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tailoring an antibacterial peptide of human lysosomal cathepsin g to enhance its broad-spectrum action against antibiotic-resistant bacterial pathogens.neutrophils contain several cationic antimicrobial proteins or peptides (caps) that exert antibiotic-like action against bacteria. these host-derived antibiotics kill susceptible bacteria by oxygen-independent mechanisms. considerable interest in their activity has been generated in recent years due not only to their likely important role in innate host defense against infection, but also their possible use as therapeutic agents in treating infections caused by antibiotic-resistant pathogens. we ...200211945165
transferrin binding in staphylococcus aureus: involvement of a cell wall-anchored protein.the ability to gain access to iron is pivotal for bacterial pathogens during infection. although much is known about iron acquisition systems in gram-negative bacteria, comparatively little is known about how gram-positive pathogens access iron from host iron sources. a previous study showed that, in the gram-positive human pathogen staphylococcus aureus, a cell surface-associated glyceraldehyde-3-phosphate dehydrogenase (gapdh) enzyme (gap, or tpn) is capable of binding human transferrin, repre ...200211952908
different aminoglycoside-resistant phenotypes in a rabbit staphylococcus aureus endocarditis infection model.the impact of different types of enzymatic resistance on the in vivo antibacterial activity of aminoglycosides (amikacin, gentamicin, and netilmicin) was studied in the rabbit endocarditis model with four strains of staphylococcus aureus. animals were treated in a manner simulating the administration of a single daily human dose. amikacin had no effect on the three kanamycin-resistant strains despite apparent susceptibility in the disk diffusion test. gentamicin appears to be the preferable amin ...200211959609
profound differences in leukocyte-endothelial cell responses to lipopolysaccharide versus lipoteichoic acid.we have investigated the effects of lps from escherichia coli, lipoteichoic acid (lta), and peptidoglycan (pepg) from staphylococcus aureus, and live s. aureus on leukocyte-endothelial interactions in vivo using intravital microscopy to visualize muscle microvasculature. systemic vs local administration of lps induced very different responses. local administration of lps into muscle induced significant leukocyte rolling, adhesion, and emigration in postcapillary venules at the site of injection. ...200211971014
staphylococcal enterotoxin h contrasts closely related enterotoxins in species reactivity.staphylococcus aureus enterotoxin h (seh) belongs to the staphylococcal enterotoxin (se) family of superantigens (sags). seh has structural similarities to other se; however, its biological properties are less well characterized. seh binds with high affinity to human major histocompatibility complex (mhc) class ii and exhibits strong mitogenic activity in human t cells, although it was found to be less potent than the related sea. surprisingly and in sharp contrast to related ses, seh did not po ...200211972634
corneal expression of the inflammatory mediator cap37.cap37 is a polymorphonuclear neutrophil (pmn)-derived inflammatory protein with potent antibiotic and chemotactic activity. to further investigate the biological significance of cap37 in infection and inflammation, a well-characterized in vivo rabbit model of bacterial keratitis was selected to study its contribution to host defenses.200211980855
staphylococcal exfoliative toxin b specifically cleaves desmoglein 1.staphylococcal scalded skin syndrome and its localized form, bullous impetigo, show superficial epidermal blister formation caused by exfoliative toxin a or b produced by staphylococcus aureus. recently we have demonstrated that exfoliative toxin a specifically cleaves desmoglein 1, a desmosomal adhesion molecule, that when inactivated results in blisters. in this study we determine the target molecule for exfoliative toxin b. exfoliative toxin b injected in neonatal mice caused superficial epid ...200211982763
antibody reactivity of a standardized human serum protein solution against a spectrum of microbial pathogens and toxins: comparison with fresh frozen plasma.in this study, we compared a standardized solution of human serum protein (hsp) and fresh frozen plasma (ffp) with regard to the antibody specificity against a number of microbial pathogens and some important pathogenicity factors of bacterial pathogens. due to the clinical use of hsp and ffp for therapeutical plasma exchange, we have chosen a spectrum of microbial pathogens for serological analysis that is critical in clinical settings. with the enzyme-linked immunosorbent assay technique, we c ...200211982956
antibacterial activities and conformations of synthetic alpha-defensin hnp-1 and analogs with one, two and three disulfide bridges.structure and biological activities of synthetic peptides corresponding to human alpha-defensin hnp-1, ac1yc2ripac3iagerrygtc4iyqgrlwafc5c6 with the s-s connectivities: c1-c6, c2-c4, c3-c5, and its variants with one, two and three disulfide bridges were investigated. oxidation of synthetic, reduced hnp-1 yielded a peptide with s-s connectivities c1-c3, c2-c4 and c5-c6, and not with the s-s linkages as in naturally occurring hnp-1. selective protection of cysteine sulfhydryls was necessary for th ...200211985703
the extracellular toll-like receptor 2 domain directly binds peptidoglycan derived from staphylococcus aureus.toll-like receptor 2 (tlr2) has been recognized to mediate cell signaling in response to peptidoglycan (pgn), a major cell wall component of gram-positive bacteria. the mechanism by which tlr2 recognizes pgn is unknown. it is not even clear whether tlr2 directly binds to pgn. in this study, we generated a soluble form of recombinant tlr2 (stlr2) possessing only its putative extracellular domain by using the baculovirus expression system to examine the direct interaction between stlr2 and pgn. st ...200211986301
identification of in vivo expressed vaccine candidate antigens from staphylococcus aureus.for the design of potent subunit vaccines, it is of paramount importance to identify all antigens immunologically recognized by a patient population infected with a pathogen. we have developed a rapid and efficient procedure to identify such commonly recognized antigens, and here we provide a comprehensive in vivo antigenic profile of staphylococcus aureus, an important human pathogen. s. aureus peptides were displayed on the surface of escherichia coli via fusion to one of two outer membrane pr ...200211997460
mitral valve endocarditis in hypertrophic cardiomyopathy: case report and literature review.mitral endocarditis complicating hypertrophic cardiomyopathy occurs predominantly on the left ventricular aspect of the anterior mitral valve leaflet in the presence of outflow tract obstruction. it is a rare condition and the estimated cumulative 10 year probability of developing endocarditis in patients with obstruction is < 5%. combined mitral valve replacement and septal myectomy has been reported in this setting. a case of community acquired staphylococcus aureus mitral valve endocarditis i ...200212010956
new aspects of the tolerance of the antiseptic povidone-iodine in different ex vivo models.investigating new possibilities for the application of 1% (v/v) iodophors, povidone-iodine (pvp-i) was better tolerated in the het-cam or explant test than 1% (w/v) silver nitrate or tetracycline. after application to the eye, at least 2.6% of used iodine were adsorbed. therefore pvp-i is more effective than silver nitrate or erythromycin, meaning a possible alternative for the prevention of ophthalmia neonatorum. pvp-i is more active against methicillin-resistant staphylococcus aureus (mrsa) in ...200212011528
induction of cytokine production in human t cells and monocytes by highly purified lipoteichoic acid: involvement of toll-like receptors and cd14.the pro-inflammatory potential of lipoteichoic acid (lta) from staphylococcus aureus is controversial. the present study was undertaken to examine the ability of highly purified and characterized s. aureus lta to stimulate the production of pro-inflammatory cytokines in human leukocytes at both mrna and protein level, and to study the involvement of toll-like receptors (tlrs) and cd14 in this response.200212011760
regulation of human b cell function by sulfasalazine and its metabolites.although sulfasalazine is a well-known disease-modifying antirheumatic drug (dmard), the mechanisms of its action remain unclear. indeed, it remains uncertain whether sulfasalazine itself or one of its metabolites is responsible for the antirheumatic effects of sulfasalazine. since one of the characteristic features of rheumatoid arthritis (ra) is chronic stimulation of b cells, we compared the effects of sulfasalazine and its metabolites on the in vitro function of human b cells. ig production ...200212013503
brachyspira (serpulina) pilosicoli of human origin interfere with the haemolytic activity and the growth of staphylococcus aureus beta-toxin producer.brachyspira (serpulina) pilosicoli related to intestinal spirochaetosis were found to interfere in vitro with the haemolytic activity and the growth of staphylococcus aureus beta-toxin producer. this interference was clearly appreciated because a reduction of the zone of the staphylococcal beta-toxin activity, the reduction and/or absence of cooperative haemolysis between bacteria, and the growth reduction of s. aureus were observed when b. (s.) pilosicoli were grown 72-96 hours sooner than s. a ...200212019720
monocyte deactivation in severe human sepsis or following cardiopulmonary bypass.we investigated the specificity for gram-negative stimuli as well as the contribution of signal transduction pathways for leukocyte hyporesponsiveness in sepsis or following cardiopulmonary bypass (cpb). whole blood of nine patients undergoing cpb and 25 patients with severe sepsis was stimulated ex vivo with lps (e. coli o111:b4) or with staphylococcus aureus cowan strain i (sac-i) lysate in the absence or presence of inhibitors of protein kinase c (pkc), protein-tyrosine kinase (ptk), or prote ...200212022753
overproduction of type 8 capsular polysaccharide augments staphylococcus aureus virulence.type 8 capsular polysaccharide (cp8) is the most prevalent capsule type in clinical isolates of staphylococcus aureus. however, its role in virulence has not been clearly defined. cp8 strains such as strain becker produce a small amount of capsule on their surface in vitro. in contrast, cp1 strains such as strain m produce a large amount of capsule, which has been shown to be an important antiphagocytic virulence factor. the cap8 and cap1 operons, required for the synthesis of cp8 and cp1, respe ...200212065477
genome sequence survey identifies unique sequences and key virulence genes with unusual rates of amino acid substitution in bovine staphylococcus aureus.staphylococcus aureus is a major cause of mastitis in bovine and other ruminant species. we here present the results of a comparative genomic analysis between a bovine mastitis-associated clone, rf122, and the recently sequenced human-associated clones, mu50 and n315, of staphylococcus aureus. a shotgun sequence survey of approximately 10% of the rf122 genome identified numerous unique sequences and those with elevated rates of nonsynonymous substitution. taken together, these analyses show that ...200212065548
mimicry of host-defense peptides by unnatural oligomers: antimicrobial beta-peptides.we have designed beta-amino acid oligomers that are helical, cationic, and amphiphilic with the intention of mimicking the biological activity of amphiphilic, cationic alpha-helical antimicrobial peptides found in nature (e.g., magainins). we have previously identified a 17-residue beta-peptide (called beta-17) with antibiotic activity similar to that of a magainin derivative against four bacterial species, including two clinical isolates that are resistant to common antibiotics. this beta-pepti ...200212071741
invasion of human keratinocytes by staphylococcus aureus and intracellular bacterial persistence represent haemolysin-independent virulence mechanisms that are followed by features of necrotic and apoptotic keratinocyte cell death.colonization of human skin by staphylococcus aureus is a characteristic feature of several inflammatory skin diseases, which is often followed by tissue invasion and severe cell damage. a crucial role has been attributed to staphylococcal haemolysins in the cytotoxicity to epidermal structures.200212072060
molecular characterization of bovine cd26 upregulated by a staphylococcal superantigen.in this report, we describe the cloning, sequencing, and expression of the bovine orthologue of cd26 (bocd26). several monoclonal antibodies specific for a molecule, activation molecule 3 (act3), aberrantly expressed on superantigen-stimulated bovine cd8(+) lymphocytes, reacted with recombinant bocd26 expressed in cos-7 and cho cells. we also showed that human cd8(+) t cells stimulated by a superantigen expressed cd26 at high levels. these results demonstrate that act3 is identical to bocd26 and ...200212073152
typing of human and bovine staphylococcus aureus by rapd-pcr and ribotyping-pcr.aims: to investigate genetic diversity among staphylococcus aureus and to delineate the geographical distribution of the strains found. methods and results: rapd-pcr and ribotyping-pcr were employed for the characterization of staph. aureus isolates from bovine and nosocomial origin. among the strains, five to nine groups were distinguished by rapd-pcr, depending on which primer was used, while ribotyping-pcr distinguished seven ribotypes. conclusions, and significance and impact of the study: t ...200212081546
activation of human t cells with nk cell markers by staphylococcal enterotoxin a via il-12 but not via il-18.we have reported recently that mouse liver nk cells and nk1 x 1+ t cells were activated by bacterial superantigens via the il-12 production from kupffer cells. in the present study, we examined the effect of staphyloccoccal enterotoxin a (sea) on human t cells with nk cell markers, cd56 or cd57 (nk-type t cells). after stimulating peripheral blood mononuclear cells (pbmc) with sea, pbmc produced a large amount of ifn- and acquired a potent antitumour cytotoxicity. the in vitro depletion of eithe ...200212109440
differential role of neutrophil fcgamma receptor iiib (cd16) in phagocytosis, bacterial killing, and responses to immune complexes.to determine the roles played by the neutrophil fcgamma receptor type ii (fcgammarii) (cd32) and fcgammariiib (cd16) in phagocytosis, bacterial killing, and activation by immune complexes (ics) and to test the hypothesis that inhibition of pathologic effector neutrophil function is possible without compromising host defense.200212115243
bacterium-induced cxcl10 secretion by osteoblasts can be mediated in part through toll-like receptor 4.two common pathogens known to cause bone infection, salmonella and staphylococcus aureus, were investigated to determine their abilities to induce chemokine expression in cultured mouse and human osteoblasts. while these cells are responsible for bone formation, we were surprised to find that they could respond to bacterial infection by upregulating expression of the chemokine cxcl10 (ip-10). however, there were significant differences in the abilities of the gram-negative bacterium salmonella a ...200212117914
internalization of staphylococcus aureus by human corneal epithelial cells: role of bacterial fibronectin-binding protein and host cell factors.wild-type staphylococcus aureus was observed to be capable of invading human corneal epithelial cells (hcec) in vitro. internalization of s. aureus required expression of fibronectin-binding proteins (fnbps); the capacity of an fnbp-deficient isogenic strain to invade hcec was reduced by more than 99%. the binding of s. aureus to hcec did not require viable bacteria, since uv-killed cells were observed to adhere efficiently. invasion of hcec by s. aureus involved active host cell mechanisms; upt ...200212117986
aortic and mitral valve surgery on the beating heart is lowering cardiopulmonary bypass and aortic cross clamp time.the concept of cardiac surgery on the beating heart is acceptable rationale for the cardiac surgery in the next millenium. beating heart (off-pump) coronary artery bypass grafting (cabg) techniques have led us to consider the possibility for performing the aortic and mitral valve surgery (mitral valve repairs and replacements - with or without cabg) on the beating heart with the technique of retrograde oxygenated coronary sinus perfusion.200212125670
intracellular activity of clinical concentrations of phenothiazines including thioridiazine against phagocytosed staphylococcus aureus.the effect of thioridazine (tz) was studied on the killing activity of human peripheral blood monocyte derived macrophages (hpbmdm) and of human macrophage cell line thp-1 at extracellular concentrations below those achievable clinically. these macrophages have nominal killing activity against bacteria and therefore, would not influence any activity that the compounds may have against intracellular localised staphylococcus aureus. the results indicated that whereas tz has an in vitro minimum inh ...200212127709
resistance mechanisms of gram-positive bacteria.the introduction and increasing use of antibiotics for antibacterial therapy has initiated a rapid development and expansion of antibiotic resistance in microorganisms, particularly in human pathogens. additionally, a shift to an increase in number and severity of gram-positive infections has been observed the last decades. common to these pathogens is their tendency to accumulate multiple resistances under antibiotic pressure and selection. methicillin-resistant staphylococcus aureus (mrsa), th ...200212139425
the structure of human macrophage inflammatory protein-3alpha /ccl20. linking antimicrobial and cc chemokine receptor-6-binding activities with human beta-defensins.human macrophage inflammatory protein-3alpha (mip-3alpha; ccl20) is a cc-type chemokine that binds to and activates cc chemokine receptor-6 (ccr6). although mip-3alpha does not share the binding site of ccr6 with any other chemokine, human beta-defensin-1 and -2, small cationic antimicrobial peptides, have also been found to bind to and activate ccr6. conversely, we have found that mip-3alpha possesses antibacterial activity of greater potency than human beta-defensin-1 and -2 against escherichi ...200212149255
the origin of the synergistic effect of muramyl dipeptide with endotoxin and peptidoglycan.although the basis for the high mortality rate for patients with mixed bacterial infections is likely to be multifactorial, there is evidence for a synergistic effect of muramyldipeptide (mdp) with lipopolysaccharide (lps) on the synthesis of proinflammatory cytokines by mononuclear phagocytes. in this study, co-incubation of human mono mac 6 cells with mdp and either lps or peptidoglycan (pgn) resulted in an apparent synergistic effect on tumor necrosis factor-alpha (tnf-alpha) secretion. altho ...200212151399
comparative pulsed-field gel electrophoresis typing of gentamicin-resistant and -susceptible methicillin-resistant staphylococcus aureus strains isolated in france between 1991 and 1998. changes in antibiotic susceptibility.using macrorestriction of genomic dna and pulsed-field gel electrophoresis, we examined 504 non-redundant, infection-causing human isolates of methicillin-resistant staphylococcus aureus susceptible (g(s): 238 isolates) or resistant to gentamicin (g(r): 266 isolates). the strains were isolated at albert chenevier hospital (créteil, france) between 1 january 1991 and 31 december 1998. their susceptibility to erythromycin, lincomycin, tetracycline, rifampicin, fusidic acid and fosfomycin was also ...200212183140
ocular infections in patients with atopic dermatitis. 200212189616
antibacterial activity in four marine crustacean decapods.a search for antibacterial activity in different body-parts of pandalus borealis (northern shrimp), pagurus bernhardus (hermit crab), hyas araneus (spider crab) and paralithodes camtschatica (king crab) was conducted. dried samples were extracted with 60% (v/v) acetonitrile, containing 0.1% (v/v) trifluoroacetic acid, and further extracted and concentrated on c18 cartridges. eluates from the solid phase extraction were tested for antibacterial, lysozyme and haemolytic activity. antibacterial act ...200212194450
evaluation of the antimicrobial potential of medicinal plants from the ivory coast.a total of 148 crude ethanol extracts from 115 plant species were tested in vitro against gram-negative strains (escherichia coli, pseudomonas aeruginosa) and the gram-positive staphylococcus aureus and enterococcus faecalis. moreover, they were submitted to antifungal assays against candida albicans and cladosporium cucumerinum, a human and a plant pathogenic microorganism, respectively, known to be good indicators of antifungal activity. no activity was detected against the gram-negative bacte ...200212203276
intravitreal penetration of cefepime after systemic administration to humans.to investigate the penetration of cefepime (a fourth-generation cephalosporin) into the vitreous after single-dose intravenous administration to human subjects.200212207129
pathology of a mouse model of x-linked chronic granulomatous disease.a colony of knockout mice (gene designation cybb tm1) has been maintained at this institution for 5 years. these mice are lacking the b subunit of nadph oxidase and are susceptible to experimental infection with aspergillus fumigatus. the purpose of this study was to document the spontaneous diseases present in these mice which are a murine model of x-linked chronic granulomatous disease and to compare these lesions to those of chronic granulomatous disease in humans. lesions were documented in ...200212213046
[antimicrobial, echinococcidial and immunostimulating properties of the drug cheblin-sk-1].the antimicrobial properties of the drug cheblin-ck-1 (cck-1) were determined in mice intraabdominally inoculated with proteus mirabilis-4691 in a dose of 140-200 million daily cultured microbial bodies. its comparison agent was ampicillin. cck-1 was found to act as an antibiotic similar to ampicillin in its effects. the antimicrobial activity of cck-1 against staphylococcus aureus and escherichia coli isolated from the contents of echinococcal cysts from patients operated on was also establishe ...200212224264
the combination of the sh metabolite of erdosteine (a mucoactive drug) and ciprofloxacin increases the inhibition of bacterial adhesiveness achieved by ciprofloxacin alone.exposure to ciprofloxacin and other fluoroquinolone antibiotics at less than minimum inhibitory concentrations (mics) reduces the production of some of the factors that contribute to bacterial virulence, particularly bacterial adhesiveness. once metabolized, erdosteine (a mucoactive drug) produces an active metabolite (met i) with a reducing sulfhydryl group that is capable of opening the disulfide bonds present in tracheobronchial mucins and pilins, a protein of bacterial fimbriae (adhesins). t ...200212224380
increased expression of clumping factor and fibronectin-binding proteins by hemb mutants of staphylococcus aureus expressing small colony variant phenotypes.small colony variants (scvs) of staphylococcus aureus are slow-growing subpopulations that cause persistent and relapsing infections. the altered phenotype of scv can arise from defects in menadione or hemin biosynthesis, which disrupt the electron transport chain and decrease atp concentrations. with scvs, virulence is altered by a decrease in exotoxin production and susceptibility to various antibiotics, allowing their intracellular survival. the expression of bacterial adhesins by scvs is poo ...200212228267
multidrug pump inhibitors uncover remarkable activity of plant antimicrobials.plant antimicrobials are not used as systemic antibiotics at present. the main reason for this is their low level of activity, especially against gram-negative bacteria. the reported mic is often in the range of 100 to 1,000 micro g/ml, orders of magnitude higher than those of common broad-spectrum antibiotics from bacteria or fungi. major plant pathogens belong to the gram-negative bacteria, which makes the low level of activity of plant antimicrobials against this group of microorganisms puzzl ...200212234835
induction of cytokine production by different staphylococcal strains.in light of the important role of cytokines in the pathogenesis of bacterial infections, we analyzed the cytokine production induced by different staphylococcus aureus (s. aureus), s. epidermidis and s. saprophyticus strains in human mononuclear cells (mncs). mncs secreted high amounts of interleukin-1beta (il-1beta) and il-6 proteins in responses to stimulation with all three species of staphylococci. interestingly, a large majority of the s. aureus strains induced significantly higher il-12 an ...200212297115
effect of protein binding on the in vitro activity and pharmacodynamics of faropenem.the influence of protein binding upon different aspects of the in vitro activity of faropenem on recently isolated staphylococcus aureus and respiratory pathogens was determined. the protein binding of faropenem was investigated in inactivated human serum and albumin by ultrafiltration. the effect of the presence of inactivated human serum and albumin on the in vitro activity of faropenem and amoxicillin was established and the influence of protein binding on the pharmacodynamic properties of fa ...200212356797
role of agr (rnaiii) in staphylococcus aureus adherence to fibrinogen, fibronectin, platelets and endothelial cells under static and flow conditions.in the present study, the adherence of staphylococcus aureus (strain 83254) and its rnaiii mutant (wa400) to immobilised fibrinogen and fibronectin, and to human endothelial cells (ec), was studied. [3h]thymidine-labelled bacteria in stationary phase were incubated on the test surfaces for 20 min under static or flow (200/s) conditions. the results showed: (a) increased adherence of the rnaiii mutant to fibrinogen under static conditions, and decreased adherence of the mutant to fibronectin and ...200212358065
role of charge properties of bacterial envelope in bactericidal action of human group iia phospholipase a2 against staphylococcus aureus.mammalian group iia phospholipases a(2) (pla(2)) potently kill staphylococcus aureus. highly cationic properties of these pla(2) are important for ca(2+)-independent binding and cell wall penetration, prerequisites for ca(2+)-dependent degradation of membrane phospholipids and bacterial killing. to further delineate charge properties of the bacterial envelope important in group iia pla(2) action against s. aureus, we examined the effects of mutations that prevent specific modifications of cell w ...200212359734
surfactant wound irrigation for the treatment of staphylococcal clinical isolates.deep wound infection involving an implanted biomaterial is a devastating complication in orthopaedic surgery. two-thirds of such infections are monomicrobial and the most commonly isolated bacteria in human osteomyelitis and orthopaedic device infection are staphylococcus aureus and staphylococcus epidermidis. the purpose of the current study was to examine the effectiveness of the previously reported sequential surfactant irrigation protocol against human-isolated clinical strains of staphyloco ...200212360010
influence of several uropathogenic microorganisms on human sperm motility parameters in vitro.the effects of certain uropathogenic microorganisms (neisseria gonorrhoeae, staphylococcus aureus, staphylococcus epidermidis and mycobacterium tuberculosis) on human sperm motility characteristics were studied in vitro.200212364972
serum concentration of hakata antigen, a member of the ficolins, is linked with inhibition of aerococcus viridans growth.hakata antigen (hakata) is a novel serum glycoprotein that consists of collagen- and fibrinogen-like domains, similar to ficolin/p35. our research suggested that serum hakata may be a target of a polysaccharide (psa) produced by aerococcus viridans.200212367778
enhancement of complement activation and opsonophagocytosis by complexes of mannose-binding lectin with mannose-binding lectin-associated serine protease after binding to staphylococcus aureus.human mannose-binding lectin (mbl) is a serum protein of the innate immune system that circulates as a complex with a group of so-called mbl-associated serine proteases (masp-1, masp-2, and masp-3). complexes of mbl-masp2 are able to activate the complement system in an ab and c1-independent fashion after binding of the lectin to appropriate microbial sugar arrays. we have evaluated the additive effect of the lectin pathway relative to other complement activation pathways and the subsequent effe ...200212370377
chlorpromazine has intracellular killing activity against phagocytosed staphylococcus aureus at clinical concentrations.chlorpromazine (cpz) has in vitro antimicrobial activity against staphylococcus aureus at concentrations that greatly exceed those achieved clinically. it is concentrated by tissues that are rich in macrophages and it is active against phagocytosed mycobacteria when the concentration in the medium is compatible with that achieved clinically. in this report we show that nontoxic concentrations of cpz below clinical levels have killing activity against s. aureus phagocytosed by human monocyte-deri ...200212373485
[in vitro and in vivo antibacterial activities of pazufloxacin mesilate, a new injectable quinolone].we investigated the in vitro and in vivo antibacterial activities of pazufloxacin mesilate (pzfx mesilate), a new injectable quinolone, and obtained the following results. 1) the mic50 and mic90 values of pzfx against clinically isolated gram-positive and -negative bacteria, ranged from 0.0125 to 12.5 micrograms/ml and 0.025 to 100 micrograms/ml, respectively. pzfx showed broad spectrum activity. the antibacterial activities of pzfx against quinolone-susceptible, methicillin-resistant staphyloco ...200212378871
staphylococcus aureus aconitase inactivation unexpectedly inhibits post-exponential-phase growth and enhances stationary-phase survival.staphylococcus aureus preferentially catabolizes glucose, generating pyruvate, which is subsequently oxidized to acetate under aerobic growth conditions. catabolite repression of the tricarboxylic acid (tca) cycle results in the accumulation of acetate. tca cycle derepression coincides with exit from the exponential growth phase, the onset of acetate catabolism, and the maximal expression of secreted virulence factors. these data suggest that carbon and energy for post-exponential-phase growth a ...200212379717
quantity of aerobic bacteria in the bony portion of the external auditory canal of children.the human external auditory canal (eac) hosts a commensal bacterial flora of mainly non-pathogens, but bacterial pathogens may also be present. the latter are important in the aetiopathogenesis of external otitis and middle ear cholesteatoma with discharge. the purpose of this study was to quantify the bacteria normally harboured in the healthy eac and on a well-defined region of the cavum conchae (cc) of children.200212393252
antibiogram and beta-lactamase production of staphylococcus aureus isolates from different human clinical specimens in edo state, nigeria.the antibiogram and beta-lactamase of 73 isolates of staphylococcus aureus from 235 different human clinical specimens were determined using standard procedures. these various clinical specimens were got from teaching hospitals and some private hospitals in edo state. the results of the antibiogram showed 100% susceptibiity to vancomycin, 78.1% to gentamicin, 71.3% to chloramphenicol, 69.8% to erythromycin and 61.6% to cloxacillin. the results of the beta-lactamase detection showed that 84.1% of ...200212403034
human neutrophil oxidative bursts and their in vitro modulation by different n-acetylcysteine concentrations.reactive oxygen species released by activated polymorphonuclear leukocytes as an expression of their defensive function are considered to be a major source of the cytotoxic oxidant stress, that triggers a self-sustaining phlogogenic loop in the respiratory system. n-acetylcysteine (cas 616-91-1, nac), a known mucolytic drug, possesses also antioxidant properties, but it undergoes a rapid and extensive first-pass metabolism resulting in low tissue availability. thus to further improve the nac bio ...200212404881
[biodistribution of low-molecular-weight proteins and technetium (99mtc) labeled peptides in an animal model of inflammation].the aim of this study was to evaluate accumulation of the low molecular peptides and proteins labelled with 99mtc in rat inflammatory/infection foci. peptides (human leukocyte dialysate--hld, thymosin fraction 5--tf5, aprotinin--apt), proteins (human igg-hig) were labelled with 99mtc using a redox polymer. the labelling efficiency was evaluated using paper, tlc and/or column chromatography and electrophoresis. the biodistribution of the labelled substances was evaluated in wistar rats with staph ...200212407925
murine beta-defensin-3 is an inducible peptide with limited tissue expression and broad-spectrum antimicrobial activity.beta-defensins are cationic peptides produced by epithelial cells that have been proposed to be an important component of immune function at mucosal surfaces. similarities between mammalian beta-defensins may permit the use of murine models to further define the role of these peptides in innate host defense. murine beta-defensin-3 (mbd-3) is a peptide that exhibits homology at the gene level to human beta-defensin-2 (hbd-2), one of four beta-defensins identified in man. the purpose of this study ...200212412627
flow cytometric analysis of procalcitonin expression in human monocytes and granulocytes.procalcitonin (pct), a precursor of calcitonin is a useful indicator of severe systemic infection and sepsis. for a better understanding of the pathophysiological background of pct induction, a study was made of the intracellular expression of pct in various human white blood cell populations-i.e. monocytes and polymorphonuclear granulocytes (pmns)-and the role of tnf-alpha in the stimulation of their pct production. the expression of pct was investigated by flow cytometric analysis with intrace ...200212413737
telomere maintenance in human b lymphocytes.telomere shortening has been causally linked to replicative senescence in human cells. to characterize telomere-length heterogeneity in peripheral blood cells of normal individuals, we analysed the mean length of telomeric repeat sequences in subpopulations of peripheral blood leucocytes, using fluorescence in situ hybridization and flow cytometry (flow-fish). although the telomere length of most haematopoietic subsets was within the same range, the mean telomere length was found to be 15% highe ...200212437664
synthesis and antibacterial activity of fused mannich ketones.new mannich ketones of fused bicyclic ketones as 1-indanones and 1-tetralones were prepared using the classical acid-catalysed mannich reaction. known members of this family were used in comparative biological tests. antibacterial activity of these new water-soluble compounds was reported against pseudomonas aeruginosa, escherichia coli, e. coli red31m4, salmonella minnesota re595, shigella sonnei re4350, staphylococcus aureus, staphylococcus saprophyticus, micrococcus luteus and bacillus subtil ...200212446038
sensitive and specific colorimetric elisas for staphylococcus aureus enterotoxins a and b in urine and buffer.we present here simple, sensitive and accurate colorimetric capture elisas for staphylococcal enterotoxins a and b. standard curves were linear over the range 0.5-1 ng/ml, and toxins could be accurately measured at 0.5 ng/ml in assay buffer or 0.1 ng/ml in human urine. cross-reactivity between serotypes was negligible. detection in serum was complicated by the presence of specific antibodies to se's in most normal sera. these assays offer a viable, cost-effective method for analysis of these ubi ...200212457885
interference of sub-inhibitory concentrations of gatifloxacin on various determinants of bacterial virulence.the physico-chemical characteristics of the molecular array on the outermost surface of bacteria modulate various bacterial functions which, when expressed in the human environment, constitute important determinants of bacterial virulence. the present study investigated the ability of subinhibitory concentrations of gatifloxacin to interfere with various virulence determinants of escherichia coli and with the adhesiveness of staphylococcus aureus. the adhesiveness of s. aureus and e. coli to hum ...200212462427
immunoglobulin purification by affinity chromatography using protein a mimetic ligands prepared by combinatorial chemical synthesis.affinity chromatography using protein a from staphylococcus aureus as the ligand has been widely used for the isolation of immunoglobulin g (igg) from various species. since ligand leakage from the affinity support can occur, time consuming analytical controls are required to detect the presence of contaminants associated with the isolated igg prior to its use for therapeutic purpose in humans. besides, protein a is an expensive bacterial product, whose isolation involves complex and labor inten ...200212472184
rp105-lacking b cells from lupus patients are responsible for the production of immunoglobulins and autoantibodies.we previously reported that b cells lacking the rp105 molecule, which proved to be highly activated b cells, are increased in the peripheral blood of patients with systemic lupus erythematosus (sle). in the present study, we attempted to determine whether rp105-negative b cells obtained from sle patients would be capable of producing autoantibodies as well as immunoglobulins.200212483730
attachment of staphylococcus aureus to eukaryotic cells and experimental pitfalls in staphylococcal adherence assays: a critical appraisal.staphylococcus aureus is a bacterial species with pathogenic potential to both humans and animals. the primary natural niche is said to be the human vestibulum nasi from where bacterial cells may spread to the environment or additional anatomical sites such as the perineum or the hands, where residence is usually transient. apparently, s. aureus is capable of a precise and balanced interaction with specific types of eukaryotic nasal cells. although a wide variety of important bacterial ligands a ...200211733080
the effects of charge and lipophilicity on the antibacterial activity of undecapeptides derived from bovine lactoferricin.we have investigated the effects of charge and lipophilicity on the antibacterial activity of an undecapeptide (fkcrrwqwrmk) derived from the sequence of bovine lactoferricin. we prepared ten analogues that were modified by the incorporation of ala, tyr, trp, met and arg residues, which are amino acids known to be important for the antibacterial activity of longer derivatives of lactoferricins. all undecapeptides contained the native trp residues in positions 6 and 8, and the arg residues in pos ...200211831560
staphylococcal alpha-toxin provokes neutrophil-dependent cardiac dysfunction: role of icam-1 and cys-leukotrienes.the role of polymorphonuclear neutrophils (pmn) in septic myocardial dysfunction is presently unknown. staphylococcus aureus infections are frequently associated with septic sequelae. therefore, we perfused isolated rat hearts with low doses of alpha-toxin, the major staphylococcal exotoxin, followed by application of human pmn, n-formyl-methionyl-leucyl-phenylalanine, and arachidonic acid. in contrast to sham-perfused hearts (no alpha-toxin), a rise in coronary perfusion pressure (cpp) and a re ...200211834515
human beta-defensin-2 production in keratinocytes is regulated by interleukin-1, bacteria, and the state of differentiation.intact human epidermis resists invasion by pathogenic microbes but the biochemical basis of its resistance is not well understood. recently, an antimicrobial peptide, human beta-defensin-2, was discovered in inflamed epidermis. we used a recombinant baculovirus/insect cell system to produce human beta-defensin-2 and confirmed that at micromolar concentrations it has a broad spectrum of antimicrobial activity, with the striking exception of staphylococcus aureus. immunostaining with a polyclonal ...200211841544
definition of a type of abnormal vaginal flora that is distinct from bacterial vaginosis: aerobic vaginitis.to define an entity of abnormal vaginal flora: aerobic vaginitis.200211845812
antibacterial properties of dermaseptin s4 derivatives with in vivo activity.derivatives of the cytotoxic peptide dermaseptin s4 have recently emerged as potential antimicrobial agents. here, we report on the antibacterial properties of three derivatives with improved toxicity profiles: a 28-residues k4k20-s4 and two shorter versions, k4-s4(1-16) and k4-s4(1-13). the range of mics of k4k20-s4 against clinical isolates of staphylococcus aureus, pseudomonas aeruginosa, and escherichia coli were, respectively, 1 to 4, 1 to 4, and 1 to 16 microg/ml. mics of the short derivat ...200211850249
retrieving biological activity from lukf-pv mutants combined with different s components implies compatibility between the stem domains of these staphylococcal bicomponent leucotoxins.bicomponent leucotoxins, such as panton-valentine leucocidin, are composed of two classes of proteins, a class s protein such as luks-pv, which bears the cell membrane binding function, and a class f protein such as lukf-pv, which interacts to form a bipartite hexameric pore. these leucotoxins induce cell activation, linked to a ca(2+) influx, and pore formation as two consecutive and independently inhibitable events. knowledge of the lukf-pv monomer structure has indicated that the stem domain ...200211854215
tissue expression of human toll-like receptors and differential regulation of toll-like receptor mrnas in leukocytes in response to microbes, their products, and cytokines.members of the toll-like receptor (tlr) family mediate dorsoventral patterning and cellular adhesion in insects as well as immune responses to microbial products in both insects and mammals. tlrs are characterized by extracellular leucine-rich repeat domains and an intracellular signaling domain that shares homology with cytoplasmic sequences of the mammalian il-1 receptor and plant disease resistance genes. ten human tlrs have been cloned as well as rp105, a protein similar to tlr4 but lacking ...200211777946
the different process of class switching and somatic hypermutation; a novel analysis by cd27(-) naive b cells.the relationship between class switch recombination (csr) and somatic hypermutation has been unclear. by using human cd27(-) naive b cells, we investigated the somatic hypermutation and producibility of immunoglobulins (igs) that occur after csr. although neither adult cd27(-) nor cord blood b cells, which showed the unmutated ig v-region genes, produced igg, igm, or iga in response to conventional stimuli, they produced igg and igm but not iga in the presence of staphylococcus aureus cowan stra ...200211781240
staphylococcus aureus alpha toxin mediates polymorphonuclear leukocyte-induced vasocontraction and endothelial dysfunction.the effect of staphylococcus aureus alpha toxin (alpha-toxin) on selectin-mediated neutrophil adhesion was investigated in polymorphonuclear leukocyte- (pmn) induced vasocontraction and endothelial dysfunction. adherence of human pmns to rat aortic endothelium increased significantly following stimulation of the endothelium with alpha-toxin (0.1, 0.5, and 1 microg/ml). this effect could be significantly attenuated by monoclonal antibodies directed against p-selectin or fucoidin, a carbohydrate k ...200211795666
discrepancy between uptake and intracellular activity of moxifloxacin in a staphylococcus aureus-human thp-1 monocytic cell model.the correlation between uptake of moxifloxacin by thp-1, a continuous line of monocytic cells devoid of intrinsic bactericidal properties, and its activity against staphylococcus aureus atcc 25923, a susceptible reference strain (mic and minimal bactericidal concentration of moxifloxacin, 0.1 mg/liter), was studied in a 5-h assay. the uptake of the drug, added to the culture medium at 0.2 to 32 mg/liter, was evaluated by high-performance liquid chromatography. the ratio of the cellular to extrac ...200211796332
fibronectin-binding proteins of staphylococcus aureus are involved in adherence to human airway epithelium.this study was designed to investigate the molecular mechanisms of staphylococcus aureus adherence to human airway epithelium. using a humanized bronchial xenograft model in the nude mouse and primary cultures of human airway epithelial cells (haec), we showed that s. aureus adhered mainly to undifferentiated haec whereas weak adherence (11- to 20-fold lower) to differentiated haec was observed (p < 0.01). a fibronectin (fn)-binding protein (fnbp)-deficient strain of s. aureus had a fivefold-low ...200211796591
relationships between staphylococcus aureus genetic background, virulence factors, agr groups (alleles), and human disease.the expression of most staphylococcus aureus virulence factors is controlled by the agr locus, which encodes a two-component signaling pathway whose activating ligand is an agr-encoded autoinducing peptide (aip). a polymorphism in the amino acid sequence of the aip and of its corresponding receptor divides s. aureus strains into four major groups. within a given group, each strain produces a peptide that can activate the agr response in the other member strains, whereas the aips belonging to dif ...200211796592
evaluation of the pathology, pathogenesis and aetiology of auricular elephantiasis in slaughter pigs.ears from slaughter pigs with auricular elephantiasis (n = 24) and the corresponding lymph nodes (lnn.) (n = 26) were grossly, histopathologically and microbiologically examined. immunostaining for igm, igg, cd3epsilon and bacterial antigens of arcanobacterium pyogenes and staphylococcus aureus was performed by indirect enzyme-based techniques. ears were variably thickened depending on the sampled area (basis, centre and apex). however, at all locations the thickness, the length from basis to ap ...200212549830
antimicrobial and antiviral activities of polyphenolics from cocos nucifera linn. (palmae) husk fiber extract.the decoction of cocos nucifera l. husk fiber has been used in northeastern brazil traditional medicine for treatment of diarrhea and arthritis. water extract obtained from coconut husk fiber and fractions from adsorption chromatography revealed antimicrobial activity against staphylococcus aureus. the crude extract and one of the fractions rich in catechin also showed inhibitory activity against acyclovir-resistant herpes simplex virus type 1 (hsv-1-acvr). all fractions were inactive against th ...200212558183
approaches to selectivity in the zn(ii)-phthalocyanine-photosensitized inactivation of wild-type and antibiotic-resistant staphylococcus aureus.a number of zn(ii)- phthalocyanines bearing peripheral substituents of cationic nature due to the presence of quaternarized anilinium or ammonium groups were shown to be efficient photoantimicrobial agents: a 4-5 log decrease in the survival of both wild-type or methicillin-resistant staphylococcus aureus was obtained upon short irradiation times in the presence of phthalocyanine concentrations as low as 0.1 microm. a careful selection of the experimental protocol, and in particular the use of s ...200212656484
[application of pulsed-field gel electrophoresis (pfge) to methicillin-resistant strains of staphylococcus aureus from humans and domestic animals].the aim of the research was to isolate and to identify the methicillin-resistant staphylococcus aureus (mrsa) strains from cattle and human and to determine their genetic relatedness comparing the dna restriction patterns.200212700438
host-pathogen interactions: leukocyte phagocytosis and associated sequelae.polymorphonuclear leukocytes (pmns) are a critical component of the human innate immune response and are the first line of defense against invading microorganisms. phagocytosis of invading microbes induces production of reactive oxygen species (ros) by pmns, which facilitates bactericidal activity. in addition to eliminating microorganisms, phagocytosis also accelerates pmn apoptosis, a process critical for resolution of inflammation. inasmuch as leukocyte phagocytosis and ros production are key ...200212815296
the bactericidal and cytotoxic effects of antimicrobial wound cleansers.objective: wound care is a part of daily activity for many athletic trainers. knowing which cleansers are effective against the bacteria that most commonly cause infection and whether they are toxic to healthy cells enables athletic trainers to make educated decisions on which cleanser to use. we compared the bactericidal effectiveness and cytotoxicity to human fibroblast cells of 4 cleansers at various dilutions. design and setting: a 4 x 4 factorial design was used for the cytotoxicity testing ...200212937444
degradation of antimicrobial histatin-variant peptides in staphylococcus aureus and streptococcus mutans.histidine-free variants of salivary histatin 5 have a broad antimicrobial activity against various bacteria. in relation to a possible therapeutic application, we were interested in the susceptibility of these small peptides (14 amino acids long) to microbial proteinases and whether this affects their antimicrobial activity. analyses by sds-page of supernatants of peptide-bacteria incubation showed a reduction in protein bands within 15 minutes' incubation, as a result of cellular internalizatio ...200312939363
identification, structure and differential expression of novel pleurocidins clustered on the genome of the winter flounder, pseudopleuronectes americanus (walbaum).antimicrobial peptides form one of the first lines of defense against invading pathogens by killing the microorganisms and/or mobilizing the host innate immune system. although over 800 antimicrobial peptides have been isolated from many different species, especially insects, few have been reported from marine fish. sequence analysis of two genomic clones (15.6 and 12.5 kb) from the winter flounder, pseudopleuronectes americanus (walbaum) resulted in the identification of multiple clustered gene ...200312950255
bioactive alkyl phenols and embelin from oxalis erythrorhiza.the benzoquinone embelin and four alkyl phenols were isolated from an argentinean collection of oxalis erythrorhiza. 3-heptadecyl-5-methoxy-phenol is reported for the first time. the structures were determined by spectroscopic methods. embelin presented inhibitory effect on methicillin-resistant staphylococcus aureus, escherichia coli and the dermatophytic fungi epidermophyton floccosum, microsporum canis, microsporum gypseum, trichophyton mentagrophytes and trichophyton rubrum with mics ranging ...200312963150
intracellular staphylococcus aureus. a mechanism for the indolence of osteomyelitis.staphylococcus aureus is the bacterial pathogen which is responsible for approximately 80% of all cases of human osteomyelitis. it can invade and remain within osteoblasts. the fate of intracellular staph. aureus after the death of the osteoblast has not been documented. we exposed human osteoblasts to staph. aureus. after infection, the osteoblasts were either lysed with triton x-100 or trypsinised. the bacteria released from both the trypsinised and lysed osteoblasts were cultured and counted. ...200312931819
lipid rafts determine efficiency of nadph oxidase activation in neutrophils.we have investigated the contribution of lipid rafts to activation of the nadph oxidase enzyme system in neutrophils. membrane-bound nadph oxidase subunits are present in the lipid raft compartment of neutrophils. cytosolic nadph oxidase components are mainly absent from but are recruited to rafts upon fcgamma receptor activation. in parallel, protein kinase c isotypes are recruited to the rafts. kinetic analysis of nadph oxidase activation revealed that rafts determine the onset but not the max ...200312935894
new antimicrobial cystatin c-based peptide active against gram-positive bacterial pathogens, including methicillin-resistant staphylococcus aureus and multiresistant coagulase-negative staphylococci.we describe the synthesis and antibacterial properties of a novel antimicrobial peptidyl derivative, (2s)-2-(nalpha-benzyloxycarbonyl-arginyl-leucylamido-1-[(e)-cinnamoylamido]-3-methylbutane, structurally based upon the inhibitory centre of the human cysteine protease inhibitor, cystatin c. the derivative, here called cystapep 1, displayed antibacterial activity against several clinically important gram-positive bacteria. it displayed minimal inhibitory and bactericidal concentrations of about ...200314629266
staphylococcus aureus pericardial abscess in a patient with liver cirrhosis: case report.pericardial abscess is a rare complication of staphylococcus aureus bacteremia. we report the case of a 40-year-old man with hepatitis c and liver cirrhosis who presented with high-grade fever and chest pain. transthoracic echocardiography showed a pericardial mass and computed tomographic scanning and transesophageal echocardiography confirmed the presence of a loculated fluid collection. his illness persisted despite i.v. antibiotics and video-assisted thoracoscopic drainage. the patient was c ...200314513994
phage conversion of exfoliative toxin a in staphylococcus aureus isolated from cows with mastitis.an exfoliative toxin produced by staphylococcus aureus is the causative agent of staphylococcal scalded-skin syndrome (ssss) in young children. recently, we reported that only few isolates of s. aureus from bovine mastitis contained the eta gene encoding exfoliative toxin a (eta) and produced eta in vitro. in this study, we isolated temperate phages from two eta-positive bovine isolates of s. aureus by treatment with mitomycin c. polymerase chain reaction (pcr) assay of the phage genomes suggest ...200314516710
the effect of cyclosporine and tacrolimus on indigenous bacterial flora in human skin grafts.allogeneic skin transplants require intensive immunosuppressive therapy. treatment protocols used for parenchymal organ grafts are not satisfactory to prevent skin graft rejection. another factor responsible for the destruction of allogeneic skin transplants is bacterial inflammation. temporary ischemia and the allogeneic reaction in transplanted skin cause increased permeability of the epidermis and the dermal capillaries, making skin grafts vulnerable to bacterial penetration. moreover, immuno ...200314529942
negative regulation of interleukin-12 production by a rapamycin-sensitive signaling pathway: a brief communication.interleukin-12 (il-12), an important cytokine in host defense against microbial pathogens, regulates natural killer and t-cell function(s) including the induction of gamma-interferon production. the major cellular sources of il-12 are monocytes/macrophages. bacteria, bacterial products, and intracellular parasites are the most efficient inducers of il-12 production. in the present study we show that a signal transduction pathway sensitive to rapamycin may have an important role in the regulation ...200314530510
[treatment of a septic patient with acquired haemophilia].acquired haemophilia is a rare bleeding diathesis caused by auto-immune depletion of factor viii. it is characterised by spontaneous haemorrhagic syndrome, which can be fatal sometimes.200314550523
[28-year-old patient with elevated serum ige levels and multiple refractory epidural and paravertebral abscesses. clinical manifestation of a job's syndrome?].the hyper-ige syndrome is a rare primary immunodeficiency characterized by recurrent staphylococcal infections and high levels of serum ige.200314551710
molecular architecture of the regulatory locus sae of staphylococcus aureus and its impact on expression of virulence factors.we characterized the sae operon, a global regulator for virulence gene expression in staphylococcus aureus. a tn917 sae mutant was obtained by screening a tn917 library of the agr mutant isp479mu for clones with altered hemolytic activity. sequence analysis of the sae operon revealed two additional open reading frames (orfs) (orf3 and orf4) upstream of the two-component regulatory genes saer and saes. four overlapping sae-specific transcripts (t1 to t4) were detected by northern blot analysis, a ...200314563862
staphylococcal peptidoglycan suppresses production of interleukin-2 by t cells through a t cell-derived factor induced by direct contact between t cells and monocytes.during the last 2 decades, the incidence of sepsis due to gram-positive bacteria has increased dramatically. nevertheless, effects of the cell-wall components that do not contain endotoxin, on immunity, are still largely unknown. here, we demonstrate, for the first time, that the gram-positive bacterial cell-wall component peptidoglycan (pgn) severely inhibits the production of interleukin (il)-2 by cultured human peripheral blood mononuclear cells stimulated with anti-cd3 and anti-cd28 antibodi ...200314593585
in vitro studies of the pharmacodynamics of teicoplanin against staphylococcus aureus, staphylococcus epidermidis and enterococcus faecium.to investigate the basic pharmacodynamic properties of teicoplanin in vitro for staphylococcus aureus, staphylococcus epidermidis and enterococcus faecium.200314616681
a novel class of cysteine protease inhibitors: solution structure of staphostatin a from staphylococcus aureus.a series of secreted proteases are included among the virulence factors documented for staphylococcus aureus. in light of increasing antibiotic resistance of this dangerous human pathogen, these proteases are considered as suitable targets for the development of novel therapeutic strategies. the recent discovery of staphostatins, endogenous, highly specific, staphylococcal cysteine protease inhibitors, opened a possibility for structure-based design of low molecular weight analogues. moreover, t ...200314621990
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