Project description:Streptococcus equi subsp. equi (SEE) is a host-restricted bacterium that causes the common infectious upper respiratory disease known as strangles in horses. Perpetuation of SEE infection appears attributable to inapparent carrier horses because it does not persist long-term in the environment, infect other host mammals or vectors, and result in short-lived immunity. Whether pathogen factors enable SEE to remain in horses without causing clinical signs remains poorly understood. Thus, our objective was to use next-generation sequencing technologies to characterize the transcriptome of isolates of SEE from horses with acute clinical strangles and inapparent carrier horses to assess pathogen-associated changes that might reflect adaptions of SEE to the host contributing to inapparent carriage. RNA sequencing of SEE isolates from Pennsylvania demonstrated no genes that were differentially expressed between acute clinical and inapparent carrier isolates of SEE.
Project description:Streptococcus equi subspecies equi (S. equi) is a major pathogen which cause strangles, a highly contagious respiratory infection, in horses and other equines. In this study, we purified the extracellular vesicles (EVs) of S. equi ATCC 39506 and evaluated them as vaccine candidates against S. equi infections in mice. Through immunization in an animal model and immunoprecipitation-mass spectrometry, we evaluated EV as vaccine candidates against S. equi infections and identified novel immunogenic proteins.
Project description:By screening a genomic lambda library of Streptococcus equi subsp. zooepidemicus, we have cloned and sequenced a gene, termed fnz, encoding a fibronectin (Fn)-binding protein called FNZ. On the basis of the deduced amino acid sequence of FNZ, the mature protein has a molecular mass of approximately 61 kDa. Analysis of FNZ reveals a structural organization similar to that of other cell surface proteins from streptococci and staphylococci. The Fn-binding activity is localized to two domains in the C-terminal part of FNZ. One domain is composed of five repeats, which contain a motif similar to what has earlier been found in other Fn-binding proteins in streptococci and staphylococci. The first and second repeats are separated by a short stretch of amino acids, including the motif LAGESGET, which is an important part of the second Fn-binding domain. This motif is also present in an Fn-binding domain (UR) in protein F of Streptococcus pyogenes. A fusion protein covering the Fn-binding domain of FNZ inhibits the binding of the 29-kDa N-terminal fragment of Fn to cells of various streptococcal species as well as to Staphylococcus aureus.
Project description:We describe a case of an infant with recurrent bacteremia caused by Streptococcus equi subsp. zooepidemicus, likely transmitted from mother to infant. Our case highlights the importance of an epidemiological history and molecular diagnostics in ascertaining insights into transmission, pathogenesis, and optimal management.
Project description:Streptococcus equi subsp. zooepidemicus is a known zoonotic pathogen. In this public health investigation conducted in Virginia, USA, in 2013, we identified a probable family cluster of S. zooepidemicus cases linked epidemiologically and genetically to infected guinea pigs. S. zooepidemicus infections should be considered in patients who have severe clinical illness and report guinea pig exposure.
Project description:BackgroundStreptococcus equi subspecies equi (S equi) is the cause of Strangles, one of the most prevalent diseases of horses worldwide. Variation within the immunodominant SeM protein has been documented, but a new eight-component fusion protein vaccine, Strangvac, does not contain live S equi or SeM and conservation of the antigens it contains have not been reported.ObjectiveTo define the diversity of the eight Strangvac antigens across a diverse S equi population.Study designGenomic description.MethodsAntigen sequences from the genomes of 759 S equi isolates from 19 countries, recovered between 1955 and 2018, were analysed. Predicted amino acid sequences in the antigen fragments of SEQ0256(Eq5), SEQ0402(Eq8), SEQ0721(EAG), SEQ0855(SclF), SEQ0935(CNE), SEQ0999(IdeE), SEQ1817(SclI) and SEQ2101(SclC) in Strangvac and SeM were extracted from the 759 assembled genomes and compared.ResultsThe predicted amino acid sequences of SclC, SclI and IdeE were identical across all 759 genomes. CNE was truncated in the genome of five (0.7%) isolates. SclF was absent from one genome and another encoded a single amino acid substitution. EAG was truncated in two genomes. Eq5 was truncated in four genomes and 123 genomes encoded a single amino acid substitution. Eq8 was truncated in three genomes, one genome encoded four amino acid substitutions and 398 genomes encoded a single amino acid substitution at the final amino acid of the Eq8 antigen fragment. Therefore, at least 1579 (99.9%) of 1580 amino acids in Strangvac were identical in 743 (97.9%) genomes, and all genomes encoded identical amino acid sequences for at least six of the eight Strangvac antigens.Main limitationsThree hundred and seven (40.4%) isolates in this study were recovered from horses in the UK.ConclusionsThe predicted amino acid sequences of antigens in Strangvac were highly conserved across this collection of S equi.
Project description:Streptococcus equi subspecies equi (S. equi) is a major pathogen which cause strangles, a highly contagious respiratory infection, in horses and other equines.In this study, we discovered potential vaccine candidates using comprehensive proteomics and reverse vaccinology. As the initial step, we divided proteome of S. equi ATCC 39506 into whole cell lysate, secretory proteome, membrane proteome and extracellular vesicle and then, comparative proteomic analysis was performed to characterize the functional features of the proteome. Especially, extracellular vesicle of S. equi was evaluated at the first time. Total 114 potential vaccine candidates (PVCs) were selected using reverse vaccinology and knowledge based annotations. Comprehensive proteomic analysis confirmed that 60 PVCs were identified in S. equi ATCC 39506. Particularly, 32 PVCs were enriched in the EV proteome, suggesting that this cellular fraction may serve as vaccine.
Project description:Cefquinome is administered in horses for the treatment of respiratory infection caused by Streptococcus equi subsp. zooepidemicus, and septicemia caused by Escherichia coli. However, there have been no attempts to use cefquinome against Streptococcus equi subsp. equi (S. equi), the causative agent of strangles. Hence the objective of this study was to calculate an optimal dosage of cefquinome against S. equi based on pharmacokinetics and pharmacodynamics integration. Cefquinome (1.0 mg/kg) was administered by intravenous and intramuscular routes to six healthy thoroughbred foals. Serum cefquinome concentrations were determined by high-performance liquid chromatography. The in vitro and ex vivo antibacterial activity were determined from minimum inhibitory concentrations (MIC) and bacterial killing curves. The optimal dosage was calculated from the integration of pharmacokinetic parameters and area under the curve (AUC24h/MIC) values. Total body clearance and volume of distribution of cefquinome after intravenous administration were 0.06 L/h/kg and 0.09 L/kg, respectively. Following intramuscular administration, a maximum concentration of 0.73 μg/mL at 1.52 h (Tmax) and a systemic bioavailability of 37.45% were observed. The MIC of cefquinome against S. equi was 0.016 μg/mL. The ex vivo AUC24h/MIC values representing bacteriostatic, and bactericidal activity were 113.11, and 143.14 h, respectively. Whereas the %T > MIC for bactericidal activity was 153.34%. In conclusion, based on AUC24h/MIC values and pharmacokinetic parameters, cefquinome when administered by intramuscularly at a dosage of 0.53 mg/kg every 24 h, would be effective against infection caused by S. equi in foals. Further studies may be necessary to confirm its therapeutic efficacy in a clinical environment.