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Volume 56,
Issue 5,
2007
Volume 56, Issue 5, 2007
- Host Response
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Evolution of antibody response and fungal antigens in the serum of a patient infected with Candida famata
More LessThe presence of fungal antibodies and antigens in the serum of a patient diagnosed in 1996 with acute zonal occult outer retinopathy caused by Candida famata infection was examined. Antibodies against C. famata increased until 1999–2000 when antifungal treatment was initiated. The antibodies were detected by ELISA and immunofluorescence analysis using C. famata. These antibodies were not immunoreactive against several Candida species tested. Positive immunofluorescence was obtained with IgM, but not IgA, IgG or IgE. Moreover, the IgM response disappeared several months after treatment with antifungal compounds, despite the fact that C. famata antigens were present in the blood. Finally, a sensitive test was developed to assay for the presence of C. famata antigens in serum based on the immunodetection of fungal antigens transferred to a nitrocellulose membrane and incubated with rabbit antibodies raised against C. famata. According to this method, the infection diminished with antifungal treatment.
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- Diagnostics, Typing And Identification
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A peptide mimetic of the mycobacterial mannosylated lipoarabinomannan: characterization and potential applications
Mannosylated lipoarabinomannan (ManLAM), a complex lipoglycan, is a major component of Mycobacterium tuberculosis, the agent of tuberculosis (TB), and is an antigen used for serological diagnosis of TB. Screening random phage-display peptide libraries with anti-ManLAM mAb CS40 for peptide epitope mimics (mimotopes) led to the isolation of a panel of peptides. One of these peptides (B11) was characterized as a ManLAM mimotope: it bound the anti-ManLAM CS40 mAb and competed with ManLAM for antibody binding. Mice immunized with keyhole limpet haemocyanin-conjugated B11 peptide in a proper adjuvant developed antibodies that recognized ManLAM. Competition experiments demonstrated that the B11 peptide inhibited binding of mAb CS40 to ManLAM in a concentration-dependent manner. The data indicated that the affinity of CS40 mAb to B11 (K D 1.33×10−8) is higher than its affinity to ManLAM (K D 3.00×10−7). The sera of TB patients, as well as the sera of mice experimentally infected with M. tuberculosis, contained significant levels of antibodies that recognized both the B11 peptide and ManLAM. The specificity and sensitivity of the ELISA B11-based test were similar to those of the ELISA ManLAM-based test, indicating that the B11 antigen could be a good substitute for ManLAM serology for the diagnosis of TB.
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Use of immunoblotting as an alternative method for serogrouping Leptospira
Leptospirosis is a worldwide zoonotic disease caused by a spirochaete bacterium, Leptospira. Serological detection of this micro-organism basically relies on a conventional microscopic agglutination test (MAT), which has some limitations and disadvantages. In the present study, immunoblotting has been applied as an alternative method for differentiating serogroups and serovars of leptospires. Leptospiral whole-cell lysates from a total of 26 serovars were subjected to immunoblotting using rabbit antisera against individual serovars. The findings clearly demonstrated that the pattern of immunoreactive bands could be used to differentiate between leptospires of different serogroups, consistent with MAT results. There was a multi-band pattern that was unique for the pathogenic Leptospira antigens and was not observed in the non-pathogenic Leptospira biflexa and non-leptospiral bacteria (i.e. Escherichia coli, Burkholderia pseudomallei and Helicobacter pylori). For pathogenic Leptospira species, a prominent smear-like band at approximately 19–30 kDa was present when the antigens were probed with the homologous antisera. The molecular size of the prominent band, although it showed a cross-reaction between members within the same serogroup, differed among different serovars. The results obtained from polyclonal antibodies (antisera) were confirmed using mAb. With its simplicity and safety of experimental procedures, it is proposed that immunoblotting may potentially be useful as an alternative method for differentiating between serogroups of leptospires.
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Genetically similar isolates of Klebsiella pneumoniae serotype K1 causing liver abscesses in three continents
The magA gene was sought in hypermucoviscous isolates of Klebsiella spp., the Klebsiella K serotype reference strains and in isolates of the K1 serotype of Klebsiella pneumoniae from the UK, Hong Kong, Israel, Taiwan and Australia. Only K1 isolates were PCR positive for magA; this gene was found in all such isolates tested. Hypermucoviscosity was not confined to magA positive isolates, nor was it found in all magA positive isolates. Comparison of XbaI PFGE profiles revealed that most (19/23) of the magA positive isolates clustered within 72 % similarity, with a further subcluster of isolates, from three different continents, clustering within >80 %. All of the 16 isolates tested within the main cluster had the same sequence type (ST 23) by multilocus sequence typing, with the exception of one isolate, which had a single nucleotide difference at one of the seven loci. This study indicates that a genotype strongly associated with highly invasive disease in Taiwan, where large numbers of cases have been reported, is geographically very widespread.
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A paradigm for the molecular identification of Mycobacterium species in a routine diagnostic laboratory
More LessThe aim of this study was to improve the identification of Mycobacterium species in the context of a UK teaching hospital. Real-time PCR assays were established to enable the rapid differentiation between Mycobacterium tuberculosis (MTB) complex and Mycobacterium species other than tuberculosis (MOTT), followed by 16S rRNA gene sequencing for the speciation of MOTT. Real-time PCR assays gave comparable results to those from the reference laboratory. The implementation of these PCR assays using an improved bead extraction method has enhanced the mycobacterial diagnostic service at the Royal Free Hospital by providing a rapid means of differentiating between MTB complex and MOTT, and would be simple to implement in similar laboratories. Sequence analysis successfully identified a range of Mycobacterium spp. representative of those encountered in the clinical setting of the authors, including Mycobacterium avium complex, Mycobacterium fortuitum group, Mycobacterium chelonae–Mycobacterium abscessus group, Mycobacterium xenopi and Mycobacterium gordonae. It provides a useful tool for the identification of MOTT when clinically indicated.
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Real-time RT-PCR for H5N1 avian influenza A virus detection
The recent recurrence of highly pathogenic avian influenza virus A H5N1 was firstly reported in mid-December 2003 and continued through 2005. This study describes a sensitive and specific real-time RT-PCR method for the detection of influenza A subtype H5 and for monitoring virus loads. Using serial dilutions of influenza A H5N1 cultures, this assay reproducibly determined the lowest detection limit to be approximately 5×10−2 50 % egg infective doses (EID50). In contrast, the minimum detection limit was approximately 3 EID50 in conventional RT-PCR with WHO primers and 10 EID50 in antigen-capture ELISA. In tests of serial dilutions of in vitro-transcribed influenza A H5 gene RNA, there was linear amplification from 40 copies to 4×108 copies of target RNA per reaction and approximately six copies, and sometimes even as few as three copies, of target RNA tested positive in our assay. Thirty-five throat swabs from ill birds were tested: 33 samples tested positive using this assay. In comparison, 27, 13 and 19 samples tested positive using conventional RT-PCR, antigen-capture ELISA and virus isolation, respectively. To evaluate further the sensitivity of this real-time RT-PCR, a standard panel and 60 H5N1 isolates that contained different clades of influenza virus A/H5N1 were tested and all tested positive. To evaluate the specificity of the assay, 60 throat swabs from patients infected with influenza virus A H1 were tested; all were negative. Thirteen other viruses were also tested and all tested negative.
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The dominance of pandemic serovars of Vibrio parahaemolyticus in expatriates and sporadic cases of diarrhoea in Thailand, and a new emergent serovar (O3 : K46) with pandemic traits
Vibrio parahaemolyticus is a major cause of gastroenteritis worldwide. A total of 95 V. parahaemolyticus isolates belonging to 23 different serovars were identified in a case–control study of expatriates and Thai adults from 2001 to 2002 in Thailand. Fifty-two per cent of isolates (49/95) were resistant to ampicillin and sulfisoxazole, but all isolates were susceptible to ciprofloxacin and trimethoprim–sulfamethoxazole, two antibiotics commonly used to treat traveller’s diarrhoea. All isolates were positive for the species-specific toxR gene, and 91 and 5 were positive for the thermostable direct haemolysin (tdh) gene and the tdh-related (trh) gene, respectively. Sixty-five isolates were assigned to the pandemic group of V. parahaemolyticus by a group-specific PCR and the presence of the orf8 gene. The pandemic isolates belonged to three recognized serovars (O3 : K6, O1 : K25, O1 : KUT) and a new serovar, O3 : K46. This new serovar harboured pandemic traits. PFGE analysis revealed that all pandemic isolates including serovar O3 : K46 were closely related and clearly distinct from the non-pandemic isolates. In summary, three well-known serovars of pandemic V. parahaemolyticus isolates were identified as a major cause of diarrhoea in Thailand and a new V. parahaemolyticus isolate, serovar O3 : K46, with pandemic traits was detected.
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Rapid determination of hospital-acquired meticillin-resistant Staphylococcus aureus lineages
More LessMultilocus sequence typing (MLST) and multi-strain microarray analysis have shown that most human Staphylococcus aureus strains belong to ten dominant clonal complexes (CCs) or lineages, each with unique surface architecture. Meticillin-resistant S. aureus (MRSA) strains currently belong to six of these lineages (CC1, CC5, CC8, CC22, CC30 and CC45), each of which has independently acquired mobile genetic elements (MGEs) carrying antibiotic resistance genes. MLST and microarrays are expensive and time consuming methods for routine determination of S. aureus lineage. A restriction-modification (RM) test has now been developed that is rapid, simple, inexpensive and accurately determines lineage of hospital-acquired MRSA. The RM test is based on three PCRs for hsdS gene variants, as hsdS genes likely control the independent evolution of S. aureus lineages. The RM test correctly identified 102 MRSA isolates as belonging to one of the six lineages/CCs. Real-time MRSA typing can be used to identify and track changes in local MRSA outbreaks, and provide support for targeting infection control strategies. Simple and accurate typing methods will also support large scale epidemiological studies, and could lead to greater understanding of the carriage, spread and virulence of different MRSA lineages.
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Sequence-based typing of genetic targets encoded outside of the O-antigen gene cluster is indicative of Shiga toxin-producing Escherichia coli serogroup lineages
More LessSerogroup classifications based upon the O-somatic antigen of Shiga toxin-producing Escherichia coli (STEC) provide significant epidemiological information on clinical isolates. Each O-antigen determinant is encoded by a unique cluster of genes present between the gnd and galF chromosomal genes. Alternatively, serogroup-specific polymorphisms might be encoded in loci that are encoded outside of the O-antigen gene cluster. Segments of the core bacterial loci mdh, gnd, gcl, ppk, metA, ftsZ, relA and metG for 30 O26 STEC strains have previously been sequenced, and comparative analyses to O157 distinguished these two serogroups. To screen these loci for serogroup-specific traits within a broader range of clinically significant serogroups, DNA sequences were obtained for 19 strains of 10 additional STEC serogroups. Unique alleles were observed at the gnd locus for each examined STEC serogroup, and this correlation persisted when comparative analyses were extended to 144 gnd sequences from 26 O-serogroups (comprising 42 O : H-serotypes). These included O157, O121, O103, O26, O5 : non-motile (NM), O145 : NM, O113 : H21, O111 : NM and O117 : H7 STEC; and furthermore, non-toxin encoding O157, O26, O55, O6 and O117 strains encoded distinct gnd alleles compared to STEC strains of the same serogroup. DNA sequencing of a 643 bp region of gnd was, therefore, sufficient to minimally determine the O-antigen of STEC through molecular means, and the location of gnd next to the O-antigen gene cluster offered additional support for the co-inheritance of these determinants. The gnd DNA sequence-based serogrouping method could improve the typing capabilities for STEC in clinical laboratories, and was used successfully to characterize O121 : H19, O26 : H11 and O177 : NM clinical isolates prior to serological confirmation during outbreak investigations.
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- Antimicrobial Agents And Chemotherapy
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Aloe vera leaf exudate induces a caspase-independent cell death in Leishmania donovani promastigotes
More LessLeishmaniasis constitutes a complex of diseases with clinical and epidemiological diversity and includes visceral leishmaniasis, a disease that is fatal when left untreated. In earlier studies, the authors reported that Aloe vera leaf exudate (AVL) is a potent antileishmanial agent effective in promastigotes of Leishmania braziliensis, Leishmania mexicana, Leishmania tropica, Leishmania major and Leishmania infantum and also in axenic amastigotes of Leishmania donovani. In the present study, it has been demonstrated that, in promastigotes of L. donovani (IC50=110 μg ml−1), AVL mediates this leishmanicidal effect by triggering a programmed cell death. Incubation of promastigotes with AVL caused translocation of phosphatidylserine to the outer leaflet of the plasma membrane as measured by annexin V binding, which was accompanied by loss of mitochondrial membrane potential, release of cytochrome c into the cytosol and concomitant nuclear alterations that included chromatin condensation, deoxynucleotidyltransferase-mediated dUTP end labelling and DNA laddering. As this AVL-induced leishmanicidal effect could not be inhibited by protease inhibitors including Z-Val-Ala-dl-Asp (methoxy)-fluoromethylketone, a broad-spectrum caspase inhibitor, non-involvement of caspases and major proteases was suggested. Additionally, AVL treatment caused no increase in cytosolic Ca2+ or generation of reactive oxygen species, indicating that although promastigote death was induced by an apoptotic-like mechanism similar to metazoan apoptosis, the pathways of induction and/or execution differed at the molecular level.
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An antifungal protein from Escherichia coli
A cytosolic protein was purified from Escherichia coli BL21 that demonstrated potent antifungal activity against pathogenic strains of Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger and Candida albicans. The MIC of purified protein from E. coli BL21 (PPEBL21) against Aspergillus species and C. albicans was 1.95–3.98 and 15.62 μg ml−1, respectively. In vitro toxicity tests demonstrated no cytotoxicity of PPEBL21 to human erythrocytes up to the tested concentrations of 1250 μg ml−1. Amphotericin B was lethal to 100 % of human erythrocytes at a concentration of 37.5 μg ml−1. The N-terminal amino acid sequence of PPEBL21 was found to be DLAEVASR, which showed 75 % sequence similarity with alcohol dehydrogenase of yeast. Mass fingerprinting by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry also substantiated these observations. The results suggested that E. coli BL21 might be an important bioresource of lead molecules for developing new peptide-based therapies for treating fungal infections.
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Enhancement of the in vitro activity of amphotericin B against the biofilms of non-albicans Candida spp. by rifampicin and doxycycline
More LessThe in vitro activity of amphotericin B (AMB) alone and in combination with rifampicin (RIF) and doxycycline (DOX) was tested against the biofilms of 30 clinical isolates of non-albicans Candida (NAC) species namely, Candida parapsilosis, Candida krusei and Candida glabrata. The killing activity of AMB at 10×MIC was significantly increased in combination with either antibiotic. With RIF, the killing activity increased by 20.6, 23.5 and 14 % against the biofilms of C. parapsilosis, C. krusei and C. glabrata, respectively; with DOX, the killing activity increased by 30.64, 35.28 and 31.13 %, respectively. Pre-exposure of the isolates to the same combinations significantly reduced the number of colonized cells in the biofilms by 20, 25.14 and 13.07 % with RIF for C. parapsilosis, C. krusei and C. glabrata, respectively, and by 18.94, 24.52 and 29.15 % with DOX, respectively. The data showed that combination of RIF or DOX with AMB enhanced the killing activity of the antifungal agent against biofilms of NAC species. Whether such an effect operates against biofilm-associated infections needs to be clarified by further in vivo studies.
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Association between fluconazole susceptibility and genetic relatedness among Candida tropicalis isolates in Taiwan
More LessAmong the 162 Candida tropicalis isolates collected in the Taiwan Surveillance of Antimicrobial Resistance of Yeasts in 1999, 23 (14.2 %) had fluconazole MICs ≥64 mg l−1, and thus fulfilled the definition of resistance. Random amplified polymorphic DNA assay showed that all 23 fluconazole-resistance C. tropicalis isolates collected from different hospitals around Taiwan were closely related. Two distinct pulsotypes associated with fluconazole susceptibility were identified when these 23 resistant isolates, along with 13 susceptible ones, were analysed by PFGE.
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- Epidemiology
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A novel serovar of Shigella dysenteriae from patients with diarrhoea in Bangladesh
Every year, around 3 % of isolates from patients with diarrhoea at Dhaka Hospital, ICDDR,B, are identified as Shigella-like organisms (SLOs) based on their activity in biochemical tests. These isolates do not react with any of the current Shigella antisera including all existing and provisional serotypes. Among these SLOs, a unique cluster of seven isolates with an identical plasmid profile was found and these isolates were further characterized by phenotypic and genotypic techniques. All were nonlactose fermenters, with an identical biochemical pattern typical of Shigella dysenteriae. They were classified as invasive since they harboured the 140 MDa invasive plasmid, were able to bind Congo red, produced keratoconjunctivitis in the guinea pig eye, and were positive by PCR for the ipaH gene and Shigella enterotoxin 2 [ShET-2] gene. All isolates were resistant to ampicillin, tetracycline and sulfamethoxazole–trimethoprim but were susceptible to mecillinam, nalidixic acid, ceftriaxone and ciprofloxacin. Six of the isolates were identical in DNA pattern by PFGE with the seventh exhibiting a closely related pattern; both patterns were distinguishable from all other Shigella and Escherichia coli patterns. An antiserum prepared against one of the isolates reacted with all isolates and did not cross-react with other Shigella and E. coli serotype reference strains. It is therefore proposed that these isolates represent a new provisional serovar of S. dysenteriae, type strain KIVI 162.
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- Clinical Microbiology And Virology
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Effect of intensive handwashing in the prevention of diarrhoeal illness among patients with AIDS: a randomized controlled study
More LessPatients with AIDS frequently develop diarrhoeal illness. In this randomized, controlled study, 260 patients were screened for those who had not had diarrhoea in the preceding 3 months and who had received a stable highly active antiretroviral therapy regimen for at least 6 weeks prior to the study enrolment. A total of 148 patients met the inclusion criteria and were enrolled: 75 patients were randomly assigned to an intensive handwashing intervention (i.e. handwashing after defecation, after cleaning infants who had defecated, before preparing food, before eating, and before and after sex) and 73 patients were randomly assigned to the control group. Patients in both groups were called weekly by telephone to determine compliance with handwashing and to determine the number of diarrhoeal episodes for the preceding week. Patients were observed for 1 year. Patients assigned to the intensive handwashing intervention group washed their hands more frequently compared with the control group (seven vs four times a day, respectively; P <0.05) and developed fewer episodes of diarrhoeal illness (1.24±0.9 vs 2.92±0.6 new episodes of diarrhoea, respectively; P <0.001) during the 1 year observation. The most common pathogens identified in both groups in patients who developed diarrhoeal illness were Giardia lamblia, Cryptosporidium, Entamoeba histolytica and Shigella flexneri. These data suggest that intensive handwashing reduces diarrhoeal illness in patients with AIDS.
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Helicobacter pylori cag pathogenicity island genotype diversity within the gastric niche of a single host
cag pathogenicity island (PAI) integrity was investigated in isolates from multiple biopsies recovered from 40 patients in an attempt to determine the co-existence of a varying cagPAI-positive to cagPAI-negative ratio in a single host. Six biopsies were obtained from each patient during the same endoscopic session. cagPAI analysis included amplification of seven loci (cagA, cagE, cagG, cagM, cagT, HP0527 and HP0524) and the left end of cagII (LEC). Absence of the island was confirmed by empty-site PCR. lspA-glmM RFLP and random amplified polymorphic DNA PCR were used for strain delineation. The number of biopsies with Helicobacter pylori-positive culture ranged from three to six per patient and a total of 218 isolates were recovered. Mixed infection was only found in two patients. Nearly one-third of the 40 patients harboured isolates with an intact cagPAI in all niches, another third of the isolates were empty-site-positive in all niches, whilst the remaining third of the isolates had a disrupted cagPAI in all or at least one of the niches. Co-existence of variants of the same strain with different cagPAI genotypes was observed in one-quarter of patients. The variations in cagPAI genotype included co-existence of: diverse cagPAI deletions in different niches, variants with intact and with partially deleted islands, variants with empty-site-positive and with partially deleted cagPAIs, and variants with an intact cagPAI and with empty-site-positive. Half of the patients with different cagPAI genotypes harboured an intact cagPAI in at least one niche. Co-existence of diverse genotypes of putative virulence factors in a single host must be considered when drawing a correlation with clinical presentation.
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Detection of antibodies to Pseudomonas aeruginosa in serum and oral fluid from patients with cystic fibrosis
More LessCystic fibrosis (CF) patients who are chronically infected with Pseudomonas aeruginosa make serum antibodies to bacterial surface LPS as well as other pseudomonas antigens. This study investigated the feasibility of using oral fluid samples for the detection of pseudomonas antibodies in CF patients and compared these results with corresponding serum antibodies. Most strains of P. aeruginosa produce two forms of LPS molecule, termed A-band (described as a common antigen) and B-band (O-serotype-specific antigen), apparently bound to a common core oligosaccharide moiety. A-band LPS was demonstrated in 45 out of 49 clinical isolates of P. aeruginosa by SDS-PAGE and immunoblotting with a specific antibody. Oral fluids were collected from 17 adult CF patients, all of whom were sputum culture positive for P. aeruginosa (13 also provided serum samples), 11 primary ciliary dyskinesia (PCD) patients and 37 healthy volunteers. Antibodies to A-band LPS were detected by immunoblotting in all of the CF patients’ oral fluids but 10 of the volunteer samples gave weak reactions with immunoblotting. Six of the PCD patients gave a weak reaction with A-band antibodies and only one demonstrated antibodies to core LPS. In a quantitative ELISA, 15 of the 17 CF patients’ oral fluids were shown to contain antibodies to A-band LPS, whilst none of the volunteer samples contained antibodies to A-band LPS. All serum samples from the CF patients were positive by both methods. Thus this is a sensitive procedure for the detection of antibodies to A-band LPS of P. aeruginosa in oral fluid and serum from patients with CF.
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- Oral Microbiology
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Enhancement of salivary IgA response to a DNA vaccine against Streptococcus mutans wall-associated protein A in mice by plasmid-based adjuvants
More LessA specific salivary IgA (sIgA) response was obtained in mice by intranasal immunization with a naked DNA vaccine consisting of the Streptococcus mutans wall-associated protein A gene (wapA) inserted into the mammalian expression vector pcDNA3.1/V5/His-TOPO. In the present study, the vaccine, referred to as pcDNA-wapA, was administered with or without the cationic lipid DMRIE-C. No mucosal response was observed in mice immunized with the vaccine alone, whereas a weak and temporal sIgA response was obtained when the vaccine was mixed with DMRIE-C. To investigate the use of pcDNA containing the interleukin 5 (IL-5) gene (pcDNA-il-5) or the cholera toxin B gene (pcDNA-ctb) as genetic adjuvants, these constructs were used in co-immunization studies. The enhancement effect was transient with pcDNA-il-5, but longer lasting with pcDNA-ctb, thus supporting the use of the latter as a genetic adjuvant to DNA vaccine.
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The in vivo dynamics of Streptococcus spp., Actinomyces naeslundii, Fusobacterium nucleatum and Veillonella spp. in dental plaque biofilm as analysed by five-colour multiplex fluorescence in situ hybridization
The formation and composition of dental plaque biofilm in vivo are important factors which influence the development of gingivitis, caries and periodontitis. Studying dental plaque biofilm in in vitro models can cause an oversimplification of the real conditions in the oral cavity. In this study, bovine enamel slabs were fixed in an individual acrylic appliance in situ to quantify dental plaque formation and composition using multiplex fluorescence in situ hybridization (FISH) and confocal laser scanning microscopy. Each of the five oligonucleotide probes used for FISH was specific for either eubacteria or one of four frequently isolated bacterial constituents belonging to early and late colonizers of tooth surfaces. The thickness of formed biofilm increased from 14.9±5.0 μm after 1 day to 49.3±11.6 μm after 7 days. Streptococcus spp. were predominant in 1-day-old dental plaque and decreased significantly after 7 days (P=0.0061). Compared to the first day, Fusobacterium nucleatum decreased after 2 days and increased significantly after 7 days (P=0.0006). The decreases of Actinomyces naeslundii content on day 2 and day 7 were significant (P=0.0028). Changes in Veillonella spp. were not significant during the study period (P >0.05). The results showed that an in vivo observation period of 7 days was required to detect significant changes in Streptococcus spp. and F. nucleatum. The multiplex FISH used is suitable for analysing the dynamics of four important bacterial constituents in the oral biofilm in epidemiological studies.
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- Models Of Infection
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Candida glabrata colonizes but does not often disseminate from the mouse caecum
More LessCandida glabrata is the second or third most frequent cause of candidaemia. The gastrointestinal tract is considered to be a major portal of entry for systemic candidiasis, but relatively few studies have investigated the pathogenesis of C. glabrata. Experiments were designed to clarify the ability of C. glabrata to disseminate from the mouse intestinal tract. Following oral inoculation, C. glabrata readily colonized the caeca [approx. 107 cells (g caecum)−1] of antibiotic-treated mice, but extraintestinal dissemination was not detected. Superimposing several mouse models of trauma and/or immunosuppression known to induce dissemination of Candida albicans and other intestinal microbes did not cause C. glabrata to disseminate often, although one exception was mice given high doses of dexamethasone for 4 days. These data support the hypothesis that the antibiotic-treated mouse intestine may be an epidemiological reservoir for C. glabrata and that this yeast tends to disseminate under specific clinical conditions.
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