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18 pages, 3953 KB  
Article
Population Genetic Architecture of the Streptococcus suis Antigen HP0197
by Guopeng Mei, Junfeng Zhang, Lijun Guan, Shangbo Ning, Yun Xue and Zhanqin Zhao
Vet. Sci. 2026, 13(4), 376; https://doi.org/10.3390/vetsci13040376 - 13 Apr 2026
Viewed by 258
Abstract
S. suis is a major zoonotic infectious disease whose serological diversity brings challenges to vaccine development. Based on the whole-genome data of 169 S. suis strains, this study conducted a systematic bioinformatics analysis of the surface antigen protein HP0197 that reveals its distribution [...] Read more.
S. suis is a major zoonotic infectious disease whose serological diversity brings challenges to vaccine development. Based on the whole-genome data of 169 S. suis strains, this study conducted a systematic bioinformatics analysis of the surface antigen protein HP0197 that reveals its distribution characteristics, sequence diversity, domain composition and antigenic epitope distribution. The results showed that the HP0197 gene, which has a detection rate of 91.72%, can be divided into seven major phylogroups (I–VII) and the following two structural types: short form (HP0197-S) and long form (HP0197-L). All sequences contained signal peptides, transmembrane structures, LPXTG anchoring motifs, as well as conserved GAGBD and G5 domains, among which tandem repeats of the G5 domain existed in the long HP0197-L type. Tertiary structure prediction indicated that HP0197 has a spatial architecture of “conserved at both ends and flexible in the middle”, in which B-cell epitopes are mainly enriched near the GAGBD and G5 domains, suggesting these regions are the key targets for inducing cross-immune protection. It systematically elucidates the diversity and structural characteristics of the HP0197 protein from the perspective of population genetics, which provides a theoretical basis for optimizing existing subunit vaccines, designing broad-spectrum multi-epitope vaccines and exploring novel anti-infection strategies. Full article
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14 pages, 1978 KB  
Article
Aptamer-Based Label-Free Colorimetric Assay Using Gold Nanoparticles for Specific Detection of Streptococcus suis
by Sirikwan Sangboonruang, Natthawat Semakul, Apinyapat Matchawong, Anuchit Sattaphan, Kanokwan Saengsawang, Chatchawan Srisawat, Khajornsak Tragoolpua and Chayada Sitthidet Tharinjaroen
Biosensors 2026, 16(4), 215; https://doi.org/10.3390/bios16040215 - 10 Apr 2026
Viewed by 286
Abstract
Streptococcus suis is a serious zoonotic pathogen responsible for rapid progression and deadly infections in both humans and pigs. With an increasing number of reported cases and considering the limitations of standard routine identification, a simple, rapid, and cost-effective approach is needed. In [...] Read more.
Streptococcus suis is a serious zoonotic pathogen responsible for rapid progression and deadly infections in both humans and pigs. With an increasing number of reported cases and considering the limitations of standard routine identification, a simple, rapid, and cost-effective approach is needed. In this study, a label-free colorimetric assay based on gold nanoparticles (AuNPs) was applied with a specific aptamer, R8-su12. This assay offered simplified detection through observable color change, enabling visual analysis by the naked eye or assessment via UV–Vis spectrophotometry. Under the optimal assay conditions, the detection procedure was carried out within 45 min. The reaction of the aptasensor and other bacterial species, including Staphylococcus aureus, S. pneumoniae, S. pyogenes, Pseudomonas aeruginosa, Escherichia coli, Enterococcus faecium, and E. faecalis, was not present, indicating the specificity of this assay. Moreover, the aptasensor exhibited high sensitivity with a limit of detection (LOD) at 1 CFU of S. suis and had broad reactivity with S. suis serotypes 1, 1/2, 9, and 14, as well as with S. suis isolated from clinical specimens. Thus, this aptasensor demonstrates proof-of-concept feasibility including clinical sample testing before practical implementation. It holds promise as a practical tool for the early screening and outbreak management of S. suis in a variety of settings, such as clinical laboratories, food safety, and the environment. Full article
(This article belongs to the Special Issue Microbial Biosensor: From Design to Applications—3rd Edition)
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19 pages, 4309 KB  
Article
Epidemiology of Major Bacterial Pathogens Associated with Porcine Respiratory Disease Complex: A Cross-Sectional Study from Intensive Swine Farms in Xinjiang, China (2024–2025)
by Yaqi Guo, Yanfang Li, Zhenglong Wen, Yan Liang, Kexun Lian, Pei Zheng and Yonggang Qu
Vet. Sci. 2026, 13(4), 366; https://doi.org/10.3390/vetsci13040366 - 9 Apr 2026
Viewed by 336
Abstract
Glaesserella parasuis (formerly Haemophilus parasuis, HPS), Actinobacillus pleuropneumoniae (APP), Streptococcus suis (SS), and Pasteurella multocida (PM) are common bacterial pathogens associated with Porcine Respiratory Disease Complex (PRDC), a major cause of economic losses in the swine industry. To address this, a cross-sectional [...] Read more.
Glaesserella parasuis (formerly Haemophilus parasuis, HPS), Actinobacillus pleuropneumoniae (APP), Streptococcus suis (SS), and Pasteurella multocida (PM) are common bacterial pathogens associated with Porcine Respiratory Disease Complex (PRDC), a major cause of economic losses in the swine industry. To address this, a cross-sectional study was conducted across 27 large-scale swine farms in Xinjiang, China (October 2024–May 2025). A total of 1239 clinical samples were analyzed by species-specific PCR, and positive samples were further serotyped. Overall, SS and HPS were the predominant pathogens, with higher detection rates in winter and spring. Notably, SS and HPS were most frequent in nasal swabs, while APP and PM predominated in tissue samples. Furthermore, co-infections were common, with HPS + SS being the most prevalent. Serotyping revealed dominance of HPS serotype 12, APP serotype 12, SS serotype 3, and PM serotypes A and B (serotypes E and F not detected). In addition, SS was also detected in environmental samples and farm workers’ nasal swabs. These findings suggest that future prevention and control strategies should focus on developing multivalent vaccines targeting the predominant serotypes identified, implementing regular serotype surveillance to guide precision immunization protocols, and strengthening environmental disinfection and biosecurity practices to reduce co-infections and occupational exposure risks. Full article
(This article belongs to the Section Veterinary Microbiology, Parasitology and Immunology)
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11 pages, 1610 KB  
Article
Pyogenic Spondylitis with Epidural Abscess Caused by Streptococcus suis Serotype 2 ST7: Tissue mNGS Confirmation and Whole-Genome Characterization of a Human Isolate
by Peiyan He, Henghui Wang, Ping Li, Yong Yan, Lei Gao and Lu Chen
Pathogens 2026, 15(3), 314; https://doi.org/10.3390/pathogens15030314 - 13 Mar 2026
Viewed by 522
Abstract
Streptococcus suis is an emerging zoonotic pathogen that typically causes bacteremia or meningitis in humans, whereas vertebral osteomyelitis with epidural abscess is exceedingly rare and may be missed. We describe a 65-year-old farmer with fever and severe low back pain after long-term bare-handed [...] Read more.
Streptococcus suis is an emerging zoonotic pathogen that typically causes bacteremia or meningitis in humans, whereas vertebral osteomyelitis with epidural abscess is exceedingly rare and may be missed. We describe a 65-year-old farmer with fever and severe low back pain after long-term bare-handed handling of raw pig lungs. Pre-treatment blood cultures yielded S. suis identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). After transient improvement on empirical therapy, fever recurred with worsening lumbar pain. Contrast-enhanced magnetic resonance imaging (MRI) demonstrated multilevel thoracolumbar pyogenic spondylitis with an epidural abscess and a sub-ligamentous abscess beneath the posterior longitudinal ligament (PLL) extending from L2 to L5. Computed tomography-guided lumbar biopsy followed by tissue metagenomic next-generation sequencing (mNGS) detected S. suis, providing concordant evidence supporting pathogen involvement at the vertebral focus. The bloodstream isolate (SS-JX2025-01) was serotype 2, sequence type 7 (ST7). It remained susceptible to β-lactams and glycopeptides but was resistant to macrolide–lincosamide and tetracycline classes, consistent with erm(B), tet(O), tet(40), and ant(6)-Ia detected by whole-genome sequencing (WGS). Virulence profiling revealed an epf+/sly+/mrp pattern with multiple adhesins and immune-evasion factors, whereas canonical 89K pathogenicity island markers were absent. Core-genome phylogeny placed SS-JX2025-01 within the Chinese ST7 lineage associated with previous outbreaks. This biopsy-supported case expands the clinical spectrum of invasive S. suis infection, highlights the value of tissue mNGS as an adjunct for supporting deep-seated foci in zoonotic infections, and underscores the importance of occupational prevention in small-scale farming households. Full article
(This article belongs to the Section Bacterial Pathogens)
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15 pages, 1479 KB  
Article
Orally Administered Porcine Intestinal Lactobacilli Improve the Respiratory Innate Immune Response Against Streptococcus pneumoniae
by Kohtaro Fukuyama, Solange Cisterna-Vergara, Ayelen Antonella Baillo, María José Lorenzo Pisarello, Weichen Gong, Keita Nishiyama, Julio Villena and Haruki Kitazawa
Animals 2026, 16(5), 825; https://doi.org/10.3390/ani16050825 - 6 Mar 2026
Viewed by 352
Abstract
Background: Respiratory bacterial infections represent a major health challenge in swine production, highlighting the need for novel immunomodulatory strategies that enhance host resistance. In this study, we investigated whether porcine intestinal lactobacilli could modulate the gut–lung axis and improve respiratory innate immunity in [...] Read more.
Background: Respiratory bacterial infections represent a major health challenge in swine production, highlighting the need for novel immunomodulatory strategies that enhance host resistance. In this study, we investigated whether porcine intestinal lactobacilli could modulate the gut–lung axis and improve respiratory innate immunity in a mouse model of Streptococcus pneumoniae infection, as a surrogate of Streptococcus suis pneumonia. Methods: Three strains of Ligilactobacillus salivarius (LAFF998, LAFF1071, and LAFF1095) were orally administered to Swiss mice prior to pneumococcal challenge. The resistance to the infection, the lung damage and the respiratory innate immune response were evaluated. Results: Only strain LAFF998 significantly reduced pulmonary bacterial loads, prevented bacteremia, and attenuated lung injury. This protective effect was associated with selective modulation of respiratory immunity, characterized by reduced neutrophilic inflammation, increased lymphocyte recruitment, and enhanced activation of alveolar macrophages expressing MHC-II. LAFF998 markedly increased the production of IFN-β, IFN-γ, IL-6, IL-10, and IL-27 in the respiratory tract, without inducing excessive inflammatory damage. Ex vivo and in vitro analyses confirmed that alveolar macrophages from LAFF998-treated mice exhibited a primed phenotype with heightened cytokine responses to pneumococcal stimulation. In contrast, strains LAFF1071 and LAFF1095 failed to confer protection or significantly modulate respiratory immune responses. Conclusions: These findings demonstrate a strict strain-dependent effect among porcine L. salivarius isolates and identify LAFF998 as a potent immunobiotic capable of enhancing respiratory innate immunity through the gut–lung axis. This work supports further studies of LAFF998 as an immunobiotic strategy for the prevention of respiratory infections in pigs. Full article
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15 pages, 2934 KB  
Article
Antimicrobial Activity of Aurisin A Against Streptococcus suis and Its Protective Effect on Epithelial Cells
by Thotsaporn Bunthiang, Siriwan Sunontarat, Nattamol Phetburom, Ruethaithip Dulyasucharit, Orapan Intharaksa, Thidarut Boonmars, Somdej Kanokmedhakul, Ratsami Lekphrom, Peechanika Chopjitt, Anusak Kerdsin and Parichart Boueroy
Int. J. Mol. Sci. 2026, 27(4), 1798; https://doi.org/10.3390/ijms27041798 - 13 Feb 2026
Viewed by 608
Abstract
Streptococcus suis is one of the most important zoonotic pathogens threatening the lives of pigs and humans. Increasingly severe antimicrobial resistance in S. suis is becoming a global issue. Therefore, there is an urgent need to discover novel antibacterial alternatives for the treatment [...] Read more.
Streptococcus suis is one of the most important zoonotic pathogens threatening the lives of pigs and humans. Increasingly severe antimicrobial resistance in S. suis is becoming a global issue. Therefore, there is an urgent need to discover novel antibacterial alternatives for the treatment of S. suis infections. The current study investigated aurisin A, an aristolane dimer sesquiterpene isolated from the luminescent mushroom Neonothopanus nambi Speg. (Marasmiaceae), against S. suis. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of aurisin A against S. suis strains were in the range of 1.94–62.5 μg/mL. Scanning electron microscopy showed that aurisin A induced alterations in the cellular structure of S. suis, including a significantly wrinkled surface, intracellular content leakage, and cell lysis. The crystal violet staining assay illustrated that aurisin A significantly inhibited biofilm formation of S. suis strains at sub-MICs and exhibited strong degrading activity against the preformed biofilms. Aurisin A significantly inhibited the adhesion, cell death, and cytotoxic activities of S. suis in lung epithelial cells in a concentration-dependent manner. Additionally, aurisin A significantly reduced the hemolytic effect of S. suis on defibrillated sheep blood, indicating protective activity of aurisin A against this bacteria. Taken together, these findings highlight aurisin A as a promising therapeutic candidate for the treatment of S. suis infections, with key roles in inhibiting biofilm formation and hemolytic activity, as well as providing protective effects to epithelial cells, including anti-adhesion, anti-cytotoxicity, and anti-cell death activities. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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16 pages, 833 KB  
Article
In Vitro Synergistic Effects of Antibiotic Combinations Against Multidrug-Resistant Streptococcus suis from Diseased Pigs
by Wiyada Chumpol, Kamonwan Lunha, Surasak Jiemsup and Suganya Yongkiettrakul
Antibiotics 2026, 15(2), 136; https://doi.org/10.3390/antibiotics15020136 - 29 Jan 2026
Viewed by 813
Abstract
Background/Objectives: Multidrug-resistant (MDR) strains of Streptococcus suis are increasingly prevalent and present significant challenges in clinical management. Given that the development of new antibiotics is a resource-intensive process and time-consuming, there is an urgent need for alternative therapeutic strategies to address resistance in [...] Read more.
Background/Objectives: Multidrug-resistant (MDR) strains of Streptococcus suis are increasingly prevalent and present significant challenges in clinical management. Given that the development of new antibiotics is a resource-intensive process and time-consuming, there is an urgent need for alternative therapeutic strategies to address resistance in the short term. One promising approach is the use of combination therapy, which involves pairing potent antibiotics with agents that may be less effective on their own, to enhance therapeutic efficacy and potentially overcome resistance mechanisms. This study aimed to investigate the in vitro antibacterial activity of combining two classes of antibiotics with distinct mechanisms of action—cell wall synthesis inhibitors and protein synthesis inhibitors—against MDR S. suis strains isolated from diseased pigs. Methods: A total of 36 MDR S. suis strains were tested using a microbroth dilution checkerboard assay to determine the minimum inhibitory concentration (MIC) of four cell wall synthesis inhibitors —amoxicillin/clavulanic acid (AMC), ampicillin (AMP), penicillin G (PEN), and vancomycin (VAN)— in combination with four protein synthesis inhibitors —gentamicin (GEN), neomycin (NEO), tilmicosin (TMS), and tylosin (TYL). Time–kill curve assays were conducted to evaluate the in vitro bactericidal activity of synergistic antibiotic combinations (PEN–GEN and AMP–NEO) against Beta-lactam-resistant and Beta-lactam-susceptible MDR S. suis strains. Results: Checkerboard analysis revealed that penicillin-gentamicin combination exhibited the most effective synergistic activity against the MDR S. suis strains (10/19, 52.6%), with ∑FIC values of 0.25–1.06 and MIC reductions from resistant to susceptible levels. Time-kill assays further confirmed the synergistic bactericidal effect of the combination, demonstrating complete bacterial clearance within 6–9 h, markedly rapid bacterial killing compared to monotherapy. Conclusions: This study demonstrates that antibiotic combinations, particularly Beta-lactams combined with aminoglycosides, show synergistic activity against pig-isolated S. suis MDR strains. The PEN-GEN combination exhibited strong synergistic and bactericidal effects, supporting combination therapy as a potential strategy to address antimicrobial resistance. Further evaluation in diverse strain backgrounds and prudent antibiotic use are essential to confirm efficacy and limit the emergence of antibiotic resistance. Full article
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2 pages, 788 KB  
Correction
Correction: Xi et al. Aerococcus viridans Phage Lysin AVPL Had Lytic Activity against Streptococcus suis in a Mouse Bacteremia Model. Int. J. Mol. Sci. 2023, 24, 16670
by Hengyu Xi, Yao Fu, Chong Chen, Xin Feng, Wenyu Han, Jingmin Gu and Yalu Ji
Int. J. Mol. Sci. 2026, 27(3), 1296; https://doi.org/10.3390/ijms27031296 - 28 Jan 2026
Viewed by 300
Abstract
In the original publication [...] Full article
(This article belongs to the Section Molecular Microbiology)
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17 pages, 7081 KB  
Article
Antibacterial Activity of Bacteriophage Lytic Enzyme Ply900
by Yuan Li, Luxiang Xu, Yuhan Zhang, Chunliu Dong and Han Zhou
Vet. Sci. 2026, 13(1), 65; https://doi.org/10.3390/vetsci13010065 - 9 Jan 2026
Viewed by 512
Abstract
S. suis is a prominent zoonotic pathogen responsible for diseases such as arthritis in piglets, swine septicemia, and meningitis. The emergence of multi-drug resistance (MDR) underscores the urgent need for the development of novel antibacterial strategies. In this context, a systematic evaluation of [...] Read more.
S. suis is a prominent zoonotic pathogen responsible for diseases such as arthritis in piglets, swine septicemia, and meningitis. The emergence of multi-drug resistance (MDR) underscores the urgent need for the development of novel antibacterial strategies. In this context, a systematic evaluation of the antibacterial potential of the bacteriophage lytic enzyme Ply900 was conducted in this study, along with an analysis of its domain functions and an in vivo study of its therapeutic dynamics. Ply900 exhibits potent in vitro lytic activity against multiple bacteria, including Streptococcus suis, Streptococcus agalactiae, and Staphylococcus aureus. Notably, it possesses broad biochemical stability, with tolerance to diverse environmental conditions. In a mouse model of S. suis serotype 2 SC19 infection, both the direct Ply900 treatment group and the triple therapy group achieved effective eradication of S. suis, with markedly improved survival rates. The remaining bacteria remained susceptible to Ply900, with no evidence of induced resistance development. Mechanistic analysis revealed that the SH3B domain of Ply900 enhances targeted cleavage efficiency by binding synergistically to peptidoglycan with the CHAP domain, with CYS-34, HIS-59, and ASP-28 serving as key amino acid sites for Ply900’s cleavage activity. Collectively, these findings lay the foundation for the potential dual applications of the lysin Ply900, both in the clinical treatment of S. suis infections and in the prevention and control of these pathogenic bacteria in livestock farming. Full article
(This article belongs to the Section Veterinary Microbiology, Parasitology and Immunology)
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19 pages, 1968 KB  
Article
Proteomic Analysis of Streptococcus suis During Exposure to Intracellular Condition of Human Macrophage U937 Cells
by Peerarin Prangsuwan, Orathai Yinsai, Sittiruk Roytrakul and Kwanjit Duangsonk
Int. J. Mol. Sci. 2026, 27(1), 128; https://doi.org/10.3390/ijms27010128 - 22 Dec 2025
Viewed by 811
Abstract
Streptococcus suis is an important zoonotic pathogen responsible for severe infections in pigs and humans. Its capacity to survive within phagocytic cells is considered a key virulence mechanism that contributes to dissemination and persistence in host tissues. This study employed comparative proteomic profiling [...] Read more.
Streptococcus suis is an important zoonotic pathogen responsible for severe infections in pigs and humans. Its capacity to survive within phagocytic cells is considered a key virulence mechanism that contributes to dissemination and persistence in host tissues. This study employed comparative proteomic profiling to investigate intracellular adaptation of S. suis serotypes 2 (SS2) and 14 (SS14) during infection of human U937 macrophages. Five isolates originating from humans and pigs were analyzed using gel electrophoresis with liquid chromatography–tandem mass spectrometry (GeLC–MS/MS), revealing 118 differentially expressed proteins grouped into 11 functional categories. Translation-related proteins represented the largest group (48%), including upregulated ribosomal subunits (30S: S2, S5, S7, S8, S12, S15; 50S: L1, L5, L18, L22, L24, L33, L35) and translation factors such as GidA/TrmFO and RimP. Enrichment of carbohydrate metabolism and DNA replication proteins, including phosphoenolpyruvate carboxylase (PEP), UDP-N-acetylglucosamine pyrophosphorylase (GlmU), and ATP-dependent DNA helicase RuvB, indicated metabolic reprogramming and stress adaptation under intracellular conditions. Stress-response proteins such as molecular chaperone DnaK were also induced, supporting their multifunctional, “moonlighting” roles in virulence and host interaction. Comparative analysis showed that SS2 expressed a broader range of adaptive proteins than SS14, consistent with its higher virulence potential. These findings reveal conserved intracellular responses centered on translation, energy metabolism, and stress tolerance, which enable S. suis to survive within human macrophages. Integration of these intracellular proteomic signatures with previous exoproteomic, peptidomic, and network-based studies highlights translational and metabolic proteins—particularly DnaK, enolase, elongation factor EF-Tu, and GlmU—as multifunctional candidates linking survival and immunogenicity. This work establishes a comparative proteomic foundation for understanding S. suis intracellular adaptation and highlights potential targets for future vaccine or therapeutic development against this zoonotic pathogen. Full article
(This article belongs to the Section Molecular Informatics)
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17 pages, 1877 KB  
Article
Serovar-Dependent Gene Regulation and Antimicrobial Tolerance in Streptococcus suis Biofilms
by Mario Delgado-García, Carmen Arenas-Fernández, Oscar Mencía-Ares, Lucía Manzanares-Vigo, Ana Isabel Pastor-Calonge, Alba González-Fernández, César B. Gutiérrez-Martín and Sonia Martínez-Martínez
Antibiotics 2025, 14(12), 1224; https://doi.org/10.3390/antibiotics14121224 - 4 Dec 2025
Viewed by 677
Abstract
Introduction: Streptococcus suis is a zoonotic pathogen of great relevance to the swine industry, characterized by high genetic diversity and multiple serovars (SVs) with varying clinical prevalence. Biofilm formation represents a key factor in its virulence, antimicrobial resistance and infection persistence. Methods: [...] Read more.
Introduction: Streptococcus suis is a zoonotic pathogen of great relevance to the swine industry, characterized by high genetic diversity and multiple serovars (SVs) with varying clinical prevalence. Biofilm formation represents a key factor in its virulence, antimicrobial resistance and infection persistence. Methods: We integrated gene expression profiling of biofilm-associated genes by RT-qPCR and antimicrobial susceptibility in planktonic and mature biofilm against five antibiotics in S. suis field isolates belonging to SV1, SV2, SV7 and SV9. Results: Expression of quorum sensing and adhesion genes (luxS, fbps, sadP and srtA) was significantly higher in SV2, the poorest biofilm formers, and inversely correlated with biofilm biomass, suggesting these factors act during early biofilm establishment. Correlation analysis indicated coordinated regulation among genes involved in quorum sensing, adhesion and capsule synthesis. Antimicrobial susceptibility testing revealed a high frequency of non-wild type phenotypes in planktonic cells for tetracycline, erythromycin and clindamycin (>80%), while ampicillin and ciprofloxacin were less frequent. Mature biofilms exhibited a significant increase in antimicrobial tolerance for all antibiotics tested, with SV2 showing the greatest susceptibility. Conclusions: These data highlight serovar-specific biofilm regulation patterns and enhanced drug tolerance in established S. suis biofilms. Full article
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16 pages, 2671 KB  
Article
Bactericidal Activity of Pradofloxacin and Other Antimicrobials Against Swine Respiratory Bacterial Pathogens
by Joseph M. Blondeau and Shantelle D. Fitch
Pathogens 2025, 14(11), 1171; https://doi.org/10.3390/pathogens14111171 - 17 Nov 2025
Viewed by 680
Abstract
Swine respiratory disease (SRD) is a complex interaction whereby viral infection predisposes the host to secondary bacterial pulmonary invasion, which may be fatal. Antimicrobial agents remain an important therapy and serve to reduce morbidity and mortality in treated animals. Pradofloxacin is the newest [...] Read more.
Swine respiratory disease (SRD) is a complex interaction whereby viral infection predisposes the host to secondary bacterial pulmonary invasion, which may be fatal. Antimicrobial agents remain an important therapy and serve to reduce morbidity and mortality in treated animals. Pradofloxacin is the newest of the veterinary antibiotics to be approved to treat SRD. It is a dual-targeting fluoroquinolone with in vitro and clinical activity against Gram-negative and -positive bacteria, along with atypical agents including anaerobes. In this study, we compared the killing of Actinobacillus pleuropneumoniae, Pasteurella multocida, and Streptococcus suis by pradofloxacin and comparator antibiotics in a 3 h kill assay, using four clinically relevant drug concentrations. Pradofloxacin was bactericidal against the three pathogens, with kill rates ranging from 94.4 to 99.9% (A. pleuropneumoniae) following 15–20 min of exposure to the maximum serum and maximum tissue drug concentration. For P. multocida, the kill rates were 68.7–96.9% following 5–30 min of drug exposure at the maximum serum drug concentration, and 91.7% following 5 min of drug exposure at the maximum tissue drug concentration. For S. suis, pradofloxacin killed 92.4–99.4% and 71.6–97.1% of cells following 60–180 min of drug exposure at the maximum serum and maximum tissue drug concentration, respectively. Pradofloxacin appears to be an important addition to the drugs currently available for treating SRD. Full article
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13 pages, 4842 KB  
Article
Deletion of the sodA Gene Impaired the Pathogenicity of Streptococcus suis Serotype 2 to Mice by Inhibiting Caspase-1/GSDMD Pathway Activation in Macrophages
by Yajuan Li, Qiuguo Fang, Peiran Feng, Yushu Li, Qinqin Sun, Yunfei Huang, Shun Li, Oladejo Ayodele Olaolu and Qiang Fu
Microorganisms 2025, 13(11), 2566; https://doi.org/10.3390/microorganisms13112566 - 10 Nov 2025
Viewed by 726
Abstract
Streptococcus suis serotype 2 (SS2) is a major zoonotic pathogen causing infectious disease in various species, whose pathogenesis is still not well understood. The sodA gene is an important virulence gene of SS2 involved in the host’s immune response against pathogens. This study [...] Read more.
Streptococcus suis serotype 2 (SS2) is a major zoonotic pathogen causing infectious disease in various species, whose pathogenesis is still not well understood. The sodA gene is an important virulence gene of SS2 involved in the host’s immune response against pathogens. This study aimed to explore the impact of superoxide dismutase A (sodA) gene deletion on the pathogenicity of SS2 to mice. In this study, mice were grouped as control, WT, and ΔsodA, which were intraperitoneally injected with PBS, wild-type strain HA9801, and ΔsodA strain, respectively. WT proved to be a more virulent strain to mice with higher bacterial loads and survival rates in mice than those for ΔsodA. Moreover, more-severe tissue damage was observed in the lungs, liver, spleen, and kidneys of mice injected with WT than with ΔsodA. Additionally, macrophages accumulate to defend against SS2, and the results indicated that sodA gene deficiency decreased macrophage recruitment. In in vitro studies, caspase-1 and gasdermin D (GSDMD) were activated in macrophages induced by SS2; however, the absence of the sodA gene significantly inhibited the expression of pro-caspase-1, caspase-1, and GSDMD-N. Moreover, deletion of the sodA gene also decreased Interleukin-1 beta (IL-1β) and Interleukin-18 (IL-18) release in macrophages induced by SS2. Taken together, the absence of the sodA gene alleviated the pathogenicity of SS2 as a result of decreased macrophage accumulation and breakage of the caspase-1/GSDMD pathway in macrophages. Full article
(This article belongs to the Section Molecular Microbiology and Immunology)
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22 pages, 7644 KB  
Article
Analysis of Antimicrobial Resistance and Virulence Factors in Multidrug-Resistant Streptococcus suis Serotype 2 Isolates Using Whole-Genome Sequencing
by Lingling Zhang, Minglu Wang, Jiale Sheng, Lumin Yu, Yike Zhao, Wei Liao, Zitong Liu, Jiang Yu and Xinglin Zhang
Microorganisms 2025, 13(11), 2552; https://doi.org/10.3390/microorganisms13112552 - 7 Nov 2025
Viewed by 968
Abstract
Multidrug-resistant (MDR) Streptococcus suis (S. suis) is a zoonotic pathogen capable of infecting pigs across all age groups, leading to conditions such as meningitis, arthritis, and endocarditis. In humans, infections can result in septic arthritis, meningitis, necrotizing fasciitis, and septicemia, which [...] Read more.
Multidrug-resistant (MDR) Streptococcus suis (S. suis) is a zoonotic pathogen capable of infecting pigs across all age groups, leading to conditions such as meningitis, arthritis, and endocarditis. In humans, infections can result in septic arthritis, meningitis, necrotizing fasciitis, and septicemia, which may be fatal. The absence of a complete genome sequence hinders comprehensive bioinformatic studies of MDR S. suis derived from pigs. In this study, we present the whole-genome sequence of MDR S. suis serotype 2 ST01 isolated from joint fluid samples obtained from pigs. Whole-genome analysis revealed that the ST01 chromosome carries 19 antibiotic resistance genes that confer resistance to major classes of antibiotic including aminoglycosides, tetracyclines, fluoroquinolones, lincosamides, polypeptide, and nitrofurans. Additionally, it contains 15 virulence factors associated with immune modulation, bacterial adherence, and stress survival. Whole-genome analysis identified 84 horizontal gene transfer elements in ST01 (comprising 28 genomic islands, 52 transposons, and 4 prophages), alongside mutations resulting in reduced virulence (302 instances) and loss of pathogenicity (34 instances). Furthermore, 18 antibiotic targets along with 21 lethal mutations were identified as potential targets for preventing, controlling, and treating infection caused by MDR S. suis serotype 2 ST01. In vivo infection experiments demonstrated that intraperitoneal inoculation with ST01 resulted in mortality among Kunming mice, with a median lethal dose (LD50) of 5.62 × 109 CFU/mL. Histopathological analysis revealed varying degrees of lesions in the infected organs of the mice. This study thus provides valuable insights into strategies aimed at combating S. suis infections and their transmission within swine populations. Full article
(This article belongs to the Section Microbiomes)
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28 pages, 5159 KB  
Article
Recombinant Extracellular Factor Protein of Streptococcus suis as Potential Candidate Protein for Antibodies Against S. suis Detection and Subunit Vaccine Development: In Silico and In Vitro Approaches
by Watcharapong Mitsuwan, Phirabhat Saengsawang, Ratchadaporn Boripun, Manuel J. Rodríguez-Ortega and Ozioma F. Nwabor
Vaccines 2025, 13(11), 1128; https://doi.org/10.3390/vaccines13111128 - 2 Nov 2025
Viewed by 1152
Abstract
Background/Objectives: Streptococcus suis is a zoonotic pathogen that causes infections in pigs and humans, leading to significant economic losses. S. suis can evade the immune system of hosts and induce persistent infections. Early detection and vaccination are crucial for controlling the disease [...] Read more.
Background/Objectives: Streptococcus suis is a zoonotic pathogen that causes infections in pigs and humans, leading to significant economic losses. S. suis can evade the immune system of hosts and induce persistent infections. Early detection and vaccination are crucial for controlling the disease in swine industries. This study aimed to investigate candidate recombinant protein for antibodies against S. suis detection and subunit vaccine development. Methods: The whole genome of S. suis BM407 was analyzed using bioinformatic tools to predict suitable proteins and genes for recombinant protein expression. Partial extracellular factor protein (epf) genes of S. suis serotype 2 DMST18783 were amplified. A 3301 bp amplicon was digested, and a specific 615 bp fragment was inserted into a pQE81L-KAN vector. Then, the constructed plasmid was cloned and expressed in Escherichia coli DH10β. Purified protein was analyzed using SDS-PAGE. In addition, translated amino acid sequences were analyzed for immune response properties, molecular docking, molecular dynamic simulation, and epitope prediction. Results: The amino acid sequence of recombinant extracellular factor protein (rEF) was revealed as a promising antigen containing putative protective regions as linear epitopes. Furthermore, the rEF was expressed as a histidine-tagged recombinant protein, and its properties were nearly similar to the predicted rEF using bioinformatic tools. Binding of the recombinant EF (rEF) protein was found to reduce fluctuations in the swine toll-like receptor 2. Furthermore, the rEF contained several regions that were predicted to be epitopes for both B-cells and T-cells. Conclusions: This study indicates that the recombinant EF fragment is a promising candidate for detecting antibodies against S. suis and as a component of a subunit vaccine. Full article
(This article belongs to the Special Issue Vaccines for Porcine Diseases)
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