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impact of recombination on bacterial evolution.genetic exchange plays a defining role in the evolution of many bacteria. the recent accumulation of nucleotide sequence data from multiple members of diverse bacterial genera has facilitated comparative studies that have revealed many features of this process. here we focus on genetic exchange that has involved homologous recombination and illustrate how nucleotide sequence data have furthered our understanding of: (i) the frequency of recombination; (ii) the impact of recombination in differen ...201020452218
pan-genome analysis provides much higher strain typing resolution than multi-locus sequence typing.the most widely used dna-based method for bacterial strain typing, multi-locus sequence typing (mlst), lacks sufficient resolution to distinguish among many bacterial strains within a species. here, we show that strain typing based on the presence or absence of distributed genes is able to resolve all completely sequenced genomes of six bacterial species. this was accomplished by the development of a clustering method, neighbour grouping, which is completely consistent with the lower-resolution ...201020019077
rapid identification of bacterial pathogens in positive blood culture bottles by use of a broad-based pcr assay coupled with high-resolution melt analysis.we evaluated a broad-based pcr assay coupled with high-resolution melt analysis for rapid bacterial identification in patients with bacterial sepsis. with a reference library of 60 clinically relevant bacterial species, 52 positive blood culture samples were tested. our assay identified 46/52 samples at the species level, with 100% concordance to culture findings.201020631110
colistin resistance in acinetobacter baumannii is mediated by complete loss of lipopolysaccharide production.infections caused by multidrug-resistant (mdr) gram-negative bacteria represent a major global health problem. polymyxin antibiotics such as colistin have resurfaced as effective last-resort antimicrobials for use against mdr gram-negative pathogens, including acinetobacter baumannii. here we show that a. baumannii can rapidly develop resistance to polymyxin antibiotics by complete loss of the initial binding target, the lipid a component of lipopolysaccharide (lps), which has long been consider ...201020855724
in vitro and in vivo activities of lcb01-0371, a new oxazolidinone.lcb01-0371 is a new oxazolidinone with cyclic amidrazone. in vitro activity of lcb01-0371 against 624 clinical isolates was evaluated and compared with those of linezolid, vancomycin, and other antibiotics. lcb01-0371 showed good activity against gram-positive pathogens. in vivo activity of lcb01-0371 against systemic infections in mice was also evaluated. lcb01-0371 was more active than linezolid against these systemic infections. lcb01-0371 showed bacteriostatic activity against staphylococcus ...201020855730
nested pcr-linked capillary electrophoresis and single-strand conformation polymorphisms for detection of macrolide-resistant mycoplasma pneumoniae in beijing, china.mycoplasma pneumoniae is usually susceptible to macrolides, but macrolide-resistant strains have been found frequently in recent years. mutations in domain v of the 23s rrna gene of m. pneumoniae interfere with the binding of macrolides to rrna and mediate macrolide resistance. in this study, we developed a rapid and inexpensive method that combines nested pcr (npcr), single-strand conformation polymorphisms (sscps), and capillary electrophoresis (ce) to detect macrolide-resistant mutants direct ...201020861333
structure of a burkholderia pseudomallei trimeric autotransporter adhesin head.pathogenic bacteria adhere to the host cell surface using a family of outer membrane proteins called trimeric autotransporter adhesins (taas). although taas are highly divergent in sequence and domain structure, they are all conceptually comprised of a c-terminal membrane anchoring domain and an n-terminal passenger domain. passenger domains consist of a secretion sequence, a head region that facilitates binding to the host cell surface, and a stalk region.201020862217
pneumococcal carriage is more common in asthmatic than in non-asthmatic young men.the aim was to investigate the prevalence of oropharyngeal carriage of streptococcus pneumoniae, haemophilus influenzae, moraxella catarrhalis, neisseria meningitidis and beta-haemolytic streptococci among asthmatic and non-asthmatic young finnish men and to identify putative risk factors.201020887345
identification of burkholderia mallei and burkholderia pseudomallei adhesins for human respiratory epithelial cells.burkholderia pseudomallei and burkholderia mallei cause the diseases melioidosis and glanders, respectively. a well-studied aspect of pathogenesis by these closely-related bacteria is their ability to invade and multiply within eukaryotic cells. in contrast, the means by which b. pseudomallei and b. mallei adhere to cells are poorly defined. the purpose of this study was to identify adherence factors expressed by these organisms.201020920184
development and characterization of protective haemophilus parasuis subunit vaccines based on native proteins with affinity to porcine transferrin and comparison with other subunit and commercial vaccines.haemophilus parasuis is the agent responsible for causing glässer's disease, which is characterized by fibrinous polyserositis, polyarthritis, and meningitis in pigs. in this study, we have characterized native outer membrane proteins with affinity to porcine transferrin (npapt) from h. parasuis serovar 5, nagasaki strain. this pool of proteins was used as antigen to developed two vaccine formulations: one was adjuvanted with a mineral oil (montanide ims 2215 vg pr), while the other was potentia ...201020926701
development and characterization of protective haemophilus parasuis subunit vaccines based on native proteins with affinity to porcine transferrin and comparison with other subunit and commercial vaccines.haemophilus parasuis is the agent responsible for causing glässer's disease, which is characterized by fibrinous polyserositis, polyarthritis, and meningitis in pigs. in this study, we have characterized native outer membrane proteins with affinity to porcine transferrin (npapt) from h. parasuis serovar 5, nagasaki strain. this pool of proteins was used as antigen to developed two vaccine formulations: one was adjuvanted with a mineral oil (montanide ims 2215 vg pr), while the other was potentia ...201020926701
serum intercellular adhesion molecule 1 variations in young children with acute otitis media.acute otitis media (aom) is an inflammatory reaction in the middle ear, most often occurring in young children. streptococcus pneumoniae, nontypeable haemophilus influenzae, and moraxella catarrhalis are the most common bacteria isolated. intercellular adhesion molecule 1 (icam-1) is involved in the innate immune response to infection by microorganisms, in effective antigen presentation, and in subsequent t-cell activation. here we prospectively studied levels of serum soluble icam-1 (sicam-1) b ...201020926702
infections of people with complement deficiencies and patients who have undergone splenectomy.the complement system comprises several fluid-phase and membrane-associated proteins. under physiological conditions, activation of the fluid-phase components of complement is maintained under tight control and complement activation occurs primarily on surfaces recognized as "nonself" in an attempt to minimize damage to bystander host cells. membrane complement components act to limit complement activation on host cells or to facilitate uptake of antigens or microbes "tagged" with complement fra ...201020930072
prolonged use of ertapenem to treat infected diabetic foot ulcers.we present the case of a diabetic man who was successfully treated with ertapenem for over 4 months for severe infection of his foot ulcers. after initial unsuccessful treatment with empirical intravenous antibiotics, ertapenem was started on microbiology advice and led to a marked improvement in the soft-tissue infection. ertapenem was continued for a total of 137 days under close clinical and biochemical monitoring and produced a complete resolution of the foot infection. this is the first doc ...201020936155
nasopharyngeal bacterial colonization during the first wheezing episode is associated with longer duration of hospitalization and higher risk of relapse in young children.the purpose of this study was to examine the association between bacterial colonization/infection and respiratory outcomes in children younger than 3 years old who were hospitalized for their first wheezing episode. this was an observational study. the primary outcome was hospitalization time and the secondary outcomes included relapses within 2 months and time to recurrent wheezing (i.e. three physician confirmed wheezing episodes) within 12 months. bacterial antibody assays for streptococcus p ...201020938703
the multifunctional host defense peptide splunc1 is critical for homeostasis of the mammalian upper airway.otitis media (om) is a highly prevalent pediatric disease caused by normal flora of the nasopharynx that ascend the eustachian tube and enter the middle ear. as om is a disease of opportunity, it is critical to gain an increased understanding of immune system components that are operational in the upper airway and aid in prevention of this disease. splunc1 is an antimicrobial host defense peptide that is hypothesized to contribute to the health of the airway both through bactericidal and non-bac ...201020949060
antimicrobial activity of doripenem and other carbapenems against gram-negative pathogens from korea.a total of 950 gram-negative bacterial isolates from patients with bacteremia and urinary tract infections were collected from tertiary-care hospitals in korea. in vitro antimicrobial susceptibility testing was performed using broth microdilution test according to clinical and laboratory standards institute protocol. in general, carbapenems such as doripenem, imipenem, and meropenem were very active against enterobacteriaceae, moraxella catarrhalis, pseudomonas aeruginosa, and acinetobacter sp. ...201020950191
etiology and antibacterial susceptibility pattern of community-acquired bacterial ocular infections in a tertiary eye care hospital in south india.to identify the etiology, incidence and prevalence of ocular bacterial infections, and to assess the in vitro susceptibility of these ocular bacterial isolates to commonly used antibiotics.201020952834
molecular characterization of fluoroquinolone resistance in mycobacterium tuberculosis: functional analysis of gyra mutation at position 74.a pcr-sequencing assay was evaluated for direct detection of mutations in the quinolone resistance-determining region (qrdr) of gyrase a (gyra) gene in fluoroquinolone-resistant mycobacterium tuberculosis in respiratory specimens. as determined by gyra qrdr analysis, complete concordance of genotypic and phenotypic fluoroquinolone resistance was demonstrated. our results indicate that the assay is a rapid and reliable method for the diagnosis of fluoroquinolone-resistant tuberculosis, facilitati ...201020956608
molecular characterization of fluoroquinolone resistance in mycobacterium tuberculosis: functional analysis of gyra mutation at position 74.a pcr-sequencing assay was evaluated for direct detection of mutations in the quinolone resistance-determining region (qrdr) of gyrase a (gyra) gene in fluoroquinolone-resistant mycobacterium tuberculosis in respiratory specimens. as determined by gyra qrdr analysis, complete concordance of genotypic and phenotypic fluoroquinolone resistance was demonstrated. our results indicate that the assay is a rapid and reliable method for the diagnosis of fluoroquinolone-resistant tuberculosis, facilitati ...201020956608
microbes responsible for acute exacerbation of copd.this study was designed to find out the microbes responsible for acute exacerbation of chronic obstructive pulmonary disease (copd). this study was carried out in the national institute of diseases of the chest & hospital (nidch), dhaka during the period of january 2003 to december 2003. the study was a prospective case control study. there were 88 male and 2 female patients. the majority of the study subjects fell within the range of 50-70 years. all were smokers. 30 stable copd patients were t ...201020956903
resistance and the management of complicated skin and skin structure infections: the role of ceftobiprole.antimicrobial resistant bacteria are an increasing concern due to the resulting increase in morbidity, mortality, and health-care costs associated with the administration of inadequate or delayed antimicrobial therapy. the implications of inadequate antimicrobial therapy in complicated skin and skin structure infections (csssis) have gained more attention recently, most likely due to the recent emergence of community-acquired methicillin resistant staphylococcus aureus (mrsa) and the already hig ...201020957140
potential of ceragenin csa-13 and its mixture with pluronic f-127 as treatment of topical bacterial infections.ceragenin csa-13 is a synthetic mimic of cationic antibacterial peptides, with facial amphiphilic morphology reproduced using a cholic acid scaffold. previous data have shown that this molecule displays broad-spectrum antibacterial activity, which decreases in the presence of blood plasma. however, at higher concentrations, csa-13 can cause lysis of erythrocytes. this study was designed to assess in vitro antibacterial and haemolytic activity of csa-13 in the presence of pluronic f-127.201020961363
potential of ceragenin csa-13 and its mixture with pluronic f-127 as treatment of topical bacterial infections.ceragenin csa-13 is a synthetic mimic of cationic antibacterial peptides, with facial amphiphilic morphology reproduced using a cholic acid scaffold. previous data have shown that this molecule displays broad-spectrum antibacterial activity, which decreases in the presence of blood plasma. however, at higher concentrations, csa-13 can cause lysis of erythrocytes. this study was designed to assess in vitro antibacterial and haemolytic activity of csa-13 in the presence of pluronic f-127.201020961363
molecular probes for diagnosis of clinically relevant bacterial infections in blood cultures.broad-range real-time pcr and sequencing of the 16s rrna gene region is a widely known method for the detection and identification of bacteria in clinical samples. however, because of the need for sequencing, such identification of bacteria is time-consuming. the aim of our study was to develop a more rapid 16s real-time pcr-based identification assay using species- or genus-specific probes. the gram-negative bacteria were divided into pseudomonas species, pseudomonas aeruginosa, escherichia col ...201020962139
epidemiology of nasopharyngeal carriage of respiratory bacterial pathogens in children and adults: cross-sectional surveys in a population with high rates of pneumococcal disease.to determine the prevalence of carriage of respiratory bacterial pathogens, and the risk factors for and serotype distribution of pneumococcal carriage in an australian aboriginal population.201020969800
mapping of the neisseria meningitidis nada cell-binding site: relevance of predicted {alpha}-helices in the nh2-terminal and dimeric coiled-coil regions.nada is a trimeric autotransporter protein of neisseria meningitidis belonging to the group of oligomeric coiled-coil adhesins. it is implicated in the colonization of the human upper respiratory tract by hypervirulent serogroup b n. meningitidis strains and is part of a multiantigen anti-serogroup b vaccine. structure prediction indicates that nada is made by a cooh-terminal membrane anchor (also necessary for autotranslocation to the bacterial surface), an intermediate elongated coiled-coil-ri ...201020971901
mapping of the neisseria meningitidis nada cell-binding site: relevance of predicted {alpha}-helices in the nh2-terminal and dimeric coiled-coil regions.nada is a trimeric autotransporter protein of neisseria meningitidis belonging to the group of oligomeric coiled-coil adhesins. it is implicated in the colonization of the human upper respiratory tract by hypervirulent serogroup b n. meningitidis strains and is part of a multiantigen anti-serogroup b vaccine. structure prediction indicates that nada is made by a cooh-terminal membrane anchor (also necessary for autotranslocation to the bacterial surface), an intermediate elongated coiled-coil-ri ...201020971901
[evaluation of the safety and efficacy of cefditoren pivoxil fine granules for pediatric use in pediatric patients with acute otitis media].a clinical practice guideline for the diagnosis and management of acute otitis media in children, in view of the causative organisms of the disease and their drug susceptibility, was issued in march 2006. in the guideline, cefditoren pivoxil (cdtr-pi, meiact ms fine granules 10% for pediatric use) is recommended as an oral cephem antibiotic for the treatment of the disease. to collect information on the appropriate use of the drug in the clinical setting after issuance of the guideline, we condu ...201020976878
differences in nasopharyngeal bacterial carriage in preschool children from different socio-economic origins.clin microbiol infect abstract: a prospective cohort study of preschool healthy children (3-6 years old) from two distinct socio-economic settings in the brussels area, belgium, was conducted during the years 2006-2008. the objectives were to evaluate nasopharyngeal colonization by streptococcus pneumoniae, staphylococcus aureus, moraxella catarrhalis and haemophilus influenzae at the time of pcv7 vaccine introduction and to assess the socio-economic level impact on flora composition and antibio ...201020977542
topical ciprofloxacin is superior to topical saline and systemic antibiotics in the treatment of tympanostomy tube otorrhea in children: the results of a randomized clinical trial.to compare the clinical failure rates among children with otorrhea through tympanostomy tubes treated with topical or systemic antibiotics versus topical saline.201020979100
bacterial infections and pediatric asthma.streptococcus pneumoniae, haemophilus influenzae and moraxella catarrhalis seem to have no role in asthma in children. mycoplasma pneumoniae and chlamydophila pneumoniae can induce wheezing and cause asthma exacerbations in children, and chronic chlamydophila infections may even participate in asthma pathogenesis. however, studies have failed to show any benefits from antibiotics for incipient or stable pediatric asthma, as well as for asthma exacerbations in children. exposure to antibiotics in ...201021029939
adhesive activity of the haemophilus cryptic genospecies cha autotransporter is modulated by variation in tandem peptide repeats.the haemophilus cryptic genospecies is an important cause of maternal genital tract and neonatal systemic infections and initiates infection by colonizing the genital or respiratory epithelium. in recent work, we identified a unique haemophilus cryptic genospecies protein called cha, which mediates efficient adherence to genital and respiratory epithelia. the cha adhesin belongs to the trimeric autotransporter family and contains an n-terminal signal peptide, an internal passenger domain that ha ...201021037000
adhesive activity of the haemophilus cryptic genospecies cha autotransporter is modulated by variation in tandem peptide repeats.the haemophilus cryptic genospecies is an important cause of maternal genital tract and neonatal systemic infections and initiates infection by colonizing the genital or respiratory epithelium. in recent work, we identified a unique haemophilus cryptic genospecies protein called cha, which mediates efficient adherence to genital and respiratory epithelia. the cha adhesin belongs to the trimeric autotransporter family and contains an n-terminal signal peptide, an internal passenger domain that ha ...201021037000
antimicrobial, antimalarial, and antileishmanial activities of mono- and bis-quaternary pyridinium compounds.pyridinium-based oxime compounds have been utilized worldwide as antidotes following exposure to anticholinesterase agents. in the event of combined chemical and biological incident, it is of vital importance to know the ability of antidotes to provide additional protection against biological threats. this paper reports results of in vitro antimicrobial and antiprotozoal activities of a series of quaternary pyridinium oximes against a number of lower pathogenicity bsl-1 and 2 agents. in general, ...201021040494
in vitro activity of ceftaroline against a broad spectrum of recent clinical anaerobic isolates.the in vitro activity of ceftaroline was compared with those of ceftriaxone, clindamycin, imipenem, metronidazole, moxifloxacin, tigecycline, and vancomycin against 514 clinical anaerobic isolates using clinical and laboratory standards institute (clsi) standard methodology. ceftaroline demonstrated good to excellent activity against gram-positive anaerobic pathogens and limited activity against gram-negative pathogens, particularly bacteroides fragilis group isolates.201021041506
in vitro activity of ceftaroline against a broad spectrum of recent clinical anaerobic isolates.the in vitro activity of ceftaroline was compared with those of ceftriaxone, clindamycin, imipenem, metronidazole, moxifloxacin, tigecycline, and vancomycin against 514 clinical anaerobic isolates using clinical and laboratory standards institute (clsi) standard methodology. ceftaroline demonstrated good to excellent activity against gram-positive anaerobic pathogens and limited activity against gram-negative pathogens, particularly bacteroides fragilis group isolates.201021041506
multicomponent moraxella catarrhalis outer membrane vesicles induce an inflammatory response and are internalized by human epithelial cells.moraxella catarrhalis is an emerging human respiratory pathogen in patients with chronic obstructive pulmonary disease (copd) and in children with acute otitis media. the specific secretion machinery known as outer membrane vesicles (omvs) is a mechanism by which gram-negative pathogens interact with host cells during infection. we identified 57 proteins in m. catarrhalis omvs using a proteomics approach combining two-dimensional sds-page and maldi-tof mass spectrometry analysis. the omvs contai ...201021044239
new insights into the enigma of immunoglobulin d.immunoglobulin d (igd) has remained a mysterious antibody class for almost half a century. igd was initially thought to be a recently evolved ig isotype expressed only by some mammalian species, but recent discoveries in fishes and amphibians demonstrate that igd was present in the ancestor of all jawed vertebrates and has important immunological functions. the structure of igd has been very dynamic throughout evolution. mammals can express igd through alternative splicing and class switch recom ...201020727035
down-regulation of porin m35 in moraxella catarrhalis by aminopenicillins and environmental factors and its potential contribution to the mechanism of resistance to aminopenicillins.the outer membrane protein m35 of moraxella catarrhalis is an antigenically conserved porin. knocking out m35 significantly increases the mics of aminopenicillins. the aim of this study was to determine the biological mechanism of this potentially new antimicrobial resistance mechanism of m. catarrhalis and the behaviour of m35 in general stress situations.201020801781
sensitization of microcin j25-resistant strains by a membrane-permeabilizing peptide.microcin j25 (mccj25) is a plasmid-encoded, 21-amino-acid, antibacterial peptide produced by escherichia coli. mccj25 inhibits rna polymerase and the membrane respiratory chain. mccj25 uptake into e. coli-sensitive strains is mediated by the outer membrane receptor fhua and the inner membrane proteins tonb, exbb, exbd, and sbma. this peptide is active on some e. coli, salmonella, and shigella species strains, while other gram-negative bacteria, such as clinical isolates of enterobacter cloacae, ...201020802073
comparative analyses of the bacterial microbiota of the human nostril and oropharynx.the nose and throat are important sites of pathogen colonization, yet the microbiota of both is relatively unexplored by culture-independent approaches. we examined the bacterial microbiota of the nostril and posterior wall of the oropharynx from seven healthy adults using two culture-independent methods, a 16s rrna gene microarray (phylochip) and 16s rrna gene clone libraries. while the bacterial microbiota of the oropharynx was richer than that of the nostril, the oropharyngeal microbiota vari ...201020802827
indirect pathogenicity of haemophilus influenzae and moraxella catarrhalis in polymicrobial otitis media occurs via interspecies quorum signaling.otitis media (om) is among the leading diseases of childhood and is caused by opportunists that reside within the nasopharynx, such as haemophilus influenzae and moraxella catarrhalis. as with most airway infections, it is now clear that om infections involve multiple organisms. this study addresses the hypothesis that polymicrobial infection alters the course, severity, and/or treatability of om disease. the results clearly show that coinfection with h. influenzae and m. catarrhalis promotes th ...201020802829
prevalence of antimicrobial-resistant pathogens in canadian hospitals: results of the canadian ward surveillance study (canward 2008).a total of 5,282 bacterial isolates obtained between 1 january and 31 december 31 2008, inclusive, from patients in 10 hospitals across canada as part of the canadian ward surveillance study (canward 2008) underwent susceptibility testing. the 10 most common organisms, representing 78.8% of all clinical specimens, were as follows: escherichia coli (21.4%), methicillin-susceptible staphylococcus aureus (mssa; 13.9%), streptococcus pneumoniae (10.3%), pseudomonas aeruginosa (7.1%), klebsiella pneu ...201020805395
vitronectin in bacterial pathogenesis: a host protein used in complement escape and cellular invasion.the multifunctional human glycoprotein vitronectin (vn) plays a significant role in cell migration, tissue repair and regulation of membrane attack complex (mac) formation. it also promotes neutrophil infiltration and, thus, enhances the inflammatory process during infection. in the host, a balanced homeostasis is maintained by vn due to neutralization of the self-reactivity of the mac. on the other hand, vn bound to the bacterial surface protects from mac-mediated lysis and enhances adhesion. g ...201020807208
the synthetic bacterial lipopeptide pam3csk4 modulates respiratory syncytial virus infection independent of tlr activation.respiratory syncytial virus (rsv) is an important cause of acute respiratory disease in infants, immunocompromised subjects and the elderly. however, it is unclear why most primary rsv infections are associated with relatively mild symptoms, whereas some result in severe lower respiratory tract infections and bronchiolitis. since rsv hospitalization has been associated with respiratory bacterial co-infections, we have tested if bacterial toll-like receptor (tlr) agonists influence rsv-a2-gfp inf ...201020808895
moraxella catarrhalis: an unrecognized pathogen of the oral cavity?abstract objective: we investigated the effect of the bacterial flora of the nose and throat on the outcome of the initial repairs of the cleft palate in the presence of prophylactic antibiotics. design: a retrospective review of 90 procedures in 66 patients who had cleft palate repair between april 2005 and june 2007 was carried out at booth hall children's hospital, manchester, uk. both isolated cleft palate (cp) and cleft lip and palate (clp) patients were included. exclusion criteria include ...201020815726
specificity in killing pathogens is mediated by distinct repertoires of human neutrophil peptides.neutrophil-derived antimicrobial peptides and proteins (amps) play an important role in the defense against microbes. absence of defense is illustrated by neutropenic patients with frequent bacterial and fungal infections. however, the specificity of the antimicrobial effects has not been adequately described. we set out to determine the specific antimicrobial pattern of polypeptides in neutrophils (polymorphonuclear leukocytes, pmns) against 4 potential human pathogens: moraxella catarrhalis, s ...201020820100
prediction of delayed recovery from pediatric community-acquired pneumonia.if children with community-acquired pneumonia (cap) do not recover within 48 hours after starting antibiotic therapy, complications are possible and a checkup must be ensured.aim of the present study was to evaluate the improvement of pediatric cap, within 48 hours after starting therapy, in relation to age, etiology, clinical/laboratory characteristics and selected antibiotics.201020670443
outbreak of corynebacterium pseudodiphtheriticum infection in cystic fibrosis patients, france.an increasing body of evidence indicates that nondiphtheria corynebacteria may be responsible for respiratory tract infections. we report an outbreak of corynebacterium pseudodiphtheriticum infection in children with cystic fibrosis (cf). to identify 18 c. pseudodiphtheriticum strains isolated from 13 french children with cf, we used molecular methods (partial rpob gene sequencing) and matrix-assisted laser desorption ionization time-of-flight (maldi-tof) mass spectrometry. clinical symptoms wer ...201020678316
[the role of macrolides in treatment of exacerbations of chronic obstructive pulmonary disease].exacerbations of chronic obstructive pulmonary disease (copd) cause a lot of hospital admissions, mortality, and strongly influence health-related quality of life. approximately half of copd exacerbations are associated with bacterial infections and many patients have lower airways colonization. current guidelines recommend antibotic therapy in course of copd exacerbation for patients with sputum purulence and suggest correlation between severity of symptoms and the type of infecting pathogen. t ...201020491344
activity of a novel series of acylides active against community-acquired respiratory pathogens.resistance to macrolides and beta-lactams has increased sharply amongst key respiratory pathogens, leading to major concern. a novel series of acylides was designed to overcome this resistance and was evaluated for in vitro and in vivo activity. this series of acylides was designed starting from clarithromycin by changing the substitution on the desosamine nitrogen, followed by conversion to 3-o-acyl and 11,12-carbamate. minimum inhibitory concentrations (mics) of acylides were determined agains ...201020493666
simple sequence repeats and genome plasticity in streptococcus agalactiae.simple sequence repeats (ssrs) and their role in phase variation have been extensively studied in gram-negative organisms, where they have been associated with antigenic variation and other adaptation strategies. in this study, we apply comparative genomics in order to find evidence of slipped-strand mispairing in the human gram-positive pathogen streptococcus agalactiae. in two consecutive screenings, 2,233 (650 + 1,583) ssrs were identified in our reference genome 2603v/r, and these loci were ...201020494995
adenoidectomy and nasopharyngeal carriage of streptococcus pneumoniae in young children.the effect of adenoidectomy on nasopharyngeal colonisation of pathogens has not previously been evaluated. the authors studied the effect of adenoidectomy on nasopharyngeal colonisation by bacteria causing otitis media and the effect of adenoidectomy on the development of pneumococcal capsular polysaccharide antibodies.201020504840
evaluation of the analytical performance of the xpert mtb/rif assay.we performed the first studies of analytic sensitivity, analytic specificity, and dynamic range for the new xpert mtb/rif assay, a nucleic acid amplification-based diagnostic system that detects mycobacterium tuberculosis and rifampin (rif) resistance in under 2 h. the sensitivity of the assay was tested with 79 phylogenetically and geographically diverse m. tuberculosis isolates, including 42 drug-susceptible isolates and 37 rif-resistant isolates containing 13 different rpob mutations or mutat ...201020504986
community-acquired bloodstream infections in africa: a systematic review and meta-analysis.data on the prevalence and causes of community-acquired bloodstream infections in africa are scarce. we searched three databases for studies that prospectively studied patients admitted to hospital with at least a blood culture, and found 22 eligible studies describing 58 296 patients, of whom 2051 (13.5%) of 15 166 adults and 3527 (8.2%) of 43 130 children had bloodstream infections. 1643 (29.1%) non-malaria bloodstream infections were due to salmonella enterica (58.4% of these non-typhoidal sa ...201020510282
the bps polysaccharide of bordetella pertussis promotes colonization and biofilm formation in the nose by functioning as an adhesin.many respiratory pathogens establish persistent infection or a carrier state in the human nasopharynx without overt disease symptoms but the presence of these in the lungs usually results in disease. although the anatomy and microenvironments between nasopharynx and lungs are different, a virulence factor with an organ-specific function in the colonization of the nasopharynx is unknown. in contrast to the severity of pertussis and mortality in non-vaccinated young children, bordetella pertussis ...201020633227
correlation of viral load of respiratory pathogens and co-infections with disease severity in children hospitalized for lower respiratory tract infection.the clinical significance of viral load and co-infections in children with respiratory infections is not clear.201020646956
exposing rodents to a combination of tobacco smoke and lipopolysaccharide results in an exaggerated inflammatory response in the lung.acute exacerbations of chronic obstructive pulmonary disease (copd), which are often associated with respiratory infections, are defined as a worsening of symptoms that require a change in medication. exacerbations are characterized by a reduction in lung function, quality of life and are associated with increased pro-inflammatory mediators in the lung. our aim was to develop an animal model to mimic aspects of this exaggerated inflammatory response by combining key etiological factors, tobacco ...201020649596
tracing phylogenomic events leading to diversity of haemophilus influenzae and the emergence of brazilian purpuric fever (bpf)-associated clones.here we report the use of a multi-genome dna microarray to elucidate the genomic events associated with the emergence of the clonal variants of haemophilus influenzae biogroup aegyptius causing brazilian purpuric fever (bpf), an important pediatric disease with a high mortality rate. we performed directed genome sequencing of strain hk1212 unique loci to construct a species dna microarray. comparative genome hybridization using this microarray enabled us to determine and compare gene complements ...201020654709
respiratory bacterial pathogens in the nasopharynx and lower airways of australian indigenous children with bronchiectasis.to test the hypothesis that bacterial density, strain diversity, and concordance of pathogens between upper and lower airways are higher in children with bronchiectasis than in those with non-bronchiectatic conditions.201020656297
biochemical and functional characterization of helicobacter pylori vesicles.helicobacter pylori can cause peptic ulcer disease and/or gastric cancer. adhesion of bacteria to the stomach mucosa is an important contributor to the vigour of infection and resulting virulence. h. pylori adheres primarily via binding of baba adhesins to abo/lewis b (leb) blood group antigens and the binding of saba adhesins to sialyl-lewis x/a (slex/a) antigens. similar to most gram-negative bacteria, h. pylori continuously buds off vesicles and vesicles derived from pathogenic bacteria often ...201020659286
efficacy and safety of nemonoxacin versus levofloxacin for community-acquired pneumonia.nemonoxacin, a novel nonfluorinated quinolone, exhibits potent in vitro and in vivo activities against community-acquired pneumonia (cap) pathogens, including multidrug-resistant streptococcus pneumoniae. patients with mild to moderate cap (n = 265) were randomized to receive oral nemonoxacin (750 mg or 500 mg) or levofloxacin (500 mg) once daily for 7 days. clinical responses were determined at the test-of-cure visit in intent-to-treat (itt), clinical per protocol (ppc), evaluable-itt, and eval ...201020660689
a decade of non-cystic fibrosis bronchiectasis 1996-2006.this study aimed to determine the aetiology, clinical presentation, co-morbidity, severity and the lobar distribution of non cystic fibrosis bronchiectasis (ncfb). we performed a retrospective review of clinical, radiological, immunological and microbiological data from 92 non-cf patients with a high resolution thoracic ct (hrct) diagnosis of bronchiectasis in the three dublin children's referral hospitals for the period 1996-2006. of 92 patients (50 female), the median age at diagnosis was 6.4 ...201020666070
in vitro antibacterial activities of s-013420, a novel bicyclolide, against respiratory tract pathogens.the in vitro activity of s-013420, a novel bicyclolide, was investigated.201020472695
expression of xylella fastidiosa fimbrial and afimbrial proteins during biofilm formation.complete sequencing of the xylella fastidiosa genome revealed characteristics that have not been described previously for a phytopathogen. one characteristic of this genome was the abundance of genes encoding proteins with adhesion functions related to biofilm formation, an essential step for colonization of a plant host or an insect vector. we examined four of the proteins belonging to this class encoded by genes in the genome of x. fastidiosa: the pila2 and pilc fimbrial proteins, which are co ...201020472735
single assay for simultaneous detection and differential identification of human and avian influenza virus types, subtypes, and emergent variants.for more than four decades the cause of most type a influenza virus infections of humans has been attributed to only two viral subtypes, a/h1n1 or a/h3n2. in contrast, avian and other vertebrate species are a reservoir of type a influenza virus genome diversity, hosting strains representing at least 120 of 144 combinations of 16 viral hemagglutinin and 9 viral neuraminidase subtypes. viral genome segment reassortments and mutations emerging within this reservoir may spawn new influenza virus str ...201020140251
biochemical analysis of lgt3, a glycosyltransferase of the bacterium moraxella catarrhalis.the lipooligosaccharide (los) of moraxella catarrhalis is unusual in that it lacks heptose. the sugar linking oligosaccharide to lipid a is a trisubstituted glucose. a single enzyme, lgt3, is suggested to trisubstitute this core sugar. the lgt3 gene encodes two distinct domains with high similarity to glucosyltransferases of the gt-a superfamily, thus encoding a bidomain, multifunctional glucosyltransferase. to characterise lgt3, the gene was amplified from m. catarrhalis, expressed in escherich ...201020153730
spectrum of activity, mutation rates, synergistic interactions, and the effects of ph and serum proteins for fusidic acid (cem-102).fusidic acid (cem-102) is a steroidal antimicrobial agent with focused gram-positive activity that acts by preventing bacterial protein synthesis via interacting with elongation factor g. a collection of 114 wild-type isolates (> 80 species) was used to define the contemporary limits of fusidic acid spectrum against gram-positive and gram-negative species. reference broth microdilution and anaerobic agar dilution methods were performed. modifications of standardized test methods included adding ...201020159376
atypical bacteria in adenoids and tonsils of children requiring adenotonsillectomy.the results of this study suggest that atypical bacteria may be involved not only in acute upper airway diseases but also in recurrent infections requiring adenoidectomy and/or tonsillectomy. therefore, their identification, followed by an appropriate treatment, should be considered.201019958241
development of a rapid automated influenza a, influenza b, and respiratory syncytial virus a/b multiplex real-time rt-pcr assay and its use during the 2009 h1n1 swine-origin influenza virus epidemic in milwaukee, wisconsin.rapid, semiautomated, and fully automated multiplex real-time rt-pcr assays were developed and validated for the detection of influenza (flu) a, flu b, and respiratory syncytial virus (rsv) from nasopharyngeal specimens. the assays can detect human h1n1, h3n2, and swine-origin (s-oiv) h1n1 flu a viruses and were effectively used to distinguish flu a infections (of all subtypes) from flu b and rsv infections during the current s-oiv outbreak in milwaukee, wi. the analytical limits of detection we ...201019959800
virulence-associated trimeric autotransporters of haemophilus parasuis are antigenic proteins expressed in vivo.glässer's disease is a re-emerging swine disease characterized by a severe septicaemia. vaccination has been widely used to control the disease, although there is a lack of extended cross-protection. trimeric autotransporters, a family of surface exposed proteins implicated in host-pathogen interactions, are good vaccine candidates. members of this family have been described in haemophilus parasuis and designated as virulence-associated trimeric autotransporters (vtaa). in this work, we produced ...201019995512
virulence-associated trimeric autotransporters of haemophilus parasuis are antigenic proteins expressed in vivo.glässer's disease is a re-emerging swine disease characterized by a severe septicaemia. vaccination has been widely used to control the disease, although there is a lack of extended cross-protection. trimeric autotransporters, a family of surface exposed proteins implicated in host-pathogen interactions, are good vaccine candidates. members of this family have been described in haemophilus parasuis and designated as virulence-associated trimeric autotransporters (vtaa). in this work, we produced ...201019995512
community-acquired upper respiratory tract infections and the role of third-generation oral cephalosporins.common community-acquired infections include those of the upper respiratory tract. in the 1990s, the antimicrobial treatment of upper respiratory tract infections focused on penicillin-resistant streptococcus pneumoniae. however, following the introduction of a pneumococcal conjugate vaccine, a decrease in invasive pneumococcal disease occurred, and in the case of otitis media a shift towards haemophilus influenzae as the predominant causative pathogen was observed. future antimicrobial therapy ...201020014898
etiology of community-acquired pneumonia: increased microbiological yield with new diagnostic methods.the microbial etiology of community-acquired pneumonia (cap) is still not well characterized. during the past few years, polymerase chain reaction (pcr)-based methods have been developed for many pathogens causing respiratory tract infections. the aim of this study was to determine the etiology of cap among adults-especially the occurrence of mixed infections among patients with cap-by implementing a new diagnostic pcr platform combined with conventional methods.201020014950
a systemic neutrophil response precedes robust cd8(+) t-cell activation during natural respiratory syncytial virus infection in infants.severe primary respiratory syncytial virus (rsv) infections are characterized by bronchiolitis accompanied by wheezing. controversy exists as to whether infants suffer from virus-induced lung pathology or from excessive immune responses. furthermore, detailed knowledge about the development of primary t-cell responses to viral infections in infants is lacking. we studied the dynamics of innate neutrophil and adaptive t-cell responses in peripheral blood in relation to the viral load and paramete ...201020015982
a systemic neutrophil response precedes robust cd8(+) t-cell activation during natural respiratory syncytial virus infection in infants.severe primary respiratory syncytial virus (rsv) infections are characterized by bronchiolitis accompanied by wheezing. controversy exists as to whether infants suffer from virus-induced lung pathology or from excessive immune responses. furthermore, detailed knowledge about the development of primary t-cell responses to viral infections in infants is lacking. we studied the dynamics of innate neutrophil and adaptive t-cell responses in peripheral blood in relation to the viral load and paramete ...201020015982
disordered microbial communities in asthmatic airways.a rich microbial environment in infancy protects against asthma [1], [2] and infections precipitate asthma exacerbations [3]. we compared the airway microbiota at three levels in adult patients with asthma, the related condition of copd, and controls. we also studied bronchial lavage from asthmatic children and controls.201020052417
high-throughput identification of bacteria and yeast by matrix-assisted laser desorption ionization-time of flight mass spectrometry in conventional medical microbiology laboratories.matrix-assisted laser desorption ionization-time of flight mass spectrometry (maldi-tof ms) is suitable for high-throughput and rapid diagnostics at low costs and can be considered an alternative for conventional biochemical and molecular identification systems in a conventional microbiological laboratory. first, we evaluated maldi-tof ms using 327 clinical isolates previously cultured from patient materials and identified by conventional techniques (vitek-ii, api, and biochemical tests). discre ...201020053859
capacity of serotype 19a and 15b/c streptococcus pneumoniae isolates for experimental otitis media: implications for the conjugate vaccine.non-vaccine streptococcus pneumoniae serotypes are increasingly associated with disease. we evaluated isolates of the same sequence type (st199) but different serotypes (15b/c, 19a) for growth in vitro, and pathogenic potential in a chinchilla otitis media model. we also developed a quantitative pcr (qpcr) assay to quantitatively assess each isolate, circumventing the need for selectable markers. in vitro studies showed faster growth of serotype 19a over 15b/c. both were equally capable of colon ...201020067753
duplex real-time reverse transcriptase pcr assays for rapid detection and identification of pandemic (h1n1) 2009 and seasonal influenza a/h1, a/h3, and b viruses.reports of a novel influenza virus type a (h1n1), now designated by the world health organization as pandemic (h1n1) 2009, emerged from the united states and mexico in april 2009. the management of the pandemic in australia required rapid and reliable testing of large numbers of specimens for the novel influenza strain and differentiation from seasonal influenza strains. a real-time reverse transcriptase pcr (rt-pcr) assay for the detection of pandemic (h1n1) 2009 was designed and used with exis ...201020071557
development of a novel dna microarray to detect bacterial pathogens in patients with chronic obstructive pulmonary disease (copd).a novel microarray was constructed with dna pcr product probes targeting species specific functional genes of nine clinically significant respiratory pathogens, including the gram-positive organisms (streptococcus pneumoniae, streptococcus pyogenes), the gram-negative organisms (chlamydia pneumoniae, coxiella burnetii haemophilus spp., legionella pneumophila, moraxella catarrhalis, and pseudomonas aeruginosa), as well as the atypical bacterium, mycoplasma pneumoniae. in a "proof-of-concept" eval ...201020074591
b cell activation by outer membrane vesicles--a novel virulence mechanism.secretion of outer membrane vesicles (omv) is an intriguing phenomenon of gram-negative bacteria and has been suggested to play a role as virulence factors. the respiratory pathogens moraxella catarrhalis reside in tonsils adjacent to b cells, and we have previously shown that m. catarrhalis induce a t cell independent b cell response by the immunoglobulin (ig) d-binding superantigen mid. here we demonstrate that moraxella are endocytosed and killed by human tonsillar b cells, whereas omv have t ...201020090836
identification of potential therapeutic targets for burkholderia cenocepacia by comparative transcriptomics.burkholderia cenocepacia is an endemic soil dweller and emerging opportunistic pathogen in patients with cystic fibrosis (cf). the identification of virulence factors and potential therapeutic targets has been hampered by the genomic diversity within the species as many factors are not shared among the pathogenic members of the species.201020090946
a two-tube combined taqman/sybr green assay to identify mycobacteria and detect single global lineage-defining polymorphisms in mycobacterium tuberculosis.we have developed a novel real-time pcr assay to identify and perform preliminary genotyping of mycobacteria in a manner tailored to our local service. within a single thermocycler run, mycobacterial 16s rdna and the mycobacterium tuberculosis global lineage-defining rd750 polymorphism are targeted in separate reaction tubes, each of which includes both taqman and sybr green chemistries. the results of this 16s-rd assay differentiate m. tuberculosis complex (mtbc) from nontuberculous mycobacteri ...201020093392
early biofilm formation on microtiter plates is not correlated with the invasive disease potential of streptococcus pneumoniae.biofilm formation has been suggested to play an important role during streptococcus pneumoniae nasopharyngeal colonization and may facilitate progression to pneumonia. to test whether the ability of s. pneumoniae to form biofilms was important for virulence we screened the ability of 30 invasive and 22 non-invasive clinical isolates of serotype 6a and 6b to form early biofilms on polystyrene microtiter plates and infect mice following intranasal and intratracheal challenge. we first determined t ...201020096771
current management of pediatric acute otitis media.acute otitis media (aom) is the most common childhood bacterial infection for which antibiotics are prescribed worldwide. the most common pathogens causing aom in children are streptococcus pneumoniae, nontypeable haemophilus influenzae, moraxella catarrhalis and group a streptococcus. antibiotic resistance is increasing among the bacterial pathogens causing aom, with percentages of penicillin- and macrolide-resistant s. pneumoniae strains estimated to be between 30 and 70%, and of beta-lactamas ...201020109045
nxl-103, a combination of flopristin and linopristin, for the potential treatment of bacterial infections including community-acquired pneumonia and mrsa.novexel is developing the novel, orally active, semisynthetic streptogramin nxl-103, which has potential therapeutic application in the treatment of community-acquired pneumonia, community- or hospital-acquired mrsa, vancomycin-resistant enterococcus, and acute bacterial skin and soft tissue infections. nxl-103 is a combination of streptogramin a:streptogramin b components, initially developed in a 70:30 dose ratio. in multiple in vitro studies, nxl-103 demonstrated potent activity against diffe ...201020112172
the use of culture-independent tools to characterize bacteria in endo-tracheal aspirates from pre-term infants at risk of bronchopulmonary dysplasia.although premature infants are increasingly surviving the neonatal period, up to one-third develop bronchopulmonary dysplasia (bpd). despite evidence that bacterial colonization of the neonatal respiratory tract by certain bacteria may be a risk factor in bpd development, little is known about the role these bacteria play. the aim of this study was to investigate the use of culture-independent molecular profiling methodologies to identify potential etiological agents in neonatal airway secretion ...201020121490
coevolution of activating and inhibitory receptors within mammalian carcinoembryonic antigen families.most rapidly evolving gene families are involved in immune responses and reproduction, two biological functions which have been assigned to the carcinoembryonic antigen (cea) gene family. to gain insights into evolutionary forces shaping the cea gene family we have analysed this gene family in 27 mammalian species including monotreme and marsupial lineages.201020132533
the interaction between respiratory viruses and pathogenic bacteria in the upper respiratory tract of asymptomatic aboriginal and non-aboriginal children.associations between respiratory viruses and the bacterial pathogens streptococcus pneumoniae, haemophilus influenzae, and moraxella catarrhalis may be important in the pathogenesis of otitis media (om). however, data on asymptomatic identification rates of respiratory viruses are limited, particularly in indigenous populations, who suffer a high burden of om.201020134359
unique host iron utilization mechanisms of helicobacter pylori revealed with iron-deficient chemically defined media.helicobacter pylori chronically infects the gastric mucosa, where it can be found free in mucus, attached to cells, and intracellularly. h. pylori requires iron for growth, but the sources of iron used in vivo are unclear. in previous studies, the inability to culture h. pylori without serum made it difficult to determine which host iron sources might be used by h. pylori. using iron-deficient, chemically defined medium, we determined that h. pylori can bind and extract iron from hemoglobin, tra ...201020176792
cem-101 activity against gram-positive organisms.the in vitro activity of cem-101, a new fluoroketolide, was determined against gram-positive organisms with various macrolide susceptibility profiles. experiments for determination of the mics and minimum bactericidal concentrations (mbcs), timed killing, single-step and multistep mutation rates, the erythromycin induction of resistance, postantibiotic effect (pae), and drug interactions were performed for cem-101; and the results were compared to those obtained with telithromycin, macrolides, a ...201020176910
in vitro antibacterial activities of jnj-q2, a new broad-spectrum fluoroquinolone.jnj-q2, a novel fluorinated 4-quinolone, was evaluated for its antibacterial potency by broth and agar microdilution mic methods in studies focused on skin and respiratory tract pathogens, including strains exhibiting contemporary fluoroquinolone resistance phenotypes. against a set of 118 recent clinical isolates of streptococcus pneumoniae, including fluoroquinolone-resistant variants bearing multiple dna topoisomerase target mutations, an mic(90) value for jnj-q2 of 0.12 microg/ml was determi ...201020176911
neutralization of genetically diverse hiv-1 strains by iga antibodies to the gp120-cd4-binding site from long-term survivors of hiv infection.to identify an hiv epitope suitable for vaccine development.201020186035
virulence and immunomodulatory roles of bacterial outer membrane vesicles.outer membrane (om) vesicles are ubiquitously produced by gram-negative bacteria during all stages of bacterial growth. om vesicles are naturally secreted by both pathogenic and nonpathogenic bacteria. strong experimental evidence exists to categorize om vesicle production as a type of gram-negative bacterial virulence factor. a growing body of data demonstrates an association of active virulence factors and toxins with vesicles, suggesting that they play a role in pathogenesis. one of the most ...201020197500
vitronectin binds to the head region of moraxella catarrhalis ubiquitous surface protein a2 and confers complement-inhibitory activity.the serum resistance of the common respiratory pathogen moraxella catarrhalis is mainly dependent on ubiquitous surface proteins (usp) a1 and a2 that interact with complement factor 3 (c3) and complement inhibitor c4b binding protein (c4bp) preventing the alternative and classical pathways of the complement system respectively. uspa2 also has the capacity to attract vitronectin that in turn binds c9 and hereby inhibits membrane attack complex (mac) formation. we found uspa2 as a major vitronecti ...201020199596
rapid differentiation of francisella species and subspecies by fluorescent in situ hybridization targeting the 23s rrna.francisella (f.) tularensis is the causative agent of tularemia. due to its low infectious dose, ease of dissemination and high case fatality rate, f. tularensis was the subject in diverse biological weapons programs and is among the top six agents with high potential if misused in bioterrorism. microbiological diagnosis is cumbersome and time-consuming. methods for the direct detection of the pathogen (immunofluorescence, pcr) have been developed but are restricted to reference laboratories.201020205957
antimicrobial characterisation of cem-101 activity against respiratory tract pathogens, including multidrug-resistant pneumococcal serogroup 19a isolates.cem-101 is a novel fluorinated macrolide-ketolide with potent activity against bacterial pathogens that are susceptible or resistant to other macrolide-lincosamide-streptogramin b (mls(b))-ketolide agents. cem-101 is being developed for oral and parenteral use in moderate to moderately severe community-acquired bacterial pneumonia. the objective of this study was to assess the activity of cem-101 and comparators against contemporary respiratory tract infection (rti) isolates. a worldwide sample ...201020211548
performance of matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of bacterial strains routinely isolated in a clinical microbiology laboratory.matrix-assisted laser desorption ionization-time of flight mass spectrometry (maldi-tof ms) has recently been introduced in diagnostic microbiology laboratories for the identification of bacterial and yeast strains isolated from clinical samples. in the present study, we prospectively compared maldi-tof ms to the conventional phenotypic method for the identification of routine isolates. colonies were analyzed by maldi-tof ms either by direct deposition on the target plate or after a formic acid- ...201020220166
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