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a new target for staphylococcus aureus associated with keratitis.staphylococcus aureus is a leading cause of keratitis, with an increased number of isolates exhibiting antibiotic resistance. therefore, we need to understand the present situation regarding drug-resistant s. aureus in the ocular site. it has been shown that 35% of s. aureus isolates from ocular sites are methicillin-resistant staphylococcus aureus (mrsa). mrsa isolates from ocular sites have a high rate of multiple mutations and high levels of resistance against fluoroquinolones. wall teichoic ...201121912228
rhesus macaques (macaca mulatta) are natural hosts of specific staphylococcus aureus lineages.currently, there is no animal model known that mimics natural nasal colonization by staphylococcus aureus in humans. we investigated whether rhesus macaques are natural nasal carriers of s. aureus. nasal swabs were taken from 731 macaques. s. aureus isolates were typed by pulsed-field gel electrophoresis (pfge), spa repeat sequencing and multi-locus sequence typing (mlst), and compared with human strains. furthermore, the isolates were characterized by several pcrs. thirty-nine percent of 731 ma ...201122028827
colonization, pathogenicity, host susceptibility, and therapeutics for staphylococcus aureus: what is the clinical relevance?staphylococcus aureus is a human commensal that can also cause a broad spectrum of clinical disease. factors associated with clinical disease are myriad and dynamic and include pathogen virulence, antimicrobial resistance, and host susceptibility. additionally, infection control measures aimed at the environmental niches of s. aureus and therapeutic advances continue to impact upon the incidence and outcomes of staphylococcal infections. this review article focuses on the clinical relevance of a ...201122160374
phagocytosis and intracellular killing of heterogeneous vancomycin-intermediate staphylococcus aureus strains.risk factors for invasive infections by heterogeneous vancomycin-intermediate staphylococcus aureus (hvisa) may involve resistance to opsonophagocytosis and bacterial killing. hvisa strains typically have a thickened cell wall with altered peptidoglycan cross-linking. to determine whether hvisa may be endowed with an increased resistance to phagocytosis, this study assessed the characteristics of uptake and killing by granulocytes of three hvisa strains. all isolates were analysed by multilocus ...201121959204
the staphylococcus aureus peptidoglycan protects mice against the pathogen and eradicates experimentally induced infection.staphylococcus aureus, in spite of antibiotics, is still a major human pathogen causing a wide range of infections. the present study describes the new vaccine a170pg, a peptidoglycan-based vaccine. in a mouse model of infection, a170pg protects mice against a lethal dose of s. aureus. protection lasts at least 40 weeks and correlates with increased survival and reduced colonization. protection extends into drug-resistant (mrsa or visa) and genetically diverse clinical strains. the vaccine is ef ...201122145040
induction of contact-dependent cd8(+) regulatory t cells through stimulation with staphylococcal and streptococcal superantigens(1).the bacterial superantigen exotoxins of staphylococcus aureus and streptococcus pyogenes are potent stimulators of polyclonal t cell proliferation. they are the causes of toxic shock syndrome but also induce cd25(+) foxp3(+) regulatory cells in the cd4 compartment. several studies have recently described different forms of antigen-induced regulatory cd8(+) t cells in the context of inflammatory diseases and chronic viral infections. in this paper we show that bacterial superantigens are potent ...201122043981
3-cyano-8-methyl-2-oxo-1,4-disubstituted-1,2,5,6,7,8-hexahydroquinolines. synthesis and biological evaluation as antimicrobial and cytotoxic agents.the synthesis, in vitro antimicrobial and cytotoxic activities of some novel hexahydroquinolines supported with various pharmacophores are described. the results revealed that 18 compounds displayed pronounced activity against staphylococcus aureus and escherichia coli bacteria beside a moderate antifungal activity. compound 25 is the most active candidate with equipotency to ampicillin against s. aureus, e. coli and pseudomonas aeruginosa, together with an obvious antifungal activity. additiona ...201122136527
methicillin resistant s. aureus in human and bovine mastitis.staphylococcus aureus is a ubiquitous organism that causes a variety of diseases including mastitis in cattle and humans. high-level resistance of s. aureus to β-lactams conferred by a meca gene encoding a modified penicillin binding protein (pbp2a) was first observed in the early 1960's. these methicillin resistant s. aureus (mrsa) have been responsible for both hospital acquired infections (ha-mrsa) and, more recently, community acquired mrsa (ca-mrsa). a small number of human mrsa mastitis ca ...201121984431
synthesis, antimicrobial and antiproliferative activity of novel silver(i) tris(pyrazolyl)methanesulfonate and 1,3,5-triaza-7-phosphadamantane complexes.five new silver(i) complexes of formulas [ag(tpms)] (1), [ag(tpms)(pph(3))] (2), [ag(tpms)(pcy(3))] (3), [ag(pta)][bf(4)] (4), and [ag(tpms)(pta)] (5) {tpms = tris(pyrazol-1-yl)methanesulfonate, pph(3) = triphenylphosphane, pcy(3) = tricyclohexylphosphane, pta = 1,3,5-triaza-7-phosphaadamantane} have been synthesized and fully characterized by elemental analyses, (1)h, (13)c, and (31)p nmr, electrospray ionization mass spectrometry (esi-ms), and ir spectroscopic techniques. the single crystal x- ...201121999582
magnetic drug targeting as new therapeutic option for the treatment of biomaterial infections.implant-associated infections are a challenging problem in surgery. bacteria in biofilms are difficult to treat as they are less susceptible to antibiotics or antiseptics which require high drug concentrations at the site of infection. we present a novel strategy to concentrate high antibiotic doses systemically at the target site using newly developed antibiotic-functionalized nanoparticles directed by a magnetic drug-targeting system. the important and effective antibiotic gentamicin served as ...201122182398
comparative ethnobotany and in-the-field antibacterial testing of medicinal plants used by the bulu and inland kaulong of papua new guinea.ethnopharmacological relevance: the island of new britain in papua new guinea is an area of great floristic and cultural diversity that has received little attention from ethnobotanists. here we present the results of a comparative medicinal ethnobotanical survey of the bulu and inland kaulong; two distinct people groups inhabiting lowland rainforest on different sides of the island. a high proportion of species are used in the treatment of bacterial infections and plants with antibacterial acti ...201122154578
antimicrobial evaluation of huilliche plant medicine used to treat wounds.the traditional use of 40 plant species used for treatment of wounds and associated infections by the huilliche people of chile was evaluated against bacterial and fungal human pathogens, especially including wound pathogens.201121939748
molecular characterization and antimicrobial susceptibility of nasal staphylococcus aureus isolates from a chinese medical college campus.staphylococcus aureus colonization and infection occur more commonly among persons living or working in crowded conditions, but characterization of s. aureus colonization within medical communities in china is lacking. a total of 144 (15.4%, 144/935) s. aureus isolates, including 28 (3.0%, 28/935) mrsa isolates, were recovered from the nares of 935 healthy human volunteers residing on a chinese medical college campus. all s. aureus isolates were susceptible to vancomycin, quinupristin/dalfoprist ...201122114670
Antibacterial and antifungal activities from leaf extracts of Cassia fistula l.: An ethnomedicinal plant.This study was carried out with an objective to investigate the antibacterial and antifungal potentials of leaves of Cassia fistula Linn. The aim of the study is to assess the antimicrobial activity and to determine the zone of inhibition of extracts on some bacterial and fungal strains. In the present study, the microbial activity of hydroalcohol extracts of leaves of Cassia fistula Linn. (an ethnomedicinal plant) was evaluated for potential antimicrobial activity against medically important ba ...201122171301
antibacterial peptides derived from caprine whey proteins, by digestion with human gastrointestinal juice.peptides in caprine whey were identified after in vitro digestion with human gastrointestinal enzymes in order to determine their antibacterial effect. the digestion was performed in two continuing steps using human gastric juice (ph 2·5) and human duodenal juice (ph 8) at 37°c. after digestion the hydrolysate was fractionated and 106 peptides were identified. from these results, twenty-two peptides, located in the protein molecules, were synthesised and antibacterial activity examined. strong a ...201121554806
the role of horizontal gene transfer in staphylococcus aureus host adaptation.staphylococcus aureus is an important human pathogen that also causes economically important infections of livestock. in a recent paper, we employed a population genomic approach to investigate the molecular basis of ruminant host adaptation by s. aureus. the data suggest that the common pathogenic clone associated with small ruminants originated in humans but has since adapted to its adopted host through a combination of allelic diversification, gene loss and acquisition of mobile genetic eleme ...201121555917
composite electrospun nanomembranes of fish scale collagen peptides/chito-oligosaccharides: antibacterial properties and potential for wound dressing.the objective of the present investigation was to evaluate the antibacterial properties and the biocompatibility of composite electrospun nanofibrous membranes (nfms) with low-molecular-weight fish scale collagen peptides (fscp) and chito-oligosaccharide (cos), to determine their potential for use as wound dressings.201121556341
adhesion mechanisms of staphylococci.staphylococcal adherence to an either biotic or abiotic surface is the critical first event in the establishment of an infection with these serious pathogens. especially staphylococcus aureus harbours a variety of proteinaceous and non-proteinaceous adhesins that mediate attachment to a multitude of host factors, such as extracellular matrix and plasma proteins and human host cells, or intercellular adhesion, which is essential for biofilm accumulation. proteinaceous adhesins may be classified i ...201121557060
influence of the recombinant human 70-kda heat-shock protein on simulation of gram-positive sepsis in rats. 201121562946
nsars is a cell-envelope-stress sensing two-component system of staphylococcus aureus.s. aureus possesses 16 two-component systems (tcs), two of which (grars & nsars) belong to the intramembrane-sensing histidine kinase (im-hk) family, conserved within the firmicutes. nsars has recently been documented as being important for nisin-resistance in s. aureus. in this study we present a characterization of nsars and reveal that, as with other im-hk tcs, it responds to disruptions in the cell-envelope. analysis using a lacz reporter-gene fusion demonstrated that nsars expression is upr ...201121565927
the saer/s gene regulatory system induces a pro-inflammatory cytokine response during staphylococcus aureus infection.community-associated methicillin-resistant staphylococcus aureus accounts for a large portion of the increased staphylococcal disease incidence and can cause illness ranging from mild skin infections to rapidly fatal sepsis syndromes. currently, we have limited understanding of s. aureus-derived mechanisms contributing to bacterial pathogenesis and host inflammation during staphylococcal disease. herein, we characterize an influential role for the saer/s two-component gene regulatory system in m ...201121603642
natural and synthetic cathelicidin peptides with anti-microbial and anti-biofilm activity against staphylococcus aureus.abstract: background: chronic infected wounds typically contain multiple genera of bacteria, including staphylococcus aureus, many of which are strong biofilm formers. bacterial biofilms are thought to be a direct impediment to wound healing. new therapies that focus on a biofilm approach may improve the recovery and healing rate for infected wounds. in this study, cathelicidins and related short, synthetic peptides were tested for their anti-microbial effectiveness as well as their ability to i ...201121605457
structure-function studies of an engineered scaffold protein derived from stefin a. ii: development and applications of the sqt variant.constrained binding peptides (peptide aptamers) may serve as tools to explore protein conformations and disrupt protein-protein interactions. the quality of the protein scaffold, by which the binding peptide is constrained and presented, is of crucial importance. sqt (stefin a quadruple mutant-tracy) is our most recent development in the stefin a-derived scaffold series. stefin a naturally uses three surfaces to interact with its targets. sqt tolerates peptide insertions at all three positions. ...201121616931
gut cavp is an innate immune protein against bacterial challenge in amphioxus branchiostoma belcheri.the importance of calcium-binding proteins in immune response of vertebrates is determined, but whether they have the role in invertebrates is largely unknown. in the present study, phylogenetic analysis indicated that calcium vector protein (cavp), a protein unique to amphioxus, shared 68% similarity in amino acid sequence with human and mouse calmodulin (cam). cavp cdna was cloned into a bacterial vector pet-32a, and its his-tagged fusion protein was produced in eschherichia coli cells (bl21). ...201121624472
Novel anti-bacterial activities of ß-defensin 1 in human platelets: suppression of pathogen growth and signaling of neutrophil extracellular trap formation.Human ß-defensins (hBD) are antimicrobial peptides that curb microbial activity. Although hBD's are primarily expressed by epithelial cells, we show that human platelets express hBD-1 that has both predicted and novel antibacterial activities. We observed that activated platelets surround Staphylococcus aureus (S. aureus), forcing the pathogens into clusters that have a reduced growth rate compared to S. aureus alone. Given the microbicidal activity of ß-defensins, we determined whether hBD fami ...201122102811
targeting the host-pathogen interface for treatment of staphylococcus aureus infection.recent emergence of methicillin-resistant staphylococcus aureus both within and outside healthcare settings has accelerated the use of once reserved last line antibiotics such as vancomycin. with increased use of antibiotics, there has been a rapid rise in the rate of resistance development to the anti-mrsa drugs. as the antibiotic pipeline becomes strained, alternative strategies are being sought for future treatment of s. aureus. here, we review several novel anti-staphylococcal strategies tha ...201122089960
Expansion of T helper type 17 lymphocytes in patients with chronic granulomatous disease.Hyper-immunoglobulin (Ig)E syndrome (HIES) is a primary immunodeficiency associated with mutations in STAT3 resulting in impaired development of T helper type 17 (Th17) lymphocytes. HIES patients with a reduced frequency of Th17 cells present with infections caused by Staphylococcus aureus and/or Candida strains. The same spectrum of pathogens is present in patients with chronic granulomatous disease (CGD).We analysed the characteristics of the Th17 compartment in HIES and CGD. HIES patients sho ...201121910722
peptidylarginine deiminases present in the airways during tobacco smoking and inflammation can citrullinate the host defense peptide ll-37 resulting in altered activities.bacterial colonization of the lower respiratory tract is frequently seen in copd and may cause exacerbations leading to deterioration of the disease. an important part of the innate lung immunity is antimicrobial peptides, not least the cathelicidin hcap-18/ll-37. peptidylarginine deiminases (padi) posttranslationally modifies proteins by converting cationic peptidylarginine residues to neutral peptidylcitrulline. increased presence of padi2 and citrullinated proteins has been demonstrated in th ...201121960546
cluster-forming property correlated with hemolytic activity by staphylococcal γ-hemolysin transmembrane pores.staphylococcal γ-hemolysin (hlg) is a pore-forming toxin consisting of two separate components, lukf (34kda) and hlg2 (32kda). here we show that hlg pores aggregate and form clusters on human erythrocyte membranes in association with increasing hemolytic activity. quantitative analysis using transmission electron microscopy and image processing revealed that the formation of single pores and clusters is related to the release of potassium ions and of hemoglobin from erythrocytes, respectively. t ...201122001207
the first detection of methicillin-resistant staphylococcus aureus st398 in pigs in korea.in order to determine the presence of methicillin-resistant staphylococcus aureus (mrsa) in pigs in korea, a total of 657 nasal swabs were collected from pigs on 66 different pig farms nationwide during february 2008-may 2009. the prevalences of mrsa positive samples in pigs and farms were 3.2% (21/657) and 22.7% (15/66), respectively. two different types were found among the 21 mrsa isolates: 17 strains of livestock-associated type (la; st398 or st541/spa t034) and 4 strains of human-associated ...201121899962
antimicrobial fibers: therapeutic possibilities and recent advances.the emergence of multi-drug-resistant bacteria such as methicillin-resistant strains of staphylococcus aureus (mrsa), vancomycin-resistant enterococci, pseudomonas aeruginosa, acinetobacter baumannii and extended-spectrum β-lactamase (carbapenemase)-producing enterobacteriaceae is becoming a serious threat. new-generation antimicrobial agents need to be developed. this includes the design of novel antimicrobial compounds and drug-delivery systems. this review provides an introduction into differ ...201122004087
chimeric anti-staphylococcal enterotoxin b antibodies and lovastatin act synergistically to provide in vivo protection against lethal doses of seb.staphylococcal enterotoxin b (seb) is one of a family of toxins secreted by staphylococcus aureus that act as superantigens, activating a large fraction of the t-cell population and inducing production of high levels of inflammatory cytokines that can cause toxic shock syndrome (tss) and death. extracellular engagement of the tcr of t-cells and class ii mhc of antigen presenting cells by seb triggers the activation of many intracellular signaling processes. we engineered chimeric antibodies to b ...201122102880
Detection of Methicillin-Resistant Staphylococcus aureus (MRSA) in Backyard Pigs and Their Owners, Michigan, USA.Methicillin-resistant Staphylococcus aureus (MRSA) have been reported in commercially raised pigs and their human handlers, raising concerns of zoonotic transmission. To determine whether MRSA in backyard-raised pigs is commonly transmitted to their human owners, a matched study of this type of pigs and their owners was conducted in selected counties in Michigan. Nasal swabs from matched owner-pig pairs (n = 50 pairs) with a few unmatched pig (n = 3) and human (n = 4) samples were collected and ...201121914153
immunopathogenesis of staphylococcus aureus pulmonary infection.staphylococcus aureus is a common human pathogen highly evolved as both a component of the commensal flora and as a major cause of invasive infection. severe respiratory infection due to staphylococci has been increasing due to the prevalence of more virulent usa300 ca-mrsa strains in the general population. the ability of s. aureus to adapt to the milieu of the respiratory tract has facilitated its emergence as a respiratory pathogen. its metabolic versatility, the ability to scavenge iron, coo ...201122037948
dna, protein binding, cytotoxicity, cellular uptake and antibacterial activities of new palladium(ii) complexes of thiosemicarbazone ligands: effects of substitution on biological activity.the coordination propensities of 4(n,n')-diethylaminosalicylaldehyde-4(n)-substituted thiosemicarbazones (h(2)l(1-4)) were investigated by reacting with an equimolar amount of [pdcl(2)(pph(3))(2)]. the new complexes were characterized by various spectroscopic techniques. the structure determination of the complexes [pd(deasal-tsc)(pph(3))] (1), [pd(deasal-mtsc)(pph(3))] (2) and [pd(deasal-etsc)(pph(3))] (3) by x-ray crystallography showed that ligands are coordinated in a dibasic tridentate ons ...201122051854
hle-inhibitory alkaloids with a polyketide skeleton from the marine-derived fungus coniothyrium cereale.the marine endophytic fungus coniothyrium cereale produces the structurally unusual polyketide-type alkaloids (-)-cereolactam (1) and (-)-cereoaldomine (3), incorporating a lactam and an imine functionality, respectively, as well as the related metabolite (-)-trypethelone (2). compounds 1 and 3 showed selective inhibition of human leukocyte elastase with ic50 values of 9.28 and 3.01 μm, respectively. compound 2 was found to be inhibitory toward mycobacterium phlei, staphylococcus aureus, and esc ...201121923104
cheminformatics-driven discovery of selective, nanomolar inhibitors for staphylococcal pyruvate kinase.we have recently mapped the protein interaction network of methicillin-resistant staphylococcus aureus (mrsa), which revealed its scale-free organization with characteristic presence of highly connected hub proteins that are critical for bacterial survival. here we report the discovery of inhibitors that are highly potent against one such hub target, staphylococcal pyruvate kinase (pk). importantly, the developed compounds demonstrate complete selectivity for the bacterial enzyme compared to all ...201122066782
a usa300 variant and other human-related methicillin-resistant staphylococcus aureus strains infecting cats and dogs in france.to characterize methicillin-resistant staphylococcus aureus (mrsa) clinical strains from cats and dogs in france, and to compare the clones identified with the distribution of french human mrsa.201122146878
staphylococcus aureus survival in human blood.methicillin-resistant staphylococcus aureus (mrsa) is abundant in hospitals and in the united states is a leading cause of mortality due to infectious agents. community-associated mrsa (ca-mrsa) strains such as usa300, which typically cause disease outside of healthcare settings, are also prevalent in the united states. although most ca-mrsa infections affect skin and soft tissue, the pathogen can enter the bloodstream and ultimately cause severe disease. in a recent paper, we used usa300-specif ...201121971187
Antibacterial potential of hGlyrichin encoded by a human gene.Emerging multidrug-resistant (MDR) bacteria are an enormous threat to human life because of their resistance to currently available antibiotics. The genes encoding antibacterial peptides have been studied extensively and are excellent candidates for a new generation of antibiotic drugs to fight MDR bacteria. In contrast to traditional antibiotics, antibacterial peptides, which do not cause drug resistance, have an unparalleled advantage. However, because most antibacterial peptides originate in ...201122083756
comparison of the effects of human β-defensin 3, vancomycin, and clindamycin on staphylococcus aureus biofilm formation.despite improvements in surgical techniques and implant design in orthopedic surgery, implantation-associated infections are still a challenging problem for surgeons. in 2006, trace quantities of human β-defensin 3 (hbd-3) were found in human bone tissue and bone cells. human β-defensin 3 is a 45-amino-acid peptide that is considered the most promising class of defensin antimicrobial peptides and may help in the prevention and treatment of implantation-associated infections. studies of the effec ...201222229614
electrospun poly(l-lactic acid)-co-poly(ɛ-caprolactone) nanofibres containing silver nanoparticles for skin-tissue engineering.silver nanoparticles (agnps) and silver ions (ag(+)) show growth-inhibitory activity against microorganisms and have been used for decades as antibacterial agents in various fields. to fabricate a nanofibrous scaffold which is antibacterial against bacteria and non-toxic to cells, we electrospun composite poly(l-lactic acid)-co-poly(ɛ-caprolactone) nanofibres containing silver nanoparticles (pllcl-agnps) with different concentrations (0.25, 0.50 and 0.75 wt%) of silver nitrate (agno(3)) in pllcl ...201222244047
Thiadiazolidinones: A new class of alanine racemase inhibitors with antimicrobial activity against methicillin-resistant Staphylococcus aureus.Methicillin-resistant Staphylococcus aureus (MRSA) is a human pathogen and a major cause of hospital-acquired infections. New antibacterial agents that have not been compromised by bacterial resistance are needed to treat MRSA-related infections. We chose the S. aureus cell wall synthesis enzyme, alanine racemase (Alr) as the target for a high-throughput screening effort to obtain novel enzyme inhibitors, which inhibit bacterial growth. Among the 'hits' identified was a thiadiazolidinone with ch ...201222146584
expression of antimicrobial peptides in diabetic foot ulcer.foot ulcers are one of the main diabetes complications due to its high frequency and difficulty of complete healing. there are several factors that participate in diabetic ulcers development and limited information exists about the role of antimicrobial peptides (amp) in its pathogenesis.201222047630
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