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 |
drug and vaccine development for the treatment and prevention of urinary tract infections. | urinary tract infections (uti) are among the most common bacterial infections in humans, affecting millions of people every year. uti cause significant morbidity in women throughout their lifespan, in infant boys, in older men, in individuals with underlying urinary tract abnormalities, and in those that require long-term urethral catheterization, such as patients with spinal cord injuries or incapacitated individuals living in nursing homes. serious sequelae include frequent recurrences, pyelon ... | 2016 | 26999391 |
second infections independently increase mortality in hospitalized patients with cirrhosis: the north american consortium for the study of end-stage liver disease (nacseld) experience. | bacterial infections are an important cause of mortality in cirrhosis, but there is a paucity of multicenter studies. the aim was to define factors predisposing to infection-related mortality in hospitalized patients with cirrhosis. a prospective, cohort study of patients with cirrhosis with infections was performed at eight north american tertiary-care hepatology centers. data were collected on admission vitals, disease severity (model for endstage liver disease [meld] and sequential organ fail ... | 2012 | 22806618 |
protective role of commensals against clostridium difficile infection via an il-1β-mediated positive-feedback loop. | clostridium difficile is a gram-positive obligate anaerobic pathogen that causes pseudomembranous colitis in antibiotic-treated individuals. commensal bacteria are known to have a significant role in the intestinal accumulation of c. difficile after antibiotic treatment, but little is known about how they affect host immunity during c. difficile infection. in this article, we report that c. difficile infection results in translocation of commensals across the intestinal epithelial barrier that i ... | 2012 | 22888139 |
active surveillance for carbapenem-resistant enterobacteriaceae using stool specimens submitted for testing for clostridium difficile. | active surveillance to identify asymptomatic carriers of carbapenem-resistant enterobacteriaceae (cre) is a recommended strategy for cre control in healthcare facilities. active surveillance using stool specimens tested for clostridium difficile is a relatively low-cost strategy to detect cre carriers. further evaluation of this and other risk factor-based active surveillance strategies is warranted. | 2013 | 24334803 |
evaluation of a new automated homogeneous pcr assay, genomera c. difficile, for rapid detection of toxigenic clostridium difficile in fecal specimens. | we evaluated a new automated homogeneous pcr assay to detect toxigenic clostridium difficile, the genomera c. difficile assay (abacus diagnostica, finland), with 310 diarrheal stool specimens and with a collection of 33 known clostridial and nonclostridial isolates. results were compared with toxigenic culture results, with discrepancies being resolved by the genexpert c. difficile pcr assay (cepheid). among the 80 toxigenic culture-positive or genexpert c. difficile assay-positive fecal specime ... | 2013 | 23804386 |
interleukin-22 regulates the complement system to promote resistance against pathobionts after pathogen-induced intestinal damage. | pathobionts play a critical role in disease development, but the immune mechanisms against pathobionts remain poorly understood. here, we report a critical role for interleukin-22 (il-22) in systemic protection against bacterial pathobionts that translocate into the circulation after infection with the pathogen clostridium difficile. infection with c. difficile induced il-22, and infected il22(-/-) mice harbored high numbers of pathobionts in extraintestinal organs despite comparable pathogen lo ... | 2014 | 25367575 |
severe clinical outcome is uncommon in clostridium difficile infection in children: a retrospective cohort study. | clostridium difficile infection (cdi) is the most common cause of health care-associated diarrhea in children and adults. although serious complications of cdi have been reported to be increasing in adults, this trend has not yet been demonstrated in children. the purpose of this study was to examine the features of cdi in a pediatric population, with special attention to the occurrence of cdi-related severe outcomes. | 2014 | 24485120 |
fidaxomicin for clostridium difficile colitis in a peritoneal dialysis patient with underlying mitochondriopathy. | | 2014 | 24525607 |
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 |
long-term changes of bacterial and viral compositions in the intestine of a recovered clostridium difficile patient after fecal microbiota transplantation. | fecal microbiota transplantation (fmt) is an effective treatment for recurrent clostridium difficile infections (rcdis). however, long-term effects on the patients' gut microbiota and the role of viruses remain to be elucidated. here, we characterized bacterial and viral microbiota in the feces of a cured rcdi patient at various time points until 4.5 yr post-fmt compared with the stool donor. feces were subjected to dna sequencing to characterize bacteria and double-stranded dna (dsdna) viruses ... | 2016 | 27148577 |
microbial and metabolic interactions between the gastrointestinal tract and clostridium difficile infection. | antibiotics disturb the gastrointestinal tract microbiota and in turn reduce colonization resistance against clostridium difficile. the mechanism for this loss of colonization resistance is still unknown but likely reflects structural (microbial) and functional (metabolic) changes to the gastrointestinal tract. members of the gut microbial community shape intestinal metabolism that provides nutrients and ultimately supports host immunity. this review will discuss how antibiotics alter the struct ... | 2013 | 24335555 |
equine hyperimmune serum protects mice against clostridium difficile spore challenge. | clostridium (c.) difficile is a common cause of nosocomial diarrhea in horses. vancomycin and metronidazole have been used as standard treatments but are only moderately effective, which highlights the need for a novel alternative therapy. in the current study, we prepared antiserum of equine origin against both c. difficile toxins a and b as well as whole-cell bacteria. the toxin-neutralizing activities of the antibodies were evaluated in vitro and the prophylactic effects of in vivo passive im ... | 2013 | 24136208 |
bacteremia due to clostridium difficile: case report and review of the literature. | the purpose of this study is to report a case of c. difficile bacteremia in a crohn's disease patient and to review the literature on previously reported cases. | 2009 | 24179365 |
trends in clostridium difficile disease: epidemiology and intervention. | clostridium difficile is the most common cause of nosocomial infectious diarrhea. the incidence of c difficile infection (cdi) is increasing in both inpatients and outpatients, and outbreaks caused by a hypervirulent strain of c difficile are resulting in more severe disease. moreover, community-associated cdi is occurring in persons who lack the traditional risk factors, which include antibiotic use, advanced age, and severe underlying disease. the clinical severity of cdi ranges from a mild, s ... | 2009 | 25237212 |
nosocomial diarrhea: evaluation and treatment of causes other than clostridium difficile. | diarrhea is common among hospitalized patients but the causes are distinct from those of diarrhea in the community. we review existing data about the epidemiology of nosocomial diarrhea and summarize recent progress in understanding the mechanisms of diarrhea. clinicians should recognize that most cases of nosocomial diarrhea have a noninfectious etiology, including medications, underlying illness, and enteral feeding. apart from clostridium difficile, the frequency of infectious causes such as ... | 2012 | 22700831 |
risk factors of mild rectal bleeding in very low birth weight infants: a case control study. | mild rectal bleeding (mrb) is a particular clinical entity different from necrotizing enterocolitis, which significantly influences neonatal care in preterm infants. we aimed to determine the risk factors and to evaluate prospectively the clinical course of mrb. | 2013 | 24283213 |
bacteriotherapy for the treatment of intestinal dysbiosis caused by clostridium difficile infection. | faecal microbiota transplantation (fmt) has been used for more than five decades to treat a variety of intestinal diseases associated with pathological imbalances within the resident microbiota, termed dysbiosis. fmt has been particularly effective for treating patients with recurrent clostridium difficile infection who are left with few clinical options other than continued antibiotic therapy. our increasing knowledge of the structure and function of the human intestinal microbiota and c. diffi ... | 2013 | 23866975 |
clinical characteristics of clostridium difficile infection in hospitalized patients with antibiotic-associated diarrhea in a university hospital in china. | the purpose of this study was to identify clinical characteristics of clostridium difficile infection (cdi) in patients with antibiotic-associated diarrhea (aad). a prospective study was conducted among patients hospitalized in fudan university hospital huashan from august 1, 2012 to july 31, 2013. toxigenic c. difficile isolates were characterized by pcr ribotyping and multilocus sequence typing. aad developed in 1.0 % (206/20437) of the antibiotic-treated hospitalized patients and toxigenic c. ... | 2014 | 24820293 |
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 |
clostridium difficile infection and takotsubo cardiomyopathy: is there a relation? | takotsubo cardiomyopathy (tcm) mimics acute coronary syndrome and is accompanied by reversible left ventricular apical ballooning in the absence of angiographically significant coronary artery stenosis. it is a transient condition that typically precedes physical or emotional triggers. | 2016 | 27583241 |
comparison of pediatric and adult antibiotic-associated diarrhea and clostridium difficile infections. | antibiotic-associated diarrhea (aad) and clostridium difficile infections (cdi) have been well studied for adult cases, but not as well in the pediatric population. whether the disease process or response to treatments differs between pediatric and adult patients is an important clinical concern when following global guidelines based largely on adult patients. a systematic review of the literature using databases pubmed (june 3, 1978-2015) was conducted to compare aad and cdi in pediatric and ad ... | 2016 | 27003987 |
in vitro antibacterial activity of rhodanine derivatives against pathogenic clinical isolates. | bacterial infections present a serious challenge to healthcare practitioners due to the emergence of resistance to numerous conventional antibacterial drugs. therefore, new bacterial targets and new antimicrobials are unmet medical needs. rhodanine derivatives have been shown to possess potent antimicrobial activity via a novel mechanism. however, their potential use as antibacterials has not been fully examined. in this study, we determined the spectrum of activity of seven rhodanine derivative ... | 2016 | 27711156 |
assessment of the overall and multidrug-resistant organism bioburden on environmental surfaces in healthcare facilities. | objective to determine the typical microbial bioburden (overall bacterial and multidrug-resistant organisms [mdros]) on high-touch healthcare environmental surfaces after routine or terminal cleaning. design prospective 2.5-year microbiological survey of large surface areas (>1,000 cm2). setting mdro contact-precaution rooms from 9 acute-care hospitals and 2 long-term care facilities in 4 states. participants samples from 166 rooms (113 routine cleaned and 53 terminal cleaned rooms). methods usi ... | 2016 | 27619507 |
vaccines for healthcare-associated infections: promise and challenge. | as antibiotic resistance increases and the rate of antibiotic development slows, it is becoming more urgent to develop novel approaches to prevent and mitigate serious bacterial and fungal infections. healthcare-associated infections (hais), including those caused by clostridium difficile, staphylococcus aureus, pseudomonas aeruginosa, acinetobacter baumannii, carbapenem-resistant enterobacteriaceae, and candida species, are a major cause of morbidity, mortality, and healthcare costs. hais are a ... | 2016 | 27208045 |
discovery and development of kibdelomycin, a new class of broad-spectrum antibiotics targeting the clinically proven bacterial type ii topoisomerase. | kibdelomycin is a complex novel antibiotic, discovered by applying a highly sophisticated chemical-genetic staphylococcus aureus fitness test (saft) approach, that inhibits the clinically established bacterial targets, gyrase and topoisomerase iv. it exhibits broad-spectrum antibacterial activity against aerobic bacteria including mrsa and acinetobacter baumannii. it is slowly bactericidal and has a low frequency of resistance. in an anaerobic environment, it exhibits narrow-spectrum activity an ... | 2016 | 27143131 |
point-prevalence survey of healthcare-associated infections in beijing, china: a survey and analysis in 2014. | point-prevalence studies can identify priorities for infection control. | 2016 | 27140419 |
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 |
differential impact of infection control strategies on rates of resistant hospital-acquired pathogens in critically ill surgical patients. | there were two major outbreaks of multi-drug resistant acinetobacter baumannii (mdra) in our general surgery and trauma intensive care units (icus) in 2004 and 2011. both required aggressive multi-faceted interventions to control. we hypothesized that the infection control response may have had a secondary benefit of reducing rates of methicillin-resistant staphylococcus aureus (mrsa), vancomycin-resistant enterococcus (vre), and clostridium difficile (c. diff). | 2014 | 25496277 |
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 |
impact of electronic surveillance on isolation practices. | to assess the impact of an electronic surveillance system on isolation practices and rates of methicillin-resistant staphylococcus aureus (mrsa). | 2013 | 23739073 |
comparative analysis of fecal microflora of healthy full-term indian infants born with different methods of delivery (vaginal vs cesarean): acinetobacter sp. prevalence in vaginally born infants. | in this study fecal microflora of human infants born through vaginal delivery (vb) and through cesarean section (cb) were investigated using culture-independent 16s rdna cloning and sequencing approach. the results obtained clearly revealed that fecal microbiota of vb infants distinctly differ from those in their counterpart cb infants. the intestinal microbiota of infants delivered by cesarean section appears to be more diverse, in terms of bacteria species, than the microbiota of vaginally del ... | 2012 | 23151789 |
the rise of carbapenem-resistant acinetobacter baumannii. | acinetobacter spp. are gram-negative bacteria that have become one of the most difficult pathogens to treat. the species a. baumannii, largely unknown 30 years ago, has risen to prominence particularly because of its ability to cause infections in immunocompromised patients. it is now a predominant pathogen in many hospitals as it has acquired resistance genes to virtually all antibiotics capable of treating gram-negative bacteria, including the fluoroquinolones and the cephalosporins. some memb ... | 2013 | 22894617 |
multidrug-resistant organisms, wounds and topical antimicrobial protection. | multidrug-resistant organisms (mdros) are increasingly implicated in both acute and chronic wound infections. the limited therapeutic options are further compromised by the fact that wound bacteria often co-exist within a biofilm community which enhances bacterial tolerance to antibiotics. as a consequence, topical antiseptics may be an important consideration for minimising the opportunity for wound infections involving mdros. the objective of this research was to investigate the antimicrobial ... | 2012 | 22640181 |
efficacy, efficiency and safety aspects of hydrogen peroxide vapour and aerosolized hydrogen peroxide room disinfection systems. | this was a head-to-head comparison of two hydrogen-peroxide-based room decontamination systems. | 2012 | 22306442 |
biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxy-4-methylvalerate) by recombinant escherichia coli expressing leucine metabolism-related enzymes derived from clostridium difficile. | an obligate anaerobic bacterium clostridium difficile has a unique metabolic pathway to convert leucine to 4-methylvalerate, in which 4-methyl-2-pentenoyl-coa (4m2pe-coa) is an intermediate of this pathway. 4m2pe-coa is also able to be converted to 3-hydroxy-4-methylvalerate (3h4mv), a branched side chain monomer unit, for synthesis of polyhydroxyalkanoate (pha) copolymer. in this study, to synthesize 3h4mv-containing pha copolymer from leucine, the leucine metabolism-related enzymes (ldha and h ... | 2014 | 24484910 |
a severe case of rat lungworm disease in hawa'i. | a 23-year-old man living on the island of hawa'i developed a life threatening case of eosinophilic meningitis caused by infection with angiostrongylus cantonensis (rat lungworm disease: rlwd). he was comatose for 3 months, incurring brain and nerve damage sufficiently extensive that he was not expected to recover. the case was complicated by secondary infections of methicillin-resistant staphylococcus aureus, clostridium difficile, and pneumonia, which resulted in an empyema requiring a thoracos ... | 2013 | 23900708 |
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 |
semicarbazone ega inhibits uptake of diphtheria toxin into human cells and protects cells from intoxication. | diphtheria toxin is a single-chain protein toxin that invades human cells by receptor-mediated endocytosis. in acidic endosomes, its translocation domain inserts into endosomal membranes and facilitates the transport of the catalytic domain (dta) from endosomal lumen into the host cell cytosol. here, dta adp-ribosylates elongation factor 2 inhibits protein synthesis and leads to cell death. the compound 4-bromobenzaldehyde n-(2,6-dimethylphenyl)semicarbazone (ega) has been previously shown to pr ... | 2016 | 27729638 |
surviving between hosts: sporulation and transmission. | to survive adverse conditions, some bacterial species are capable of developing into a cell type, the "spore," which exhibits minimal metabolic activity and remains viable in the presence of multiple environmental challenges. for some pathogenic bacteria, this developmental state serves as a means of survival during transmission from one host to another. spores are the highly infectious form of these bacteria. upon entrance into a host, specific signals facilitate germination into metabolically ... | 2016 | 27726794 |
generic aspects of the airborne spread of human pathogens indoors and emerging air decontamination technologies. | indoor air can be an important vehicle for a variety of human pathogens. this review provides examples of airborne transmission of infectious agents from experimental and field studies and discusses how airborne pathogens can contaminate other parts of the environment to give rise to secondary vehicles leading air-surface-air nexus with possible transmission to susceptible hosts. the following groups of human pathogens are covered because of their known or potential airborne spread: vegetative b ... | 2016 | 27590695 |
semicarbazone ega inhibits uptake of diphtheria toxin into human cells and protects cells from intoxication. | diphtheria toxin is a single-chain protein toxin that invades human cells by receptor-mediated endocytosis. in acidic endosomes, its translocation domain inserts into endosomal membranes and facilitates the transport of the catalytic domain (dta) from endosomal lumen into the host cell cytosol. here, dta adp-ribosylates elongation factor 2 inhibits protein synthesis and leads to cell death. the compound 4-bromobenzaldehyde n-(2,6-dimethylphenyl)semicarbazone (ega) has been previously shown to pr ... | 2016 | 27428999 |
crystal structures of the spoiid lytic transglycosylases essential for bacterial sporulation. | bacterial spores are the most resistant form of life known on earth and represent a serious problem for (i) bioterrorism attack, (ii) horizontal transmission of microbial pathogens in the community, and (iii) persistence in patients and in a nosocomial environment. stage ii sporulation protein d (spoiid) is a lytic transglycosylase (lt) essential for sporulation. the lt superfamily is a potential drug target because it is active in essential bacterial processes involving the peptidoglycan, which ... | 2016 | 27226615 |
a cumulative spore killing approach: synergistic sporicidal activity of dilute peracetic acid and ethanol at low ph against clostridium difficile and bacillus subtilis spores. | background. alcohol-based hand sanitizers are the primary method of hand hygiene in healthcare settings, but they lack activity against bacterial spores produced by pathogens such as clostridium difficile and bacillus anthracis. we previously demonstrated that acidification of ethanol induced rapid sporicidal activity, resulting in ethanol formulations with ph 1.5-2 that were as effective as soap and water washing in reducing levels of c difficile spores on hands. we hypothesized that the addit ... | 2016 | 26885539 |
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 |
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 |
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 |
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 |
efficacy of sporicidal wipes for inactivation of a bacillus anthracis surrogate. | to evaluate five commercially available sporicidal wipes and two disinfecting wipes for their ability to inactivate bacillus atrophaeus spores deposited onto various material surfaces. | 2014 | 25220421 |
tailored cyclodextrin pore blocker protects mammalian cells from clostridium difficile binary toxin cdt. | some clostridium difficile strains produce, in addition to toxins a and b, the binary toxin clostridium difficile transferase (cdt), which adp-ribosylates actin and may contribute to the hypervirulence of these strains. the separate binding and translocation component cdtb mediates transport of the enzyme component cdta into mammalian target cells. cdtb binds to its receptor on the cell surface, cdta assembles and cdtb/cdta complexes are internalised. in acidic endosomes, cdtb mediates the deliv ... | 2014 | 25029374 |
identification of a novel zinc metalloprotease through a global analysis of clostridium difficile extracellular proteins. | clostridium difficile is a major cause of infectious diarrhea worldwide. although the cell surface proteins are recognized to be important in clostridial pathogenesis, biological functions of only a few are known. also, apart from the toxins, proteins exported by c. difficile into the extracellular milieu have been poorly studied. in order to identify novel extracellular factors of c. difficile, we analyzed bacterial culture supernatants prepared from clinical isolates, 630 and r20291, using liq ... | 2013 | 24303041 |
characterization of the collagen-like exosporium protein, bcla1, of clostridium difficile spores. | spores of clostridium difficile are essential for infection, persistence and transmission of c. difficile infections (cdi). proteins of the surface of c. difficile spores are thought to be essential for initiation and persistence of cdi. in this work, we demonstrate that three c. difficile collagen-like exosporium proteins (bcla) encoded in the c. difficile 630 genome are expressed during sporulation and localize to the spore via their n-terminal domains. using polyclonal antibodies against the ... | 2014 | 24269655 |
cyclodextrin derivatives as anti-infectives. | cyclodextrin derivatives can be utilized as anti-infectives with pore-forming proteins as the targets. the highly efficient selection of potent inhibitors was achieved because per-substituted cyclodextrins have the same symmetry as the target pores. inhibitors of several bacterial toxins produced by bacillus anthracis, staphylococcus aureus, clostridium perfringens, clostridium botulinum, and clostridium difficile were identified from a library of ∼200 cd derivatives. it was demonstrated that mu ... | 2013 | 24011515 |
architecture and assembly of the gram-positive cell wall. | the bacterial cell wall is a mesh polymer of peptidoglycan--linear glycan strands cross-linked by flexible peptides--that determines cell shape and provides physical protection. while the glycan strands in thin 'gram-negative' peptidoglycan are known to run circumferentially around the cell, the architecture of the thicker 'gram-positive' form remains unclear. using electron cryotomography, here we show that bacillus subtilis peptidoglycan is a uniformly dense layer with a textured surface. we f ... | 2013 | 23600697 |
identification of novel host-targeted compounds that protect from anthrax lethal toxin-induced cell death. | studying how pathogens subvert the host to cause disease has contributed to the understanding of fundamental cell biology. bacillus anthracis, the causative agent of anthrax, produces the virulence factor lethal toxin to disarm host immunity and cause pathology. we conducted a phenotypic small molecule screen to identify inhibitors of lethal toxin-induced macrophage cell death and used an ordered series of secondary assays to characterize the hits and determine their effects on cellular function ... | 2013 | 23343607 |
in vivo activity of oritavancin in animal infection models and rationale for a new dosing regimen in humans. | oritavancin is a novel glycopeptide antibiotic with concentration-dependent killing of gram-positive cocci and pharmacokinetics characterized by extensive tissue distribution and a long terminal half-life. its development was hindered by a 16- to 32-fold underestimation of activity against staphylococci and enterococci because of oritavancin's sticking to vials and tubes. dose-fractionation studies in animal models suggested the peak concentration was the major index for efficacy. once-daily int ... | 2012 | 22431852 |
targeting bacterial toxins. | protein toxins constitute the main virulence factors of several species of bacteria and have proven to be attractive targets for drug development. lead candidates that target bacterial toxins range from small molecules to polymeric binders, and act at each of the multiple steps in the process of toxin-mediated pathogenicity. despite recent and significant advances in the field, a rationally designed drug that targets toxins has yet to reach the market. this review presents the state of the art i ... | 2012 | 22441768 |
contamination of healthcare workers' hands with bacterial spores. | clostridium species and bacillus spp. are spore-forming bacteria that cause hospital infections. the spores from these bacteria are transmitted from patient to patient via healthcare workers' hands. although alcohol-based hand rubbing is an important hand hygiene practice, it is ineffective against bacterial spores. therefore, healthcare workers should wash their hands with soap when they are contaminated with spores. however, the extent of health care worker hand contamination remains unclear. ... | 2016 | 27236515 |
hygienic characteristics and microbiological hazard identification in horse and donkey raw milk. | today the interest toward horse (equus caballus) and donkey (equus asinus) milk for human consumption is receiving a renewed attention because of its particular composition, hypoallergenicity, and nutraceutical properties. the realistic perspective of global use of this aliment in balanced diets, especially for infancy and geriatrics, poses the need for a more in depth knowledge on milk hygiene and on the health status of dairy animals, as a prerequisite of consumers' safety. the aim of this pap ... | 2017 | 27033528 |
secreted compounds of the probiotic bacillus clausii strain o/c inhibit the cytotoxic effects induced by clostridium difficile and bacillus cereus toxins. | although the use of probiotics based on bacillus strains to fight off intestinal pathogens and antibiotic-associated diarrhea is widespread, the mechanisms involved in producing their beneficial effects remain unclear. here, we studied the ability of compounds secreted by the probiotic bacillus clausii strain o/c to counteract the cytotoxic effects induced by toxins of two pathogens, clostridium difficile and bacillus cereus, by evaluating eukaryotic cell viability and expression of selected gen ... | 2016 | 27001810 |
uptake and levels of the antibiotic berberine in individual dormant and germinating clostridium difficile and bacillus cereus spores as measured by laser tweezers raman spectroscopy. | spores of clostridium difficile and bacillus cereus are major causes of nosocomial diarrhoea and foodborne disease. our aim was to measure the dynamics of the uptake of the antibiotic berberine by individual germinating spores and the levels of berberine accumulated in germinated spores. | 2016 | 26861569 |
in pursuit of protein targets: proteomic characterization of bacterial spore outer layers. | bacillus cereus, responsible for food poisoning, and clostridium difficile, the causative agent of clostridium difficile-associated diarrhea (cdad), are both spore-forming pathogens involved in food spoilage, food intoxication, and other infections in humans and animals. the proteinaceous coat and the exosporium layers from spores are important for their resistance and pathogenicity characteristics. the exosporium additionally provides an ability to adhere to surfaces eventually leading to spore ... | 2013 | 23998435 |
probiotics for the treatment of clostridium difficile associated disease. | the purpose of this review paper is to update the current and potential future role of probiotics for clostridium difficile-associated disease (cdad). included in this review, is an update on the testing of newer probiotics (e.g., bacillus coagulans gbi-30, 6086) in animal models of cdad. there is a focus on the modulation of signal transduction pathways (i.e., transcription factors like camp response element-binding, activator protein 1, and nuclear factor kappa b), as well as the inhibition of ... | 2013 | 23946887 |
bacillus coagulans gbi-30, 6086 limits the recurrence of clostridium difficile-induced colitis following vancomycin withdrawal in mice. | recently, we found that the probiotic strain bacillus coagulans gbi-30, 6086 (ganedenbc30) improved indices of clostridium difficile (c. difficile)-induced colitis in mice (fitzpatrick et al., gut pathogens, 2011). our goal was to determine if bc30 could also prevent the recurrence of c. difficile-induced colitis in mice, following initial treatment with vancomycin. during study days 0 through 5, mice were treated with antibiotics. on day 6, the c. difficile strain vpi 10463 was given by oro-gas ... | 2012 | 23088680 |
development of syn-004, an oral beta-lactamase treatment to protect the gut microbiome from antibiotic-mediated damage and prevent clostridium difficile infection. | the gut microbiome, composed of the microflora that inhabit the gastrointestinal tract and their genomes, make up a complex ecosystem that can be disrupted by antibiotic use. the ensuing dysbiosis is conducive to the emergence of opportunistic pathogens such as clostridium difficile. a novel approach to protect the microbiome from antibiotic-mediated dysbiosis is the use of beta-lactamase enzymes to degrade residual antibiotics in the gastrointestinal tract before the microflora are harmed. here ... | 2016 | 27262694 |
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 |
hard surface biocontrol in hospitals using microbial-based cleaning products. | healthcare-associated infections (hais) are one of the most frequent complications occurring in healthcare facilities. contaminated environmental surfaces provide an important potential source for transmission of many healthcare-associated pathogens, thus indicating the need for new and sustainable strategies. | 2014 | 25259528 |
a chimeric toxin vaccine protects against primary and recurrent clostridium difficile infection. | the global emergence of clostridium difficile infection (cdi) has contributed to the recent surge in severe antibiotic-associated diarrhea and colonic inflammation. c. difficile produces two homologous glucosylating exotoxins, tcda and tcdb, both of which are pathogenic and require neutralization to prevent disease occurrence. however, because of their large size and complex multifunctional domain structures, it has been a challenge to produce native recombinant toxins that may serve as vaccine ... | 2012 | 22615245 |
mucosal antibodies to the c terminus of toxin a prevent colonization of clostridium difficile. | mucosal immunity is considered important for protection against clostridium difficile infection (cdi). we show that in hamsters immunized with bacillus subtilis spores expressing a carboxy-terminal segment (tcda26-39) of c. difficile toxin a, no colonization occurs in protected animals when challenged with c. difficile strain 630. in contrast, animals immunized with toxoids showed no protection and remained fully colonized. along with neutralizing toxins, antibodies to tcda26-39 (but not to toxo ... | 2017 | 28167669 |
application of nuclear magnetic resonance to detect toxigenic clostridium difficile from stool specimens: a proof of concept. | we evaluated the performance of an early prototype core molecular mirroring nuclear magnetic resonance detection platform (mentor-100) to detect toxigenic clostridium difficile from stool. this technology uses customized nanoparticles bound to target specific oligonucleotide probes that form binaries in the presence of nucleic acid from the target microorganism. liquid patient stool specimens were seeded with c. difficile or other clostridium species to determine the analytical sensitivity and s ... | 2017 | 28081922 |
dipicolinic acid release by germinating clostridium difficile spores occurs through a mechanosensing mechanism. | classically, dormant endospores are defined by their resistance properties, particularly their resistance to heat. much of the heat resistance is due to the large amount of dipicolinic acid (dpa) stored within the spore core. during spore germination, dpa is released and allows for rehydration of the otherwise-dehydrated core. in bacillus subtilis, 7 proteins are encoded by the spova operon and are important for dpa release. these proteins receive a signal from the activated germinant receptor a ... | 2017 | 27981237 |
a recombination directionality factor controls the cell type-specific activation of σk and the fidelity of spore development in clostridium difficile. | the strict anaerobe clostridium difficile is the most common cause of nosocomial diarrhea, and the oxygen-resistant spores that it forms have a central role in the infectious cycle. the late stages of sporulation require the mother cell regulatory protein σk. in bacillus subtilis, the onset of σk activity requires both excision of a prophage-like element (skinbs) inserted in the sigk gene and proteolytical removal of an inhibitory pro-sequence. importantly, the rearrangement is restricted to the ... | 2016 | 27631621 |
germinants and their receptors in clostridia. | many anaerobic spore-forming clostridial species are pathogenic, and some are industrially useful. although many are strict anaerobes, the bacteria persist under aerobic and growth-limiting conditions as multilayered metabolically dormant spores. for many pathogens, the spore form is what most commonly transmits the organism between hosts. after the spores are introduced into the host, certain proteins (germinant receptors) recognize specific signals (germinants), inducing spores to germinate an ... | 2016 | 27432831 |
detecting cortex fragments during bacterial spore germination. | the process of endospore germination in clostridium difficile, and other clostridia, increasingly is being found to differ from the model spore-forming bacterium, bacillus subtilis. germination is triggered by small molecule germinants and occurs without the need for macromolecular synthesis. though differences exist between the mechanisms of spore germination in species of bacillus and clostridium, a common requirement is the hydrolysis of the peptidoglycan-like cortex which allows the spore co ... | 2016 | 27403726 |
impact of standard test protocols on sporicidal efficacy. | there has been an increase in the availability of commercial sporicidal formulations. any comparison of sporicidal data from the literature is hampered by the number of different standard tests available and the use of diverse test conditions including bacterial strains and endospore preparation. | 2016 | 27133281 |
characterization of clostridium difficile spores lacking either spovac or dipicolinic acid synthetase. | the spore-forming obligate anaerobe clostridium difficile is a leading cause of antibiotic-associated diarrhea around the world. in order for c. difficile to cause infection, its metabolically dormant spores must germinate in the gastrointestinal tract. during germination, spores degrade their protective cortex peptidoglycan layers, release dipicolinic acid (dpa), and hydrate their cores. in c. difficile, cortex hydrolysis is necessary for dpa release, whereas in bacillus subtilis, dpa release i ... | 2016 | 27044622 |
the spoiiq-spoiiiah complex of clostridium difficile controls forespore engulfment and late stages of gene expression and spore morphogenesis. | engulfment of the forespore by the mother cell is a universal feature of endosporulation. in bacillus subtilis, the forespore protein spoiiq and the mother cell protein spoiiiah form a channel, essential for endosporulation, through which the developing spore is nurtured. the two proteins also form a backup system for engulfment. unlike in b. subtilis, spoiiq of clostridium difficile has intact lytm zinc-binding motifs. we show that spoiiq or spoiiiah deletion mutants of c. difficile result in a ... | 2016 | 26690930 |
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 |