Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

S. aureus is a significant cause of late-onset sepsis in neonates. Increasing antibiotic resistance, however, requires additional treatment options. Lysostaphin, an endopeptidase, has that potential. The objective of this study is to compare lysostaphin versus vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) in a neonatal mouse model. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against MRSA strain USA300 were determined using standard methods. To determine pharmacokinetics, neonatal pups received either vancomycin or lysostaphin intraperitoneal and serum samples were obtained. To evaluate efficacy, pups were infected s.c. and littermates randomized to receive either saline, vancomycin, or lysostaphin intraperitoneal. Pups were observed for survival and growth. Quantitative blood cultures were obtained 24 h after infection. The MIC/MBC for vancomycin and lysostaphin were 0.71/1.19 microg/mL and <0.008/0.015 microg/mL, respectively. Mean lysostaphin concentrations ranged from 2.34 to 8.92 microg/mL. Mean vancomycin concentrations ranged from 1.72 to 11.2 microg/mL. Lysostaphin improved survival compared with placebo (p < 0.00001) and vancomycin (p < 0.03). There was no significant difference in growth among the groups. All treatment regimens resulted in less bacteremia compared with placebo (p < 0.0001). Lysostaphin appears to be more effective than vancomycin in treating MRSA in a neonatal model.
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PMID:Treatment of methicillin-resistant Staphylococcus aureus in neonatal mice: lysostaphin versus vancomycin. 1912 12

Bacteriophage endolysins have shown great efficacy in killing Gram-positive bacteria. PlyC, a group C streptococcal phage lysin, represents the most efficient lysin characterized to date, with a remarkably high specificity against different streptococcal species, including the important pathogen Streptococcus pyogenes. However, PlyC is a unique lysin, in terms of both its high activity and structure (two distinct subunits). We sought to discover and characterize a phage lysin active against S. pyogenes with an endolysin architecture distinct from that of PlyC to determine if it relies on the same mechanism of action as PlyC. In this study, we identified and characterized an endolysin, termed PlyPy (phage lysin from S. pyogenes), from a prophage infecting S. pyogenes. By in silico analysis, PlyPy was found to have a molecular mass of 27.8 kDa and a pI of 4.16. It was active against a majority of group A streptococci and displayed high levels of activity as well as binding specificity against group B and C streptococci, while it was less efficient against other streptococcal species. PlyPy showed the highest activity at neutral pH in the presence of calcium and NaCl. Surprisingly, its activity was not affected by the presence of the group A-specific carbohydrate, while the activity of PlyC was partly inhibited. Additionally, PlyPy was active in vivo and could rescue mice from systemic bacteremia. Finally, we developed a novel method to determine the peptidoglycan bond cleaved by lysins and concluded that PlyPy exhibits a rare d-alanyl-l-alanine endopeptidase activity. PlyPy thus represents the first lysin characterized from Streptococcus pyogenes and has a mechanism of action distinct from that of PlyC.
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PMID:A highly active and negatively charged Streptococcus pyogenes lysin with a rare D-alanyl-L-alanine endopeptidase activity protects mice against streptococcal bacteremia. 2463 88

Immunodeficient mice transplanted with human hematopoietic stem cells (HSCs) have been referred to as "Human Immune System" (HIS) mice and are a translational platform for studying human immune responses in vivo. Human HSC sources used in generating HIS mice include fetal liver (FL), umbilical cord blood (CB), and adult bone marrow (BM). Since HSCs from FL, CB, and BM are produced at various stages of human development, we tested whether mice transplanted with these three HSCs differ in their immune responses. We found that compared with CB HSCs or FL HSCs, adult BM HSCs reconstitute the immune system poorly. The resulting HIS mice do not mount an antibody response to Borrelia hermsii infection and as a consequence suffer persistently high levels of bacteremia. While both CB and FL HSCs yield comparable levels of immune reconstitution of HIS mice resulting in robust anti-B. hermsii immune responses, FL HSC-transplanted mice exhibited a discernable difference in their human B cell maturity as identified by an increased frequency of CD10+ immature B cells and relatively smaller lymphoid follicles compared with CB HSC-transplanted mice. Although CB HSC-transplanted mice generated robust antibody responses to B. hermsii and specific protein antigens of B. hermsii, they failed to respond to Salmonella typhi Vi polysaccharide, a classical T cell-independent antigen. This situation resembles that seen in human infants and young children. Therefore, CB HSC-transplanted mice may serve as a translation platform to explore approaches to overcome the impaired antipolysaccharide responses characteristic of human infants.
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PMID:Humoral Immunity in Mice Transplanted with Hematopoietic Stem Cells Derived from Human Umbilical Cord Blood Recapitulates That of Human Infants. 3132 44