Suis Strains Research Articles

Role of Bacterial and Host DNases on Host-Pathogen Interaction during Streptococcus suis Meningitis.

Streptococcus suis is a zoonotic agent causing meningitis in pigs and humans. Neutrophils, as the first line of defense against S. suis infections, release neutrophil extracellular traps (NETs) to entrap pathogens. In this study, we investigated the role of the secreted nuclease A of S. suis (SsnA) as a NET-evasion factor in vivo and in vitro. Piglets were intranasally infected with S. suis strain 10 or an isogenic ssnA mutant. DNase and NET-formation were analyzed in cerebrospinal fluid (CSF) and brain tissue. Animals infected with S. suis strain 10 or S. suis 10ΔssnA showed the presence of NETs in CSF and developed similar clinical signs. Therefore, SsnA does not seem to be a crucial virulence factor that contributes to the development of meningitis in pigs. Importantly, DNase activity was detectable in the CSF of both infection groups, indicating that host nucleases, in contrast to bacterial nuclease SsnA, may play a major role during the onset of meningitis. The effect of DNase 1 on neutrophil functions was further analyzed in a 3D-cell culture model of the porcine blood–CSF barrier. We found that DNase 1 partially contributes to enhanced killing of S. suis by neutrophils, especially when plasma is present. In summary, host nucleases may partially contribute to efficient innate immune response in the CSF.

Population structure, genetic diversity and pathotypes of Streptococcus suis isolated during the last 13\xa0years from diseased pigs in Switzerland

Streptococcus (S.) suis is a globally important swine pathogen, which comprises certain zoonotic serotypes. In this study, a detailed characterization of 88 porcine S. suis isolates was performed by analyzing capsular (cps) types, multilocus sequence typing (MLST) and investigation of the minimum core genome (MCG). In order to focus on the virulence potential of presumable invasive disease-associated S. suis isolates, virulence-associated gene profiles were assessed followed by screening a chosen subset of S. suis strains with a molecular pathotyping tool. Results showed a high genetic variability within this strain collection. In total, seventeen cps types were identified with a predominance of cps type 9 (15.9%) and 6 (14.8%). MLST revealed 48 sequence types (STs) including 41 novel ones. The population structure of S. suis was heterogenous and isolates belonged to eight different clonal complexes (CCs) including CC28 (9.1%), CC1109 (8%), CC13/149 (6.8%), CC1237 (5.7%), CC1 (3.4%), CC17 (3.4%), CC87 (2.3%), and CC1112 (1.1%), whereas a significant portion of isolates (60.2%) could not be assigned to any described CCs. Virulence-associated markers, namely extracellular protein factor (epf), muramidase-released protein (mrp), and suilysin (sly), showed a link with STs rather than with cps types. With this study an expanded knowledge about the population structure and the genetic diversity of S. suis could be achieved, which helps to contribute to an optimal public health surveillance system by promoting a focus on strains with an increased virulence and zoonotic potential.

The epidemiological investigation of co-infection of major respiratory bacteria with pseudorabies virus in intensive pig farms in China.

Porcine respiratory disease complex (PRDC), a respiratory disease caused by a variety of factors, is one of the most common problems in the intensive pig farms. To investigate the mixed infection incidence of wild‐type pseudorabies virus (WT PRV) and respiratory bacteria, a total of 1,293 clinical samples were collected from pigs with typical respiratory signs from 14 different provinces of China from September 2016 to February 2018. The WT PRV was detected by ELISA targeting gE antibody while the bacteria were detected by bacterial isolation and serotyping by PCR. The results revealed that the detection rate of A. pleuropneumoniae and B. bronchiseptica infection associated with WT PRV infection were 6.30% and 15.99%, respectively, which were significantly higher than those without WT PRV infection (3.41% and 4.41%) at the farm level (p < .05). There were no significant differences in the detection rate of H. parasuis, S. suis or P. multocida between WT PRV positive and negative farms (p > .05). However, the detection rate of attenuated H. parasuis and S. suis strains were 68.19% and 64.75%, respectively, in WT PRV infected farms, which were significantly higher than those (41.56% and 52.25%) in WT PRV free farms (p < .05). The prevalent serotypes of H. parasuis‐5/12 and S. suis‐2 were also investigated by multiplex PCR. These results indicated that the presence of WT PRV increased the chance of bacterial infection and the number of pathogenic strains in the respiratory system of pigs. Therefore, the eradication of pseudorabies is an effective approach to prevent and control the bacterial respiratory diseases in the intensive pig farms in China.

Identification of conditionally essential genes for Streptococcus suis infection in pigs

ABSTRACT Streptococcus suis is a Gram-positive bacterium and zoonotic pathogen that causes meningitis and sepsis in pigs and humans. The aim of this study was to identify genes required for S. suis infection. We created Tn-Seq libraries in a virulent S. suis strain 10, which was used to inoculate pigs in an intrathecal experimental infection. Comparative analysis of the relative abundance of mutants recovered from different sites of infection (blood, cerebrospinal fluid, and meninges of the brain) identified 361 conditionally essential genes, i.e. required for infection, which is about 18% of the genome. The conditionally essential genes were primarily involved in metabolic and transport processes, regulation, ribosomal structure and biogenesis, transcription, and cell wall membrane and envelope biogenesis, stress defenses, and immune evasion. Directed mutants were created in a set of 10 genes of different genetic ontologies and their role was determined in ex vivo models. Mutants showed different levels of sensitivity to survival in whole blood, serum, cerebrospinal fluid, thermic shock, and stress conditions, as compared to the wild type. Additionally, the role of three selected mutants was validated in co-infection experiments in which pigs were infected with both wild type and isogenic mutant strains. The genetic determinants of infection identified in this work contribute to novel insights in S. suis pathogenesis and could serve as targets for novel vaccines or antimicrobial drugs.

Knockdown of Mg2+/Mn2+ dependent protein phosphatase 1A promotes apoptosis in BV2 cells infected with Brucella suis strain 2 vaccine.

The ability to inhibit host macrophage apoptosis is one of the survival strategies of intracellular bacteria, including Brucella. In the present study the role of Mg2+/Mn2+ dependent protein phosphatase 1A (PPM1A) in the apoptosis of Brucella suis (B. suis) strain 2 vaccine-infected BV2 cells was investigated. Compared with control cells, the protein expression levels of cleaved caspase-3 were markedly increased in PPM1A short hairpin (sh)RNA-transfected BV2 cells. Flow cytometry analysis showed that treatment with JNK activator anisomycin significantly increased the rate of apoptosis in BV2 cells in comparison with the control cells. Furthermore, PPM1A shRNA significantly increased the levels of JNK phosphorylation and the levels of cleaved caspase-3 in BV2 cells infected with B. suis strain 2 in comparison with the control cells. DAPI staining showed nuclear condensation in B. suis infected BV2 cells transfected with PPM1A shRNA in comparison with the control shRNA cells. Flow cytometry analysis showed that PPM1A shRNA significantly increased the percentage of apoptotic BV2 cells infected with B. suis strain 2 compared with those transfected with control shRNA. Taken together, these data suggested that knockdown of PPM1A promotes apoptosis in B. suis strain 2-infected BV2 cells and that PPM1A may be a potential target in the development of treatments to inhibit intracellular growth of B. suis.

First isolation and characterization of Brucella suis from yak.

Brucella spp., facultative intracellular pathogens that can persistently colonize animal host cells and cause zoonosis, affect public health and safety. A Brucella strain was isolated from yak in Qinghai Province. To detect whether this isolate could cause an outbreak of brucellosis and to reveal its genetic characteristics, several typing and whole-genome sequencing methods were applied to identify its species and genetic characteristics. Phylogenetic analysis based on MLVA and whole-genome sequencing revealed the genetic characteristics of the isolated strain. The results showed that the isolated strain is a B. suis biovar 1 smooth strain, and this isolate was named B. suis QH05. The results of comparative genomics and MLVA showed that B. suis QH05 is not a vaccine strain. Comparison with other B. suis strains isolated from humans and animals indicated that B. suis QH05 may be linked to specific animal and human sources. In conclusion, B. suis QH05 does not belong to the Brucella epidemic species in China, and as the first isolation of B. suis from yak, this strain expands the host range of B. suis.

Draft Genome Sequence of a Streptococcus suis Isolate from a Case of Cattle Meningitis.

Streptococcus suis is primarily a pig pathogen and a zoonotic agent. Recently, the isolation of S. suis strain 10-36905 from a case of meningitis in cattle was reported. The draft genome sequence of this isolate demonstrates its divergent relationship with other S. suis strains.

Evaluation of Reactivity of Monoclonal Antibodies Against Omp25 of Brucella spp.

Brucellosis is a serious zoonosis occurring mainly in developing countries, and its diagnosis is largely dependent on serologic detection and bacterial culture. In this study, we developed the murine monoclonal antibodies (mAbs) against a conserved and major outer membrane protein 25 (Omp25) of Brucella species (B. spp.) for use in clinical diagnosis. The mAbs to Omp25 were produced by hybridoma technique, which were utilized for developing various immunoassays for detection of Brucellae, including Western blot (WB), enzyme-linked immunosorbent assay (ELISA), immunochemical staining (ICS), immunofluorescence staining (IFS), and flow cytometry assay (FCM). A number of five mAbs (2B10, 4A12, 4F10, 6C12, and 8F3) specific to Omp25 were selected, including 2 IgG1, 2 IgG2a, and 1 IgG2b. Among them, mAbs 6C12, 8F3, and 4A12 reacted highly with B. melitensis (M5-90), B. abortus (S19, 104M, and 2308), and B. suis strain (S2). No cross-reactivity with Yersinia enterocolitica O:9, Salmonella spp., and Escherichia coli was found. By mapping Omp25 epitopes, mAb 6C12 was found as reacting with a semi-conformational epitope, and mAbs 4A12 and 8F3 as recognizing a different linear epitope, respectively. The paired mAbs were tested for detecting Brucella species, suggesting that 8F3 was suitable for solid phase capture and 6C12 or 4A12 was suitable for conjugation with HRP for detection of Brucella Omp25 in ELISA. The FCM was established by mAb 6C12 for detecting intracellular Brucellae-infected peripheral blood mononuclear cells (PBMCs) from brucellosis patients. In conclusion, mAbs against Omp25 are precious reagents for detection of Brucellae in clinical samples with various immunoassays. mAb 6C12-based FCM could be potentially used for the monitoring of therapeutic efficacy for brucellosis in clinical practice.

PREVALENCE OF CHLAMYDIACEAE AND TETRACYCLINE RESISTANCE GENES IN WILD BOARS OF CENTRAL EUROPE.

Our aim was to investigate the occurrence and distribution of Chlamydia suis and other Chlamydiaceae in the wild boar (Sus scrofa) population of Switzerland and Northern Italy and the detection of tetracycline resistance genes by PCR. We collected a total of 471 conjunctival swabs (n=292), rectal swabs (n=147), and lung tissue samples (n=32) belonging to 292 wild boars. The prevalence of Chlamydiaceae in the investigated wild boar populations was very low (1.4%, 4/292). We found C. suis in rectal or conjunctival swabs but not in lung samples. The low chlamydial prevalence might be attributed to limited contacts between wild boars and outdoor domestic pigs due to strict biosecurity measures or limited numbers of rural pig herds. The tetA(C) gene fragment was detected in six samples, which were all negative for Chlamydiaceae, and was probably not of chlamydial origin but more likely from other bacteria. The low tetracycline resistance rate in wild boar might be explained by the lack of selective pressure. However, transmission of resistance genes from domestic pigs to wild boar or selective pressure in the environment could lead to the development and spread of tetracycline-resistant C. suis strains in wild boars.

Survival of Streptococcus suis in Porcine Blood Is Limited by the Antibody- and Complement-Dependent Oxidative Burst Response of Granulocytes.

Bacteremia is a hallmark of invasive Streptococcus suis infections of pigs, often leading to septicemia, meningitis, or arthritis. An important defense mechanism of neutrophils is the generation of reactive oxygen species (ROS). In this study, we report high levels of ROS production by blood granulocytes after intravenous infection of a pig with high levels of S. suis-specific antibodies and comparatively low levels of bacteremia. This prompted us to investigate the working hypothesis that the immunoglobulin-mediated oxidative burst contributes to the killing of S. suis in porcine blood. Several S. suis strains representing serotypes 2, 7, and 9 proved to be highly susceptible to the oxidative burst intermediate hydrogen peroxide, already at concentrations of 0.001%. The induction of ROS in granulocytes in ex vivo-infected reconstituted blood showed an association with pathogen-specific antibody levels. Importantly, inhibition of ROS production by the NADPH oxidase inhibitor apocynin led to significantly increased bacterial survival in the presence of high specific antibody levels. The oxidative burst rate of granulocytes partially depended on complement activation, as shown by specific inhibition. Furthermore, treatment of IgG-depleted serum with a specific IgM protease or heat to inactivate complement resulted in >3-fold decreased oxidative burst activity and increased bacterial survival in reconstituted porcine blood in accordance with an IgM-complement-oxidative burst axis. In conclusion, this study highlights an important control mechanism of S. suis bacteremia in the natural host: the induction of ROS in blood granulocytes via specific immunoglobulins such as IgM.

Isolation and characterization of Streptococcus suis strains from swine in Jiangsu province, China.

The aim of this study is to investigate Streptococcus suis strains present in Jiangsu province, China. In all, 1650 nasal and anal swab samples and 100 tonsils were collected from clinically healthy swine. Culture characteristics, colony morphology and PCR-based analysis of the glutamate dehydrogenase (gdh) gene were performed for S. suis identification, and eight isolates were confirmed to be S. suis. The isolates serogroups were identified by agglutinating test, including 4, 7, 3, 5 and 8. Gene profiling by PCR showed that the manN, purD, orf2, gdh genes were conserved among the isolates and that 50% of the isolates carried dltA, pgdA, srtA and sspA. Antimicrobial susceptibility test showed the isolates displayed resistance to clindamycin, erythromycin, tetracycline, penicillin G, vancomycin and linezolid; while none was resistant to chloramphenicol, multi-drug resistance was seen in most of the isolates. Finally, the LD50 (assessed by zebrafish) of isolates RD105 was 2·6431×105 and HA24 was 7·1198×106 , which showed RD105 more virulent and was consistent with the results of virulence factor identification. There is a very low proportion of S. suis in the healthy pigs. The virulence factors were related to pathogenicity. Bacteria in Nantong possess greater virulence potential than those in Huaian. Systematic investigation of S. suis provided the most basic theoretical support for the prevention and control of swine streptococcosis.

Tools for Molecular Epidemiology of Streptococcus suis.

Diseases caused by Streptococcus suis are a significant economic and welfare concern in pigs as well as in humans. Several molecular methods have been applied to investigate S. suis strain diversity and identify phylogenetic groups. Multilocus sequence typing (MLST), commonly used to differentiate between S. suis strains, has been instrumental in identifying that the species is genetically highly diverse. Recent advances in whole-genome analysis have resulted in schemes permitting the classification of S. suis populations as pathogenic or non-pathogenic, or disease-associated or non-disease associated. Here, we review these and other molecular approaches that can be used for surveillance, outbreak tracking, preventative health management, effective treatment and control, as well as vaccine development, including PCR based-assays that are easy to apply in modest diagnostic settings and which allow for the rapid screening of a large number of isolates at relatively low cost, granting the identification of several major clonal complexes of the S. suis population.

Complete Genome Sequence of Helicobacter suis Strain SNTW101c, Originally Isolated from a Patient with Nodular Gastritis.

Helicobacter suis strain SNTW101c, which was originally obtained from a patient with nodular gastritis, has been maintained in mouse stomach because of difficulty culturing it in vitro Recently, we succeeded in culturing this strain in vitro Here, we report the complete genome sequence of H. suis strain SNTW101c.

Streptococcus suis in Brazil: Genotypic, Virulence, and Resistance Profiling of Strains Isolated from Pigs between 2001 and 2016

Streptococcus suis remains an important challenge for the worldwide swine industry. Considering that Brazil is a major pork producer and exporter, proper monitoring of the pathogen and resistance rates are required. We present here the characterization of Brazilian S. suis strains isolated over a 15 year period by pulsed-field gel electrophoresis (PFGE) typing, capsular, virulence, and antimicrobial resistance profiling. Serotype prevalence revealed a predominance of serotype 2/½ followed by 3, 7, 1/14, 6, 8, 18, 28, and 27; the latter had not yet been reported in Brazil. Resistance profiling enabled the differentiation of nine profiles presenting resistance to three and up to eight antimicrobial classes. Even though an association between the most resistant strains and isolation year starting from 2009 was observed, a high frequency of multidrug-resistant strains isolated from 2001 to 2003 was also detected. This suggests that despite the isolation period, S. suis strains already presented high resistance selection pressure. A slight association of serotype 2/½ with some virulence profiles and PFGE pulsotypes was also identified. Nevertheless, no clonal dispersion or persistency of clones over the analyzed years and herds was detected.

The Impact of SsPI-1 Deletion on Streptococcus suis Virulence.

(1) Background: Streptococcus suis is an important zoonotic pathogen that infects pigs and can occasionally cause life-threatening systemic infections in humans. Two large-scale outbreaks of streptococcal toxic shock-like syndrome in China suggest that the pathogenicity of S. suis has been changing in recent years. Genetic analysis revealed the presence of a chromosomal pathogenicity island (PAI) designated SsPI-1 in Chinese epidemic S. suis strains. The purpose of this study is to define the role of SsPI-1 in the virulence of S. suis. (2) Methods: A SsPI-1 deletion mutant was compared to the wild-type strain regarding the ability to attach to epithelial cells, to cause host disease and mortality, and to stimulate host immune response in experimental infection of piglets. (3) Results: Deletion of SsPI-1 significantly reduces adherence of S. suis to epithelial cells and abolishes the lethality of the wild-type strain in piglets. The SsPI-1 mutant causes no significant pathological lesions and exhibits an impaired ability to induce proinflammatory cytokine production. (4) Conclusions: Deletion of the SsPI-1 PAI attenuates the virulence of this pathogen. We conclude that SsPI-1 is a critical contributor to the evolution of virulence in epidemic S. suis.

Investigation of the molecular characteristics of Brucella isolates from Guangxi Province, China

BackgroundHuman brucellosis has become a severe public health problem in China’s Guangxi Province, and there has been higher prevalence of brucellosis in this region after 2010. Both multiple locus variable-number tandem repeat analysis (MLVA) and multilocus sequence typing (MLST) assay schedules were used to genotype isolates and determine relationships among isolates.ResultsA total of 40 isolates of Brucella were obtained from humans, pigs, and dogs from 1961 to 2016. There were at least three species of Brucella detected in Guangxi Province, Brucella melitensis, Brucella suis, and Brucella canis, with 16, 17, and 7 isolates, respectively. Of which B. suis biovar 3 was the predominant species resulting in pig brucellosis in the area examined before 2000s. Moreover, B. melitensis biovar 3 was found to be mainly responsible for human brucellosis during 2012–2016. All B. melitensis isolates in this study belonged to East Mediterranean lineage. MLVA-11 genotype 116 was the dominant genotype and represented 81.2% of the isolates. MLVA cluster analysis showed there to be 44% (7/16) brucellosis cases caused by B. melitensis with a profile of outbreak epidemic from 2012 to 2016. However, nearly 83.3% (20/24) of brucellosis cases resulting from both B. suis and B. canis showed no epidemiological links or sporadic characteristics. MLVA-16 analysis confirmed extensive genotype-sharing events between B. melitensis isolates from Guangxi and other northern provinces within China. These data revealed that there are potential epidemiology links among these strains. B. suis strains of this study showed a unique genetic lineage at the global level and may have existed historically in this area. However, present B. canis isolates were closely related to previously reported isolates in Korea, where they may have originated. MLST typing showed that the population structure of Brucella strains had changed considerably in this province; ST17 and ST21, two previously predominant populations appeared to have been replaced by recently emerging ST8 group.ConclusionsOur investigation data have inspired the hypothesis that Guangxi Province had been subject to an imported human brucellosis epidemic. Our data suggest that strains found in Northern regions of China are the principal source of infections in recent cases of human brucellosis in Guangxi Province. Comparative genomic analysis from more strains is necessary to confirm this hypothesis. This work will facilitate better understanding of the epidemiology and improve the effectiveness of control and prevention of brucellosis in this region.

Changes in antimicrobial resistance phenotypes and genotypes in Streptococcus suis strains isolated from pigs in the Tokai area of Japan.

Streptococcus suis strains isolated from porcine endocarditis and tonsils in the Tokai area of Japan during 2004–2007 and 2014–2016 (n=114) were tested for antimicrobial susceptibility and distribution of selected resistance genes. No strains showed resistance to penicillin, ampicillin, cefotaxime, meropenem, vancomycin, and levofloxacin. High resistance to tetracycline (80.7%), clindamycin (65.8%), erythromycin (56.1%), and clarithromycin (56.1%) was observed. In chloramphenicol and sulfamethoxazole-trimethoprim, there was a trend towards increased resistance between the first (2004–2007) and second (2014–2016) periods. tet(O) and erm(B) genes were the most frequently detected, and tet(M) and mef(A/E) genes were only detected in strains isolated during 2014–2016. These results indicate that chloramphenicol and sulfamethoxazole-trimethoprim resistance, and tet(M) and mef(A/E) genes emerged in S. suis of this area after 2014.

From Stable to Lab-Investigating Key Factors for Sudden Deaths Caused by Streptococcus suis.

Swine stocks are endemically infected with the major porcine pathogen Streptococcus (S.) suis. The factors governing the transition from colonizing S. suis residing in the tonsils and the exacerbation of disease have not yet been elucidated. We analyzed the sudden death of fattening pigs kept under extensive husbandry conditions in a zoo. The animals died suddenly of septic shock and showed disseminated intravascular coagulopathy. Genotypic and phenotypic characterizations of the isolated S. suis strains, a tonsillar isolate and an invasive cps type 2 strain, were conducted. Isolated S. suis from dead pigs belonged to cps type 2 strain ST28, whereas one tonsillar S. suis isolate harvested from a healthy animal belonged to ST1173. Neither S. suis growth, induction of neutrophil extracellular traps, nor survival in blood could explain the sudden deaths. Reconstituted blood assays with serum samples from pigs of different age groups from the zoo stock suggested varying protection of individuals against pathogenic cps type 2 strains especially in younger pigs. These findings highlight the benefit of further characterization of the causative strains in each case by sequence typing before autologous vaccine candidate selection.

Genomic Epidemiology of Streptococcus suis Sequence Type 7 Sporadic Infections in the Guangxi Zhuang Autonomous Region of China.

Streptococcus suis is an important zoonotic pathogen. Serotype 2 and sequence type (ST) 1 are the most frequently reported strains in both infected humans and pigs. ST7 is only endemic to China, and it was responsible for outbreaks in 1998 and 2005 in China. In the present study, 38 sporadic ST7 S. suis strains, which mostly caused sepsis, were collected from patients in the Guangxi Zhuang Autonomous Region (GX) between 2007 and 2018. Of 38 sporadic ST7 strains, serotype 14 was the most frequent (27 strains, 71.1%), followed by serotype 2 (11 strains, 28.9%). The phylogenetic structure of the ST7 population, including epidemic and sporadic ST7 strains, was constructed using mutational single-nucleotide polymorphisms (SNPs). High diversity within the ST7 population was revealed and divided into five lineages. Only one sporadic ST7 strain, GX14, from a Streptococcal toxic-shock-like syndrome (STSLS) patient was clustered into the same lineage as the epidemic strains. GX14 and the epidemic strains diverged in 1974. The sporadic ST7 strains of GX were mainly clustered into lineage 5, which emerged in 1980. Comparing to genome of epidemic strain, the major differences in genome of sporadic ST7 strains of GX was the absence of 89 kb pathogenicity island (PAI) specific to epidemic strain and insertion of 128 kb ICE_phage tandem MGE or ICE portion of the MGE. These mobile elements play a significant role in the horizontal transfer of antibiotic resistance genes in sporadic ST7 strains. Our results enhanced the understanding of the evolution of the ST7 strains and their ability to cause life-threatening infections in humans.

Astragalus polysaccharide strengthens the inflammatory and immune responses of Brucella suis S2-infected mice and macrophages.

Brucella infection is one of the most serious zoonoses worldwide, affecting humans and domestic and wild animals. Astragalus polysaccharide (APS) is extracted from astragalus, which exhibits bioactive properties, including immunomodulation and anti-tumour and antiviral activity. The present study revealed that APS treatment promoted macrophage activation, the production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-12 and interferon-γ, and Brucella clearance in murine macrophages and spleens. APS treatment was also demonstrated to protect the integrity of macrophages during infection with live attenuated Brucella suis strain 2 (B. suis S2). The results from in vitro experiments were consistent with the findings from the in vivo study, showing the elevated secretion of TNF-α and nitric oxide in APS-treated murine peritoneal macrophages following B. suis S2 infection. The current study demonstrated the potential of APS in the control and treatment of Brucella infection, and the enhancement of host inflammatory and immune responses.