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respiratory diphtheria in an asylum seeker from afghanistan arriving to finland via sweden, december 2015.in december 2015, an asylum seeker originating from afghanistan was diagnosed with respiratory diphtheria in finland. he arrived in finland from sweden where he had already been clinically suspected and tested for diphtheria. corynebacterium diphtheriae was confirmed in sweden and shown to be genotypically and phenotypically toxigenic. the event highlights the importance of early case detection, rapid communication within the country and internationally as well as preparedness plans of diphtheri ...201626840007
public health action following an outbreak of toxigenic cutaneous diphtheria in an auckland refugee resettlement centre.global forced displacement has climbed to unprecedented levels due largely to regional conflict. degraded public health services leave displaced people vulnerable to multiple environmental and infectious hazards including vaccine preventable disease. while diphtheria is rarely notified in new zealand, a 2 person outbreak of cutaneous diphtheria occurred in refugees from afghanistan in february 2015 at the refugee resettlement centre in auckland. both cases had uncertain immunisation status. the ...201628043222
the 1925 diphtheria antitoxin run to nome - alaska: a public health illustration of human-animal collaboration.diphtheria is an acute toxin-mediated superficial infection of the respiratory tract or skin caused by the aerobic gram-positive bacillus corynebacterium diphtheriae. the epidemiology of infection and clinical manifestations of the disease vary in different parts of the world. historical accounts of diphtheria epidemics have been described in many parts of the world since antiquity. developed in the late 19th century, the diphtheria antitoxin (dat) played a pivotal role in the history of public ...201628032302
cnaa domains in bacterial pili are efficient dissipaters of large mechanical shocks.pathogenic bacteria adhere despite severe mechanical perturbations induced by the host, such as coughing. in gram-positive bacteria, extracellular protein appendages termed pili are necessary for adherence under mechanical stress. however, little is known about the behavior of gram-positive pili under force. here, we demonstrate a mechanism by which gram-positive pili are able to dissipate mechanical energy through mechanical unfolding and refolding of isopeptide bond-delimited polypeptide loops ...201626884173
[effect of antibiotics on toxin formation by corynebacterium diphtheriae]. 201624544855
disulfide-bond-forming pathways in gram-positive bacteria.disulfide bonds are important for the stability and function of many secreted proteins. in gram-negative bacteria, these linkages are catalyzed by thiol-disulfide oxidoreductases (dsb) in the periplasm. protein oxidation has been well studied in these organisms, but it has not fully been explored in gram-positive bacteria, which lack traditional periplasmic compartments. recent bioinformatics analyses have suggested that the high-gc-content bacteria (i.e., actinobacteria) rely on disulfide-bond- ...201626644434
diphtheroids-important nosocomial pathogens.diphtheroids are defined as aerobic, non-sporulating, pleomorphic gram-positive bacilli which are more uniformly stained than corynebacterium diphtheriae, lack the metachromatic granules and are arranged in a palisade manner. they are usually commensals of the skin and mucous membranes. they differ from c.diphtheriae in biochemical rea-ctions as well as in toxin production. since, they are usually found as commensals on the skin, they are often considered as mere contaminants when isolated from ...201628208859
microbial ecosystem analysis in root canal infections refractory to endodontic treatment.the purpose of this study was to combine multiple displacement amplification and checkerboard dna-dna hybridization to qualitatively and quantitatively evaluate the microbiota present in infections refractory to endodontic treatment.201627377440
extraction and bioactive profile of the compounds produced by rhodococcus sp. vld-10.a potent actinobacterial strain isolated from the marine samples of bheemunipatnam beach, visakhapatnam, india, was identified as rhodococcus sp. vld-10 using the conventional and genomic (16s rrna) approaches. bioactive compounds responsible for the antimicrobial activity of the strain were elucidated by cultivating the strain vld-10 in a modified yeast extract-malt extract-lactose broth followed by subsequent chromatographic and spectroscopic analyses. extraction, purification, and structural ...201628330333
toxigenic corynebacterium ulcerans isolated from a wild bird (ural owl) and its feed (shrew-moles): comparison of molecular types with human isolates.corynebacterium ulcerans is a pathogen causing diphtheria-like illness to humans. in contrast to diphtheria by corynebacterium diphtheriae circulating mostly among humans, c. ulcerans infection is zoonotic. the present study aimed to clarify how a zoonotic pathogen c. ulcerans circulates among wild birds and animals.201627000873
more than 20 years after re-emerging in the 1990s, diphtheria remains a public health problem in latvia.in 1994, the world health organization (who) declared the goal of eliminating diphtheria within the who european region by the year 2000. however, in 1990 an epidemic emerged within the russian federation and spread to other countries, including latvia, by 1994. we describe national surveillance and immunisation coverage data in latvia from 1994 to 2014 and present historical data from 1946. we defined a laboratory-confirmed case as a clinical case in which toxin-producing corynebacterium diphth ...201627934582
development, validation and implementation of a quadruplex real-time pcr assay for identification of potentially toxigenic corynebacteria.toxigenic corynebacteria are uncommon in the uk; however, laboratory confirmation by the national reference laboratory can inform public health action according to national guidelines. standard phenotypic tests for identification and toxin expression of isolates can take from ≥24 to ≥48 h from receipt. to decrease the time to result, a real-time pcr (qpcr) assay was developed for confirmation of both identification of corynebacterium diphtheriae and corynebacterium ulcerans/corynebacterium pseud ...201627902437
pathogenic properties of a corynebacterium diphtheriae strain isolated from a case of osteomyelitis.corynebacterium diphtheriae is typically recognized as a colonizer of the upper respiratory tract (respiratory diphtheria) and the skin (cutaneous diphtheria). however, different strains of corynebacteriumdiphtheriae can also cause invasive infections. in this study, the characterization of a non-toxigenic corynebacteriumdiphtheriae strain (designated br-inca5015) isolated from osteomyelitis in the frontal bone of a patient with adenoid cystic carcinoma was performed. pathogenic properties of th ...201627902402
first report on the draft genome sequences of corynebacterium diphtheriae isolates from india.we report here the draft genome sequences of five corynebacterium diphtheriae isolates of indian origin. the c. diphtheriae isolates th1141, th510, th1526, th1337, and th2031 belong to sequence type st-50, st-295, st-377, st-405, and st-405, with an average genome size of 2.5 mbp.201627881543
impact of lytr-cpsa-psr proteins on cell wall biosynthesis in corynebacterium glutamicum.proteins of the lcp (lytr, cpsa, psr) family have been shown to inherit important roles in bacterial cell wall biosynthesis. however, their exact function in the formation of the complex cell wall structures of the corynebacteriales, including the prominent pathogens mycobacterium tuberculosis and corynebacterium diphtheriae, remains unclear. here, we analyzed the role of the lcp proteins lcpa and lcpb of corynebacterium glutamicum, both of which localize at regions of nascent cell wall biosynth ...201627551018
outbreak investigation for toxigenic corynebacterium diphtheriae wound infections in refugees from northeast africa and syria in switzerland and germany by whole genome sequencing.toxigenic corynebacterium diphtheriae is an important and potentially fatal threat to patients and public health. during the current dramatic influx of refugees into europe, our objective was to use whole genome sequencing for the characterization of a suspected outbreak of c. diphtheriae wound infections among refugees. after conventional culture, we identified c. diphtheriae using matrix-assisted laser desorption/ionization time-of-flight (maldi-tof) and investigated toxigenicity by pcr. whole ...201627585943
process optimization for an industrial-scale production of diphtheria toxin by corynebacterium diphtheriae pw8.in this study, several parameters affecting the toxin production of corynebacterium diphtheriae parke williams 8 (pw8) were investigated in detail. the comparison studies of amino acid profile in nz amine a-based medium (nz medium) and beef digest-based medium (bd medium) suggested that an insufficient supply of amino acids was not responsible for low toxin yield observed in nz medium. supplementation of additional amino acids and growth promoting nutrient (in a form of yeast extract) into nz me ...201627640957
recent outbreaks of diphtheria in dibrugarh district, assam, india.diphtheria is still a significant child health problem in countries with low immunization coverage. reports of diphtheria in adult population are also increasing. here we describe three recent outbreaks of diphtheria in dibrugarh district, assam in two consecutive years. the study was undertaken in assam medical college & hospital, dibrugarh after the diagnosis of two diphtheria cases in the month of september and october 2015 and another in january 2016. outbreak investigation was done after de ...201627630847
microbiological and molecular characterization of corynebacterium diphtheriae isolated in algeria between 1992 and 2015.the objectives of this study were to undertake the microbiological and molecular characterization of corynebacterium diphtheriae isolates collected in algeria during epidemic and post-epidemic periods between 1992 and 2015. microbiological characterization includes the determination of biotype and toxigenicity status using phenotypic and genotypic methods. antimicrobial susceptibility was determined by the e-test method. molecular characterization was performed by multi-locus sequence typing. in ...201627585941
corynebacterium diphtheriae hmut: dissecting the roles of conserved residues in heme pocket stabilization.the heme-binding protein hmut is part of the corynebacterium diphtheriae heme uptake pathway and is responsible for the delivery of heme to the hmuuv abc transporter. hmut binds heme with a conserved his/tyr heme axial ligation motif. sequence alignment revealed additional conserved residues of potential importance for heme binding: r237, y272 and m292. in this study, site-directed mutations at these three positions provided insight into the nature of axial heme binding to the protein and its ef ...201627561288
genetics and genomics of the genus amycolatopsis.actinobacteria are gram-positive filamentous bacteria which contains some of the most deadly human pathogens (mycobacterium tuberculosis, m. leprae, corynebacterium diphtheriae, nocardia farcinica), plant pathogens (streptomyces scabies, leifsonia xyli) along with organisms that produces antibiotic (streptomycetes, amycolatopsis, salinospora). interestingly, these bacteria are equipped with an extraordinary capability of producing antibiotics and other metabolites which have medicinal properties ...201627407288
the chrsa and hrrsa two-component systems are required for transcriptional regulation of the hema promoter in corynebacterium diphtheriae.corynebacterium diphtheriae utilizes heme and hemoglobin (hb) as iron sources for growth in low-iron environments. in c. diphtheriae, the two-component signal transduction systems (tcss) chrsa and hrrsa are responsive to hb levels and regulate the transcription of promoters for hmuo, hrtab, and hema chrsa and hrrsa activate transcription at the hmuo promoter and repress transcription at hema in an hb-dependent manner. in this study, we show that hrrsa is the predominant repressor at hema and tha ...201627381918
postbooster antibodies from humans as source of diphtheria antitoxin.diphtheria antitoxin for therapeutic use is in limited supply. a potential source might be affinity-purified antibodies originally derived from plasma of adults who received a booster dose of a vaccine containing diphtheria toxoid. these antibodies might be useful for treating even severe cases of diphtheria.201627314309
evolution, epidemiology and diversity of corynebacterium diphtheriae: new perspectives on an old foe.diphtheria is a debilitating disease caused by toxigenic corynebacterium diphtheriae strains and has been effectively controlled by the toxoid vaccine, yet several recent outbreaks have been reported across the globe. moreover, non-toxigenic c. diphtheriae strains are emerging as a major global health concern by causing severe pharyngitis and tonsillitis, endocarditis, septic arthritis and osteomyelitis. molecular epidemiological investigations suggest the existence of outbreak-associated clones ...201627291708
development of a recombinant immunotoxin for the immunotherapy of autoreactive lymphocytes expressing mog-specific bcrs.myelin oligodendrocyte glycoprotein (mog) is one of the major autoantigens in multiple sclerosis (ms), therefore selective depletion of autoreactive lymphocytes exposing mog-specific b cell receptors (bcrs) would be beneficial in terms of ms treatment.201627099070
potency of a human monoclonal antibody to diphtheria toxin relative to equine diphtheria anti-toxin in a guinea pig intoxication model.prompt administration of anti-toxin reduces mortality following corynebacterium diphtheriae infection. current treatment relies upon equine diphtheria anti-toxin (dat), with a 10% risk of serum sickness and rarely anaphylaxis. the global dat supply is extremely limited; most manufacturers have ceased production. s315 is a neutralizing human igg1 monoclonal antibody to diphtheria toxin that may provide a safe and effective alternative to equine dat and address critical supply issues. to guide dos ...201627070129
reoxidation of the thiol-disulfide oxidoreductase mdba by a bacterial vitamin k epoxide reductase in the biofilm-forming actinobacterium actinomyces oris.post-translocational protein folding in the gram-positive biofilm-forming actinobacterium actinomyces oris is mediated by a membrane-bound thiol-disulfide oxidoreductase named mdba, which catalyzes oxidative folding of nascent polypeptides transported by the sec translocon. reoxidation of mdba involves a bacterial vitamin k epoxide reductase (vkor)-like protein that contains four cysteine residues c93/c101 and c175/c178 with the latter forming a canonical cxxc thioredoxin-like motif; however, th ...201728289087
simultaneous detection of 13 key bacterial respiratory pathogens by combination of multiplex pcr and capillary electrophoresis.lower respiratory tract infections continue to pose a significant threat to human health. it is important to accurately and rapidly detect respiratory bacteria. to compensate for the limits of current respiratory bacteria detection methods, we developed a combination of multiplex polymerase chain reaction (pcr) and capillary electrophoresis (mpce) assay to detect thirteen bacterial pathogens responsible for lower respiratory tract infections, including streptococcus pneumoniae, haemophilus influ ...201728807095
characterization of corynebacterium diphtheriae, c. confusum and c. amycolatum isolated from sows with genitourinary infection.porcine corynebacterium infection is still poorly studied, even though the pig has been described as an asymptomatic carrier of corynebacterium species, including the zoonotic species c. ulcerans, c. confusum and c. amycolatum. here we present the identification, molecular and antimicrobial susceptibility characterization of coryneform bacteria isolated from sows with urinary tract infection. c. diphtheriae, c. confusum and c. amycolatum were isolated from sows with urinary infection and metriti ...201728757016
molecular characterization of corynebacterium diphtheriae outbreak isolates, south africa, march-june 2015.in 2015, a cluster of respiratory diphtheria cases was reported from kwazulu-natal province in south africa. by using whole-genome analysis, we characterized 21 corynebacterium diphtheriae isolates collected from 20 patients and contacts during the outbreak (1 patient was infected with 2 variants of c. diphtheriae). in addition, we included 1 cutaneous isolate, 2 endocarditis isolates, and 2 archived clinical isolates (ca. 1980) for comparison. two novel lineages were identified, namely, toxigen ...201728726616
epidemiology of diphtheria in india, 1996-2016: implications for prevention and control.diphtheria is an acute disease caused by exotoxin-producing corynebacterium diphtheriae. globally, diphtheria has been showing a declining trend due to effective childhood vaccination programs. a substantial proportion of global burden of diphtheria is contributed by india. hospital-based surveillance studies as well as diphtheria outbreaks published in last 20 years (1996-2016) indicate that diphtheria cases are frequent among school-going children and adolescents. in some indian states, muslim ...201728722581
comparative genomic and phylogenetic analysis of a toxigenic clinical isolate of corynebacterium diphtheriae strain b-d-16-78 from malaysia.in this study, we report the comparative genomics and phylogenetic analysis of corynebacterium diphtheriae strain b-d-16-78 that was isolated from a clinical specimen in 2016. the complete genome of c. diphtheriae strain b-d-16-78 was sequenced using pacbio single molecule, real-time sequencing technology and consists of a 2,474,151-bp circular chromosome with an average gc content of 53.56%. the core genome of c. diphtheriae was also deduced from a total of 74 strains with complete or draft gen ...201728711373
the glyceraldehyde-3-phosphate dehydrogenase gapdh of corynebacterium diphtheriae is redox-controlled by protein s-mycothiolation under oxidative stress.mycothiol (msh) is the major low molecular weight (lmw) thiol in actinomycetes and functions in post-translational thiol-modification by protein s-mycothiolation as emerging thiol-protection and redox-regulatory mechanism. here, we have used shotgun-proteomics to identify 26 s-mycothiolated proteins in the pathogen corynebacterium diphtheriae dsm43989 under hypochlorite stress that are involved in energy metabolism, amino acid and nucleotide biosynthesis, antioxidant functions and translation. t ...201728694441
analysis of corynebacterium diphtheriae macrophage interaction: dispensability of corynomycolic acids for inhibition of phagolysosome maturation and identification of a new gene involved in synthesis of the corynomycolic acid layer.corynebacterium diphtheriae is the causative agent of diphtheria, a toxin mediated disease of upper respiratory tract, which can be fatal. as a member of the cmnr group, c. diphtheriae is closely related to members of the genera mycobacterium, nocardia and rhodococcus. almost all members of these genera comprise an outer membrane layer of mycolic acids, which is assumed to influence host-pathogen interactions. in this study, three different c. diphtheriae strains were investigated in respect to ...201728686600
resurgence of diphtheria in rural areas of north karnataka, india.a diphtheria outbreak was identified from vijayapura (formerly bijapur) district in the south indian state of karnataka in 2011. there was a surge in the number of throat swab samples received under the integrated disease surveillance programme (idsp) in north karnataka since then.201728681814
diphtheria in mayotte, 2007-2015.epidemiology of diphtheria in the southwestern indian ocean is poorly documented. we analyzed 14 cases of infection with toxigenic corynebacterium diphtheriae reported during 2007-2015 in mayotte, a french department located in this region. local control of diphtheria is needed to minimize the risk for importation of the bacterium into disease-free areas.201728628446
cutaneous corynebacterium infection presenting with disseminated skin nodules and ulceration.in the context of the european migrant crisis, more and more cases of cutaneous diphtheria are seen. a typical presentation includes painful cutaneous ulcerations with grayish-whitish pseudomembranes. here we present 2 male eritrean patients suffering from cutaneous nontoxigenic corynebacterium diphtheriae (patient 1) and corynebacterium striatum (patient 2) infection.201728611629
conformational control of udp-galactopyranose mutase inhibition.udp-galactopyranose mutase (glf or ugm) catalyzes the formation of uridine 5'-diphosphate-α-d-galactofuranose (udp-galf) from udp-galactopyranose (udp-galp). the enzyme is required for the production of galf-containing glycans. ugm is absent in mammals, but members of the corynebacterineae suborder require ugm for cell envelope biosynthesis. the need for ugm in some pathogens has prompted the search for inhibitors that could serve as antibiotic leads. optimizing inhibitor potency, however, has b ...201728608671
functional characterization of the collagen-binding protein dip2093 and its influence on host-pathogen interaction and arthritogenic potential of corynebacterium diphtheriae.corynebacterium diphtheriae is typically recognized as the a etiological agent of diphtheria, a toxaemic infection of the respiratory tract; however, both non-toxigenic and toxigenic strains are increasingly isolated from cases of invasive infections. the molecular mechanisms responsible for bacterial colonization and dissemination to host tissues remain only partially understood. in this report, we investigated the role of dip2093, described as a putative adhesin of the serine-aspartate repeat ...201728535857
toll-like receptor 2 and mincle cooperatively sense corynebacterial cell wall glycolipids.nontoxigenic corynebacterium diphtheriae and corynebacterium ulcerans cause invasive disease in humans and animals. host sensing of corynebacteria is largely uncharacterized, albeit the recognition of lipoglycans by toll-like receptor 2 (tlr2) appears to be important for macrophage activation by corynebacteria. the members of the order corynebacterineae (e.g., mycobacteria, nocardia, and rhodococci) share a glycolipid-rich cell wall dominated by mycolic acids (termed corynomycolic acids in coryn ...201728483856
diagnosis in france of a non-toxigenic tox gene-bearing strain of corynebacterium diphtheriae in a young male back from senegal.cutaneous diphtheria is uncommon in europe. in this study, we report a case of imported cutaneous infection due to a non-toxigenic but tox gene-bearing (nttb) strain of corynebacterium diphtheriae. the nttb strains are recognized as emerging pathogens across europe, and physicians and bacteriologists should be aware of the circulation of these strains.201728480263
an isolated outbreak of diphtheria in south africa, 2015.an outbreak of respiratory diphtheria occurred in two health districts in the province of kwazulu-natal in south africa in 2015. a multidisciplinary outbreak response team was involved in the investigation and management of the outbreak. fifteen cases of diphtheria were identified, with ages ranging from 4 to 41 years. of the 12 cases that were under the age of 18 years, 9 (75%) were not fully immunized for diphtheria. the case fatality was 27%. ninety-three household contacts, 981 school or wor ...201728478776
high-yield production of recombinant crm197, a non-toxic mutant of diphtheria toxin, in the periplasm of escherichia coli.a high cell density fed-batch process was developed for production of recombinant crm197, a non-toxic mutant of diphtheria toxin widely used as a carrier in polysaccharide-protein conjugate vaccines. fully soluble recombinant crm197 was obtained in high yields and with an authentic n-terminus, by targeting the protein to the periplasm of escherichia coli using the signal recognition particle (srp)-dependent signal sequence of flgi. response surface methodology (rsm) was used to optimize the set- ...201728397983
changes in the conjunctival bacterial flora of patients hospitalized in an intensive care unit.to identify the changes in aerobic conjunctival bacterial flora and to correlate culture results with physical health and the duration of patients' hospitalization in an intensive care unit (icu).201728380097
corynebacterium species causing breast abscesses among patients attending a tertiary care hospital in chennai, south india.corynebacterium species other than corynebacterium diphtheriae were mostly considered contaminants in the past, but there are reports of their association with wide variety of human infections lately. in this study, we look into corynebacterium species isolated from breast abscess patients and assess their antimicrobial susceptibility pattern and treatment outcomes.201728264610
first draft genome sequences of malaysian clinical isolates of corynebacterium diphtheriae.corynebacterium diphtheriae has caused multiple isolated diphtheria cases in malaysia over the years. here, we report the first draft genome sequences of 15 malaysia c. diphtheriae clinical isolates collected from the years 1981 to 2016.201728254972
sequence analysis of toxin gene-bearing corynebacterium diphtheriae strains, australia.by conducting a molecular characterization of corynebacterium diphtheriae strains in australia, we identified novel sequences, nonfunctional toxin genes, and 5 recent cases of toxigenic cutaneous diphtheria. these findings highlight the importance of extrapharyngeal infections for toxin gene-bearing (functional or not) and non-toxin gene-bearing c. diphtheriae strains. continued surveillance is recommended.201727983494
characterization of the second conserved domain in the heme uptake protein htaa from corynebacterium diphtheriae.htaa is a heme-binding protein that is part of the heme uptake system in corynebacterium diphtheriae. htaa contains two conserved regions (cr1 and cr2). it has been previously reported that both domains can bind heme; the cr2 domain binds hemoglobin more strongly than the cr1 domain. in this study, we report the biophysical characteristics of htaa-cr2. uv-visible spectroscopy and resonance raman experiments are consistent with this domain containing a single heme that is bound to the protein thr ...201727974280
comparing galactan biosynthesis in mycobacterium tuberculosis and corynebacterium diphtheriae.the suborder corynebacterineae encompasses species like corynebacterium glutamicum, which has been harnessed for industrial production of amino acids, as well as corynebacterium diphtheriae and mycobacterium tuberculosis, which cause devastating human diseases. a distinctive component of the corynebacterineae cell envelope is the mycolyl-arabinogalactan (mag) complex. the mag is composed of lipid mycolic acids, and arabinofuranose (araf) and galactofuranose (galf) carbohydrate residues. elucidat ...201728039359
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