更新于：2024-11-01

金葡球菌金属蛋白酶

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与金葡球菌金属蛋白酶相关的药物

SRD-441

靶点

MMPs x 金葡球菌金属蛋白酶

作用机制

MMPs抑制剂 [+1]

在研机构-

原研机构

Serentis, Inc.

在研适应症-

非在研适应症

特应性皮炎

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与金葡球菌金属蛋白酶相关的临床试验

ACTRN12622001421729 / Completed临床1期

A pivotal in vivo bioequivalence study comparing two formulations of 21-acetoxyl group-11 beta-hydroxy-6 Alpha-Methyls-17-propiono Oxy-1,4-pregnen diethylene-3,20-diketone ointment, using the appropriate dose duration (ED50) calculated from the Pilot dose duration-response study, using healthy male and female volunteers who meet the responder and detector criteria.

开始日期2023-01-18

申办/合作机构

Zenith Technology Corp. Ltd.

NCT01531517 / Terminated临床3期

Study of the Efficacy of Topical Application of Royal Jelly and Panthenol (PedyPhar® Ointment) on the Diabetic Foot Ulcers, An Open Label, Randomized, Non-placebo-controlled Study

Clinical Trial Phase III-b
Study Sponsor:
European Egyptian Pharmaceutical Industries
Sample Size:
120 patients (60 per arm)
Study Population:
Patients with Diabetic foot ulcer of any stage after proper surgical treatment - if needed. Those patients will be recruited from patients attending the Diabetic foot Center at Faculty of Medicine - Alexandria University and the outpatient clinic at Faculty of Medicine, Cairo University.
Recruitment Period: 9 months
Dose application: thick layer of 2-3 mm applied to the dressing then dressing applied to the ulcer.
Endpoints: Complete healing of the ulcer OR 5 months of application of the ointment whichever comes first

开始日期2011-07-01

申办/合作机构

European Egyptian Pharmaceutical Industry

NCT00882245 / Completed临床2期

A Phase II, Double-Blind, Vehicle Controlled Study to Determine the Efficacy, Safety and Toleration of SRD441 Ointment in Patients With Atopic Dermatitis

Atopic Dermatitis is a chronic inflammatory skin disease that affect 10 to 15% of children and 2 to 10% of adults. AD is characterised by an itchy skin eruption and may cover large parts of the body. The exact cause is unknown but is thought to be an interplay between genetic and and environmental factors. The objective of this study is to determine whether SRD441 ointment is a safe and effective therapy for mild to moderate Atopic Dermatitis.

开始日期2009-04-01

申办/合作机构

Serentis Ltd.

100 项与金葡球菌金属蛋白酶相关的临床结果

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100 项与金葡球菌金属蛋白酶相关的转化医学

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0 项与金葡球菌金属蛋白酶相关的专利（医药）

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项与金葡球菌金属蛋白酶相关的文献（医药）

2024-10-01·Microbial Pathogenesis

Emergence of methicillin-resistant Staphylococcus aureus (MRSA) RdJ clone (CC5-ST105-SCCmecII-t002) in Santa Catarina, Brazil

Article

作者: Mazzon, Ricardo Ruiz ; Ferreira, Fabienne Antunes ; Lincopan, Nilton ; Duarte, Matheus Luís ; Eto, Carolina ; Esposito, Fernanda ; Melocco, Gregory

The emergence of highly successful genetic lineages of methicillin-resistant Staphylococcus aureus (MRSA) poses a challenge in human healthcare due to increased morbidity and mortality rates. The RdJ clone (CC5-ST105-SCCmecII-t002 lineage), previously identified in Rio de Janeiro, Brazil, was linked to bloodstream infections and features a mutation in the aur gene (encoding aureolysin). Additionally, clinical isolates derived from this clone were more effective at evading monocytic immune responses. This study aimed to detect the RdJ clone among clinical MRSA isolated in Santa Catarina (SC) and examine its antimicrobial resistance and phagocytosis evasion capabilities. Our findings revealed the RdJ clone in 20 % of MRSA isolates, all exhibiting multiresistance. RdJ clone isolates from SC did not demonstrate a decreased rate of phagocytosis compared to CC5 non-RdJ isolates. Structural analysis suggests that the aur mutation is unlikely to significantly impact aureolysin activity. Genomic analysis of one isolate unveiled a genetic variant of the RdJ clone, sharing lineage and gene distribution but lacking the aur mutation. This study enhances the understanding of the clinical and epidemiologic risks associated with the RdJ clone and the biological mechanisms underlying its spreading in SC.

2024-04-10·mBio

Increased production of aureolysin and staphopain A is a primary determinant of the reduced virulence of Staphylococcus aureus sarA mutants in osteomyelitis

Article

作者: Ramirez, Aura M ; Smeltzer, Mark S ; Beenken, Karen E ; Campbell, Mara J

ABSTRACT We previously demonstrated that mutation of sarA in Staphylococcus aureus limits biofilm formation, cytotoxicity for osteoblasts and osteoclasts, and virulence in osteomyelitis, and that all of these phenotypes can be attributed to the increased production of extracellular proteases. Here we extend these studies to assess the individual importance of these proteases alone and in combination with each other using the methicillin-resistant USA300 strain LAC, the methicillin-susceptible USA200 strain UAMS-1, and isogenic sarA mutants that were also unable to produce aureolysin (Aur), staphopain A (ScpA), staphylococcal serine protease A (subsp.), staphopain B (SspB), and the staphylococcal serine protease-like proteins A-F (SplA-F). Biofilm formation was restored in LAC and UAMS-1 sarA mutants by subsequent mutation of aur and scpA , while mutation of aur had the greatest impact on cytotoxicity to mammalian cells, particularly with conditioned medium (CM) from the more cytotoxic strain LAC. However, SDS-PAGE and western blot analysis of CM confirmed that mutation of sspAB was also required to mimic the phenotype of sarA mutants unable to produce any extracellular proteases. Nevertheless, in a murine model of post-traumatic osteomyelitis, mutation of aur and scpA had the greatest impact on restoring the virulence of LAC and UAMS-1 sarA mutants, with concurrent mutation of sspAB and the spl operon having relatively little effect. These results demonstrate that the increased production of Aur and ScpA in combination with each other is a primary determinant of the reduced virulence of S. aureus sarA mutants in diverse clinical isolates including both methicillin-resistant and methicillin-susceptible strains. IMPORTANCE Previous work established that SarA plays a primary role in limiting the production of extracellular proteases to prevent them from limiting the abundance of S. aureus virulence factors. Eliminating the production of all 10 extracellular proteases in the methicillin-resistant strain LAC has also been shown to enhance virulence in a murine sepsis model, and this has been attributed to the specific proteases Aur and ScpA. The importance of this work lies in our demonstration that the increased production of these same proteases largely accounts for the decreased virulence of sarA mutants in a murine model of post-traumatic osteomyelitis not only in LAC but also in the methicillin-susceptible human osteomyelitis isolate UAMS-1. This confirms that sarA -mediated repression of Aur and ScpA production plays a critical role in the posttranslational regulation of S. aureus virulence factors in diverse clinical isolates and diverse forms of S. aureus infection.

2023-01-01·Frontiers in microbiology

Genus-wide genomic characterization of Macrococcus: insights into evolution, population structure, and functional potential.

Article

作者: Pierneef, Rian ; Matle, Itumeleng ; Carroll, Laura M ; Magwedere, Kudakwashe ; Mafuna, Thendo

IntroductionMacrococcus species have been isolated from a range of mammals and mammal-derived food products. While they are largely considered to be animal commensals, Macrococcus spp. can be opportunistic pathogens in both veterinary and human clinical settings. This study aimed to provide insight into the evolution, population structure, and functional potential of the Macrococcus genus, with an emphasis on antimicrobial resistance (AMR) and virulence potential.MethodsAll high-quality, publicly available Macrococcus genomes (n = 104, accessed 27 August 2022), plus six South African genomes sequenced here (two strains from bovine clinical mastitis cases and four strains from beef products), underwent taxonomic assignment (using four different approaches), AMR determinant detection (via AMRFinderPlus), and virulence factor detection (using DIAMOND and the core Virulence Factor Database).ResultsOverall, the 110 Macrococcus genomes were of animal commensal, veterinary clinical, food-associated (including food spoilage), and environmental origins; five genomes (4.5%) originated from human clinical cases. Notably, none of the taxonomic assignment methods produced identical results, highlighting the potential for Macrococcus species misidentifications. The most common predicted antimicrobial classes associated with AMR determinants identified across Macrococcus included macrolides, beta-lactams, and aminoglycosides (n = 81, 61, and 44 of 110 genomes; 73.6, 55.5, and 40.0%, respectively). Genes showing homology to Staphylococcus aureus exoenzyme aureolysin were detected across multiple species (using 90% coverage, n = 40 and 77 genomes harboring aureolysin-like genes at 60 and 40% amino acid [AA] identity, respectively). S. aureus Panton-Valentine leucocidin toxin-associated lukF-PV and lukS-PV homologs were identified in eight M. canis genomes (≥40% AA identity, >85% coverage). Using a method that delineates populations using recent gene flow (PopCOGenT), two species (M. caseolyticus and M. armenti) were composed of multiple within-species populations. Notably, M. armenti was partitioned into two populations, which differed in functional potential (e.g., one harbored beta-lactamase family, type II toxin-antitoxin system, and stress response proteins, while the other possessed a Type VII secretion system; PopCOGenT p < 0.05).DiscussionOverall, this study leverages all publicly available Macrococcus genomes in addition to newly sequenced genomes from South Africa to identify genomic elements associated with AMR or virulence potential, which can be queried in future experiments.