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Applied and Environmental Microbiology Apr 2021Streptococcal toxic shock-like syndrome (STSLS) caused by the epidemic strain of leads to severe inflammation and high mortality. The life and health of humans and...
Streptococcal toxic shock-like syndrome (STSLS) caused by the epidemic strain of leads to severe inflammation and high mortality. The life and health of humans and animals are also threatened by the increasingly severe antimicrobial resistance in There is an urgent need to discover novel strategies for the treatment of infection. Suilysin (SLY) is considered to be an important virulence factor in the pathogenesis of In this study, ellipticine hydrochloride (EH) was reported as a compound that antagonizes the hemolytic activity of SLY. , EH was found to effectively inhibit SLY-mediated hemolytic activity. Furthermore, EH had a strong affinity for SLY, thereby directly binding to SLY to interfere with the hemolytic activity. Meanwhile, it was worth noting that EH was also found to have a significant antibacterial activity. , compared with traditional ampicillin, EH not only significantly improved the survival rate of mice infected with 2 strain Sc19 but also relieved lung pathological damage. Furthermore, EH effectively decreased the levels of inflammatory cytokines (interleukin-6 [IL-6], tumor necrosis factor alpha [TNF-α]) and blood biochemistry enzymes (alanine transaminase [ALT], aspartate transaminase [AST], creatine kinase [CK]) in Sc19-infected mice. Additionally, EH markedly reduced the bacterial load of tissues in Sc19-infected mice. In conclusion, our findings suggest that EH can be a potential compound for treating infection in view of its antibacterial and antihemolysin activity. In recent years, the inappropriate use of antibiotics has unnecessarily caused the continuous emergence of resistant bacteria. The antimicrobial resistance of has also become an increasingly serious problem. Targeting virulence can reduce the selective pressure of bacteria on antibiotics, thereby alleviating the development of bacterial resistance to a certain extent. Meanwhile, the excessive inflammatory response caused by infection is considered the primary cause of acute death. Here, we found that ellipticine hydrochloride (EH) exhibited effective antibacterial and antihemolysin activities against , compared with ampicillin, EH had a significant protective effect on serotype 2 strain Sc19-infected mice. Our results indicated that EH, with dual antibacterial and antivirulence effects, will contribute to treating infections and alleviating the antimicrobial resistance of to a certain extent. More importantly, EH may develop into a promising drug for the prevention of acute death caused by excessive inflammation.
Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Cytokines; Disease Models, Animal; Ellipticines; Female; Hemolysin Proteins; Hemolysis; Mice, Inbred BALB C; Streptococcal Infections; Streptococcus suis; Virulence Factors; Mice
PubMed: 33674433
DOI: 10.1128/AEM.03165-20 -
BMC Veterinary Research Oct 2019Streptococcus suis is a prominent pathogen causing septicemia and meningitis in swine and humans. Bacitracin is used widely as a growth promoter in animal feed and to...
BACKGROUND
Streptococcus suis is a prominent pathogen causing septicemia and meningitis in swine and humans. Bacitracin is used widely as a growth promoter in animal feed and to control the spread of necrotic enteritis in most developing countries. This study aimed to characterize a novel membrane transporter module Sst comprising SstE, SstF, and SstG for bacitracin resistance.
RESULTS
Comparative genomics and protein homology analysis found a potential efflux pump SstFEG encoded upstream of well-known bacitracin-resistance genes bceAB and bceRS. A four-fold decrease in bacitracin susceptibility was observed in sstFEG deletion mutant comparing with S. suis wildtype strain CZ130302. Further studies indicated that the bacitracin tolerance mediated by SstFEG is not only independent of the BceAB transporter, but also regulated by the two-component system BceSR. Given that SstFEG are harbored by almost all virulent strains, but not in the avirulent strains, we managed to explore its potential role in bacterial pathogencity. Indeed, our results showed that SstFEG is involved in S. suis colonization and virulence in animal infection model by its potential competitive survival advantage against host bactericidal effect.
CONCLUSION
To our knowledge, this is the first study to functionally characterize the bacitracin efflux pump in S. suis to provide evidence regarding the important roles of the novel ABC transporter system SstFEG with respect to drug resistance and virulence.
Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents, Local; Bacitracin; Bacterial Proteins; Drug Resistance, Bacterial; Female; Gene Deletion; Gene Expression Regulation, Bacterial; Membrane Transport Proteins; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Streptococcal Infections; Streptococcus suis; Virulence
PubMed: 31660968
DOI: 10.1186/s12917-019-2115-2 -
Journal of Bacteriology Oct 2011Streptococcus suis causes infections in pigs and occasionally in humans, resulting in manifestations as meningitis, sepsis, arthritis, and septic shock. For survival...
Streptococcus suis causes infections in pigs and occasionally in humans, resulting in manifestations as meningitis, sepsis, arthritis, and septic shock. For survival within the host, S. suis requires numerous nutrients including trace metals. Little is known about the specific proteins involved in metal scavenging in S. suis. In this study we evaluated the role of the putative high-affinity metal binding lipoprotein TroA in metal acquisition and virulence. A mutant strain deficient in the expression of TroA (ΔtroA mutant) was constructed. Growth of the ΔtroA mutant in Todd-Hewitt broth was similar to wild-type growth; however, growth of the ΔtroA mutant in cation-deprived Todd-Hewitt broth and in porcine serum was strongly reduced compared to growth of wild-type bacteria. Supplementing the medium with extra manganese but not with magnesium, zinc, copper, nickel, or iron restored growth to wild-type levels, indicating that TroA is specifically required for growth in environments low in manganese. The ΔtroA mutant also showed increased susceptibility to H2O2, suggesting that TroA is involved in counteracting oxidative stress. Furthermore, the expression of the troA gene was subject to environmental regulation at the transcript level. In a murine S. suis infection model, the ΔtroA mutant displayed a nonvirulent phenotype. These data indicate that S. suis TroA is involved in manganese acquisition and is required for full virulence in mice.
Topics: Animals; Bacterial Proteins; Female; Hydrogen Peroxide; Manganese; Mice; Oxidative Stress; Streptococcal Infections; Streptococcus suis; Virulence
PubMed: 21784944
DOI: 10.1128/JB.05305-11 -
PeerJ 2022is a zoonotic pathogen that can cause invasive infections in humans who are in close contact with infected pigs or contaminated pork-derived products. serotype 2...
BACKGROUND
is a zoonotic pathogen that can cause invasive infections in humans who are in close contact with infected pigs or contaminated pork-derived products. serotype 2 sequence type (ST) 1 strains are mostly associated with meningitis, whereas ST104 strains are mostly recovered from sepsis cases in humans. No data are available for comparison of the ST1 and ST104 strains at the genomic level, particularly concerning virulence-associated genes. Thus, genomic comparison of both STs was performed in this study.
METHODS
An ST1 isolate (ID26154) from the cerebrospinal fluid of a patient with meningitis and an ST104 isolate (ID24525) from the blood of a patient with sepsis were subjected to shotgun pyrosequencing using the 454 GS Junior System. Genomic comparison was conducted between the ST1 isolate and the ST104 isolate using the Artemis Comparison Tool (ACT) to identify the region of differences (RDs) between ST1 and ST104.
RESULTS
Fifty-eight RDs were unique to the ST104 genome and were mainly involved in metabolism and cell functional activities, cell wall anchored proteins, bacteriophages and mobile genetic elements, ABC-type transporters, two-component signal transductions, and lantibiotic proteins. Some virulence genes mostly found in ST1 strains were also present in the ST104 genome. Whole-genome comparison is a powerful tool for identifying genomic region differences between different STs of serotype 2, leading to the identification of the molecular basis of virulence involved in the pathogenesis of the infection.
Topics: Humans; Animals; Swine; Streptococcus suis; Serogroup; Streptococcal Infections; Genomics; Sepsis
PubMed: 36221266
DOI: 10.7717/peerj.14144 -
Emerging Infectious Diseases Dec 2019Streptococcus suis is an emerging agent of zoonotic bacterial meningitis in Asia. We describe the epidemiology of S. suis cases and clinical signs and microbiological...
Streptococcus suis is an emerging agent of zoonotic bacterial meningitis in Asia. We describe the epidemiology of S. suis cases and clinical signs and microbiological findings in persons with meningitis in Bali, Indonesia, using patient data and bacterial cultures of cerebrospinal fluid collected during 2014-2017. We conducted microbiological assays using the fully automatic VITEK 2 COMPACT system. We amplified and sequenced gene fragments of glutamate dehydrogenase and recombination/repair protein and conducted PCR serotyping to confirm some serotypes. Of 71 cases, 44 were confirmed as S. suis; 29 isolates were serotype 2. The average patient age was 48.1 years, and 89% of patients were male. Seventy-seven percent of patients with confirmed cases recovered without complications; 11% recovered with septic shock, 7% with deafness, and 2% with deafness and arthritis. The case-fatality rate was 11%. Awareness of S. suis infection risk must be increased in health promotion activities in Bali.
Topics: Adult; Aged; Bacterial Proteins; Biomarkers; DNA Restriction Enzymes; Female; Geography, Medical; History, 21st Century; Humans; Indonesia; Male; Meningitis, Pneumococcal; Middle Aged; Phylogeny; Polymerase Chain Reaction; Public Health Surveillance; Serotyping; Streptococcus suis; Symptom Assessment
PubMed: 31742523
DOI: 10.3201/eid2512.181709 -
Revista Chilena de Infectologia :... Oct 2012
Topics: Streptococcus suis
PubMed: 23282499
DOI: 10.4067/S0716-10182012000600012 -
PloS One 2019Streptococcus suis is an economically important pathogen of pigs as well as a zoonotic cause of human disease. Serotyping is used for further characterization of...
Streptococcus suis is an economically important pathogen of pigs as well as a zoonotic cause of human disease. Serotyping is used for further characterization of isolates; some serotypes seem to be more virulent and more widely spread than others. This study characterizes a collection of German field isolates of Streptococcus suis from pigs dating from 1996 to 2016 with respect to capsular genes (cps) specific for individual serotypes and pathotype by multiplex PCR and relates results to the clinical background of these isolates. The most prominent finding was the reduction in prevalence of serotype-2/serotype-1/2 among invasive isolates during this sampling period, which might be attributed to widely implemented autogenous vaccination programs in swine against serotype 2 in Germany. In diseased pigs (systemically ill; respiratory disease) isolates of serotype-1/serotype-14, serotype-2/serotype-1/2, serotype 3 to 5 and 7 to 9 were most frequent while in carrier isolates a greater variety of cps types was found. Serotype-1/serotype-14 seemed to be preferentially located in joints, serotype 4 and serotype 3 in the central nervous system, respectively. The virulence associated extracellular protein factor was almost exclusively associated with invasive serotype-1/serotype-14 and serotype-2/serotype-1/2 isolates. In contrast, lung isolates of serotype-2/serotype-1/2 mainly harbored the gene for muramidase-released protein. Serotype 4 and serotype 9 isolates from clinically diseased pigs most frequently carried the muramidase-released protein gene and the suilysin gene. When examined by transmission electron microscopy all but one of the isolates which were non-typable by molecular and serological methods showed various amounts of capsular material indicating potentially new serotypes among these isolates. Given the variety of cps types/serotypes detected in pigs, not only veterinarians but also medical doctors should consider other serotypes than just serotype 2 when investigating potential human cases of Streptococcus suis infection.
Topics: Animals; Antigens, Bacterial; Bacterial Capsules; Bacterial Proteins; Carrier State; Genes, Bacterial; Germany; Humans; Microscopy, Electron, Transmission; Molecular Typing; Serotyping; Streptococcal Infections; Streptococcus suis; Sus scrofa; Swine; Swine Diseases; Zoonoses
PubMed: 30653570
DOI: 10.1371/journal.pone.0210801 -
Emerging Microbes & Infections Dec 2024is a significant and emerging zoonotic pathogen. ST1 and ST7 strains are the primary agents responsible for human infections in China, including the Guangxi Zhuang...
is a significant and emerging zoonotic pathogen. ST1 and ST7 strains are the primary agents responsible for human infections in China, including the Guangxi Zhuang Autonomous Region (GX). To enhance our understanding of ST1 population characteristics, we conducted an investigation into the phylogenetic structure, genomic features, and virulence levels of 73 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 strains.
Topics: Streptococcus suis; Streptococcal Infections; China; Humans; Phylogeny; Virulence; Animals; Mice; Genome, Bacterial; Genomic Islands; Female; Genomics; Virulence Factors
PubMed: 38578304
DOI: 10.1080/22221751.2024.2339946 -
Microbiological Research 2019Streptococcus suis has received increasing attention for its involvement in severe infections in pigs and humans; however, their pathogenesis remains unclear. ClpX and...
Streptococcus suis has received increasing attention for its involvement in severe infections in pigs and humans; however, their pathogenesis remains unclear. ClpX and ClpP, two subunits of the ATP-dependent caseinolytic protease Clp, play key roles in bacterial adaptation to various environmental stresses. In this study, a virulent S. suis serotype 2 strain, ZY05719, was employed to construct clpX and clpP deletion mutants (ΔclpX and ΔclpP, respectively) and their complementation strains. Both ΔclpX and ΔclpP displayed significantly reduced adaptability compared with the wild-type strain, evident through several altered phenotypes: formation of long cell chains, tendency to aggregate in culture, and reduced growth under acidic pH and HO-induced oxidative stress. ClpP and ClpX were required for the optimal growth during heat and cold stress, respectively. An in vitro experiment on RAW264.7 macrophage cells showed significantly increased sensitivity of ΔclpX and ΔclpP to phagocytosis compared with the wild-type strain. Mouse infection assays verified the deletion of clpX and clpP led to not only fewer clinical symptoms and lower mortality but also to a marked attenuation in bacterial colonization. These virulence-related phenotypes were restored by genetic complementation. Furthermore, the deletion of clpX or clpP caused a significant decrease in the expression of sodA, tpx, and apuA compared with the wild-type strain, suggesting that these genes may be regulated by ClpX and ClpP as downstream response factors to facilitate the bacterial tolerance against various environmental stresses. Taken together, these results suggest that ClpX and ClpP play important roles in stress tolerance for achieving the full virulence of S. suis serotype 2 during infection.
Topics: ATPases Associated with Diverse Cellular Activities; Animals; Bacterial Proteins; Biofilms; Cold-Shock Response; Endopeptidase Clp; Gene Deletion; Gene Expression Regulation, Bacterial; Heat-Shock Response; Hydrogen Peroxide; Hydrogen-Ion Concentration; Mice; Molecular Chaperones; Osmotic Pressure; Oxidative Stress; Phagocytosis; RAW 264.7 Cells; Streptococcal Infections; Streptococcus suis; Transcriptome; Virulence; Virulence Factors
PubMed: 31178057
DOI: 10.1016/j.micres.2019.04.003 -
Emerging Microbes & Infections Dec 2021is one of the important emerging zoonotic pathogens. Serotype 2 is most prevalent in patients worldwide. In the present study, we first isolated one serotype 7 strain...
is one of the important emerging zoonotic pathogens. Serotype 2 is most prevalent in patients worldwide. In the present study, we first isolated one 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 serotype 7 population characteristics, we investigated the phylogenetic structure, genomic features, and virulence of serotype 7 population, including 35 strains and 79 genomes. Significant diversities were revealed in 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 serotype 7 representative strains were classified as virulent strains using the C57BL/6 mouse model. Virulence-associated genes preferentially present in highly pathogenic serotype 2 strains were not suitable as virulence indicators for serotype 7 strains. Integrative mobilizable elements were widespread and may play a critical role in disseminating antibiotic resistance genes of serotype 7 strains. Our study confirmed serotype 7 is a non-negligible pathotype and deepened the understanding of the population structure of serotype 7, which provided valuable information for the improved surveillance of this serotype.
Topics: Aged; Animals; Anti-Bacterial Agents; Bacteremia; Bacterial Zoonoses; China; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Female; Genome, Bacterial; Humans; Interspersed Repetitive Sequences; Mice, Inbred C57BL; Microbial Sensitivity Tests; Multilocus Sequence Typing; Phylogeny; Pneumonia, Bacterial; Polymorphism, Single Nucleotide; Serogroup; Streptococcal Infections; Streptococcus suis; Swine; Swine Diseases; Virulence; Virulence Factors; Mice
PubMed: 34635002
DOI: 10.1080/22221751.2021.1988725