Publications

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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
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
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
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
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
[effect of antibiotics on toxin formation by corynebacterium diphtheriae]. 201624544855
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
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
immunological characterization of diphtheria toxin recovered from corynebacterium pseudotuberculosis.diphtheria toxin (dt) is a potent toxin produced by the so-called diphtheria group which includes corynebacterium diphtheriae (c. diphtheriae), corynebacterium ulcerans (c. ulcerans), and corynebacterium pseudotuberculosis (c. pseudotuberculosis). the present investigation is aimed to study in detail the production of dt by c. pseudotuberculosis. twenty isolates were obtained from sheep diseased with caseous lymphadenitis (cla) and twenty-six isolates were obtained from 26 buffaloes diseased wit ...201626981011
a case of pharyngeal diphtheria in germany, june 2015.in june 2015, a 45-year-old man suffering from acute necrotic tonsillitis and throat phlegmon was hospitalized in nuremberg, germany. after emergency surgery the patient was initially treated with antibiotics.201626883545
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
a novel experimental platform for toxigenic and non-toxigenic corynebacterium ulcerans infection in mice.corynebacterium ulcerans is a zoonotic pathogen that can produce diphtheria toxin and causes an illness categorized as diphtheria in the european union because its clinical appearance is similar to that of diphtheria caused by corynebacterium diphtheriae. despite the importance of the pathogen in public health, the organism's mechanism of infection has not been extensively studied, especially in experimental animal models. therefore in the present study we constructed an intranasal infection sys ...201626607400
[cutaneous diphtheria after a minor injury in sri lanka].cutaneous dipththeria is an infectious bacterial disease endemic in tropical regions, but rarely diagnosed in germany. following travel in sri lanka, a 60-year-old german presented to our dermatological clinic with a skin ulcer and extensive erythematous erosive edema of his left foot. corynebacterium diphtheriae was isolated from a swab of the lesion. there were no clinical signs of toxic diphtheria. the patient was treated with penicillin g and erythromycin, followed by a slow healing of the l ...201626525966
corynebacterium diphtheriae in a free-roaming red fox: case report and historical review on diphtheria in animals.corynebacterium diphtheriae, the classical causative agent of diphtheria, is considered to be nearly restricted to humans. here we report the first finding of a non-toxigenic c. diphtheriae biovar belfanti strain in a free-roaming wild animal.201626424684
caenorhabditis elegans star formation and negative chemotaxis induced by infection with corynebacteria.caenorhabditis elegans is one of the major model systems in biology based on advantageous properties such as short life span, transparency, genetic tractability and ease of culture using an escherichia coli diet. in its natural habitat, compost and rotting plant material, this nematode lives on bacteria. however, c. elegans is a predator of bacteria, but can also be infected by nematopathogenic coryneform bacteria such microbacterium and leucobacter species, which display intriguing and diverse ...201626490043
cutaneous ulcers in a returning traveller: a rare case of imported diphtheria in the uk.we describe a case of cutaneous diphtheria in the uk, presenting as lower leg ulcers in a returning traveller, and discuss the epidemiology, significance and public health implications of this disease and the therapeutic options available. a 65-year-old woman presented with a 6-week history of multiple ulcers appearing on her legs following a holiday in kenya. culture of biopsy tissue grew corynebacterium diphtheriae. a cascade of therapeutic and public health interventions followed, many of whi ...201626455435
non-toxigenic penicillin-resistant cutaneous c. diphtheriae infection: a case report and review of the literature.here, we report a case of non-toxigenic corynebacterium diphtheriae in a previously healthy 14-year-old girl that was acquired in ethiopia and presented locally. this is the first clinical case of penicillin-resistant c. diphtheriae in the uk. this is significant finding because penicillin is the recommended first-line agent for the prophylaxis against and treatment of c. diphtheriae in patients who are not allergic to penicillin.201625027172
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
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
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
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
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
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
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
a thiol-disulfide oxidoreductase of the gram-positive pathogen corynebacterium diphtheriae is essential for viability, pilus assembly, toxin production and virulence.the gram-positive pathogen corynebacterium diphtheriae exports through the sec apparatus many extracellular proteins that include the key virulence factors diphtheria toxin and the adhesive pili. how these proteins attain their native conformations after translocation as unfolded precursors remains elusive. the fact that the majority of these exported proteins contain multiple cysteine residues and that several membrane-bound oxidoreductases are encoded in the corynebacterial genome suggests the ...201526294390
corynebacterium diphtheriae methionine sulfoxide reductase a exploits a unique mycothiol redox relay mechanism.methionine sulfoxide reductases are conserved enzymes that reduce oxidized methionines in proteins and play a pivotal role in cellular redox signaling. we have unraveled the redox relay mechanisms of methionine sulfoxide reductase a of the pathogen corynebacterium diphtheriae (cd-msra) and shown that this enzyme is coupled to two independent redox relay pathways. steady-state kinetics combined with mass spectrometry of cd-msra mutants give a view of the essential cysteine residues for catalysis. ...201525752606
heme binding by corynebacterium diphtheriae hmut: function and heme environment.the heme uptake pathway (hmu) of corynebacterium diphtheriae utilizes multiple proteins to bind and transport heme into the cell. one of these proteins, hmut, delivers heme to the abc transporter hmuuv. in this study, the axial ligation of the heme in ferric hmut is probed by examination of wild-type (wt) hmut and a series of conserved heme pocket residue mutants, h136a, y235a, and m292a. characterization by uv-visible, resonance raman, and magnetic circular dichroism spectroscopies indicates th ...201526478504
smooth and rough biotypes of arcanobacterium haemolyticum can be genetically distinguished at the arcanolysin locus.arcanobacterium haemolyticum is a gram-positive, β-hemolytic emerging human pathogen that is classified into smooth or rough biotypes. this bacterial species is also a rare pathogen of animals. smooth biotypes possess smooth colony edges, are moderate to strong in β-hemolysis, and predominately cause wound infections. in contrast, rough biotypes possess rough and irregular colony edges, have weak to no β-hemolytic activity, and predominately cause pharyngitis. using horse erythrocytes we confirm ...201526382754
recent developments in understanding the iron acquisition strategies of gram positive pathogens.iron is a versatile redox-active catalyst and a required cofactor within a diverse array of biological processes. to almost all organisms, iron is both essential and potentially toxic, where homeostatic concentrations must be stringently maintained. within the iron-restricted host, the survival and proliferation of microbial invaders is contingent upon exploiting the host iron pool. bacteria express a multitude of complex, and often redundant means of acquiring iron, including surface-associated ...201525862688
virulence factor genes detected in the complete genome sequence of corynebacterium uterequi dsm 45634, isolated from the uterus of a maiden mare.the complete genome sequence of the type strain corynebacterium uterequi dsm 45634 from an equine urogenital tract specimen comprises 2,419,437 bp and 2,163 protein-coding genes. candidate virulence factors are homologs of dip0733, dip1281, and dip1621 from corynebacterium diphtheriae and of sialidase precursors from trueperella pyogenes and chlamydia trachomatis.201526227590
history and practice: antibodies in infectious diseases.antibodies and passive antibody therapy in the treatment of infectious diseases is the story of a treatment concept which dates back more than 120 years, to the 1890s, when the use of serum from immunized animals provided the first effective treatment options against infections with clostridium tetani and corynebacterium diphtheriae. however, after the discovery of penicillin by fleming in 1928, and the subsequent introduction of the much cheaper and safer antibiotics in the 1930s, serum therapy ...201526104697
a disulfide bond-forming machine is linked to the sortase-mediated pilus assembly pathway in the gram-positive bacterium actinomyces oris.export of cell surface pilins in gram-positive bacteria likely occurs by the translocation of unfolded precursor polypeptides; however, how the unfolded pilins gain their native conformation is presently unknown. here, we present physiological studies to demonstrate that the fima pilin of actinomyces oris contains two disulfide bonds. alanine substitution of cysteine residues forming the c-terminal disulfide bridge abrogates pilus assembly, in turn eliminating biofilm formation and polymicrobial ...201526170452
[the comparative analysis of techniques of identification of corynebacterium non diphtheriae].the comparative analysis was carried out concerning effectiveness of three techniques of identification of corynebacterium non diphtheriae: bacteriological, molecular genetic (sequenation on 16sprna) andmass-spectrometric (maldi-tofms). the analysis covered 49 strains of corynebacterium non diphtheriae (c.pseudodiphheriticum, c.amycolatum, c.propinquum, c.falsenii) and 2 strains of corynebacterium diphtheriae isolated under various pathology form urogenital tract and upper respiratory ways. the ...201527032253
role of active-site residues tyr55 and tyr114 in catalysis and substrate specificity of corynebacterium diphtheriae c-s lyase.in recent years, there has been increased interest in bacterial methionine biosynthesis enzymes as antimicrobial targets because of their pivotal role in cell metabolism. c-s lyase from corynebacterium diphtheriae is a pyridoxal 5'-phosphate-dependent enzyme in the transsulfuration pathway that catalyzes the α,β-elimination of sulfur-containing amino acids, such as l-cystathionine, to generate ammonia, pyruvate, and homocysteine, the immediate precursor of l-methionine. in order to gain deeper i ...201525354840
adherence and invasive properties of corynebacterium diphtheriae strains correlates with the predicted membrane-associated and secreted proteome.non-toxigenic corynebacterium diphtheriae strains are emerging as a major cause of severe pharyngitis and tonsillitis as well as invasive diseases such as endocarditis, septic arthritis, splenic abscesses and osteomyelitis. c. diphtheriae strains have been reported to vary in their ability to adhere and invade different cell lines. to identify the genetic basis of variation in the degrees of pathogenicity, we sequenced the genomes of four strains of c. diphtheriae (iss 3319, iss 4060, iss 4746 a ...201526452736
tellurite resistance: a putative pitfall in corynebacterium diphtheriae diagnosis?corynebacterium diphtheriae strains continue to circulate worldwide causing diphtheria and invasive diseases, such as endocarditis, osteomyelitis, pneumonia and catheter-related infections. presumptive c. diphtheriae infections diagnosis in a clinical microbiology laboratory requires a primary isolation consisting of a bacterial culture on blood agar and agar containing tellurite (teo3(2-)). in this study, nine genome sequenced and four unsequenced strains of c. diphtheriae from different source ...201526459339
pocket analysis of the full-length cholix toxin. an assessment of the structure-dynamics of the apo catalytic domain.cholix toxin from vibrio cholerae is the third member of the diphtheria toxin (dt) group of mono-adp-ribosyltransferase (mart) bacterial toxins. it shares structural and functional properties with pseudomonas aeruginosa exotoxin a and corynebacterium diphtheriae dt. cholix toxin is an important model for the development of antivirulence approaches and therapeutics against these toxins from pathogenic bacteria. herein, we have used the high-resolution x-ray structure of full-length cholix complex ...201525559625
molecular and epidemiological review of toxigenic diphtheria infections in england between 2007 and 2013.human infections caused by toxigenic corynebacteria occur sporadically across europe. in this report, we undertook the epidemiological and molecular characterization of all toxigenic corynebacterium strains isolated in england between january 2007 and december 2013. epidemiological aspects include case demographics, risk factors, clinical presentation, treatment, and outcome. molecular characterization was performed using multilocus sequence typing (mlst) alongside traditional phenotypic methods ...201525502525
acetylation of trehalose mycolates is required for efficient mmpl-mediated membrane transport in corynebacterineae.pathogenic species of mycobacteria and corynebacteria, including mycobacterium tuberculosis and corynebacterium diphtheriae, synthesize complex cell walls that are rich in very long-chain mycolic acids. these fatty acids are synthesized on the inner leaflet of the cell membrane and are subsequently transported to the periplasmic space as trehalose monomycolates (tmm), where they are conjugated to other cell wall components and to tmm to form trehalose dimycolates (tdm). mycobacterial tmm, and th ...201525427102
late-onset prosthetic valve endocarditis caused by nontoxigenic corynebacterium diphtheriae.in developed countries, corynebacterium diphtheriae infection is rare due to efficient immunization programs. however, cases of nontoxigenic strains of c. diphtheriae infections, including endocarditis, have been reported recently. although the incidence remains low, these infections are associated with high morbidity and mortality. this report describes the first and atypical case of bacteremia and endocarditis caused by nontoxigenic c. diphtheriae var. gravis after introduction of immunization ...201526322885
structure of the response regulator chra in the haem-sensing two-component system of corynebacterium diphtheriae.chra is a response regulator (rr) in the two-component system involved in regulating the degradation and transport of haem (fe-porphyrin) in the pathogen corynebacterium diphtheriae. here, the crystal structure of full-length chra is described at a resolution of 1.8 å. chra consists of an n-terminal regulatory domain, a long linker region and a c-terminal dna-binding domain. a structural comparison of chra with other rrs revealed substantial differences in the relative orientation of the two dom ...201526249683
seroprevalence and determinants of immunity to diphtheria for children living in two districts of contrasting incidence during an outbreak in east java, indonesia.in 2012, an ongoing outbreak of diphtheria in indonesia was focused in the province of east java. there was a need to assess vaccine coverage and immunity gaps in children.201526226444
corynebacterium diphtheriae putative tellurite-resistance protein (cdce8392_0813) contributes to the intracellular survival in human epithelial cells and lethality of caenorhabditis elegans.corynebacterium diphtheriae, the aetiologic agent of diphtheria, also represents a global medical challenge because of the existence of invasive strains as causative agents of systemic infections. although tellurite (teo32-) is toxic to most microorganisms, teo32--resistant bacteria, including c. diphtheriae, exist in nature. the presence of teo32--resistance (ter) determinants in pathogenic bacteria might provide selective advantages in the natural environment. in the present study, we investig ...201526107188
crystal structure of dsba from corynebacterium diphtheriae and its functional implications for cuep in gram-positive bacteria.in gram-negative bacteria in the periplasmic space, the dimeric thioredoxin-fold protein dsbc isomerizes and reduces incorrect disulfide bonds of unfolded proteins, while the monomeric thioredoxin-fold protein dsba introduces disulfide bonds in folding proteins. in the gram-negative bacteria salmonella enterica serovar typhimurium, the reduced form of cuep scavenges the production of hydroxyl radicals in the copper-mediated fenton reaction, and dsbc is responsible for keeping cuep in the reduced ...201526082031
a case of necrotizing epiglottitis due to nontoxigenic corynebacterium diphtheriae.diphtheria is a rare cause of infection in highly vaccinated populations and may not be recognized by modern clinicians. infections by nontoxigenic corynebacterium diphtheriae are emerging. we report the first case of necrotizing epiglottitis secondary to nontoxigenic c diphtheriae. a fully vaccinated child developed fever, poor oral intake, and sore throat and was found to have necrotizing epiglottitis. necrotizing epiglottitis predominantly occurs in the immunocompromised host. laboratory eval ...201526055849
[features of biofilm morphology, formed by corynebacterium diphtheriae gravis tox+ strains].study the structure of homogenous microbial communities of corynebacterium diphtheriae gravis tox+ strains during formation of biofilms in vitro.201526016345
[recombinant fluorescent models for studying of diphtheria toxin].diphtheria toxin is the main pathogenicity factor of causative agent of diphtheria corynebacterium diphtheriae. due to the small molecule size, it is of considerable interestfor the development of synthetic protein molecules with transporting function, e.g. immunotoxins. expression and characterization of nontoxic recombinant fluorescent derivates of diphtheria toxin and its nontoxic mutant crm 197 were described in this article. obtained proteins may be applied in studies of receptor-binding an ...201525898753
a comparative structure-function analysis of active-site inhibitors of vibrio cholerae cholix toxin.cholix toxin from vibrio cholerae is a novel mono-adp-ribosyltransferase (mart) toxin that shares structural and functional properties with pseudomonas aeruginosa exotoxin a and corynebacterium diphtheriae diphtheria toxin. herein, we have used the high-resolution x-ray structure of full-length cholix toxin in the apo form, nad(+) bound, and 10 structures of the cholix catalytic domain (c-domain) complexed with several strong inhibitors of toxin enzyme activity (nap, pj34, and the p-series) to s ...201525756608
diphtheria outbreak in maranhão, brazil: microbiological, clinical and epidemiological aspects.we describe microbiological, clinical and epidemiological aspects of a diphtheria outbreak that occurred in maranhão, brazil. the majority of the 27 confirmed cases occurred in partially (n = 16) or completely (n = 10) immunized children (n = 26). clinical signs and characteristic symptoms of diphtheria such as cervical lymphadenopathy and pseudomembrane formation were absent in 48% and 7% of the cases, respectively. complications such as paralysis of lower limbs were observed. three cases resul ...201525703400
characterization of dip0733, a multi-functional virulence factor of corynebacterium diphtheriae.corynebacterium diphtheriae is typically recognized as an extracellular pathogen. however, a number of studies revealed its ability to invade epithelial cells, indicating a more complex pathogen-host interaction. the molecular mechanisms controlling and facilitating internalization of cor. diphtheriae are poorly understood. in this study, we investigated the role of dip0733 as virulence factor to elucidate how it contributes to the process of pathogen-host cell interaction. based on in vitro exp ...201525635272
corynebacterium diphtheriae infections currently and in the past.along with the introduction of common obligatory vaccinations against diphtheria, the disease has been limited in developed countries. however, diphtheria is still endemic in developing countries. due to a growing popularity of visiting these countries, there is a risk of importation of the disease to europe. studies revealed that over 60% of persons aged >40 years in the polish population do not have a protective level of antibodies against diphtheria. furthermore, an access to diphtheria antit ...201526519837
genomic analysis of a nontoxigenic, invasive corynebacterium diphtheriae strain from brazil.we report the complete genome sequence and analysis of an invasive corynebacterium diphtheriae strain that caused endocarditis in rio de janeiro, brazil. it was selected for sequencing on the basis of the current relevance of nontoxigenic strains for public health. the genomic information was explored in the context of diversity, plasticity and genetic relatedness with other contemporary strains.201526517665
opposite nucleotide usage biases in different parts of the corynebacterium diphtheriae spac gene.in this work we described a bacterial open reading frame with two different directions of nucleotide usage biases in its two parts. the level of gc-content in third codon positions (3gc) is equal to 40.17 ± 0.22% during the most of the length of corynebacterium diphtheriae spac gene. however, in the 3'-end of the same gene (from codon #1600 to codon #1873) 3gc level is equal to 64.61 ± 0.91%. using original methodology ('vvtak sliding window' and 'vvtak varinvar') we approved that there is an on ...201526561319
colonisation with toxigenic corynebacterium diphtheriae in a scottish burns patient, june 2015.on 12 june 2015, corynebacterium diphtheriae was identified in a skin swab from a burns patient in scotland. the isolate was confirmed to be genotypically and phenotypically toxigenic. multilocus sequence typing of three patient isolates yielded sequence type st 125. the patient was clinically well. we summarise findings of this case, and results of close contact identification and screening: 12 family and close contacts and 32 hospital staff have been found negative for c. diphtheriae.201526691231
bacterial colony: first report of donut colony morphology among diphtheroids isolated in blood.isolation of diphtheroids in human clinical specimens is not uncommon. several studies have highlighted the significance of these bacteria in human infection, which morphologically resemble corynebacterium diphtheriae. previous studies have noted that occurrence of these bacteria in specimens like the blood should not be ignored as they can result in serious infections like endocarditis and sepsis among debilitated individuals, including the neonates. we report isolation of diphtheroid bacterium ...201526677424
synergistic hemolysins of coagulase-negative staphylococci (cons).a total of 104 coagulase negative staphylococci, belonging to s. capitis, s. hominis, s. haemolyticus and s. warneri, originating from the collection of the department of pharmaceutical microbiology (zmf), medical university of lodz, poland, were tested for their synergistic hemolytic activity. 83% of strains produced δ-hemolysin, however, the percentage of positive strains of s. haemolyticus, s. warneri, s. capitis and s. hominis was different - 98%, 78%, 75% and 68%, respectively. highly pure ...201526634231
persistence of corynebacterium diphtheriae in delhi & national capital region (ncr).despite the introduction of mass immunization, diphtheria continues to play a major role as a potentially lethal infectious disease in many countries. delay in the specific therapy of diphtheria may result in death and, therefore, accurate diagnosis of diphtheria is imperative. this study was carried out at national centre for disease control (ncdc), delhi, india, on samples of suspected diphtheria cases referred from various government hospitals of delhi and neighbouring areas during 2012-2014. ...201526609038
urinary tract infection with corynebacterium aurimucosum after urethroplasty stricture of the urethra: a case report.corynebacteria have an important place among the commensal flora of the skin and mucous membranes. except for corynebacterium diphtheriae, they were once considered contaminants of mucosa. recent publications in medical bacteriology have highlighted the importance of several species, such as c. aurimucosum. to the best of our knowledge, we report the first isolation of this strain from urine.201526155836
structural and antigenic features of the synthetic sf23 peptide corresponding to the receptor binding fragment of diphtheria toxin.the sf23 peptide corresponding to the receptor binding fragment of diphtheria toxin (residues 508-530) has been synthesized. this fragment forming a protruding beta hairpin has been chosen because it is the less mutable b-cell epitope. affine chromatography and elisa show that antibodies from the sera of persons infected by toxigenic corynebacterium diphtheriae and those immunized by diphtheria toxoid are able to bind the synthetic sf23 peptide. there are antibodies recognizing the sf23 peptide ...201525062832
new diphtheria toxin repressor types depicted in a romanian collection of corynebacterium diphtheriae isolates.corynebacterium diphtheriae is the etiological agent of diphtheria, a potential fatal disease caused by a corynephage toxin. the expression of this diphtheria toxin is controlled via an iron-dependent repressor with various functions (dtxr). some mutations in the dtxr gene are associated with diminished activity or even with total loss of dtxr function. we conducted a molecular study to characterize the dtxr alleles harbored by 34 isolates of c. diphtheriae recovered from romanian patients betwe ...201424293345
a mutated cytosine deaminase gene, coda (d314a), as an efficient negative selection marker for gene targeting in rice.gene targeting (gt) is a powerful tool manipulating a gene of interest in a given genome specifically and precisely. to achieve efficient gt in higher plants, both positive and negative selection markers are required. in particular, a strong negative selection system is needed for enrichment of cells to eliminate those cells in which random integration of the introduced dna has occurred in gt experiments. currently, non-conditional negative selection marker genes are used for gt experiments in r ...201424371307
invasion of endothelial cells and arthritogenic potential of endocarditis-associated corynebacterium diphtheriae.although infection by corynebacterium diphtheriae is a model of extracellular mucosal pathogenesis, different clones have been also associated with invasive infections such as sepsis, endocarditis, septic arthritis and osteomyelitis. the mechanisms that promote c. diphtheriae infection and haematogenic dissemination need further investigation. in this study we evaluated the association and invasion mechanisms with human umbilical vein endothelial cells (huvecs) and experimental arthritis in mice ...201424344208
diphtheria in andhra pradesh-a clinical-epidemiological study.clinical diphtheria is on the increase worldwide, mainly affecting developing countries. we sought to understand its presentation among patients at sir ronald ross institute of tropical and communicable diseases in hyderabad, andhra pradesh, india.201424295558
[mechanisms of formation of post-vaccinal immune response in children immunized with apdt and adt-m preparations].study the mechanisms of formation of cell and humoral immunity against pertussis, diphtheria and tetanus in children immunized with immunobiological preparations (apdt vaccine and adt anatoxin).201425051700
toxigenic cutaneous diphtheria in a returned traveller.diphtheria is rarely reported in australia. a case of cutaneous diphtheria was reported to the south australian department for health and ageing in april 2013 in an australian-born 18-year-old female following travel in india. the case presented with a skin ulcer on her toe. toxigenic corynebacterium diphtheriae was isolated from a swab of the lesion. the case was treated with antibiotics. the public health response included infection control advice, assessing the case and household contacts for ...201425631591
[the sensitivity to antibiotics of biofilm cultures of toxigenic strains corynebacterium diphtheriae].the article presents analysis of sensitivity to antibacterial preparations of typical and biofilm culture of museum strain of corynebacterium diphtheriae gravis tox+ sv-665. the strain was obtained from the l.a. tarasevitch state research institute of standardization and control of medical biological preparations. the second strain c. diphtheriaecirculates gravis tox+ circulates in population of the rostov oblast and it was recovered from patient with diagnosis of "localized form of diphtheria" ...201425335402
multilocus sequence typing of corynebacterium ulcerans provides evidence for zoonotic transmission and for increased prevalence of certain sequence types among toxigenic strains.human-to-human-transmitted corynebacterium diphtheriae was historically the main pathogen causing diphtheria and has therefore been studied extensively in the past. more recently, diphtheria caused by toxigenic corynebacterium ulcerans is an emerging disease in several industrial countries, including the united kingdom, the united states, france, and germany. however, toxigenic c. ulcerans has so far been almost neglected in the development of epidemiologic tools. one of the most important tools ...201425320226
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