elements were described, and pathogenic determinants matched to human and swine strains were identified. Phylogenetic tree analysis on the core genome alignment revealed strain SS/UPM/MY/F001 was distinct from other S. suis strains. This study provided insight into the detection and genomic features of the S. suis isolate of a companion cat and highlighted its potential for antimicrobial resistance and pathogenicity.
Topics: Cats; Animals; Streptococcus suis; Streptococcal Infections; Cat Diseases; Dogs; Whole Genome Sequencing; Dog Diseases; Malaysia; Phylogeny; Pets; Drug Resistance, Bacterial; Zoonoses; Multilocus Sequence Typing; Genome, Bacterial; Anti-Bacterial Agents; Humans; Bacterial Zoonoses
PubMed: 38852139
DOI: 10.47665/tb.41.1.012 -
Journal of Clinical Microbiology Sep 2023an emerging zoonotic pathogen, causes invasive infections and substantial economic losses in the pig industry worldwide. Antimicrobial resistance against 22 antibiotics...
an emerging zoonotic pathogen, causes invasive infections and substantial economic losses in the pig industry worldwide. Antimicrobial resistance against 22 antibiotics was studied for 200 . strains collected in different geographical regions of France. Most of the strains (86%) showed resistance to at least one antibiotic with a low rate of resistance to fluoroquinolones, penicillins, pleuromutilin, and diaminopyrimidine-sulfonamides, and a higher rate to macrolides-lincosamides and tetracycline. Multi-resistance patterns were observed in 138 strains; three of them being resistant to six antibiotic families. Statistical analyses highlighted a decrease in the resistance to trimethoprim-sulfamethoxazole, in our collection, between the two periods studied-before 2010 and after 2015-as well as an impact of the geographical origin with a higher rate of resistance to macrolides-lincosamides and penicillin in Brittany than in the other French regions. Furthermore, macrolides-lincosamides and tetracycline resistance patterns were more likely to be found in pig isolates than in human and wild boar isolates. A difference in resistance was also observed between serotypes. Most of the penicillin-resistant strains belong to serotypes 1, 5, 9, 11, 12, 15, 27, and 29. Finally, penicillin and pleuromutilin resistances were mostly found in "non-clinical" isolates. The empirical treatment of human and porcine infections due to in France can therefore still be carried out with beta-lactams. However, this study emphasizes the need to monitor antimicrobial resistance in this zoonotic pathogen.
Topics: Humans; Animals; Swine; Anti-Bacterial Agents; Streptococcus suis; Drug Resistance, Bacterial; Penicillins; France; Lincosamides; Macrolides; Sus scrofa; Pleuromutilins
PubMed: 37655935
DOI: 10.1128/jcm.00164-23 -
Biomedicine & Pharmacotherapy =... Dec 2023Antimicrobial resistance is a worldwide problem that urges novel alternatives to treat infections. In attempts to find novel molecules, we assess the antimicrobial...
Essential oils of Pinus sylvestris, Citrus limon and Origanum vulgare exhibit high bactericidal and anti-biofilm activities against Neisseria gonorrhoeae and Streptococcus suis.
Antimicrobial resistance is a worldwide problem that urges novel alternatives to treat infections. In attempts to find novel molecules, we assess the antimicrobial potential of seven essential oils (EO) of different plants (Pinus sylvestris, Citrus limon, Origanum vulgare, Cymbopogon martini, Cinnamomum cassia, Melaleuca alternifolia and Eucalyptus globulus) against two multidrug-resistant bacteria species, i.e. Neisseria gonorrhoeae and Streptococcus suis. EOs of P. sylvestris and C. limon revealed higher bactericidal activity (MIC ≤ 0.5 mg/mL) and capacity to rapidly disperse biofilms of several N. gonorrhoeae clinical isolates than other EOs. Examination of biofilms exposed to both EO by electron microscopy revealed a reduction of bacterial aggregates, high production of extracellular vesicles, and alteration of cell integrity. This activity was dose-dependent and was enhanced in DNase I-treated biofilms. Antibiotic susceptibility studies confirmed that both EOs affected the outer membrane permeability, and analysis of EO- susceptibility of an LPS-deficient mutant suggested that both EO target the LPS bilayer. Further analysis revealed that α- and β-pinene and d-limonene, components of both EO, contribute to such activity. EO of C. martini, C. cassia, and O. vulgare exhibited promising antimicrobial activity (MIC ≤ 0.5 mg/mL) against S. suis, but only EO of O. vulgare exhibited a high biofilm dispersal activity, which was also confirmed by electron microscopy studies. To conclude, the EO of P. sylvestris, C. limon and O. vulgare studied in this work exhibit bactericidal and anti-biofilm activities against gonococcus and streptococcus, respectively.
Topics: Oils, Volatile; Neisseria gonorrhoeae; Pinus sylvestris; Origanum; Streptococcus suis; Citrus; Lipopolysaccharides; Anti-Bacterial Agents; Anti-Infective Agents; Biofilms; Microbial Sensitivity Tests
PubMed: 37857249
DOI: 10.1016/j.biopha.2023.115703 -
BMC Veterinary Research Dec 2023Accurate measurement of disease associated with endemic bacterial agents in pig populations is challenging due to their commensal ecology, the lack of disease-specific...
Detection and disease diagnosis trends (2017-2022) for Streptococcus suis, Glaesserella parasuis, Mycoplasma hyorhinis, Actinobacillus suis and Mycoplasma hyosynoviae at Iowa State University Veterinary Diagnostic Laboratory.
BACKGROUND
Accurate measurement of disease associated with endemic bacterial agents in pig populations is challenging due to their commensal ecology, the lack of disease-specific antemortem diagnostic tests, and the polymicrobial nature of swine diagnostic cases. The main objective of this retrospective study was to estimate temporal patterns of agent detection and disease diagnosis for five endemic bacteria that can cause systemic disease in porcine tissue specimens submitted to the Iowa State University Veterinary Diagnostic Laboratory (ISU VDL) from 2017 to 2022. The study also explored the diagnostic value of specific tissue specimens for disease diagnosis, estimated the frequency of polymicrobial diagnosis, and evaluated the association between phase of pig production and disease diagnosis.
RESULTS
S. suis and G. parasuis bronchopneumonia increased on average 6 and 4.3%, while S. suis endocarditis increased by 23% per year, respectively. M. hyorhinis and A. suis associated serositis increased yearly by 4.2 and 12.8%, respectively. A significant upward trend in M. hyorhinis arthritis cases was also observed. In contrast, M. hyosynoviae arthritis cases decreased by 33% average/year. Investigation into the diagnostic value of tissues showed that lungs were the most frequently submitted sample, However, the use of lung for systemic disease diagnosis requires caution due to the commensal nature of these agents in the respiratory system, compared to systemic sites that diagnosticians typically target. This study also explored associations between phase of production and specific diseases caused by each agent, showcasing the role of S. suis arthritis in suckling pigs, meningitis in early nursery and endocarditis in growing pigs, and the role of G. parasuis, A. suis, M. hyorhinis and M. hyosynoviae disease mainly in post-weaning phases. Finally, this study highlighted the high frequency of co-detection and -disease diagnosis with other infectious etiologies, such as PRRSV and IAV, demonstrating that to minimize the health impact of these endemic bacterial agents it is imperative to establish effective viral control programs.
CONCLUSIONS
Results from this retrospective study demonstrated significant increases in disease diagnosis for S. suis, G. parasuis, M. hyorhinis, and A. suis, and a significant decrease in detection and disease diagnosis of M. hyosynoviae. High frequencies of interactions between these endemic agents and with viral pathogens was also demonstrated. Consequently, improved control programs are needed to mitigate the adverse effect of these endemic bacterial agents on swine health and wellbeing. This includes improving diagnostic procedures, developing more effective vaccine products, fine-tuning antimicrobial approaches, and managing viral co-infections.
Topics: Humans; Swine; Animals; Mycoplasma hyorhinis; Mycoplasma hyosynoviae; Streptococcus suis; Actinobacillus suis; Mycoplasma Infections; Iowa; Retrospective Studies; Universities; Swine Diseases; Arthritis; Endocarditis
PubMed: 38087358
DOI: 10.1186/s12917-023-03807-w -
European Archives of... May 2024This study aimed to explore the diagnostic sensitivity of 3D heavily weighted T2-weighted MRI (T2MRI) and high-resolution computed tomography (HRCT) in patients with...
OBJECTIVES
This study aimed to explore the diagnostic sensitivity of 3D heavily weighted T2-weighted MRI (T2MRI) and high-resolution computed tomography (HRCT) in patients with cochlear fibrosis associated with Streptococcus suis (S. suis) meningitis and the practicality of Cochlear implantation (CI) treatments.
METHODS
Between January 2020 and December 2022, we enrolled four patients with rare cochlear S. suis meningitis with associated hearing loss despite aggressive or non-aggressive follow-up antibiotic treatment. Clinical imaging data, surgical performances and post-surgical-electrode impedance were evaluated.
RESULTS
Combined with HRCT and T2MRI, the cochlea had varying degrees of fibrosis and ossification in different cases. However, the electrodes were successfully and wholly inserted after intraoperative removal of the ossified and fibrotic foci. Post-surgical electrode impedance values of MP1 + 2 mode were normal in all 4 cases at initial activation.
CONCLUSION
In patients with S. suis meningitis and associated cochlear fibrosis, T2MRI examination of the inner ear was more sensitive than HRCT. This research highlights the feasibility of CI treatment in S. suis meningitis patients with severe cochlear fibrosis.
PubMed: 38758241
DOI: 10.1007/s00405-024-08730-w