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Frontiers in Pharmacology 2024Streptococcus suis () is a zoonotic pathogen threatening public health. Aditoprim (ADP), a novel veterinary medicine, exhibits an antibacterial effect against . In this...
Streptococcus suis () is a zoonotic pathogen threatening public health. Aditoprim (ADP), a novel veterinary medicine, exhibits an antibacterial effect against . In this study, a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model was used to determine the dosage regimens of ADP against and withdrawal intervals. The PBPK model of ADP injection can predict drug concentrations in plasma, liver, kidney, muscle, and fat. A semi-mechanistic pharmacodynamic (PD) model, including susceptible subpopulation and resistant subpopulation, is successfully developed by a nonlinear mixed-effect model to evaluate antibacterial effects. An integrated PBPK/PD model is conducted to predict the time-course of bacterial count change and resistance development under different ADP dosages. ADP injection, administrated at 20 mg/kg with 12 intervals for 3 consecutive days, can exert an excellent antibacterial effect while avoiding resistance emergence. The withdrawal interval at the recommended dosage regimen is determined as 18 days to ensure food safety. This study suggests that the PBPK/PD model can be applied as an effective tool for the antibacterial effect and safety evaluation of novel veterinary drugs.
PubMed: 38694922
DOI: 10.3389/fphar.2024.1378034 -
Medicina 2024Streptococcus suis (S. suis) is a globally prevalent swine pathogen, capable of generating infections in humans who were in contact with the animal or its raw meat....
Streptococcus suis (S. suis) is a globally prevalent swine pathogen, capable of generating infections in humans who were in contact with the animal or its raw meat. Clinical manifestations range from asymptomatic cases to systemic involvement, with low mortality, but with the possibility of leaving definitive sequelae such as ataxia and hearing loss. There are few case reports, due to lack of knowledge of the disease and its atypical presentation. The objective of this article is to report the case of a man with an occupational history of contact with pigs, who was admitted for meningitis and in whom the isolation of S. suis was obtained in cerebrospinal fluid and paired blood cultures; He completed antibiotic treatment adjusted to bacterial sensitivity, and was left with mild hearing loss as a consequence.
Topics: Animals; Humans; Male; Anti-Bacterial Agents; Meningitis, Bacterial; Streptococcal Infections; Streptococcus suis; Swine
PubMed: 38683518
DOI: No ID Found -
Biomedicines Apr 2024The increasing prevalence of antimicrobial resistance against zoonotic bacteria, including , highlights the need for new therapeutical strategies, including the...
The increasing prevalence of antimicrobial resistance against zoonotic bacteria, including , highlights the need for new therapeutical strategies, including the repositioning of drugs. In this study, susceptibilities of bacterial isolates were tested toward ten different 3-amidinophenyalanine (Phe(3-Am)) derivatives via determination of minimum inhibitory concentration (MIC) values. Some of these protease inhibitors, like compounds MI-432, MI-471, and MI-476, showed excellent antibacterial effects against . Their drug interaction potential was investigated using human liver microsomal cytochrome P450 (CYP450) measurements. In our work, non-tumorigenic IPEC-J2 cells and primary porcine hepatocytes were infected with , and the putative beneficial impact of these inhibitors was investigated on cell viability (Neutral red assay), on interleukin (IL)-6 levels (ELISA technique), and on redox balance (Amplex red method). The antibacterial inhibitors prevented -induced cell death (except MI-432) and decreased proinflammatory IL-6 levels. It was also found that MI-432 and MI-476 had antioxidant effects in an intestinal cell model upon infection. Concentration-dependent suppression of CYP3A4 function was found via application of all three inhibitors. In conclusion, our study suggests that the potential antiviral Phe(3-Am) derivatives with 2',4' dichloro-biphenyl moieties can be considered as effective drug candidates against infection due to their antibacterial effects.
PubMed: 38672139
DOI: 10.3390/biomedicines12040783 -
BMC Infectious Diseases Apr 2024Streptococcus suis is one of the most common zoonotic pathogens, in humans and can cause meningitis, endocarditis, arthritis and sepsis. Human cases of Streptococcus...
Streptococcus suis is one of the most common zoonotic pathogens, in humans and can cause meningitis, endocarditis, arthritis and sepsis. Human cases of Streptococcus suis infection have been reported worldwide, and most of those cases occurred in Asia. Hearing loss is the most common sequela of Streptococcus suis meningitis. Streptococcus suis infection complicated with acute cerebral infarction has rarely been reported. Therefore, to provide a reference for this disease, we reported a case of acute multiple brain infarctions associated with Streptococcus suis infection. In our report, a 69yearold male patient had Streptococcus suis meningitis and sepsis, which were associated with multiple acute cerebral infarctions in the pons and bilateral frontotemporal parietal occipital lobes. After treatment, the patient exhibited cognitive impairment, dyspraxia and irritability. There are limited case reports of cerebral infarction associated with Streptococcus suis infection, and further research is needed to determine the best treatment method.
Topics: Humans; Streptococcus suis; Male; Streptococcal Infections; Aged; Brain Infarction; Meningitis, Bacterial; Sepsis; Anti-Bacterial Agents
PubMed: 38671388
DOI: 10.1186/s12879-024-09318-9 -
Antibiotics (Basel, Switzerland) Mar 2024Oxazolidinone resistance, especially transmissible resistance, is a major public health concern, and the origin of this resistance mechanism is not yet resolved. This...
Oxazolidinone resistance, especially transmissible resistance, is a major public health concern, and the origin of this resistance mechanism is not yet resolved. This study aims to delve into the phylogenetic origin of the transmissible oxazolidinone resistance mechanisms conferring cross-resistance to other drugs of human and veterinary importance. The amino acid sequences of the five cfr ribosomal methylases and optrA and poxtA were used as queries in searches against 219,549 bacterial proteomes in the NCBI RefSeq database. Hits with >40% amino acid identity and >80% query coverage were aligned, and phylogenetic trees were reconstructed. All five cfr genes yielded highly similar trees, with rlmN housekeeping ribosomal methylases located basal to the sister groups of S-adenosyl-methionine-dependent methyltransferases from various Deltaproteobacteria and Actinomycetia, including antibiotic-producing species, and the monophyletic group of cfr genes. The basal branches of the latter contained paenibacilli and other soil bacteria; they then could be split into the clades [cfr(C):cfr(E)] and [[cfr:cfr(B)]:cfr(D)], always with different Bacillaceae in their stems. Lachnospiraceae were encountered in the basal branches of both optrA and poxtA trees. The ultimate origin of the cfr genes is the rlmN housekeeping ribosomal methylases, which evolved into a suicide-avoiding methylase in antibiotic producers; a soil organism (Lachnospiraceae, Paenibacilli) probably acted as a transfer organism into pathogenic bacteria. In the case of optrA, the porcine pathogenic was present in all branches, while the proteins closest to poxtA originated from Clostridia.
PubMed: 38666987
DOI: 10.3390/antibiotics13040311 -
PLoS Pathogens Apr 2024Integrative and conjugative elements (ICEs) play a vital role in bacterial evolution by carrying essential genes that confer adaptive functions to the host. Despite...
Type II and IV toxin-antitoxin systems coordinately stabilize the integrative and conjugative element of the ICESa2603 family conferring multiple drug resistance in Streptococcus suis.
Integrative and conjugative elements (ICEs) play a vital role in bacterial evolution by carrying essential genes that confer adaptive functions to the host. Despite their importance, the mechanism underlying the stable inheritance of ICEs, which is necessary for the acquisition of new traits in bacteria, remains poorly understood. Here, we identified SezAT, a type II toxin-antitoxin (TA) system, and AbiE, a type IV TA system encoded within the ICESsuHN105, coordinately promote ICE stabilization and mediate multidrug resistance in Streptococcus suis. Deletion of SezAT or AbiE did not affect the strain's antibiotic susceptibility, but their duple deletion increased susceptibility, mainly mediated by the antitoxins SezA and AbiEi. Further studies have revealed that SezA and AbiEi affect the genetic stability of ICESsuHN105 by moderating the excision and extrachromosomal copy number, consequently affecting the antibiotic resistance conferred by ICE. The DNA-binding proteins AbiEi and SezA, which bind palindromic sequences in the promoter, coordinately modulate ICE excision and extracellular copy number by binding to sequences in the origin-of-transfer (oriT) and the attL sites, respectively. Furthermore, AbiEi negatively regulates the transcription of SezAT by binding directly to its promoter, optimizing the coordinate network of SezAT and AbiE in maintaining ICESsuHN105 stability. Importantly, SezAT and AbiE are widespread and conserved in ICEs harbouring diverse drug-resistance genes, and their coordinated effects in promoting ICE stability and mediating drug resistance may be broadly applicable to other ICEs. Altogether, our study uncovers the TA system's role in maintaining the genetic stability of ICE and offers potential targets for overcoming the dissemination and evolution of drug resistance.
Topics: Streptococcus suis; Toxin-Antitoxin Systems; Bacterial Proteins; Drug Resistance, Multiple, Bacterial; Streptococcal Infections; Anti-Bacterial Agents; Conjugation, Genetic; Animals; Interspersed Repetitive Sequences
PubMed: 38640137
DOI: 10.1371/journal.ppat.1012169 -
PloS One 2024Streptococcus suis (S. suis) infections in weaned pigs are common and responsible for a high consumption of antimicrobials, and their presence is assumed to be...
Using Implementation Mapping to develop an intervention program to support veterinarians' adherence to the guideline on Streptococcus suis clinical practice in weaned pigs.
Streptococcus suis (S. suis) infections in weaned pigs are common and responsible for a high consumption of antimicrobials, and their presence is assumed to be multi-factorial. A specific evidence-based veterinary guideline to support the control of S. suis in weaned pigs was developed for veterinary practitioners in the Netherlands in 2014. Adherence to the S. suis clinical practice guideline helps veterinary practitioners to prevent and control the disease in a systematical approach and thereby improve antimicrobial stewardship and contribute to the prevention of antimicrobial resistance in animals and humans. The impact of such a clinical practice guideline on (animal) disease management depends not only on its content, but also largely on the extent to which practitioners adhere to the clinical guideline in practice. When the S. suis guideline was published, no specific activities were undertaken to support veterinarians' uptake and implementation, thereby contributing to suboptimal adherence in clinical practice. As the S. suis guideline was comprehensively written by veterinary experts following an evidence-based approach, our aim was not to judge the (scientific) quality of the guideline but to study the possibility to improve the currently low adherence of this guideline in veterinary practice. This paper describes the systematic development, using Implementation Mapping, of a theory-based intervention program to support swine veterinarians' adherence to the S. suis guideline. The knowledge, skills, beliefs about capabilities, and beliefs about consequences domains are addressed in the program, which includes seven evidence-based methods (modelling, tailoring, feedback, discussion, persuasive communication, active learning, and self-monitoring) for use in program activities such as a peer-learning meeting and an e-learning module. The intervention program has been developed for practicing swine veterinarians, lasts eight months, and is evaluated through a stepped-wedge design. The Implementation Mapping approach ensured that all relevant adopters and implementers were involved, and that outcomes, determinants (influencing factors), and objectives were systematically discussed.
Topics: Animals; Humans; Swine; Streptococcus suis; Veterinarians; Anti-Infective Agents; Streptococcal Infections; Animal Diseases; Swine Diseases
PubMed: 38635508
DOI: 10.1371/journal.pone.0299905 -
Veterinary Microbiology Jun 2024Streptococcus 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...
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 β-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.
Topics: Animals; Streptococcus suis; Swine; Swine Diseases; Switzerland; Genetic Variation; Streptococcal Infections; Anti-Bacterial Agents; Microbial Sensitivity Tests; Whole Genome Sequencing; Drug Resistance, Bacterial; Virulence; Serogroup; Polymorphism, Single Nucleotide
PubMed: 38608374
DOI: 10.1016/j.vetmic.2024.110084 -
Revista Da Sociedade Brasileira de... 2024Streptococcus suis has been widely reported as a pathogen in animals, especially pigs. In terms of human health implications, it has been characterized as a zoonosis...
Streptococcus suis has been widely reported as a pathogen in animals, especially pigs. In terms of human health implications, it has been characterized as a zoonosis associated with the consumption of pork products and occupational exposure, particularly in Southeast Asian countries. Here, we present a rare case of human S. suis infection in Brazil, diagnosed in an older adult swine farmer, a small rural producer residing in the semi-arid region of Bahia, Brazil.
Topics: Animals; Humans; Swine; Streptococcus suis; Brazil; Zoonoses; Streptococcal Infections; Meningitis, Bacterial
PubMed: 38597526
DOI: 10.1590/0037-8682-0610-2023 -
Veterinary World Feb 2024Among serotypes, serotype 2 is the most significant serotype that causes serious diseases in pigs and humans worldwide. The present study aimed to estimate the global...
BACKGROUND AND AIM
Among serotypes, serotype 2 is the most significant serotype that causes serious diseases in pigs and humans worldwide. The present study aimed to estimate the global prevalence of serotype 2 isolated from pigs, determine its trend, and explore the factors associated with this serotype.
MATERIALS AND METHODS
We retrieved relevant published studies from PubMed, Scopus, and the Web of Science. The retrieved citations were screened for possible inclusion. Relevant data were then extracted from the included studies. The random-effects model was used for all meta-analyses. A subgroup meta-analysis was used to assess the heterogeneity of the prevalence for four characteristics (continents, sampling organs, reporting unit, and pig's health status). A cumulative meta-analysis was performed to determine the cumulative prevalence over time. Meta-regression analysis was used to determine the trend of pooled prevalence of serotype 2 over time.
RESULTS
Of 600 articles retrieved, 36 studies comprising a total sample size of 6939 isolates or samples from 16 countries of four continents were included for meta-analysis. The pooled prevalence of serotype 2 isolated from pigs was 13.6% (95% confidence interval [CI], 10.7%-17.1%), with high heterogeneity among the included studies (Cochran's Q, 431.6; p < 0.001; I = 91.9%; Table-1). No statistical significance was observed among subgroups of the four characteristics examined. However, the pooled prevalence of serotype 2 was as high as 16.0% (95% CI, 12.5%-20.3%; n = 16) in diseased pigs compared with 9.9% (95% CI, 5.6%-17.0%; n = 15) in healthy pigs. The pooled prevalence of serotype 2 isolated from pigs did not significantly decrease over time [regression coefficient = -0.020 (95% CI, 0.046-0.006, p = 0.139)]. The pooled prevalence of serotype 2 isolated from pigs fluctuated slightly between 13.2% and 17.8% from 2007 to 2023, although the pooled prevalence gradually decreased from 30.6% in 1987 to over 20% in 2003.
CONCLUSION
The global prevalence of serotype 2 isolated from pigs was estimated to be 13.6% (approximately 10% in healthy pigs and around 16% in diseased pigs). serotype 2 isolated from pigs did not change significantly over time. These results indicate that serotype 2 remains a problem for the pig industry and poses a threat to human health.
PubMed: 38595647
DOI: 10.14202/vetworld.2024.233-244