Publications

structural characterization of zinc-bound zmp1, a zinc-dependent metalloprotease secreted by clostridium difficile.	proteases are commonly secreted by microorganisms. in some pathogens, they can play a series of functional roles during infection, including maturation of cell surface or extracellular virulence factors, interference with host cell signaling, massive host tissue destruction, and dissolution of infection-limiting clots through degradation of the host proteins devoted to the coagulation cascade. we previously reported the identification and characterization of zmp1, a zinc-dependent metalloproteas ...	2016	26711661
anti-infectious human vaccination in historical perspective.	a brief history of vaccination is presented since the jenner's observation, through the first golden age of vaccinology (from pasteur's era to 1938), the second golden age (from 1940 to 1970), until the current period. in the first golden age, live, such as bacille calmette guérin (bcg), and yellow fever, inactivated, such as typhoid, cholera, plague, and influenza, and subunit vaccines, such as tetanus and diphtheria toxoids, have been developed. in the second golden age, the cell culture techn ...	2016	26606466
pore-forming activity of clostridial binary toxins.	clostridial binary toxins (clostridium perfringens iota toxin, clostridium difficile transferase, clostridium spiroforme toxin, clostridium botulinum c2 toxin) as bacillus binary toxins, including bacillus anthracis toxins consist of two independent proteins, one being the binding component which mediates the internalization into cell of the intracellularly active component. clostridial binary toxins induce actin cytoskeleton disorganization through mono-adp-ribosylation of globular actin and ar ...	2016	26278641
new role for fda-approved drugs in combating antibiotic-resistant bacteria.	antibiotic resistance in medically relevant bacterial pathogens, coupled with a paucity of novel antimicrobial discoveries, represents a pressing global crisis. traditional drug discovery is an inefficient and costly process; however, systematic screening of food and drug administration (fda)-approved therapeutics for other indications in humans offers a rapid alternative approach. in this study, we screened a library of 780 fda-approved drugs to identify molecules that rendered raw 264.7 murine ...	2016	27067323
long-term effects on luminal and mucosal microbiota and commonly acquired taxa in faecal microbiota transplantation for recurrent clostridium difficile infection.	faecal microbiota transplantation (fmt) is an effective treatment for recurrent clostridium difficile infection (rcdi). it restores the disrupted intestinal microbiota and subsequently suppresses c. difficile. the long-term stability of the intestinal microbiota and the recovery of mucosal microbiota, both of which have not been previously studied, are assessed herein. further, the specific bacteria behind the treatment efficacy are also investigated.	2016	27724956
fecal microbiota transplantation by freeze-dried oral capsules for recurrent clostridium difficile infection.		2016	27822485
fecal transplantation indications in ulcerative colitis. preliminary study.	fecal microbiota transplantation is used with success in persistent (more than two episodes) clostridium difficile infection; it has also gained importance and started to be used in inflammatory bowel disease. there are theoretical arguments that justify its use in ulcerative colitis or crohn's disease. based on our clinical cases we tried to evaluate the indications of fecal microbiota transplantation young patients with ulcerative colitis and multiple relapses, in which biological or immunosup ...	2016	27152073
a new lab developed real time pcr assay for direct detection of c. difficle from stool sample without dna extraction.	clostridium difficile is a major cause of nosocomial antibiotic-associated infectious diarrhea and pseudomembranous colitis. detection of c. difficile by anaerobic bacterial culture and/or cytotoxicity assays has been largely replaced by rapid enzyme immunoassays (eia). however, due to the lack of sensitivity of stool eia, we developed a multiplex real-time pcr assay targeting the c. difficile toxin genes tcdb. stool samples from hospitalized pediatric patients suspected of having c. difficile-a ...	2016	27829823
evaluation of luminex xtag gastrointestinal pathogen panel assay for detection of multiple diarrheal pathogens in fecal samples in vietnam.	diarrheal disease is a complex syndrome that remains a leading cause of global childhood morbidity and mortality. the diagnosis of enteric pathogens in a timely and precise manner is important for making treatment decisions and informing public health policy, but accurate diagnosis is a major challenge in industrializing countries. multiplex molecular diagnostic techniques may represent a significant improvement over classical approaches. we evaluated the luminex xtag gastrointestinal pathogen p ...	2016	26865681
use of single molecule sequencing for comparative genomics of an environmental and a clinical isolate of clostridium difficile ribotype 078.	how the pathogen clostridium difficile might survive, evolve and be transferred between reservoirs within the natural environment is poorly understood. some ribotypes are found both in clinical and environmental settings. whether these strains are distinct from each another and evolve in the specific environments is not established. the possession of a highly mobile genome has contributed to the genetic diversity and ongoing evolution of c. difficile. interpretations of genetic diversity have be ...	2016	27964731
heat shock increases conjugation efficiency in clostridium difficile.	clostridium difficile infection has increased in incidence and severity over the past decade, and poses a unique threat to human health. however, genetic manipulation of c. difficile remains in its infancy and the bacterium remains relatively poorly characterised. low-efficiency conjugation is currently the only available method for transfer of plasmid dna into c. difficile. this is practically limiting and has slowed progress in understanding this important pathogen. conjugation efficiency vari ...	2016	27377776
evaluation and selection of bacillus species based on enzyme production, antimicrobial activity, and biofilm synthesis as direct-fed microbial candidates for poultry.	social concern about misuse of antibiotics as growth promoters (agp) and generation of multidrug-resistant bacteria have restricted the dietary inclusion of antibiotics in livestock feed in several countries. direct-fed microbials (dfm) are one of the multiple alternatives commonly evaluated as substitutes of agp. sporeformer bacteria from the genus bacillus have been extensively investigated because of their extraordinary properties to form highly resistant endospores, produce antimicrobial com ...	2016	27812526
the type b flagellin of hypervirulent clostridium difficile is modified with novel sulfonated peptidylamido-glycans.	glycosylation of flagellins is a well recognized property of many bacterial species. in this study, we describe the structural characterization of novel flagellar glycans from a number of hypervirulent strains of c. difficile we used mass spectrometry (nano-lc-ms and ms/ms analysis) to identify a number of putative glycopeptides that carried a variety of glycoform substitutions, each of which was linked through an initial n-acetylhexosamine residue to ser or thr. detailed analysis of a lldgsstei ...	2016	27758867
role of glycosyltransferases modifying type b flagellin of emerging hypervirulent clostridium difficile lineages and their impact on motility and biofilm formation.	clostridium difficile is the principal cause of nosocomial infectious diarrhea worldwide. the pathogen modifies its flagellin with either a type a or type b o-linked glycosylation system, which has a contributory role in pathogenesis. we study the functional role of glycosyltransferases modifying type b flagellin in the 023 and 027 hypervirulent c. difficile lineages by mutagenesis of five putative glycosyltransferases and biosynthetic genes. we reveal their roles in the biosynthesis of the flag ...	2016	27703012
dissimilar fitness associated with resistance to fluoroquinolones influences clonal dynamics of various multiresistant bacteria.	fitness cost associated with resistance to fluoroquinolones was recently shown to vary across clones of methicillin-resistant staphylococcus aureus and extended-spectrum β-lactamase-producing klebsiella pneumoniae. the resulting dissimilar fitness should have influenced the clonal dynamics and thereby the rates of resistance for these pathogens. moreover, a similar mechanism was recently proposed for the emergence of the h30 and h30r lineages of esbl-producing e. coli and the major international ...	2016	27458434
synthesis and antimicrobial evaluation of amixicile-based inhibitors of the pyruvate-ferredoxin oxidoreductases of anaerobic bacteria and epsilonproteobacteria.	amixicile is a promising derivative of nitazoxanide (an antiparasitic therapeutic) developed to treat systemic infections caused by anaerobic bacteria, anaerobic parasites, and members of the epsilonproteobacteria (campylobacter and helicobacter). amixicile selectively inhibits pyruvate-ferredoxin oxidoreductase (pfor) and related enzymes by inhibiting the function of the vitamin b1 cofactor (thiamine pyrophosphate) by a novel mechanism. here, we interrogate the amixicile scaffold, guided by doc ...	2016	27090174
clostridium difficile enterocolitis and reactive arthritis: a case report and review of the literature.	reactive arthritis is a rare complication of clostridium difficile enterocolitis, especially in children. we review the 6 pediatric cases published in the english and non-english literature and discuss their clinical presentation, outcome, treatment, and pathophysiology. we also report the seventh case of clostridium difficile reactive arthritis in a 6-year-old boy who was treated with amoxicillin-clavulanate for 10 days because of an upper respiratory infection. after the antibiotic course, the ...	2016	27190666
oscillating behavior of clostridium difficile min proteins in bacillus subtilis.	in rod-shaped bacteria, the proper placement of the division septum at the midcell relies, at least partially, on the proteins of the min system as an inhibitor of cell division. the main principle of min system function involves the formation of an inhibitor gradient along the cell axis; however, the establishment of this gradient differs between two well-studied gram-negative and gram-positive bacteria. while in gram-negative escherichia coli, the min system undergoes pole-to-pole oscillation, ...	2016	26817670
primase is required for helicase activity and helicase alters the specificity of primase in the enteropathogen clostridium difficile.	dna replication is an essential and conserved process in all domains of life and may serve as a target for the development of new antimicrobials. however, such developments are hindered by subtle mechanistic differences and limited understanding of dna replication in pathogenic microorganisms. clostridium difficile is the main cause of healthcare-associated diarrhoea and its dna replication machinery is virtually uncharacterized. we identify and characterize the mechanistic details of the putati ...	2016	28003473
'get in early'; biofilm and wax moth (galleria mellonella) models reveal new insights into the therapeutic potential of clostridium difficile bacteriophages.	clostridium difficile infection (cdi) is a global health threat associated with high rates of morbidity and mortality. conventional antibiotic cdi therapy can result in treatment failure and recurrent infection. c. difficile produces biofilms which contribute to its virulence and impair antimicrobial activity. some bacteriophages (phages) can penetrate biofilms and thus could be developed to either replace or supplement antibiotics. here, we determined the impact of a previously optimized 4-phag ...	2016	27630633
ecological effect of solithromycin on normal human oropharyngeal and intestinal microbiota.	solithromycin is a new fluoroketolide. the purpose of the present study was to investigate the effect of orally administered solithromycin on the human oropharyngeal and intestinal microbiota. thirteen healthy volunteers (median age, 27.3 years) received oral solithromycin at 800 mg on day 1 followed by 400 mg daily on days 2 to 7. fecal and saliva samples were collected at baseline and on days 2, 5, 7, 9, 14, and 21 for pharmacokinetic and microbiological analyses. plasma samples were collected ...	2016	27139483
pilin vaccination stimulates weak antibody responses and provides no protection in a c57bl/6 murine model of acute clostridium difficile infection.	clostridium difficile is the leading cause of nosocomial infections in the united states, adding billions of dollars per year to health care costs. a vaccine targeted against the bacterium would be extremely beneficial in decreasing the morbidity and mortality caused by c. difficile-associated disease; a vaccine directed against a colonization factor would hinder the spread of the bacterium as well as prevent disease. type iv pili (t4ps) are extracellular appendages composed of protein monomers ...	2016	27375958
clostridium difficile infection.		2016	27917073
pathophysiology of clostridium difficile-associated diarrhea.		2016	27917094
active and secretory iga-coated bacterial fractions elucidate dysbiosis in clostridium difficile infection.	the onset of clostridium difficile infection (cdi) has been associated with treatment with wide-spectrum antibiotics. antibiotic treatment alters the activity of gut commensals and may result in modified patterns of immune responses to pathogens. to study these mechanisms during cdi, we separated bacteria with high cellular rna content (the active bacteria) and their inactive counterparts by fluorescence-activated cell sorting (facs) of the fecal bacterial suspension. the gut dysbiosis due to th ...	2016	27303742
diverticular disease of the colon does not increase risk of repeat c. difficile infection.	studies have suggested that colonic diverticulosis might increase the likelihood of repeat clostridium difficile infection (cdi). our study was designed to compare rates of repeat infection in patients with and without colon diverticula.	2016	23442832
[cost of clostridium difficile associated diarrhea in spain].	there are not available adequate studies of the costs of clostridium difficile-associated diarrhea (cdad) in spain. the aim of the study is to estimate the cost of cdad for the national health service (nhs).	2016	23748655
high-throughput dna sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria.	fecal microbiota transplantation (fmt) is becoming a more widely used technology for treatment of recurrent clostridum difficile infection (cdi). while previous treatments used fresh fecal slurries as a source of microbiota for fmt, we recently reported the successful use of standardized, partially purified and frozen fecal microbiota to treat cdi. here we report that high-throughput 16s rrna gene sequencing showed stable engraftment of gut microbiota following fmt using frozen fecal bacteria fr ...	2016	23333862
which are the antibodies to watch in 2013?	the start of the new year signals that it is time for mabs' annual review of the therapeutic monoclonal antibodies (mabs) in active phase 2/3 or phase 3 clinical studies. the entire clinical pipeline currently includes ~350 mabs, but most of these are in early development. as of the beginning of 2013, our "antibodies to watch" list includes 28 single mabs and one mab mixture that are undergoing evaluation in phase 3 studies for inflammatory or immunological disorders, cancers, high cholesterol, ...	2016	23254906
a sialic acid aldolase from peptoclostridium difficile nap08 with 4-hydroxy-2-oxo-pentanoate aldolase activity.	sialic acid aldolases (e.c.4.1.3.3) catalyze the reversible aldol cleavage of n-acetyl-d-neuraminic acid (neu5ac) to from n-acetyl-d-mannosamine (mannac) and pyruvate. in this study, a sialic acid aldolase (pdnal) from peptoclostridium difficile nap08 was expressed in escherichia coli bl21 (de3). this homotetrameric enzyme was purified with a specific activity of 18.34u/mg for the cleavage of neu5ac. the optimal ph and temperature for aldol addition reaction were 7.4 and 65°c, respectively. pdna ...	2016	27542750
complete genome sequence of peptoclostridium difficile strain z31.	peptoclostridium (clostridium) difficile is a spore-forming bacterium responsible for nosocomial infections in humans. it is recognized as an important agent of diarrhea and colitis in several animal species and a possible zoonotic agent. despite the known importance of p. difficile infection in humans and animals, no vaccine or other effective measure to control the disease is commercially available. a possible alternative treatment for p. difficile infection is the use of a nontoxigenic strain ...	2016	28828039
[fecal microbiota transplant in the treatment of recurrent clostridium difficile infection: a case report].	clostridium difficile infection is a major cause of nosocomial diarrhea. its incidence has increased in the past 20 years and is associated with a significant morbidity and mortality. relapsing is frequent after treatment and the management of these recurrent clostridium difficile infections is challenging. several studies over the years have shown that fecal microbiota transplantion is associated with a high degree of success. fecal microbiota transplantion is now part of the european recommend ...	2016	28525191
a retrospective comparison of fecal microbial transplantation methods for recurrent clostridium difficile infection.	antibiotic treatment of clostridium difficile infection (cdi) has a high failure rate. fecal microbiota transplantation (fmt) has proven very effective in treating these recurrences.	2016	28471618
exploiting a host-commensal interaction to promote intestinal barrier function and enteric pathogen tolerance.	commensal intestinal bacteria can prevent pathogenic infection; however, limited knowledge of the mechanisms by which individual bacterial species contribute to pathogen resistance has restricted their potential for therapeutic application. here, we examined how colonization of mice with a human commensal enterococcus faecium protects against enteric infections. we show that e. faecium improves host intestinal epithelial defense programs to limit salmonella enterica serotype typhimurium pathogen ...	2016	28580440
[antimicrobials : some practical considerations].	antibiotics are frequently prescribed in hospitalized and in outpatients. we review four important aspects for their daily prescription. in elderly patients, the prescription should take into account changes in the volume of distribution and the usual decline in renal function even in the absence of chronic kidney disease. particular antibiotics can trigger infection with clostridium difficile. we discuss actual and novel strategies for its prevention. renal toxicity of antibiotics includes acut ...	2016	28675267
clostridium difficile colitis: review of the therapeutic approach.	clostridium difficile infection (cdi) is the leading cause of antibiotic-associated and nosocomial infectious diarrhea. presenting as clostridium difficile colitis, it is a significant cause of morbidity and mortality. metronidazole is regarded as the agent of choice for cdl therapy and also for the first recurrence in most patients with mild to moderate cdi. vancomycin is recommended as an initial therapy for patients with severe cdi. with recent food and drug administration-approval fidaxomici ...	2016	22990077
surgical management of severe colitis in the intensive care unit.	severe colitis, an umbrella encompassing several entities, is one of the most common acute gastrointestinal disorders resulting in critical illness. clostridium difficile infection is responsible for the majority of nosocomial diarrhea with fulminant c difficile colitis (cdc) carrying a high mortality. optimal outcomes can be achieved by early identification and treatment of fulminant cdc, with appropriate surgical intervention when indicated. ischemic colitis, on the other hand, is uncommon wit ...	2015	24859995
development of clostridium difficile colitis in peritoneal dialysis patients treated for peritonitis.		2015	23212865
[dificid: fewer recurrences of clostridium difficile].		2015	23379054
cost-effectiveness analysis evaluating fidaxomicin versus oral vancomycin for the treatment of clostridium difficile infection in the united states.	fidaxomicin is a novel treatment for clostridium difficile infections (cdis). this new treatment, however, is associated with a higher acquisition cost compared with alternatives. the objective of this study was to evaluate the cost-effectiveness of fidaxomicin or oral vancomycin for the treatment of cdis.	2015	23538181
[anaerobic bacteria 150 years after their discovery by pasteur].	in 2011 we celebrated the 150th anniversary of the discovery of anaerobic bacteria by louis pasteur. the interest of the biomedical community on such bacteria is still maintained, and is particularly focused on clostridium difficile. in the past few years important advances in taxonomy have been made due to the genetic, technological and computing developments. thus, a significant number of new species related to human infections have been characterised, and some already known have been reclassi ...	2015	23648369
the utility of repeat enzyme immunoassay testing for the diagnosis of clostridium difficile infection: a systematic review of the literature.	over the last 20 years, the prevalence of healthcare-associated clostridium difficile (c. diff) disease has increased. while multiple tests are available for the diagnosis of c. diff infection, enzyme immunoassay (eia) testing for toxin is the most used. repeat eia testing, although of limited utility, is common in medical practice. to assess the utility of repeat eia testing to diagnose c. diff infections. systematic literature review. eligible studies performed >1 eia test for c. diff toxin an ...	2015	23023352
structural and evolutionary analyses show unique stabilization strategies in the type iv pili of clostridium difficile.	type iv pili are produced by many pathogenic gram-negative bacteria and are important for processes as diverse as twitching motility, biofilm formation, cellular adhesion, and horizontal gene transfer. however, many gram-positive species, including clostridium difficile, also produce type iv pili. here, we identify the major subunit of the type iv pili of c. difficile, pila1, and describe multiple 3d structures of pila1, demonstrating the diversity found in three strains of c. difficile. we also ...	2015	25599642
cyclic digmp regulates production of sortase substrates of clostridium difficile and their surface exposure through zmpi protease-mediated cleavage.	in gram-positive pathogens, surface proteins may be covalently anchored to the bacterial peptidoglycan by sortase, a cysteine transpeptidase enzyme. in contrast to other gram-positive bacteria, only one single sortase enzyme, srtb, is conserved between strains of clostridium difficile. sortase-mediated peptidase activity has been reported in vitro, and seven potential substrates have been identified. here, we demonstrate the functionality of sortase in c. difficile. we identify two sortase-ancho ...	2015	26283789
dna sequence signatures for rapid detection of six target bacterial pathogens using pcr assays.	using streptococcus pyogenes as a model, we previously established a stepwise computational workflow to effectively identify species-specific dna signatures that could be used as pcr primer sets to detect target bacteria with high specificity and sensitivity. in this study, we extended the workflow for the rapid development of pcr assays targeting enterococcus faecalis, enterococcus faecium, clostridium perfringens, clostridium difficile, clostridium tetani, and staphylococcus aureus, which are ...	2015	26279626
a catalytic dna activated by a specific strain of bacterial pathogen.	pathogenic strains of bacteria are known to cause various infectious diseases and there is a growing demand for molecular probes that can selectively recognize them. here we report a special dnazyme (catalytic dna), rfd-cd1, that shows exquisite specificity for a pathogenic strain of clostridium difficile (c. difficile). rfd-cd1 was derived by an in vitro selection approach where a random-sequence dna library was allowed to react with an unpurified molecular mixture derived from this strain of c ...	2015	26676768
increased toxin expression in a clostridium difficile mfd mutant.	the symptoms of clostridium difficile infection are mediated primarily by two toxins, tcda and tcdb, the expression of which is governed by a multitude of factors including nutrient availability, growth phase and cell stress. several global regulators have been implicated in the regulation of toxin expression, such as ccpa and cody.	2015	26679502
meta-genomic analysis of toilet waste from long distance flights; a step towards global surveillance of infectious diseases and antimicrobial resistance.	human populations worldwide are increasingly confronted with infectious diseases and antimicrobial resistance spreading faster and appearing more frequently. knowledge regarding their occurrence and worldwide transmission is important to control outbreaks and prevent epidemics. here, we performed shotgun sequencing of toilet waste from 18 international airplanes arriving in copenhagen, denmark, from nine cities in three world regions. an average of 18.6 gb (14.8 to 25.7 gb) of raw illumina paire ...	2015	26161690
ferric uptake regulator fur control of putative iron acquisition systems in clostridium difficile.	clostridium difficile is an anaerobic, gram-positive, spore-forming opportunistic pathogen and is the most common cause of hospital-acquired infectious diarrhea. although iron acquisition in the host is a key to survival of bacterial pathogens, high levels of intracellular iron can increase oxidative damage. therefore, expression of iron acquisition mechanisms is tightly controlled by transcriptional regulators. we identified a c. difficile homologue of the master bacterial iron regulator fur. u ...	2015	26148711
diversity and evolution in the genome of clostridium difficile.	clostridium difficile infection (cdi) is the leading cause of antimicrobial and health care-associated diarrhea in humans, presenting a significant burden to global health care systems. in the last 2 decades, pcr- and sequence-based techniques, particularly whole-genome sequencing (wgs), have significantly furthered our knowledge of the genetic diversity, evolution, epidemiology, and pathogenicity of this once enigmatic pathogen. c. difficile is taxonomically distinct from many other well-known ...	2015	26085550
excretion of host dna in feces is associated with risk of clostridium difficile infection.	clostridium difficile infection (cdi) is intricately linked to the health of the gastrointestinal tract and its indigenous microbiota. in this study, we assessed whether fecal excretion of host dna is associated with cdi development. assuming that shedding of epithelial cell increases in the inflamed intestine, we used human dna excretion as a marker of intestinal insult. whole-genome shotgun sequencing was employed to quantify host dna excretion and evaluate bacterial content in fecal samples c ...	2015	26090486
multiplex real-time pcr method for simultaneous identification and toxigenic type characterization of clostridium difficile from stool samples.	the aim of this study was to develop and validate a multiplex real-time pcr assay for simultaneous identification and toxigenic type characterization of clostridium difficile.	2015	25932438
clonalframeml: efficient inference of recombination in whole bacterial genomes.	recombination is an important evolutionary force in bacteria, but it remains challenging to reconstruct the imports that occurred in the ancestry of a genomic sample. here we present clonalframeml, which uses maximum likelihood inference to simultaneously detect recombination in bacterial genomes and account for it in phylogenetic reconstruction. clonalframeml can analyse hundreds of genomes in a matter of hours, and we demonstrate its usefulness on simulated and real datasets. we find evidence ...	2015	25675341
gastrointestinal dysbiosis and the use of fecal microbial transplantation in clostridium difficile infection.	the impact of antibiotics on the human gut microbiota is a significant concern. antibiotic-associated diarrhea has been on the rise for the past few decades with the increasing usage of antibiotics. clostridium difficile infections (cdi) have become one of the most prominent types of infectious diarrheal disease, with dramatically increased incidence in both the hospital and community setting worldwide. studies show that variability in the innate host response may in part impact upon cdi severit ...	2015	26600975
experience with cultivated microbiota transplant: ongoing treatment of clostridium difficile patients in sweden.		2015	26031676
fecal microbiota transplantation as novel therapy in gastroenterology: a systematic review.	to study the clinical efficacy and safety of fecal microbiota transplantation (fmt). we systematically reviewed fmt used as clinical therapy.	2015	25954111
extensive identification of bacterial riboflavin transporters and their distribution across bacterial species.	riboflavin, the precursor for the cofactors flavin mononucleotide (fmn) and flavin adenine dinucleotide, is an essential metabolite in all organisms. while the functions for de novo riboflavin biosynthesis and riboflavin import may coexist in bacteria, the extent of this co-occurrence is undetermined. the ribm, ribn, rfuabcd and the energy-coupling factor-ribu bacterial riboflavin transporters have been experimentally characterized. in addition, impx, rfnt and ribxy are proposed as riboflavin tr ...	2015	25938806
an assessment of antimicrobial resistant disease threats in canada.	antimicrobial resistance (amr) of infectious agents is a growing concern for public health organizations. given the complexity of this issue and how widespread the problem has become, resources are often insufficient to address all concerns, thus prioritization of amr pathogens is essential for the optimal allocation of risk management attention. since the epidemiology of amr pathogens differs between countries, country-specific assessments are important for the determination of national priorit ...	2015	25905797
effectiveness of fecal-derived microbiota transfer using orally administered capsules for recurrent clostridium difficile infection.	clostridium difficile infection (cdi), a complication of antibiotic-induced injury to the gut microbiome, is a prevalent and dangerous cause of infectious diarrhea. antimicrobial therapy for cdi is typically effective for acute symptoms, but up to one third of patients later experience recurrent cdi. fecal-derived microbiota transplantation (fmt) can ameliorate the underlying dysbiosis and is highly effective for recurrent cdi. traditional methods of fmt are limited by patient discomfort, risk a ...	2015	25885020
fecal microbiota transplantation and successful resolution of multidrug-resistant-organism colonization.	we report a case in which fecal microbiota transplantation (fmt) utilized for relapsing clostridium difficile colitis successfully eradicated colonization with several multidrug-resistant organisms (mdros). fmt may have an additive benefit of reducing mdro carriage and should be further investigated as a potential measure to eradicate additional potentially virulent organisms beyond c. difficile.	2015	25878340
complicated fecal microbiota transplantation in a tetraplegic patient with severe clostridium difficile infection.	a 65-year-old male suffering from acute spinal cord injury leading to incomplete tetraplegia presented with severe recurrent clostridium difficile (c. difficile) infection subsequent to antibiotic treatment for pneumonia. after a history of ineffective antimicrobial therapies, including metronidazole, vancomycin, fidaxomicin, rifaximin and tigecycline, leading to several relapses, the patient underwent colonoscopic fecal microbiota transplantation from his healthy son. four days subsequent to th ...	2015	25834343
fecal microbiota transplant protocol for clostridium difficile infection.	fecal microbiota transplant has become more acceptable as a therapeutic for recurrent clostridium difficile infection. the fda has an enforcement discretion policy for practitioner's performing this therapy, which includes informed consent for this experimental treatment. this manuscript describes a typical procedure that can be followed that includes the important aspects of this preparation and treatment.	2015	25805532
targeting surface-layer proteins with single-domain antibodies: a potential therapeutic approach against clostridium difficile-associated disease.	clostridium difficile is a leading cause of death from gastrointestinal infections in north america. antibiotic therapy is effective, but the high incidence of relapse and the rise in hypervirulent strains warrant the search for novel treatments. surface layer proteins (slps) cover the entire c. difficile bacterial surface, are composed of high-molecular-weight (hmw) and low-molecular-weight (lmw) subunits, and mediate adherence to host cells. passive and active immunization against slps has enh ...	2015	25936376
fever and cardiac arrest in a patient with a left ventricular assist device.	a 68-year-old avid deer hunter with ischemic cardiomyopathy underwent left ventricular assist device (lvad) implantation for destination therapy two years ago. he was living an active lifestyle, tracking deer and fishing in a midwestern forest in november. his wife removed an engorged tick on his thorax. a few days later, he experienced fever, confusion, and ataxia and was hospitalized with septic shock and ventricular fibrillation. the lvad site had no signs of trauma, drainage, warmth, or tend ...	2015	26380334
structural basis of proline-proline peptide bond specificity of the metalloprotease zmp1 implicated in motility of clostridium difficile.	clostridium difficile is a pathogenic bacterium causing gastrointestinal diseases from mild diarrhea to toxic megacolon. in common with other pathogenic bacteria, c. difficile secretes proteins involved in adhesion, colonization, and dissemination. the recently identified zmp1 is an extracellular metalloprotease showing a unique specificity for pro-pro peptide bonds. the endogenous substrates of zmp1 are two surface proteins implicated in adhesion of c. difficile to surface proteins of human cel ...	2015	26211609
unlocking the sporicidal potential of ethanol: induced sporicidal activity of ethanol against clostridium difficile and bacillus spores under altered physical and chemical conditions.	due to their efficacy and convenience, alcohol-based hand sanitizers have been widely adopted as the primary method of hand hygiene in healthcare settings. however, alcohols lack activity against bacterial spores produced by pathogens such as clostridium difficile and bacillus anthracis. we hypothesized that sporicidal activity could be induced in alcohols through alteration of physical or chemical conditions that have been shown to degrade or allow penetration of spore coats.	2015	26177038
diverse supramolecular structures formed by self-assembling proteins of the bacillus subtilis spore coat.	bacterial spores (endospores), such as those of the pathogens clostridium difficile and bacillus anthracis, are uniquely stable cell forms, highly resistant to harsh environmental insults. bacillus subtilis is the best studied spore-former and we have used it to address the question of how the spore coat is assembled from multiple components to form a robust, protective superstructure. b. subtilis coat proteins (coty, cote, cotv and cotw) expressed in escherichia coli can arrange intracellularly ...	2015	25872412
protein composition of the outermost exosporium-like layer of clostridium difficile 630 spores.	clostridium difficile spores are considered the morphotype of infection, transmission and persistence of c. difficile infections. there is a lack of information on the composition of the outermost exosporium layer of c. difficile spores. using recently developed exosporium removal methods combined with ms/ms, we have established a gel-free approach to analyze the proteome of the exosporium of c. difficile spores of strain 630. a total of 184 proteins were found in the exosporium layer of c. diff ...	2015	25849250
mechanisms of ricin toxin neutralization revealed through engineered homodimeric and heterodimeric camelid antibodies.	novel antibody constructs consisting of two or more different camelid heavy-chain only antibodies (vhhs) joined via peptide linkers have proven to have potent toxin-neutralizing activity in vivo against shiga, botulinum, clostridium difficile, anthrax, and ricin toxins. however, the mechanisms by which these so-called bispecific vhh heterodimers promote toxin neutralization remain poorly understood. in the current study we produced a new collection of ricin-specific vhh heterodimers, as well as ...	2015	26396190
the analysis of the occurrence of nosocomial infections in the neurosurgical ward in the district hospital from 2003-2012.	the patients in the neurosurgical ward are exposed to many risk factors causing nosocomial infections. these factors are related to operations, invasive diagnosing and monitoring of the nervous system and mechanical support of vital functions. therefore, the objective of the undertaken studies was to assess the prevalence and structure of the healthcare-associated infections (hai) in patients hospitalized in the neurosurgical ward in the st. lukas district hospital in tarnów.	2015	26519848
antibacterial discovery and development: from gene to product and back.	concern over the reports of antibiotic-resistant bacterial infections in hospitals and in the community has been publicized in the media, accompanied by comments on the risk that we may soon run out of antibiotics as a way to control infectious disease. infections caused by enterococcus faecium, staphylococcus aureus, klebsiella species, clostridium difficile, acinetobacter baumannii, pseudomonas aeruginosa, escherichia coli, and other enterobacteriaceae species represent a major public health b ...	2015	26339625
pathogen transfer and high variability in pathogen removal by detergent wipes.	the rise in health care-associated infections has placed a greater emphasis on cleaning and disinfection practices. the majority of policies advocate using detergent-based products for routine cleaning, with detergent wipes increasingly being used; however, there is no information about their ability to remove and subsequently transfer pathogens in practice.	2015	25997876
kibdelomycin is a bactericidal broad-spectrum aerobic antibacterial agent.	bacterial resistance to antibiotics continues to grow and pose serious challenges, while the discovery rate for new antibiotics declines. kibdelomycin is a recently discovered natural-product antibiotic that inhibits bacterial growth by inhibiting the bacterial dna replication enzymes dna gyrase and topoisomerase iv. it was reported to be a broad-spectrum aerobic gram-positive agent with selective inhibition of the anaerobic bacterium clostridium difficile. we have extended the profiling of kibd ...	2015	25845866
bloodstream infections among carriers of carbapenem-resistant klebsiella pneumoniae: etiology, incidence and predictors.	carriers of carbapenem-resistant klebsiella pneumoniae (crkp) are increasingly recognised through active surveillance in much of the world. we studied incidence, aetiology and predictors of bloodstream infections (bsi) among such carriers. via a retrospective cohort study conducted in a tertiary care teaching hospital, we examined occurrence of bsi within 45 days of crkp carrier detection. three nested case-control studies were conducted to analyse parameters associated with all-cause (all), gra ...	2015	25636924
evaluation of hydrogen peroxide vapor for the inactivation of nosocomial pathogens on porous and nonporous surfaces.	clostridium difficile spores and multidrug-resistant (mdr) organisms, such as methicillin-resistant staphylococcus aureus (mrsa), vancomycin-resistant enterococcus (vre), and mdr acinetobacter baumannii, are important nosocomial pathogens that are difficult to eliminate from the hospital environment. we evaluated the efficacy of hydrogen peroxide vapor (hpv), a no-touch automated room decontamination system, for the inactivation of a range of pathogens dried onto hard nonporous and porous surfac ...	2015	25564129
safety and clinical outcomes of carbapenem de-escalation as part of an antimicrobial stewardship programme in an esbl-endemic setting.	to evaluate the safety and clinical outcomes of patients who received carbapenem de-escalation as guided by an antimicrobial stewardship programme (asp) in a setting where esbl-producing enterobacteriaceae are endemic.	2015	25473028
ecological effect of ceftaroline-avibactam on the normal human intestinal microbiota.	ceftaroline-avibactam is a new combination of the antibiotic ceftaroline with a novel non-β-lactam β-lactamase inhibitor, avibactam. the purpose of the present study was to investigate the effect of ceftaroline-avibactam on the human intestinal microbiota. fourteen healthy volunteers received ceftaroline-avibactam (600 mg ceftaroline fosamil and 600 mg avibactam) intravenously over 2 h every 8 h on days 1 to 6 and as a single dose on day 7. fecal samples were collected on day -1 (within 24 h of ...	2015	25987638
impact of prophylactic levofloxacin on rates of bloodstream infection and fever in neutropenic patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation.	few studies have evaluated the role of antibacterial prophylaxis during neutropenia in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation (hsct). at our center, levofloxacin prophylaxis was initiated in june 2006 in patients with myeloma who were undergoing autologous hsct. we compared the incidence of bloodstream infection (bsi) and fever and neutropenia (fn) within 30 days of transplantation before (january 2003 to may 2006) and after (june 2006 to apr ...	2015	26150022
binding to histo-blood group antigen-expressing bacteria protects human norovirus from acute heat stress.	this study aims to investigate if histo-blood group antigen (hbga) expressing bacteria have any protective role on human norovirus (nov) from acute heat stress. eleven bacterial strains were included, belonging to escherichia coli, enterobacter cloacae, enterobacter aerogenes, clostridium difficile, bifidobacterium adolescentis, and b. longum. hbga expression of the bacteria as well as binding of human nov virus-like particles (vlps, gi.1, and gii.4 strains) to the bacteria were detected by flow ...	2015	26191052
clostridium difficile drug pipeline: challenges in discovery and development of new agents.	in the past decade clostridium difficile has become a bacterial pathogen of global significance. epidemic strains have spread throughout hospitals, while community acquired infections and other sources ensure a constant inoculation of spores into hospitals. in response to the increasing medical burden, a new c. difficile antibiotic, fidaxomicin, was approved in 2011 for the treatment of c. difficile-associated diarrhea. rudimentary fecal transplants are also being trialed as effective treatments ...	2015	25760275
disruption of the gut microbiome: clostridium difficile infection and the threat of antibiotic resistance.	clostridium difficile is well recognized as the leading cause of antibiotic-associated diarrhea, having a significant impact in both health-care and community settings. central to predisposition to c. difficile infection is disruption of the gut microbiome by antibiotics. being a gram-positive anaerobe, c. difficile is intrinsically resistant to a number of antibiotics. mobile elements encoding antibiotic resistance determinants have also been characterized in this pathogen. while resistance to ...	2015	26703737
development of gut inflammation in mice colonized with mucosa-associated bacteria from patients with ulcerative colitis.	disturbances in the intestinal microbial community (i.e. dysbiosis) or presence of the microbes with deleterious effects on colonic mucosa has been linked to the pathogenesis of inflammatory bowel diseases. however the role of microbiota in induction and progression of ulcerative colitis (uc) has not yet been fully elucidated.	2015	26697117
colonization resistance of the gut microbiota against clostridium difficile.	antibiotics strongly disrupt the human gut microbiota, which in consequence loses its colonization resistance capacity, allowing infection by opportunistic pathogens such as clostridium difficile. this bacterium is the main cause of antibiotic-associated diarrhea and a current problem in developed countries, since its incidence and severity have increased during the last years. furthermore, the emergence of antibiotic resistance strains has reduced the efficiency of the standard treatment with a ...	2015	27025628
loss of microbiota-mediated colonization resistance to clostridium difficile infection with oral vancomycin compared with metronidazole.	antibiotic administration disrupts the intestinal microbiota, increasing susceptibility to pathogens such as clostridium difficile. metronidazole or oral vancomycin can cure c. difficile infection, and administration of these agents to prevent c. difficile infection in high-risk patients, although not sanctioned by infectious disease society of america guidelines, has been considered. the relative impacts of metronidazole and vancomycin on the intestinal microbiota and colonization resistance ar ...	2015	25920320
interactions between the gastrointestinal microbiome and clostridium difficile.	antibiotics have significant and long-lasting effects on the intestinal microbiota and consequently reduce colonization resistance against pathogens, including clostridium difficile. by altering the community structure of the gut microbiome, antibiotics alter the intestinal metabolome, which includes both host- and microbe-derived metabolites. the mechanisms by which antibiotics reduce colonization resistance against c. difficile are unknown yet important for development of preventative and ther ...	2015	26488281
multicenter evaluation of the biofire filmarray gastrointestinal panel for etiologic diagnosis of infectious gastroenteritis.	the appropriate treatment and control of infectious gastroenteritis depend on the ability to rapidly detect the wide range of etiologic agents associated with the disease. clinical laboratories currently utilize an array of different methodologies to test for bacterial, parasitic, and viral causes of gastroenteritis, a strategy that suffers from poor sensitivity, potentially long turnaround times, and complicated ordering practices and workflows. additionally, there are limited or no testing met ...	2015	25588652
prevalence of clostridium difficile among paediatric patients in a tertiary care hospital, coastal karnataka, south india.	the study was intended to analyse the burden of clostridium difficile (c. difficile) and associated intestinal pathogens from children with diarrhoea who were hospitalized in a tertiary care teaching hospital of south india.	2015	25859452
coxiella burnetii phagocytosis is regulated by gtpases of the rho family and the rhoa effectors mdia1 and rock.	the gtpases belonging to the rho family control the actin cytoskeleton rearrangements needed for particle internalization during phagocytosis. rock and mdia1 are downstream effectors of rhoa, a gtpase involved in that process. coxiella burnetii, the etiologic agent of q fever, is internalized by the host´s cells in an actin-dependent manner. nevertheless, the molecular mechanism involved in this process has been poorly characterized. this work analyzes the role of different gtpases of the rho fa ...	2015	26674774
regulation of clostridium difficile spore formation by the spoiiq and spoiiia proteins.	sporulation is an ancient developmental process that involves the formation of a highly resistant endospore within a larger mother cell. in the model organism bacillus subtilis, sporulation-specific sigma factors activate compartment-specific transcriptional programs that drive spore morphogenesis. σg activity in the forespore depends on the formation of a secretion complex, known as the "feeding tube," that bridges the mother cell and forespore and maintains forespore integrity. even though the ...	2015	26465937
spore cortex hydrolysis precedes dipicolinic acid release during clostridium difficile spore germination.	bacterial spore germination is a process whereby a dormant spore returns to active, vegetative growth, and this process has largely been studied in the model organism bacillus subtilis. in b. subtilis, the initiation of germinant receptor-mediated spore germination is divided into two genetically separable stages. stage i is characterized by the release of dipicolinic acid (dpa) from the spore core. stage ii is characterized by cortex degradation, and stage ii is activated by the dpa released du ...	2015	25917906
morphological and genetic characterization of group i clostridium botulinum type b strain 111 and the transcriptional regulator spoiiid gene knockout mutant in sporulation.	clostridium botulinum is a heat-resistant spore-forming bacterium that causes the serious paralytic illness botulism. heat-resistant spores may cause food sanitation hazards and sporulation plays a central role in the survival of c. botulinum. we observed morphological changes and investigated the role of the transcriptional regulator spoiiid in the sporulation of c. botulinum type b strain 111 in order to elucidate the molecular mechanism in c. botulinum. c. botulinum type b formed heat-resista ...	2015	25652599
diverse mechanisms regulate sporulation sigma factor activity in the firmicutes.	sporulation allows bacteria to survive adverse conditions and is essential to the lifecycle of some obligate anaerobes. in bacillus subtilis, the sporulation-specific sigma factors, σ(f), σ(e), σ(g), and σ(k), activate compartment-specific transcriptional programs that drive sporulation through its morphological stages. the regulation of these sigma factors was predicted to be conserved across the firmicutes, since the regulatory proteins controlling their activation are largely conserved. howev ...	2015	25646759
spoiiid-mediated regulation of σk function during clostridium difficile sporulation.	the spore-forming bacterial pathogen clostridium difficile is a leading cause of health-care-associated diarrhea worldwide. although c. difficile spore formation is essential for disease transmission, the regulatory pathways that control this developmental process have only been partially characterized. in the well-studied spore-former bacillus subtilis, the highly conserved σ(e) , spoiiid and σ(k) regulatory proteins control gene expression in the mother cell to ensure proper spore formation. t ...	2015	25393584
prevalence of gastrointestinal pathogenic bacteria in patients with diarrhoea attending groote schuur hospital, cape town, south africa.	diarrhoea due to gastrointestinal infections is a significant problem facing the south african (sa) healthcare system. infections can be acquired both from the community and from the hospital environment itself, the latter acting as a reservoir for potential pathogenic bacteria.	2015	26242530
conventional and molecular methods in the diagnosis of community-acquired diarrhoea in children under 5 years of age from the north-eastern region of poland.	the purpose of this study was to determine the main causative agents of community-acquired acute diarrhoea in children using conventional methods and pcr.	2015	26159845
predictors of monomicrobial necrotizing soft tissue infections.	broad-spectrum antibiotic therapy is critical in the management of necrotizing soft tissue infections (nsti) in the emergency setting. clindamycin often is included empirically to cover monomicrobial gram-positive pathogens but probably is of little value for polymicrobial infections and is associated with significant side effects, including the induction of clostridium difficile colitis. however, there have been no studies predicting monomicrobial infections prior to obtaining cultures. the pur ...	2015	26110633
bacillus amyloliquefaciens as prophylactic treatment for clostridium difficile-associated disease in a mouse model.	probiotics might offer an attractive alternative for standard antibiotic therapy to treat clostridium difficile infections (cdi). we specifically selected a bacillus amyloliquefaciens strain for its high in vitro antibacterial activity against c. difficile and tested its efficacy to prevent cdi in a mouse model.	2015	25800047
probiotics for the prevention of antibiotic-associated diarrhoea in older patients: a systematic review.	here, we evaluated the efficacy of probiotic interventions in prevention of antibiotic-associated diarrhoea (aad) and clostridium difficile diarrhoea (cdd) in older patients.	2015	25805164
glucosyltransferase activity of clostridium difficile toxin b is essential for disease pathogenesis.	clostridium difficile tcdb harbors a glucosyltransferase that targets host rho gtpases. however, the role of the enzyme activity in the induction of host intestinal disease has not been demonstrated. in this study, we established a mouse acute intestinal disease model by cecum injection of wild type and glucosyltransferase-deficient tcdb and a chronic model by delivering toxin intraluminally via engineered surrogate host bacillus megaterium. we demonstrated, for the first time, that the glucosyl ...	2015	26091306
a chimeric protein comprising the glucosyltransferase and cysteine proteinase domains of toxin b and the receptor binding domain of toxin a induces protective immunity against clostridium difficile infection in mice and hamsters.	clostridium difficile is the major cause of hospital-acquired infectious diarrhea and colitis in developed countries. the pathogenicity of c. difficile is mainly mediated by the release of 2 large potent exotoxins, toxin a (tcda) and toxin b (tcdb), both of which require neutralization to prevent disease occurrence. we have generated a novel chimeric protein, designated mtcd138, comprised of the glucosyltransferase and cysteine proteinase domains of tcdb and the receptor binding domain of tcda a ...	2015	26036797