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1.
Emerg Microbes Infect ; 13(1): 2352435, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38703011

ABSTRACT

Streptococcus suis is a major bacterial pathogen in pigs and an emerging zoonotic pathogen. Different S. suis serotypes exhibit diverse characteristics in population structure and pathogenicity. Surveillance data highlight the significance of S. suis serotype 4 (SS4) in swine streptococcusis, a pathotype causing human infections. However, except for a few epidemiologic studies, the information on SS4 remains limited. In this study, we investigated the population structure, pathogenicity, and antimicrobial characteristics of SS4 based on 126 isolates, including one from a patient with septicemia. We discovered significant diversities within this population, clustering into six minimum core genome (MCG) groups (1, 2, 3, 4, 7-2, and 7-3) and five lineages. Two main clonal complexes (CCs), CC17 and CC94, belong to MCG groups 1 and 3, respectively. Numerous important putative virulence-associated genes are present in these two MCG groups, and 35.00% (7/20) of pig isolates from CC17, CC94, and CC839 (also belonging to MCG group 3) were highly virulent (mortality rate ≥ 80%) in zebrafish and mice, similar to the human isolate ID36054. Cytotoxicity assays showed that the human and pig isolates of SS4 strains exhibit significant cytotoxicity to human cells. Antimicrobial susceptibility testing showed that 95.83% of strains isolated from our labs were classified as multidrug-resistant. Prophages were identified as the primary vehicle for antibiotic resistance genes. Our study demonstrates the public health threat posed by SS4, expanding the understanding of SS4 population structure and pathogenicity characteristics and providing valuable information for its surveillance and prevention.


Subject(s)
Serogroup , Streptococcal Infections , Streptococcus suis , Swine Diseases , Streptococcus suis/pathogenicity , Streptococcus suis/genetics , Streptococcus suis/classification , Streptococcus suis/drug effects , Streptococcus suis/isolation & purification , Animals , Swine , Humans , Streptococcal Infections/microbiology , Streptococcal Infections/veterinary , Swine Diseases/microbiology , Virulence , Mice , Genome, Bacterial , Zebrafish , Anti-Bacterial Agents/pharmacology , Phylogeny , Microbial Sensitivity Tests , Virulence Factors/genetics
2.
Emerg Microbes Infect ; 13(1): 2339946, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38578304

ABSTRACT

Streptococcus suis is a significant and emerging zoonotic pathogen. ST1 and ST7 strains are the primary agents responsible for S. suis human infections in China, including the Guangxi Zhuang Autonomous Region (GX). To enhance our understanding of S. suis ST1 population characteristics, we conducted an investigation into the phylogenetic structure, genomic features, and virulence levels of 73 S. suis ST1 human strains from GX between 2005 and 2020. The ST1 GX strains were categorized into three lineages in phylogenetic analysis. Sub-lineage 3-1a exhibited a closer phylogenetic relationship with the ST7 epidemic strain SC84. The strains from lineage 3 predominantly harboured 89K-like pathogenicity islands (PAIs) which were categorized into four clades based on sequence alignment. The acquirement of 89K-like PAIs increased the antibiotic resistance and pathogenicity of corresponding transconjugants. We observed significant diversity in virulence levels among the 37 representative ST1 GX strains, that were classified as follows: epidemic (E)/highly virulent (HV) (32.4%, 12/37), virulent plus (V+) (29.7%, 11/37), virulent (V) (18.9%, 7/37), and lowly virulent (LV) (18.9%, 7/37) strains based on survival curves and mortality rates at different time points in C57BL/6 mice following infection. The E/HV strains were characterized by the overproduction of tumour necrosis factor (TNF)-α in serum and promptly established infection at the early phase of infection. Our research offers novel insights into the population structure, evolution, genomic features, and pathogenicity of ST1 strains. Our data also indicates the importance of establishing a scheme for characterizing and subtyping the virulence levels of S. suis strains.


Subject(s)
Genome, Bacterial , Genomic Islands , Phylogeny , Streptococcal Infections , Streptococcus suis , Streptococcus suis/genetics , Streptococcus suis/pathogenicity , Streptococcus suis/classification , Streptococcus suis/isolation & purification , Streptococcal Infections/microbiology , Streptococcal Infections/veterinary , Streptococcal Infections/epidemiology , China/epidemiology , Humans , Virulence , Animals , Mice , Female , Genomics , Virulence Factors/genetics
3.
Int J Biol Macromol ; 268(Pt 2): 131839, 2024 May.
Article in English | MEDLINE | ID: mdl-38663699

ABSTRACT

Streptococcus suis (S. suis) is a significant zoonotic microorganism that causes a severe illness in both pigs and humans and is characterized by severe meningitis and septicemia. Suilysin (SLY), which is secreted by S. suis, plays a crucial role as a virulence factor in the disease. To date, the interaction between SLY and host cells is not fully understood. In this study, we identified the interacting proteins between SLY and human brain microvascular endothelial cells (HBMECs) using the TurboID-mediated proximity labeling method. 251 unique proteins were identified in TurboID-SLY treated group, of which six plasma membrane proteins including ARF6, GRK6, EPB41L5, DSC1, TJP2, and PNN were identified. We found that the proteins capable of interacting with SLY are ARF6 and PNN. Subsequent investigations revealed that ARF6 substantially increased the invasive ability of S. suis in HBMECs. Furthermore, ARF6 promoted SLY-induced the activation of p38 MAPK signaling pathway in HBMECs. Moreover, ARF6 promoted the apoptosis in HBMECs through the activation of p38 MAPK signaling pathway induced by SLY. Finally, we confirmed that ARF6 could increase the virulence of SLY in C57BL/6 mice. These findings offer valuable insights that contribute to a deeper understanding of the pathogenic mechanism of SLY.


Subject(s)
ADP-Ribosylation Factor 6 , ADP-Ribosylation Factors , Apoptosis , Endothelial Cells , Hemolysin Proteins , Streptococcus suis , Streptococcus suis/pathogenicity , Streptococcus suis/metabolism , Humans , Animals , Apoptosis/drug effects , Mice , ADP-Ribosylation Factors/metabolism , ADP-Ribosylation Factors/genetics , Endothelial Cells/metabolism , Endothelial Cells/drug effects , Endothelial Cells/microbiology , Hemolysin Proteins/metabolism , Hemolysin Proteins/pharmacology , p38 Mitogen-Activated Protein Kinases/metabolism , Streptococcal Infections/microbiology , Streptococcal Infections/metabolism , Virulence , Brain/metabolism
4.
Vet Microbiol ; 293: 110084, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38608374

ABSTRACT

Streptococcus suis is an important pathogen causing severe disease in pigs and humans, giving rise to economic losses in the pig production industry. Out of 65 S. suis isolates collected from diseased pigs in Switzerland between 2019 and 2022, 57 isolates were thoroughly examined by phenotypic and whole genome sequence (WGS) based characterization. The isolates' genomes were sequenced allowing for a comprehensive analysis of their distribution in terms of serovar, sequence type (ST), clonal complex (CC), and classical virulence markers. Antimicrobial resistance (AMR) genes were screened, and phenotypic susceptibility to eight classes of antimicrobial agents was examined. Serovar 6, devoid of any resistance genes, was found to be most prevalent, followed by serovars 1, 3, 1/2, and 9. Thirty STs were identified, with ST1104 being the most prevalent. Serovar 2 and serovar 1/2 were associated with CC1, potentially containing the most virulent variants. Based on single nucleotide polymorphism (SNP) analyses, fifteen isolates belonged to one of seven putative transmission clusters each consisting of two or three isolates. High phenotypic AMR rates were detected for tetracyclines (80%) and macrolides (35%) and associated with the resistance genes tet(O) and erm(B), respectively. In contrast, susceptibility to ß-lactam antibiotics and phenicols was high. Determination of phenotypic AMR profiling, including the minimum inhibitory concentrations (MICs) of the tested antimicrobial agents, sets a baseline for future studies. The study provides valuable insights into the genetic diversity and antimicrobial susceptibility of Swiss S. suis isolates, facilitating the identification of emerging clones relevant to public health concerns.


Subject(s)
Anti-Bacterial Agents , Genetic Variation , Microbial Sensitivity Tests , Streptococcal Infections , Streptococcus suis , Swine Diseases , Animals , Streptococcus suis/genetics , Streptococcus suis/drug effects , Streptococcus suis/pathogenicity , Streptococcus suis/classification , Streptococcus suis/isolation & purification , Swine , Swine Diseases/microbiology , Switzerland/epidemiology , Streptococcal Infections/veterinary , Streptococcal Infections/microbiology , Anti-Bacterial Agents/pharmacology , Whole Genome Sequencing , Drug Resistance, Bacterial/genetics , Virulence/genetics , Serogroup , Polymorphism, Single Nucleotide
5.
Vet Microbiol ; 288: 109928, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38056180

ABSTRACT

Streptococcus suis serotype 2 (SS2) has been reported to be a highly invasive pathogen in swine and a zoonotic agent for humans. Although many bacterial virulence factors have been identified, our an insightful understanding of SS2 pathogenicity is lacking. The gene nadR, encoding nicotinamide-nucleotide adenylyltransferase, was first reported as a regulator and transporter of the intracellular NAD synthesis pathway in Salmonella typhimurium. In this study, we constructed a mutant strain of nadR (ΔnadR) to test the phenotypic and virulence variations between the deletion mutant and the wild-type strain ZY05719. The phenotypic experimental results showed that ΔnadR obviously inhibited cell growth and exhibited shorter chains than WT. The growth defect of ΔnadR was caused by the loss of the function of nadR for transporting the substrates nicotinamide mononucleotide and nicotinamide riboside in the intracellular NAD synthesis pathway. In the process of interaction with the host, ΔnadR participated in adherence and invasion to the host cells, and it was more easily cleared by RAW264.7 macrophages. More importantly, both zebrafish and BALB/c mice in vivo virulence experimental results showed that ΔnadR dramatically attenuated the virulence of SS2, and the ability of ΔnadR to colonize tissues was notably reduced in comparison with that of WT in the BALB/c mice infection model. To the best of our knowledge, this is the first time to demonstrate that nadR not only plays an important role in bacterial growth, but also in connection with the virulence of SS2 as a global transcriptional regulator.


Subject(s)
Streptococcal Infections , Streptococcus suis , Swine Diseases , Animals , Mice , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , NAD/metabolism , Serogroup , Streptococcal Infections/veterinary , Streptococcal Infections/microbiology , Streptococcus suis/pathogenicity , Swine , Virulence/genetics , Zebrafish
6.
J Microbiol ; 61(4): 433-448, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37010796

ABSTRACT

Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that can infect humans in contact with infected pigs or their byproducts. It can employ different types of genes to defend against oxidative stress and ensure its survival. The thioredoxin (Trx) system is a key antioxidant system that contributes adversity adaptation and pathogenicity. SS2 has been shown to encode putative thioredoxin genes, but the biological roles, coding sequence, and underlying mechanisms remains uncharacterized. Here, we demonstrated that SSU05_0237-ORF, from a clinical SS2 strain, ZJ081101, encodes a protein of 104 amino acids with a canonical CGPC active motif and an identity 70-85% similar to the thioredoxin A (TrxA) in other microorganisms. Recombinant TrxA efficiently catalyzed the thiol-disulfide oxidoreduction of insulin. The deletion of TrxA led to a significantly slow growth and markedly compromised tolerance of the pathogen to temperature stress, as well as impaired adhesion ability to pig intestinal epithelial cells (IPEC-J2). However, it was not involved in H2O2 and paraquat-induced oxidative stress. Compared with the wild-type strain, the ΔTrxA strain was more susceptible to killing by macrophages through increasing NO production. Treatment with TrxA mutant strain also significantly attenuated cytotoxic effects on RAW 264.7 cells by inhibiting inflammatory response and apoptosis. Knockdown of pentraxin 3 in RAW 264.7 cells was more vulnerable to phagocytic activity, and TrxA promoted SS2 survival in phagocytic cells depending on pentraxin 3 activity compared with the wild-type strain. Moreover, a co-inoculation experiment in mice revealed that TrxA mutant strain is far more easily cleared from the body than the wild type strain in the period from 8-24 h, and exhibits significantly attenuated oxidative stress and liver injury. In summary, we reveal the important role of TrxA in the pathogenesis of SS2.


Subject(s)
Macrophages , Streptococcal Infections , Streptococcus suis , Animals , Humans , Mice , Bacterial Proteins/metabolism , Hydrogen Peroxide/pharmacology , Hydrogen Peroxide/metabolism , Macrophages/metabolism , Macrophages/microbiology , Serogroup , Streptococcus suis/metabolism , Streptococcus suis/pathogenicity , Swine , Thioredoxins/genetics , Thioredoxins/metabolism , Thioredoxins/pharmacology , Virulence
7.
Sci Rep ; 11(1): 23919, 2021 12 14.
Article in English | MEDLINE | ID: mdl-34907269

ABSTRACT

Streptococcus suis has been well-recognized as a zoonotic pathogen worldwide, and the diversity and unpredictable adaptive potential of sporadic human strains represent a great risk to the public health. In this study, S. suis LSM178, isolated from a patient in contact with pigs and raw pork, was assessed as a hyper-virulent strain and interpreted for the virulence based on its genetic information. The strain was more invasive for Caco-2 cells than two other S. suis strains, SC19 and P1/7. Sequence analysis designated LSM178 with serotype 2 and a novel sequence type 1005. Phylogenetic analysis showed that LSM178 clustered with highly virulent strains including all human strains and epidemic strains. Compared with other strains, these S. suis have the most and the same virulent factors and a type I-89 K pathogenicity island. Further, groups of genes were identified to distinguish these highly virulent strains from other generally virulent strains, emphasizing the key roles of genes modeling transcription, cell barrier, replication, recombination and repair on virulence regulation. Additionally, LSM178 contains a novel prophage conducive potentially to pathogenicity.


Subject(s)
Genome, Bacterial , Genomic Islands , Phylogeny , Streptococcal Infections , Streptococcus suis , Virulence Factors , Animals , Humans , Sequence Analysis, DNA , Streptococcal Infections/genetics , Streptococcal Infections/metabolism , Streptococcus suis/genetics , Streptococcus suis/isolation & purification , Streptococcus suis/metabolism , Streptococcus suis/pathogenicity , Swine , Virulence Factors/biosynthesis , Virulence Factors/genetics
8.
Vet Res ; 52(1): 145, 2021 Dec 19.
Article in English | MEDLINE | ID: mdl-34924012

ABSTRACT

Streptococcus suis is a zoonotic pathogen of swine involved in arthritis, polyserositis, and meningitis. Colonization of piglets by S. suis is very common and occurs early in life. The clinical outcome of infection is influenced by the virulence of the S. suis strains and the immunity of the animals. Here, the role of innate immunity was studied in cesarean-derived colostrum-deprived piglets inoculated intranasally with either virulent S. suis strain 10 (S10) or non-virulent S. suis strain T15. Colonization of the inoculated piglets was confirmed at the end of the study by PCR and immunohistochemistry. Fever (≥40.5 °C) was more prevalent in piglets inoculated with S10 compared to T15 at 4 h after inoculation. During the 3 days of monitoring, no other major clinical signs were detected. Accordingly, only small changes in transcription of genes associated with the antibacterial innate immune response were observed at systemic sites, with S10 inducing an earlier response than T15 in blood. Local inflammatory response to the inoculation, evaluated by transcriptional analysis of selected genes in nasal swabs, was more sustained in piglets inoculated with the virulent S10, as demonstrated by transcription of inflammation-related genes, such as IL1B, IL1A, and IRF7. In contrast, most of the gene expression changes in trachea, lungs, and associated lymph nodes were observed in response to the non-virulent T15 strain. Thus, S. suis colonization in the absence of systemic infection induces an innate immune response in piglets that appears to be related to the virulence potential of the colonizing strain.


Subject(s)
Immunity, Innate , Streptococcal Infections , Streptococcus suis , Swine Diseases , Virulence , Animals , Immunity, Innate/immunology , Streptococcal Infections/immunology , Streptococcal Infections/veterinary , Streptococcal Infections/virology , Streptococcus suis/pathogenicity , Swine , Swine Diseases/immunology , Swine Diseases/virology
9.
PLoS Genet ; 17(11): e1009864, 2021 11.
Article in English | MEDLINE | ID: mdl-34748531

ABSTRACT

Mutation rates vary both within and between bacterial species, and understanding what drives this variation is essential for understanding the evolutionary dynamics of bacterial populations. In this study, we investigate two factors that are predicted to influence the mutation rate: ecology and genome size. We conducted mutation accumulation experiments on eight strains of the emerging zoonotic pathogen Streptococcus suis. Natural variation within this species allows us to compare tonsil carriage and invasive disease isolates, from both more and less pathogenic populations, with a wide range of genome sizes. We find that invasive disease isolates have repeatedly evolved mutation rates that are higher than those of closely related carriage isolates, regardless of variation in genome size. Independent of this variation in overall rate, we also observe a stronger bias towards G/C to A/T mutations in isolates from more pathogenic populations, whose genomes tend to be smaller and more AT-rich. Our results suggest that ecology is a stronger correlate of mutation rate than genome size over these timescales, and that transitions to invasive disease are consistently accompanied by rapid increases in mutation rate. These results shed light on the impact that ecology can have on the adaptive potential of bacterial pathogens.


Subject(s)
Adaptation, Biological/genetics , Communicable Diseases, Emerging/microbiology , Mutation Rate , Streptococcal Infections/microbiology , Streptococcus suis/genetics , Zoonoses/microbiology , Animals , Ecology , Streptococcus suis/isolation & purification , Streptococcus suis/pathogenicity , Virulence/genetics
10.
Emerg Microbes Infect ; 10(1): 1960-1974, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34635002

ABSTRACT

Streptococcus suis is one of the important emerging zoonotic pathogens. Serotype 2 is most prevalent in patients worldwide. In the present study, we first isolated one S. suis serotype 7 strain GX69 from the blood culture of a patient with septicemia complicated with pneumonia in China. In order to deepen the understanding of S. suis serotype 7 population characteristics, we investigated the phylogenetic structure, genomic features, and virulence of S. suis serotype 7 population, including 35 strains and 79 genomes. Significant diversities were revealed in S. suis serotype 7 population, which were clustered into 22 sequence types (STs), five minimum core genome (MCG) groups, and six lineages. Lineages 1, 3a, and 6 were mainly constituted by genomes from Asia. Genomes of Lineages 2, 3b, and 5a were mainly from Northern America. Most of genomes from Europe (41/48) were clustered into Lineage 5b. In addition to strain GX69, 13 of 21 S. suis serotype 7 representative strains were classified as virulent strains using the C57BL/6 mouse model. Virulence-associated genes preferentially present in highly pathogenic S. suis serotype 2 strains were not suitable as virulence indicators for S. suis serotype 7 strains. Integrative mobilizable elements were widespread and may play a critical role in disseminating antibiotic resistance genes of S. suis serotype 7 strains. Our study confirmed S. suis serotype 7 is a non-negligible pathotype and deepened the understanding of the population structure of S. suis serotype 7, which provided valuable information for the improved surveillance of this serotype.


Subject(s)
Bacteremia/microbiology , Drug Resistance, Multiple, Bacterial/genetics , Genome, Bacterial/genetics , Pneumonia, Bacterial/microbiology , Streptococcus suis/drug effects , Streptococcus suis/genetics , Aged , Animals , Anti-Bacterial Agents/pharmacology , Bacterial Zoonoses/microbiology , China , Disease Models, Animal , Female , Humans , Interspersed Repetitive Sequences/genetics , Mice, Inbred C57BL , Microbial Sensitivity Tests , Multilocus Sequence Typing , Phylogeny , Polymorphism, Single Nucleotide/genetics , Serogroup , Streptococcal Infections/microbiology , Streptococcus suis/isolation & purification , Streptococcus suis/pathogenicity , Swine , Swine Diseases/microbiology , Virulence , Virulence Factors/genetics
11.
J Microbiol ; 59(10): 949-957, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34491523

ABSTRACT

Streptococcus suis serotype 2 (S. suis 2) is an important zoonotic pathogen that presents a significant threat both to pigs and to workers in the pork industry. The initial steps of S. suis 2 pathogenesis are unclear. In this study, we found that the type II histidine triad protein HtpsC from the highly virulent Chinese isolate 05ZYH33 is structurally similar to internalin A (InlA) from Listeria monocytogenes, which plays an important role in mediating listerial invasion of epithelial cells. To determine if HtpsC and InlA function similarly, an isogenic htpsC mutant (ΔhtpsC) was generated in S. suis by homologous recombination. The htpsC deletion strain exhibited a diminished ability to adhere to and invade epithelial cells from different sources. Double immunofluorescence microscopy also revealed reduced survival of the ΔhtpsC mutant after co-cultivation with epithelium. Adhesion to epithelium and invasion by the wild type strain was inhibited by a monoclonal antibody against E-cadherin. In contrast, the htpsC-deficient mutant was unaffected by the same treatment, suggesting that E-cadherin is the host-cell receptor that interacts with HtpsC and facilitates bacterial internalization. Based on these results, we propose that HtpsC is involved in the process by which S. suis 2 penetrates host epithelial cells, and that this protein is an important virulence factor associated with cell adhesion and invasion.


Subject(s)
Bacterial Proteins/metabolism , Epithelial Cells/microbiology , Hydrolases/metabolism , Streptococcal Infections/microbiology , Streptococcal Infections/veterinary , Streptococcus suis/metabolism , Streptococcus suis/pathogenicity , Bacterial Adhesion , Bacterial Proteins/genetics , Humans , Hydrolases/genetics , Streptococcus suis/genetics , Virulence
12.
Appl Environ Microbiol ; 87(20): e0137521, 2021 09 28.
Article in English | MEDLINE | ID: mdl-34378993

ABSTRACT

Streptococcus suis is an emerging zoonotic pathogen that causes severe swine and human infections. Metals are essential nutrients for life; however, excess metals are toxic to bacteria. Therefore, maintenance of intracellular metal homeostasis is important for bacterial survival. Here, we characterize a DtxR family metalloregulator, TroR, in S. suis. TroR is located upstream of the troABCD operon, whose expression was found to be significantly downregulated in response to excess manganese (Mn). Deletion of troR resulted in reduced growth when S. suis was cultured in metal-replete medium supplemented with elevated concentrations of zinc (Zn), copper (Cu), or cobalt (Co). Mn supplementation could alleviate the growth defects of the ΔtroR mutant under Zn and Co excess conditions; however, it impaired the growth of the wild-type (WT) and complemented (CΔtroR) strains under Cu excess conditions. The growth of ΔtroR was also inhibited in metal-depleted medium supplemented with elevated concentrations of Mn. Moreover, the ΔtroR mutant accumulated increased levels of intracellular Mn and Co, rather than Zn and Cu. Deletion of troR in S. suis led to significant upregulation of the troABCD operon. Furthermore, troA expression in the WT strain was induced by ferrous iron [Fe(II)] and Co and repressed by Mn and Cu; the repression of troA was mediated by TroR. Finally, TroR is required for S. suis virulence in an intranasal mouse model. Together, these data suggest that TroR is a negative regulator of the TroABCD system and contributes to resistance to metal toxicity and virulence in S. suis. IMPORTANCE Metals are essential nutrients for life; however, the accumulation of excess metals in cells can be toxic to bacteria. In the present study, we identified a metalloregulator, TroR, in Streptococcus suis, which is an emerging zoonotic pathogen. In contrast to the observations in other species that TroR homologs usually contribute to the maintenance of homeostasis of one or two metals, we demonstrated that TroR is required for resistance to the toxicity conferred by multiple metals in S. suis. We also found that deletion of troR resulted in significant upregulation of the troABCD operon, which has been demonstrated to be involved in manganese acquisition in S. suis. Moreover, we demonstrated that TroR is required for the virulence of S. suis in an intranasal mouse model. Collectively, these results suggest that TroR is a negative regulator of the TroABCD system and contributes to resistance to metal toxicity and virulence in S. suis.


Subject(s)
Bacterial Proteins/genetics , Drug Resistance/genetics , Metals, Heavy/toxicity , Repressor Proteins/genetics , Streptococcus suis/drug effects , Virulence/genetics , ATP-Binding Cassette Transporters/genetics , Animals , Female , Gene Expression Regulation, Bacterial/drug effects , Mice, Inbred BALB C , Operon , Periplasmic Binding Proteins , Streptococcal Infections , Streptococcus suis/genetics , Streptococcus suis/growth & development , Streptococcus suis/pathogenicity
13.
FEMS Microbiol Lett ; 368(13)2021 07 09.
Article in English | MEDLINE | ID: mdl-34223887

ABSTRACT

The capsule (cap) of Streptococcus suis is an anti-phagocytic element and is one of the major virulence factors. However, we have found cap-positive and cap-negative isolates in porcine endocarditis. Here, we compared genome sequences of multiple cap-negative isolates with those of a cap-positive isolate from a single endocarditis. Cap-positive and cap-negative isolates from the same pig were phylogenetically closest compared with those from other pigs. Some of cap-negative isolates from the same pig showed different mutations in capsular polysaccharide synthesis (cps) genes, suggesting that these isolates arisen in pigs after infection. Different mutations in whole-genomes were also found among isolates with identical mutations in cps genes, indicating that mutations in cps genes and the whole-genome occurred independently. Since cap-negative isolates are rarely found in lesions of other diseases, these results suggest that endocarditis lesions may simply favored cap-negative mutants to survive the niches, leading to their persistence in the lesions.


Subject(s)
Bacterial Capsules/metabolism , Endocarditis/veterinary , Streptococcal Infections/veterinary , Streptococcus suis/genetics , Swine Diseases/microbiology , Animals , Bacterial Capsules/genetics , Endocarditis/microbiology , Genome, Bacterial , Genomics , Phylogeny , Streptococcal Infections/microbiology , Streptococcus suis/metabolism , Streptococcus suis/pathogenicity , Swine , Virulence
14.
Vet Microbiol ; 260: 109164, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34247113

ABSTRACT

Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that poses a serious threat to human health and the swine industry. The survival and travel in the bloodstream are the important causes for SS2, contributing to bacteremia, septicemia even septic shock. However, the related mechanism remains largely unknown. Preliminary experiment demonstrated that SS2 could largely attach to the surface of neutrophils, implying that this phenomenon maybe contributed to the travel of SS2 in bloodstream and then influenced its pathogenicity. To confirm this hypothesis, using a previously established screening method that combines affinity chromatography (based on liquid chromatography-tandem mass spectrometry) with shotgun proteomics, three candidate proteins (HP0487, HP1765, and HP1111) were identified from SS2 that could interact with neutrophils. Next, by constructing the deletion mutations, we demonstrated that HP0487 of three proteins could significantly influence the adhesion of SS2 to neutrophils. Furthermore, HP0487 was shown to contribute to the anti-phagocytosis of SS2 to neutrophils and RAW264.7 cells. More importantly, the deletion of HP0487 significantly reduced lethality and bacterial loads in vivo of SS2. Thus, our findings demonstrate that HP0487 contributes to SS2 virulence by mediating the adhesion and anti-phagocytosis of SS2 to neutrophils, promoting a better understanding about the pathogenesis of SS2.


Subject(s)
Streptococcal Infections/veterinary , Streptococcus suis/pathogenicity , Swine Diseases/microbiology , Animals , Bacterial Adhesion , Mice , Neutrophils/microbiology , Phagocytosis , Proteomics , RAW 264.7 Cells , Serogroup , Streptococcal Infections/microbiology , Streptococcus suis/immunology , Streptococcus suis/physiology , Swine , Virulence
15.
Microbiol Res ; 250: 126814, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34256310

ABSTRACT

Streptococcus suis (S. suis) is a major bacterial pathogen in the swine industry and an emerging zoonotic agent. S. suis produces an important extracellular component, capsular polysaccharide (CPS), based on which dozens of serotypes have been identified. Through virulence genotyping, we revealed the relatedness between subpopulations of S. suis serotype 2 (SS2), S. suis serotype 3 (SS3) and S. suis serotype 7 (SS7) strains despite their serotype differences. Multilocus sequence typing (MLST) was used to characterize the whole S. suis population and revealed capsule switching between S. suis strains. Importantly, capsule switching occurred in the SS2, SS3 and SS7 strains belonging to CC28 and CC29, which are phylogenetically distinct from the main CC1 SS2 lineage. To further explore capsule switching in S. suis, comparative genomic analyses were performed using available complete S. suis genomes. Phylogenetic analyses suggested that the SS2 strains could be divided into two clades (1 and 2), and those classified into clade 2 colocalized with SS3 and SS7 strains, in accordance with the above virulence genotyping and MLST analyses. Clade 2 SS2 strains presented high genetic similarity to SS3 and SS7 and shared common competence and defensive elements with them but were significantly different from Clade 1 SS2 strains. Notably, although the cps loci shared by Clade 1 and 2 SS2 strains were almost identical, a specific region of the cps locus of strain NSUI002 (Clade 2 SS2) could be found in the SS3 cps locus but not in the Clade 1 SS2 strain. These data indicated that the SS2 strains in CC28 and CC29 might have acquired the cps locus through capsule switching, which could explain the distinct genetic lineages within the SS2 population.


Subject(s)
Bacterial Capsules/genetics , Genome, Bacterial , Streptococcal Infections/veterinary , Streptococcus suis/genetics , Streptococcus suis/pathogenicity , Animals , Bacterial Capsules/physiology , Bacterial Typing Techniques , Genotyping Techniques , Multilocus Sequence Typing , Phylogeny , Serogroup , Streptococcal Infections/microbiology , Streptococcus suis/classification , Swine , Swine Diseases/microbiology , Virulence/genetics
16.
Vet Microbiol ; 260: 109183, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34304027

ABSTRACT

Streptococcus suis serotype (cps) 1 and cps14 have been detected in association with severe diseases such as meningitis and polyarthritis in pigs. Though these two cps are very similar, only cps14 is an important zoonotic agent in Asia and only cps1 is described to be associated with diseases in suckling piglets rather than weaning piglets. The main objective of this study was to assess restriction of survival of cps14 and cps1 in porcine blood by IgG and IgM putatively cross-reacting with these two cps. Furthermore, we differentiate recent European cps1/14 strains by agglutination, cpsK sequencing, MLST and virulence-associated gene profiling. Our data confirmed cps1 of clonal complex 1 as an important pathotype causing polyarthritis in suckling piglets in Europe. The experimental design included also bactericidal assays with blood samples drawn at different ages of piglets naturally infected with different S. suis cps types including cps1 but not cps14. We report survival of a cps1 and a cps14 strain (both of sequence type 1) in blood of suckling piglets with high levels of maternal IgG binding to the bacterial surface. In contrast, killing of cps1 and cps14 was recorded in older piglets due to an increase of IgM as demonstrated by specific cleavage of IgM. Heterologous absorption of antibodies with cps1 or cps14 is sufficient to significantly increase the survival of the other cps. In conclusion, IgM elicited by natural S. suis infection is crucial for killing of S. suis cps1 and cps14 in older weaning piglets and has most likely the potential to cross-react between cps1 and cps14.


Subject(s)
Antibodies, Bacterial/immunology , Arthritis/veterinary , Meningitis/veterinary , Streptococcal Infections/veterinary , Streptococcus suis/immunology , Swine Diseases/microbiology , Animals , Arthritis/microbiology , Bacterial Typing Techniques/veterinary , Cross Reactions , Meningitis/microbiology , Multilocus Sequence Typing/veterinary , Serogroup , Streptococcal Infections/microbiology , Streptococcus suis/pathogenicity , Swine , Virulence , Weaning
17.
Vet Microbiol ; 259: 109149, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34147764

ABSTRACT

Streptococcus suis is a zoonotic pathogen that can cause invasive infections in humans and pigs. The S. suis cps31 strains (SS31) were frequently isolated from healthy or diseased pigs and one human infection case caused by SS31 was reported in Thailand in 2015. However, except for a few epidemiologic studies, little information is available for SS31. To characterize SS31, a total of 75 SS31 strains were analyzed, including 52 strains that were isolated from healthy or diseased pigs and 23 strains whose information was accessed from NCBI. The MLST analysis showed that SS31 exhibited high heterogeneity. The phylogenetic analysis and minimum core-genome (MCG) classification revealed that 75 strains were clustered into 3 lineages. Strains from NCBI mainly at Lineage 2 belong to MCG7-3, and most of strains from China at Lineage 3 belong to MCG7-2. This finding indicated that their evolutionary path was different. All SS31 strains were resistant to more than three classes of antimicrobial agents, and major antimicrobial resistance genes for strains from Lineage 3 were carried by prophages. This observation is different from the previous observation that integrative conjugative elements and integrative and mobilizable elements are major vehicles of antimicrobial resistance genes for S. suis. In addition to strains isolated from diseased pigs, seven of 47 strains isolated from clinically healthy pigs were also pathogenic in a zebrafish infection model. These findings reveal unique characteristics of SS31 and contribute to establishing public health surveillance for SS31 and clarifying the diversity of S. suis.


Subject(s)
Anti-Bacterial Agents/pharmacology , Phylogeny , Streptococcal Infections/veterinary , Streptococcus suis/drug effects , Streptococcus suis/pathogenicity , Animals , Drug Resistance, Multiple, Bacterial , Evolution, Molecular , Genotype , Mice , Mice, Inbred BALB C , Microbial Sensitivity Tests , Multilocus Sequence Typing , Streptococcal Infections/microbiology , Streptococcus suis/classification , Streptococcus suis/genetics , Swine , Swine Diseases/microbiology , Virulence/genetics , Zebrafish
18.
Virulence ; 12(1): 1538-1549, 2021 12.
Article in English | MEDLINE | ID: mdl-34077309

ABSTRACT

Streptococcus suis (S. suis) is an important rising pathogen that causes serious diseases in humans and pigs. Although some putative virulence factors of S. suis have been identified, its pathogenic mechanisms are largely unclear. Here, we identified a putative virulence-associated factor MutT, which is unique to S. suis serotype 2 (SS2) virulent strains. To investigate the biological roles of MutT in the SS2 virulent strain ZY05719, the mutT knockout mutant (ΔmutT) was generated and used to explore the phenotypic and virulent variations between the parental and ΔmutT strains. We found that the mutT mutation significantly inhibited cell growth ability, shortened the chain length, and displayed a high susceptibility to H2O2-induced oxidative stress. Moreover, this study revealed that MutT induced the adhesion and invasion of SS2 to host cells. Deletion of mutT increased microbial clearance in host tissues of the infected mice. Sequence alignment results suggested that mutT was encoded in a strain-specific manner, in which the detection was strongly linked to bacterial pathogenicity. In both zebrafish and mice infection models, the virulence of ΔmutT was largely reduced compared with that of ZY05719. Overall, this study provides compelling evidence that MutT is indispensable for the virulence of SS2 and highlights the biological role of MutT in bacteria pathogenesis during infection.


Subject(s)
Bacterial Proteins/genetics , Streptococcal Infections , Streptococcus suis , Virulence Factors , Animals , Disease Models, Animal , Hydrogen Peroxide , Mice , Oxidative Stress , Serogroup , Streptococcal Infections/veterinary , Streptococcus suis/genetics , Streptococcus suis/pathogenicity , Swine , Virulence , Virulence Factors/genetics , Zebrafish
19.
Arch Microbiol ; 203(7): 4715-4726, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34028569

ABSTRACT

The eukaryotic-type serine/threonine kinase of Streptococcus suis serotype 2 (SS2) performs critical roles in bacterial pathogenesis. In this study, isobaric tags for relative and absolute quantification (iTRAQ) MS/MS were used to analyze the protein profiles of wild type strain SS2-1 and its isogenic STK deletion mutant (Δstk). A total of 281 significant differential proteins, including 147 up-regulated and 134 down-regulated proteins, were found in Δstk. Moreover, 69 virulence factors (VFs) among these 281 proteins were predicted by the Virulence Factor Database (VFDB), including 38 downregulated and 31 up-regulated proteins in Δstk, among which 15 down regulated VFs were known VFs of SS2. Among the down-regulated proteins, high temperature requirement A (HtrA), glutamine synthase (GlnA), ferrichrome ABC transporter substrate-binding protein FepB, and Zinc-binding protein AdcA are known to be involved in bacterial survival and/or nutrient and energy acquisition under adverse host conditions. Overall, our results indicate that STK regulates the expression of proteins involved in virulence of SS2 and its adaption to stress environments.


Subject(s)
Bacterial Proteins , Protein Serine-Threonine Kinases , Proteome , Streptococcus suis , Adaptation, Physiological/genetics , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Proteomics , Streptococcus suis/enzymology , Streptococcus suis/genetics , Streptococcus suis/pathogenicity , Stress, Physiological/genetics , Tandem Mass Spectrometry , Virulence/genetics
20.
Vet Microbiol ; 258: 109102, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33991786

ABSTRACT

Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that causes serious economic losses in the pig industry. Phosphorylation is an important mechanism of protein modification. Recent studies have reported that the serine/threonine kinase (STK) gene contributes to the growth and virulence of SS2. However, the mechanism underlying the regulatory functions of STK in SS2 has not been thoroughly elucidated to date. In this study, phosphoproteomic analysis was performed to determine substrates of the STK protein. Twenty-two proteins with different cell functions were identified as potential substrates of STK. Phosphoglucosamine mutase (GlmM) was selected for further investigation among them. In vitro phosphorylation assay and immunoprecipitation assay indicated that GlmM was phosphorylated by STK at the Ser-101 site and the phosphorylation level of GlmM can be affected. We observed that compared to the wild-type strain ZY05719, the glmM-deficient strain (ΔglmM) and the glmM S101A point mutation strain (CΔglmM S101A) showed aberrant cell morphology and attenuated virulence, including enlarged cell volume, absent capsule, decreased resistance, lower survival caused by unusual peptidoglycan synthesis, and significantly attenuated pathogenicity in a mouse infection model. Additionally, compared to ZY05719 and CΔglmM, GlmM enzyme acivities and peptidoglycan concentrations of the stk-deficient strain (Δstk), CΔglmM S101A decreased significantly. These experiments revealed that STK phosphorylates GlmM at the Ser-101 site to impact GlmM enzyme activity and control cell wall peptidoglycan synthesis to affect SS2 pathogenicity.


Subject(s)
Cell Wall/metabolism , Phosphoglucomutase/metabolism , Protein Serine-Threonine Kinases/metabolism , Streptococcus suis/metabolism , Animals , Computational Biology , Female , Gene Expression Regulation, Bacterial , Gene Expression Regulation, Enzymologic , Mice , Mice, Inbred BALB C , Phosphoglucomutase/genetics , Phosphorylation , Protein Serine-Threonine Kinases/genetics , Random Allocation , Streptococcal Infections/microbiology , Streptococcus suis/classification , Streptococcus suis/pathogenicity , Virulence
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