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PloS One 2024The porcine pathogen and zoonotic agent Streptococcus suis induces an exacerbated inflammation in the infected hosts that leads to sepsis, meningitis, and sudden death....
The porcine pathogen and zoonotic agent Streptococcus suis induces an exacerbated inflammation in the infected hosts that leads to sepsis, meningitis, and sudden death. Several virulence factors were described for S. suis of which the capsular polysaccharide (CPS) conceals it from the immune system, and the suilysin exhibits cytotoxic activity. Although neutrophils are recruited rapidly upon S. suis infection, their microbicidal functions appear to be poorly activated against the bacteria. However, during disease, the inflammatory environment could promote neutrophil activation as mediators such as the granulocyte colony-stimulating factor granulocyte (G-CSF) and the granulocyte-macrophages colony-stimulating factor (GM-CSF) prime neutrophils and enhance their responsiveness to bacterial detection. Thus, we hypothesized that CPS and suilysin prevent an efficient activation of neutrophils by S. suis, but that G-CSF and GM-CSF rescue neutrophil activation, leading to S. suis elimination. We evaluated the functions of porcine neutrophils in vitro in response to S. suis and investigated the role of the CPS and suilysin on cell activation using isogenic mutants of the bacteria. We also studied the influence of G-CSF and GM-CSF on neutrophil response to S. suis by priming the cells with recombinant proteins. Our study confirmed that CPS prevents S. suis-induced activation of most neutrophil functions but participates in the release of neutrophil-extracellular traps (NETs). Priming with G-CSF did not influence cell activation, but GM-CSF strongly promote IL-8 release, indicating its involvement in immunomodulation. However, priming did not enhance microbicidal functions. Studying the interaction between S. suis and neutrophils-first responders in host defense-remains fundamental to understand the immunopathogenesis of the infection and to develop therapeutical strategies related to neutrophils' defense against this bacterium.
Topics: Animals; Swine; Colony-Stimulating Factors; Granulocyte-Macrophage Colony-Stimulating Factor; Neutrophils; Streptococcus suis; Granulocyte Colony-Stimulating Factor
PubMed: 38261585
DOI: 10.1371/journal.pone.0296844 -
Virulence Dec 2024Pathogenic bacteria have evolved many strategies to evade surveillance and attack by complements. is an important zoonotic pathogen that infects humans and pigs....
Pathogenic bacteria have evolved many strategies to evade surveillance and attack by complements. is an important zoonotic pathogen that infects humans and pigs. Hyaluronidase (HylA) has been reported to be a potential virulence factor of . However, in this study, it was discovered that the genomic region encoding HylA of the virulent strain SC19 and other ST1 strains was truncated into four fragments when aligned with a strain containing intact HylA and possessing hyaluronidase activity. As a result, SC19 had no hyaluronidase activity, but one truncated HylA fragment, designated as HylS,' directly interacted with complement C3b, as confirmed by western ligand blotting, pull-down, and ELISA assays. The deposition of C3b and membrane attack complex (MAC) formation on the surface of a HylS'-deleted mutant (Δ) was significantly increased compared to wild-type SC19. In human sera and whole blood, Δ survival was significantly reduced compared to that in SC19. The resistance of Δ to macrophages and human polymorphonuclear neutrophil PMNs also decreased. In a mouse infection model, Δ showed reduced lethality and lower bacterial load in the organs compared to that of SC19. We conclude that the truncated hyaluronidase HylS' fragment contributes to complement evasion and the pathogenesis of .
Topics: Mice; Animals; Humans; Swine; Immune Evasion; Complement C3b; Streptococcus suis; Hyaluronoglucosaminidase; Virulence Factors; Complement System Proteins; Immunologic Factors; Streptococcal Infections; Bacterial Proteins
PubMed: 38251716
DOI: 10.1080/21505594.2024.2306691 -
Virulence Dec 2024The arginine deiminase system (ADS) has been identified in various bacteria and functions to supplement energy production and enhance biological adaptability. The...
The arginine deiminase system (ADS) has been identified in various bacteria and functions to supplement energy production and enhance biological adaptability. The current understanding of the regulatory mechanism of ADS and its effect on bacterial pathogenesis is still limited. Here, we found that the XRE family transcriptional regulator XtrSs negatively affected virulence and significantly repressed ADS transcription when the bacteria were incubated in blood. Electrophoretic mobility shift (EMSA) and lacZ fusion assays further showed that XtrSs directly bind to the promoter of ArgR, an acknowledged positive regulator of bacterial ADS, to repress ArgR transcription. Moreover, we provided compelling evidence that could utilize arginine via ADS to adapt to acid stress, while Δ enhanced this acid resistance by upregulating the ADS operon. Moreover, whole ADS-knockout increased arginine and antimicrobial NO in the infected macrophage cells, decreased intracellular survival, and even caused significant attenuation of bacterial virulence in a mouse infection model, while Δ consistently presented the opposite results. Our experiments identified a novel ADS regulatory mechanism in , whereby XtrSs regulated ADS to modulate NO content in macrophages, promoting intracellular survival. Meanwhile, our findings provide a new perspective on how evade the host's innate immune system.
Topics: Animals; Mice; Arginine; Bacterial Proteins; Gene Expression Regulation, Bacterial; Hydrolases; Macrophages; Streptococcal Infections; Streptococcus suis
PubMed: 38251714
DOI: 10.1080/21505594.2024.2306719 -
Veterinary Sciences Jan 2024This study aimed to update the serotype distribution in Spain by analysing 302 clinical isolates recovered from diseased pigs between 2020 and 2022. The main objectives...
This study aimed to update the serotype distribution in Spain by analysing 302 clinical isolates recovered from diseased pigs between 2020 and 2022. The main objectives were to identify prevalent serotypes, differentiate specific serotypes 1, 14, 2, and 1/2, investigate specific genotypic and phenotypic antimicrobial resistance features, and explore associations between resistance genes and phenotypic resistances. Serotypes 9 (21.2%), 1 (16.2%), 2 (15.6%), 3 (6%), and 7 (5.6%) were the most prevalent, whereas serotypes 14 and 1/2 corresponded with 4.3% and 0.7% of all isolates. Antimicrobial resistance genes, including (O), (B), (B), (E), (M), and (A/E), were analysed, which were present in 85.8%, 65.2%, 7%, 7%, 6.3%, and 1% of the samples, respectively. Susceptibility testing for 18 antimicrobials revealed high resistance levels, particularly for clindamycin (88.4%), chlortetracycline (89.4%), and sulfadimethoxine (94.4%). Notably, seven significant associations ( < 0.0001) were detected, correlating specific antimicrobial resistance genes to the observed phenotypic resistance. These findings contribute to understanding the serotype distribution and its antibiotic resistance profiles in Spain, offering valuable insights for veterinary and public health efforts in managing -associated infections.
PubMed: 38250946
DOI: 10.3390/vetsci11010040 -
Veterinary Sciences Jan 2024Locomotor and central nervous system disorders occur during pig rearing, but there is no systematic recording of the different causative agents in Germany. Joint and...
Locomotor and central nervous system disorders occur during pig rearing, but there is no systematic recording of the different causative agents in Germany. Joint and meningeal swabs, kidneys, lungs, and eight different lymph nodes per pig were cultured, and isolated pathogens were identified using polymerase chain reactions (PCRs). The and pathotype of () isolates were determined using multiplex-PCR. was the most important pathogen in the infected joints (70.8%) and meningeal swabs (85.4%) and was most frequently detected in both sites in suckling and weaning piglets. To elucidate the possible portal of entry of , eight different lymph nodes from 201 pigs were examined in a prospective study. was detected in all examined lymph nodes ( = 1569), including the mesenteric lymph nodes (15.8%; = 121/765), with 9 (37.2%; = 147) and 2 (24.3%; = 96) being the most dominating types. In piglets with a systemic infection, different lymph nodes are frequently infected with the invasive strain, which does not help clarify the portal of entry for .
PubMed: 38250923
DOI: 10.3390/vetsci11010017 -
PLoS Pathogens Jan 2024Streptococcus suis serotype 2 is an important encapsulated bacterial swine pathogen and zoonotic agent for which no effective vaccine exists. The interaction with B...
Streptococcus suis serotype 2 is an important encapsulated bacterial swine pathogen and zoonotic agent for which no effective vaccine exists. The interaction with B cells and the humoral response against S. suis are poorly understood despite their likely relevance for a potential vaccine. We evaluated germinal center (GC) B cell kinetics, as well as the production and role of S. suis-specific antibodies following infections in a mouse model. We found that mice infected with S. suis developed GC that peaked 13-21 days post-infection. GC further increased and persisted upon periodic reinfection that mimics real life conditions in swine farms. Anti-S. suis IgM and several IgG subclasses were produced, but antibodies against the S. suis capsular polysaccharide (CPS) were largely IgM. Interestingly, depletion of total IgG from the wild-type mice sera had no effect on bacterial killing by opsonophagocytosis in vitro. Somatic hypermutation and isotype switching were dispensable for controlling the infection or anti-CPS IgM production. However, T cell-deficient (Tcrb-/-) mice were unable to control bacteremia, produce optimal anti-CPS IgM titers, or elicit antibodies with opsonophagocytic activity. SAP deficiency, which prevents GC formation but not extrafollicular B cell responses, ablated anti S. suis-IgG production but maintained IgM production and eliminated the infection. In contrast, B cell deficient mice were unable to control bacteremia. Collectively, our results indicate that the antibody response plays a large role in immunity against S. suis, with GC-independent but T cell-dependent germline IgM being the major effective antibody specificities. Our results further highlight the importance IgM, and potentially anti-CPS antibodies, in clearing S. suis infections and provide insight for future development of S. suis vaccines.
Topics: Animals; Mice; Swine; Streptococcus suis; Antibodies, Bacterial; Immunoglobulin G; Immunoglobulin M; Vaccines; T-Lymphocytes; Bacteremia; Streptococcal Infections
PubMed: 38241393
DOI: 10.1371/journal.ppat.1011957 -
Microbiology Spectrum Feb 2024() has been increasingly recognized as a porcine zoonotic pathogen that threatens the health of both pigs and humans. Multidrug-resistant is becoming increasingly...
() has been increasingly recognized as a porcine zoonotic pathogen that threatens the health of both pigs and humans. Multidrug-resistant is becoming increasingly prevalent, and novel strategies to treat bacterial infections caused by these organisms are desperately needed. In the present study, an untargeted metabolomics analysis showed that the significant decrease in methionine content and the methionine biosynthetic pathway were significantly affected by the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis in drug-resistant . The addition of L-methionine restored the bactericidal activity of macrolides, doxycycline, and ciprofloxacin on and . Further studies showed that the exogenous addition of methionine affects methionine metabolism by reducing S-adenosylmethionine synthetase activity and the contents of S-adenosylmethionine, S-adenosyl homocysteine, and S-ribose homocysteine. Methionine can decrease the total methylation level and methylesterase activity in multidrug resistant . The drug transport proteins and efflux pump genes were significantly downregulated in by exogenous L-methionine. Moreover, the exogenous addition of methionine can reduce the survival of by affecting oxidative stress and metal starvation in bacteria. Thus, L-methionine may influence the development of resistance in through methyl metabolism and metal starvation. This study provides a new perspective on the mitigation of drug resistance in .IMPORTANCEBacterial antibiotic resistance has become a severe threat to human and animal health. Increasing the efficacy of existing antibiotics is a promising strategy against antibiotic resistance. Here, we report that L-methionine enhances the efficacy of macrolides, doxycycline, and ciprofloxacin antibiotics in killing , including multidrug-resistant pathogens. We investigated the mechanism of action of exogenous methionine supplementation in restoring macrolides in and the role of the methionine cycle pathway on methylation levels, efflux pump genes, oxidative stress, and metal starvation in . It provides a theoretical basis for the rational use of macrolides in clinical practice and also identifies a possible target for restoring drug resistance in .
Topics: Humans; Animals; Swine; Streptococcus suis; Macrolides; Methionine; Doxycycline; Streptococcal Infections; Anti-Bacterial Agents; Ciprofloxacin; Homocysteine
PubMed: 38230928
DOI: 10.1128/spectrum.02803-23 -
Virulence Dec 2024(), a significant zoonotic bacterial pathogen impacting swine and human, is associated with severe systemic diseases such as streptococcal toxic shock-like syndrome,...
(), a significant zoonotic bacterial pathogen impacting swine and human, is associated with severe systemic diseases such as streptococcal toxic shock-like syndrome, meningitis, septicaemia, and abrupt fatality. The multifaceted roles of complement components C5a and C3a extend to orchestrating inflammatory cells recruitment, oxidative burst induction, and cytokines release. Despite the pivotal role of subtilisin-like serine proteases in pathogenicity, their involvement in immune evasion remains underexplored. In the present study, we identify two cell wall-anchored subtilisin-like serine proteases in , SspA-1 and SspA-2, as binding partners for C3a and C5a. Through Co-Immunoprecipitation, Enzyme-Linked Immunosorbent and Far-Western Blotting Assays, we validate their interactions with the aforementioned components. However, SspA-1 and SspA-2 have no cleavage activity against complement C3a and C5a performed by Cleavage assay. Chemotaxis assays reveal that recombinant SspA-1 and SspA-2 effectively attenuate monocyte chemotaxis towards C3a and C5a. Notably, the , and mutant strains exhibit compromised survival in blood, and resistance of opsonophagocytosis, alongside impaired survival in blood and colonization compared to the parental strain SC-19. Critical insights from the murine and larva infection models further underscore the significance of in altering mortality rates. Collectively, our findings indicate that SspA-1 and SspA-2 are novel binding proteins for C3a and C5a, thereby shedding light on their pivotal roles in immune evasion and the pathogenesis.
Topics: Animals; Humans; Swine; Mice; Immune Evasion; Complement C3a; Streptococcus suis; Cytokines; Subtilisins; Streptococcal Infections
PubMed: 38170683
DOI: 10.1080/21505594.2023.2301246 -
The Canadian Veterinary Journal = La... Jan 2024The objective of this study was to monitor fecal shedding in nursery pigs on a farm with a history of disease involving serotypes 2 and 9.
OBJECTIVE
The objective of this study was to monitor fecal shedding in nursery pigs on a farm with a history of disease involving serotypes 2 and 9.
ANIMAL AND PROCEDURE
Four cohorts of pigs ( = 480) were monitored from weaning to end of nursery. Rectal swabs from 297 pigs were tested and serotypes 15 ( = 7), 31 ( = 3), or untypeable ( = 6) isolates were recovered from 16 (5.4%) pigs.
RESULTS
There was no significant association between fecal shedding and diarrhea. isolates recovered from pigs euthanized due to neurological signs or severe lameness were serotypes 9 (meninges) and 31 (tonsil) or untypeable (meninges, tonsil). Serotypes 9 (meninges, tonsil), 15 (spleen, tonsil), 16 (tonsil), 29 and 33 (nasal swabs), and untypeable (meninges, tonsil, and lung) isolates were identified in lame pigs.
CONCLUSION AND CLINICAL RELEVANCE
These results suggest that feces may not be a source of infection for the serotypes producing disease in pigs; however, the association between fecal shedding and diarrhea needs further investigation. The coincidence of untypeable isolates in feces from healthy pigs and their isolation from meninges of pigs with neurological signs warrants further investigation to determine the molecular characteristics of those isolates.
Topics: Swine; Animals; Serogroup; Streptococcus suis; Streptococcal Infections; Swine Diseases; Diarrhea
PubMed: 38164374
DOI: No ID Found -
The Journal of Antimicrobial... Feb 2024Streptococcus suis is an important pig pathogen and an emerging zoonotic agent. In a previous study, we described a high proportion of penicillin-resistant serotype 9 S....
BACKGROUND
Streptococcus suis is an important pig pathogen and an emerging zoonotic agent. In a previous study, we described a high proportion of penicillin-resistant serotype 9 S. suis (SS9) isolates on pig farms in Italy.
OBJECTIVES
We hypothesized that resistance to penicillin emerged in some SS9 lineages characterized by substitutions at the PBPs, contributing to the successful spread of these lineages in the last 20 years.
METHODS
Sixty-six SS9 isolates from cases of streptococcosis in pigs were investigated for susceptibility to penicillin, ceftiofur and ampicillin. The isolates were characterized for ST, virulence profile, and antimicrobial resistance genes through WGS. Multiple linear regression models were employed to investigate the associations between STs, year of isolation, substitutions at the PBPs and an increase in MIC values to β-lactams.
RESULTS
MIC values to penicillin increased by 4% each year in the study period. Higher MIC values for penicillin were also positively associated with ST123, ST1540 and ST1953 compared with ST16. The PBP sequences presented a mosaic organization of blocks. Within the same ST, substitutions at the PBPs were generally more frequent in recent isolates. Resistance to penicillin was driven by substitutions at PBP2b, including K479T, D512E and K513E, and PBP2x, including T551S, while reduced susceptibility to ceftiofur and ampicillin were largely dependent on substitutions at PBP2x.
CONCLUSIONS
Here, we identify the STs and substitutions at the PBPs responsible for increased resistance of SS9 to penicillin on Italian pig farms. Our data highlight the need for monitoring the evolution of S. suis in the coming years.
Topics: Animals; Swine; Penicillins; Penicillin-Binding Proteins; Streptococcus suis; Bacterial Proteins; Streptococcus pneumoniae; Serogroup; Aminoacyltransferases; Microbial Sensitivity Tests; Penicillin Resistance; Genomics; Ampicillin; Clone Cells; Anti-Bacterial Agents; Cephalosporins
PubMed: 38153239
DOI: 10.1093/jac/dkad395