bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extended-Spectrum β-Lactamase-Producing
Enterobacteriaceae
in Community and Private Health Care Centers
Authors: Arpin Corinne , Dubois Véronique , Coulange Laure , André Catherine , Fischer Isabelle , Noury Patrick , Grobost Frédéric , Brochet Jean-Philippe , Jullin Jacqueline , Dutilh Brigitte , Larribet Gilberte , Lagrange Isabelle , Quentin Claudine 
Published: October 2003

ABSTRACT

In 1999, 39 of 2,599 isolates of the family
Enterobacteriaceae
(1.5%) collected by eight private laboratories in the Aquitaine region in France produced an extended-spectrum β-lactamase (ESBL). Among these were 19
Enterobacter aerogenes
isolates; 8
Klebsiella pneumoniae
isolates; 6
Escherichia coli
isolates; 3
Proteus mirabilis
isolates; and 1 isolate each of
Serratia marcescens
,
Morganella morganii
, and
Providencia stuartii
. ESBL producers were isolated from 38 patients, including 33 residents of 11 clinics or nursing homes and 5 ambulatory patients. Seven different ESBLs were characterized. These mainly consisted of TEM-24 (25 isolates) and TEM-21 (9 isolates), but TEM-15 (2 isolates) and TEM-3, TEM-19, SHV-4, and CTX-M-1 (1 isolate each) were also characterized. Seven strains showed the coexistence of different TEM- and/or SHV-encoding genes, including a new SHV-1 variant, SHV-44, defined by the substitution R205L previously reported for SHV-3 in association with S238G. The epidemiology of the ESBL producers was investigated by random amplification of polymorphic DNA, typing by enterobacterial repetitive intergenic consensus PCR, analysis of resistance cotransferred with the ESBL, and analysis of the restriction profiles of the ESBL-encoding plasmids. Of the TEM-24-expressing strains, 18 were
E. aerogenes
isolates, including 9 from the same clinic, that were representatives of the epidemic clone disseminating in France. Of the TEM-21-producing strains that belonged to different species of the family
Enterobacteriaceae
(
E. coli
,
K. pneumoniae
, and
P. mirabilis
), 8 were isolated in the same nursing home. Outbreaks due to strain and/or plasmid dissemination in these clinic and nursing home were demonstrated. The presence of ESBL producers in five ambulatory patients probably resulted from nosocomial acquisition. Our data highlight the serious need to monitor patients for ESBL-producing
Enterobacteriaceae
in general practice.
Effects of Triclosan-Containing Rinse on the Dynamics and Antimicrobial Susceptibility of In Vitro Plaque Ecosystems
Authors: McBain Andrew J. , Bartolo Robert G. , Catrenich Carl E. , Charbonneau Duane , Ledder Ruth G. , Gilbert Peter 
Published: October 2003

ABSTRACTDental plaque microcosms were established under a feast-famine regimen within constant-depth film fermentors and exposed four times daily postfeeding to a triclosan (TR)-containing rinse (dentifrice) (TRD). This was diluted so that the antimicrobial content was 0.6 mg/ml. Microcosms were characterized by heterotrophic plate counts and PCR-denaturing gradient gel electrophoresis (DGGE) with primers specific for the V2-V3 region of the eubacterial 16S rRNA gene (rDNA). Dominant isolates and PCR amplicons were identified by partial sequencing of 16S rDNA. TRD caused considerable decreases in the counts of both gram-negative organisms and total anaerobic cells, transiently lowered the numbers of streptococci and actinomycetes, and markedly increased the proportion of lactobacilli. DGGE indicated the presence of putatively unculturable bacteria and showed that aPorphyromonassp. andSelenomonas infelixhad been inhibited by TRD. Pure culture studies of 10 oral bacteria (eight genera) showed thatNeisseria subflava,Prevotella nigrescens, andPorphyromonas gingivaliswere highly susceptible to TR, while the lactobacilli and streptococci were the least susceptible. Clonal expansion of the lactobacilli in the pulsed microcosm could be explained on the basis of TR activity. The mean MICs of TR, chlorhexidine, erythromycin, penicillin V, and vancomycin for the population before and after 5 days of exposure to TRD showed few significant changes. In conclusion, changes in plaque microcosm populations following repeated exposure to TRD showed inhibition of the most susceptible flora and clonal expansion of less susceptible species.
Relevance of Soft-Tissue Penetration by Levofloxacin for Target Site Bacterial Killing in Patients with Sepsis
Authors: Zeitlinger M. A. , Dehghanyar P. , Mayer B. X. , Schenk B. S. , Neckel U. , Heinz G. , Georgopoulos A. , Müller M. , Joukhadar C. 
Published: October 2003

ABSTRACT

Antimicrobial therapy of soft tissue infections in patients with sepsis sometimes lacks efficiency, despite the documented susceptibility of the causative pathogen to the administered antibiotic. In this context, impaired equilibration between the antibiotic concentrations in plasma and those in tissues in critically ill patients has been discussed. To characterize the impact of tissue penetration of anti-infective agents on antimicrobial killing, we used microdialysis to measure the concentration-versus-time profiles of levofloxacin in the interstitial space fluid of skeletal muscle in patients with sepsis. Subsequently, we applied an established dynamic in vivo pharmacokinetic-in vitro pharmacodynamic approach to simulate bacterial killing at the site of infection. The population mean areas under the concentration-time curves (AUCs) for levofloxacin showed that levofloxacin excellently penetrates soft tissues, as indicated by the ratio of the AUC from time zero to 8 h (AUC
0-8
) for muscle tissue (AUC
0-8 muscle
) to the AUC
0-8
for free drug in plasma (AUC
0-8 plasma free
) (AUC
0-8 muscle
/AUC
0-8 plasma free
ratio) of 0.85. The individual values of tissue penetration and maximum concentration (
C
max
) in muscle tissue were highly variable. No difference in bacterial killing of a select
Staphylococcus aureus
strain for which the MIC was 0.5 μg/ml was found between individuals after exposure to dynamically changing concentrations of levofloxacin in plasma and tissue in vitro. In contrast, the decrease in the bacterial counts of
Pseudomonas aeruginosa
(MIC = 2 μg/ml) varied extensively when the bacteria were exposed to levofloxacin at the concentrations determined from the individual concentration-versus-time profiles obtained in skeletal muscle. The extent of bacterial killing could be predicted by calculating individual
C
max
/MIC and AUC
0-8 muscle
/AUC
0-8 plasma free
ratios (
R
= 0.96 and 0.93, respectively). We have therefore shown in the present study that individual differences in the tissue penetration of levofloxacin may markedly affect target site killing of bacteria for which MICs are close to 2 μg/ml.
In Vitro Activities of a New Des-Fluoro(6) Quinolone, Garenoxacin, against Clinical Anaerobic Bacteria
Authors: Liebetrau A. , Rodloff A. C. , Behra-Miellet J. , Dubreuil L. 
Published: October 2003

ABSTRACT

The antimicrobial activities of garenoxacin and eight other antibiotics against 641 anaerobic isolates were evaluated with the NCCLS agar dilution method. Overall, the MICs of garenoxacin for 50 and 90% of the strains tested (in micrograms per milliliter) were as follows:
Bacteroides fragilis
group, 0.5 and 2;
Prevotella
spp., 0.25 and 2;
Fusobacterium
spp., 0.25 and 0.5;
Porphyromonas
spp., 0.125 and 0.25;
Bilophila wadsworthia
, 0.5 and 1;
Veillonella
spp., 0.25 and 0.5;
Clostridium
spp., 0.25 and 1;
Clostridium difficile
, 2 and >64;
Bifidobacterium
spp., 1 and 2;
Eggerthella lenta
, 0.25 and 1;
Propionibacterium
spp., 0.5 and 0.5; gram-positive cocci, 0.125 and 0.25.
One of Two Human Lactoferrin Variants Exhibits Increased Antibacterial and Transcriptional Activation Activities and Is Associated with Localized Juvenile Periodontitis
Authors: Velliyagounder Kabilan , Kaplan Jeffrey B. , Furgang David , Legarda Diana , Diamond Gill , Parkin Ruth E. , Fine Daniel H. 
Published: October 2003

ABSTRACTThe iron-binding protein lactoferrin is a ubiquitous and abundant constituent of human exocrine secretions. Lactoferrin inhibits bacterial growth by sequestering essential iron and also exhibits non-iron-dependent antibacterial, antifungal, antiviral, antitumor, anti-inflammatory, and immunoregulatory activities. All of these non-iron-dependent activities are mediated by the highly charged N terminus of lactoferrin. In this study we characterized a Lys/Arg polymorphism at position 29 in the N-terminal region of human lactoferrin that results from a single nucleotide polymorphism in exon 1 of the human lactoferrin gene. We expressed cDNAs encoding both lactoferrin variants in insect cells and purified the two proteins by ion exchange chromatography. The two lactoferrin variants exhibited nearly identical iron-binding and iron-releasing activities and equivalent bactericidal activities against a strain of the gram-negative bacteriumActinobacillus actinomycetemcomitans. When tested against the gram-positive speciesStreptococcus mutansandStreptococcus mitis, however, lactoferrin containing Lys at position 29 exhibited significantly greater bactericidal activity than did lactoferrin containing Arg. In addition, the Lys-containing lactoferrin stimulated bovine tracheal epithelial cells to synthesize much higher levels of tracheal antimicrobial peptide mRNA than did the Arg-containing variant. A genotyping assay that distinguished between the two alleles based on a polymorphicEarI restriction site showed that the Lys and Arg alleles had frequencies of 24% and 76%, respectively, among 17 healthy human subjects, and 72% and 28%, respectively, among nine patients with localized juvenile periodontitis. Our findings suggest that these two lactoferrin variants are functionally different and that these differences may contribute to the pathogenesis of localized juvenile periodontitis.
Induction of Capsule Growth inCryptococcus neoformansby Mammalian Serum and CO2
Authors: Zaragoza Oscar , Fries Bettina C. , Casadevall Arturo 
Published: October 2003

ABSTRACTThe pathogenic fungusCryptococcus neoformanshas a polysaccharide capsule that is essential for virulence in vivo. Capsule size is known to increase during animal infection, and this phenomenon was recently associated with virulence. Although various conditions have been implicated in promoting capsule growth, including CO2concentration, osmolarity, and phenotypic switching, it is difficult to reproduce the capsule enlargement effect in the laboratory. In this study, we report that serum can induce capsule growth, and we describe the conditions that induce this effect, not only by serum but also by CO2. Capsule enlargement was dependent on the medium used, and this determined whether the strain responded to serum or CO2efficiently. Serum was most effective in inducing capsule growth under nutrient-limited conditions. There was considerable variability between strains in their response to either serum or CO2, with some strains requiring both stimuli. Sera from several animal sources were each highly efficient in inducing capsule growth. The cyclic AMP (cAMP) pathway and Ras1 were both necessary for serum-induced capsule growth. The lack of induction in theras1mutant was not complemented by exogenous cAMP, indicating that these pathways act in parallel. However, both cAMP and Ras1 were dispensable for inducing a partial capsule growth by CO2, suggesting that multiple pathways participate in this process. The ability of serum to induce capsule growth suggests a mechanism for the capsular enlargement observed during animal infection.
Therapeutic Activity of an Engineered Synthetic Killer Antiidiotypic Antibody Fragment against Experimental Mucosal and Systemic Candidiasis
Authors: Polonelli Luciano , Magliani Walter , Conti Stefania , Bracci Luisa , Lozzi Luisa , Neri Paolo , Adriani Daniela , De Bernardis Flavia , Cassone Antonio 
Published: October 2003

ABSTRACTPeptides derived from the sequence of a single-chain, recombinant, antiidiotypic antibody (IdAb; KT-scFv) acting as a functional internal image of a microbicidal, wide-spectrum yeast killer toxin (KT) were synthesized and studied for their antimicrobial activity by using the KT-susceptibleCandida albicansas model organism. A decapeptide containing the first three amino acids (SAS) of the light chain CDR1 was selected and optimized by alanine replacement of a single residue. This peptide exerted a strong candidacidal activity in vitro, with a 50% inhibitory concentration of 0.056 μM, and was therefore designated killer peptide (KP). Its activity was neutralized by laminarin, a β1-3 glucan molecule, but not by pustulan, a β1-6 glucan molecule. KP also competed with the binding of a KT-like monoclonal IdAb to germinating cells of the fungus. In a rat model of vaginal candidiasis, local, postchallenge administration of KP was efficacious in rapidly abating infections caused by fluconazole-susceptible or -resistantC. albicansstrains. In systemic infection of BALB/c or SCID mice preinfected intravenously with a lethal fungal load, KP caused a highly significant prolongation of the median survival time, with >80% of the animals still surviving after >60 days, whereas >90% of control mice died within 3 to 5 days. KP is therefore the first engineered peptide derived from a recombinant IdAb retaining KT microbicidal activity, probably through the interaction with the β-glucan KT receptor on target microbial cells.
Antibodies to
Plasmodium falciparum
Rifin Proteins Are Associated with Rapid Parasite Clearance and Asymptomatic Infections
Authors: Abdel-Latif Mohamed S. , Dietz Klaus , Issifou Saadou , Kremsner Peter G. , Klinkert Mo-Quen 
Published: October 2003

ABSTRACT

Plasmodium falciparum
rifin proteins, belonging to the largest known family of variable infected-erythrocyte surface-expressed proteins encoded by
rif
genes, were recently shown to be capable of inducing a strong immune response in
P. falciparum
-infected adults living in an area in Gabon where malaria is endemic. In the present study, the levels of antirifin antibodies were analyzed in serum obtained from 60 children from the same area who were admitted to hospital and diagnosed with severe malaria. High antirifin antibody concentrations in these individuals correlated significantly with their capacity to rapidly clear their parasites from the circulation after the start of chemotherapy. A doubling of antirifin antibody concentrations reduced the clearance time by 5 h (95% confidence interval, 4.1 to 6.9 h). In the same group of children, who were followed up for 2 years, antirifin antibody levels did not correlate with a reduced rate of reinfection or with a delay in the time to the first reinfection. However, the initial antirifin antibody levels were sustained over the study period. The likelihood that these antibodies could confer a certain degree of protection against malaria is supported by our findings of statistically higher levels of antirifin antibodies to all four rifin proteins in a group of 42 asymptomatic parasitemic children.
PPE Antigen Rv2430c of
Mycobacterium tuberculosis
Induces a Strong B-Cell Response
Authors: Choudhary Rakesh Kumar , Mukhopadhyay Sangita , Chakhaiyar Prachee , Sharma Naresh , Murthy K. J. R. , Katoch V. M. , Hasnain Seyed E. 
Published: October 2003

ABSTRACT

The variation in sequence and length in the C-terminal region among members of the unique PE (Pro-Glu) and PPE (Pro-Pro-Glu) protein families of
Mycobacterium tuberculosis
is a likely source of antigenic variation, giving rise to the speculation that these protein families could be immunologically important. Based on in silico analysis, we selected a hypothetical open reading frame (ORF) encoding a protein belonging to the PPE family and having epitopes with predictably higher antigenic indexes. Reverse transcriptase PCR using total RNA extracted from in vitro-cultured
M. tuberculosis
H37Rv generated an mRNA product corresponding to this gene, indicating the expression of this ORF (Rv2430c) at the mRNA level. Recombinant protein expressed in
Escherichia coli
was used to screen the sera of
M. tuberculosis
-infected patients, as well as those of clinically healthy controls (
n
= 10), by enzyme-linked immunosorbent assay. The panel of patient sera comprised sera from fresh infection cases (category 1;
n
= 32), patients with relapsed tuberculosis (category 2;
n
= 30), and extrapulmonary cases (category 3;
n
= 30). Category 2 and 3 sera had strong antibody responses to the PPE antigen, equal to or higher than those to other well-known antigens, such as Hsp10 or purified protein derivative (PPD). However, a higher percentage of patients belonging to category 1, as opposed to clinically healthy controls, showed stronger antibody response against the PPE protein when probed with anti-immunoglobulin M (IgM) (71 versus 37.5%) or anti-IgG (62.5 versus 28.12%). Our results reveal that this PPE ORF induces a strong B-cell response compared to that generated by
M. tuberculosis
Hsp10 or PPD, pointing to the immunodominant nature of the protein.
Critical Role of the Complement System in Group BStreptococcus-Induced Tumor Necrosis Factor Alpha Release
Authors: Levy Ofer , Jean-Jacques Rochelle M. , Cywes Colette , Sisson Richard B. , Zarember Kol A. , Godowski Paul J. , Christianson Jennifer L. , Guttormsen Hilde-Kari , Carroll Michael C. , Nicholson-Weller Anne , Wessels Michael R. 
Published: October 2003

ABSTRACTGroup BStreptococcus(GBS) is a major cause of newborn sepsis and meningitis and induces systemic release of tumor necrosis factor alpha (TNF-α), believed to play a role in morbidity and mortality. While previous studies have shown that GBS can induce TNF-α release from monocytes and macrophages, little is known about the potential modulating effect of plasma or serum on GBS-induced TNF-α release, and there are conflicting reports as to the host receptors involved. In a human whole-blood assay system, GBS type III COH-1 potently induced substantial monocyte TNF-α release in adult peripheral blood and, due to a higher concentration of monocytes, 10-fold-greater TNF-α release in newborn cord blood. Remarkably, GBS-induced TNF-α release from human monocytes was enhanced ∼1,000-fold by heat-labile serum components. Experiments employing C2-, C3-, or C7-depleted serum demonstrated that C3 activation via the alternative pathway is crucial for potent GBS-induced TNF-α release. Accordingly, whole blood from C3-deficient mice demonstrated significantly reduced GBS-induced TNF-α release. Preincubation with human serum enhanced the TNF-α-inducing activity of GBS in a C3- and factor B-dependent manner, implying deposition of complement components via the alternative pathway. GBS-induced TNF-α release was inhibited by monoclonal antibodies directed against each of the components of CR3 and CR4: the common integrin β subunit CD18 and the α subunits CD11b (of CR3) and CD11c (of CR4). Blood derived from CR3 (CD11b/CD18)-deficient mice demonstrated a markedly diminished TNF-α response to GBS. We conclude that the ability of plasma and serum to greatly amplify GBS-induced TNF-α release reflects the activity of the alternative complement pathway that deposits fragments on GBS and thereby enhances CR3- and CR4-mediated monocyte activation.
Forssman Synthetase Expression Results in Diminished Shiga Toxin Susceptibility
Authors: Elliott Sean P. , Yu Min , Xu Huaijin , Haslam David B. 
Published: October 2003

ABSTRACT

Forssman glycolipid (FG), the product of Forssman synthetase (FS), is widely expressed among nonprimate mammalian species. Here, we describe a molecular and genetic relationship between FG expression and Shiga toxin (Stx) susceptibility. We have isolated the FS cDNA from human, canine, and murine cells. Whereas the murine and canine FS genes express a functional enzyme, the human FS cDNA was found to express a protein that lacks FS activity, despite a high degree of sequence identity with the enzymatically active murine and canine FS genes. In order to examine the relationship between FG expression and Stx susceptibility, Vero cells were transfected with the three FS orthologues or a vector control. Complementation with the human FS cDNA had no effect on Stx susceptibility, whereas stable expression of the canine and murine FS resulted in markedly decreased susceptibility to toxin. Among individual cells, an inverse correlation between FG expression and Stx binding was demonstrated. Moreover, only strongly FG-reactive cells were capable of growing in the presence of Stx. These cells were found to have high levels of FG expression and a correspondingly diminished GbO
3
content. We conclude that expression of a functionally active FS modifies Stx receptor glycolipids to FG and results in markedly decreased susceptibility to toxin. We speculate that inactivation of the FS gene during primate evolution may account, at least in part, for the marked susceptibility of human cells to Stx.
TheLeishmania infantumAcidic Ribosomal Protein P0 Administered as a DNA Vaccine Confers Protective Immunity toLeishmania majorInfection in BALB/c Mice
Authors: Iborra Salvador , Soto Manuel , Carrión Javier , Nieto Ana , Fernández Edgar , Alonso Carlos , Requena Jose M. 
Published: October 2003

ABSTRACTIn this study, we examined the immunogenic properties of theLeishmania infantumacidic ribosomal protein P0 (LiP0) in the BALB/c mouse model. The humoral and cellular responses induced by the administration of the LiP0 antigen, either as soluble recombinant LiP0 (rLiP0) or as a plasmid DNA formulation (pcDNA3-LiP0), were determined. Also, the immunological response associated with a prime-boost strategy, consisting of immunization with pcDNA3-LiP0 followed by a boost with rLiP0, was assayed. Immunization with rLiP0 induced a predominant Th2-like humoral response, but no anti-LiP0 antibodies were induced after immunization with pcDNA3-LiP0, whereas a strong humoral response consisting of a mixed immunoglobulin G2a (IgG2a)-IgG1 isotype profile was induced in mice immunized with the prime-boost regime. For all three immunization protocols, rLiP0-stimulated production of gamma interferon (IFN-γ) in both splenocytes and lymph node cells from immunized mice was observed. However, it was only when mice were immunized with pcDNA3-LiP0 that noticeable protection againstL. majorinfection was achieved, as determined by both lesion development and parasite burden. Immunization of mice withLiP0-DNA primes both CD4+and CD8+T cells, which, with theL. majorchallenge, were boosted to produce significant levels of IL-12-dependent, antigen-specific IFN-γ. Taken together, these data indicate that genetic vaccination with LiP0 induces protective immunological effector mechanisms, yet the immunological response elicited by LiP0 is not sufficient to keep the infection from progressing.
Commensal Bacteria Increase Invasion of Intestinal Epithelium bySalmonella entericaSerovar Typhi
Authors: Lyczak Jeffrey B. 
Published: October 2003

ABSTRACTThe intestinal microflora consists of a heterogeneous population of microorganisms and has many effects on the health status of its human host. Here, it is shown that the products of certain strains of bacteria normally present in the intestinal microflora are able to trigger redistribution of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in epithelial cells. CFTR is used bySalmonella entericaserovar Typhi as a receptor on epithelial cells which mediate the translocation of this microorganism to the gastric submucosa. Serovar Typhi-epithelial cell adhesion and CFTR-dependent invasion by serovar Typhi of epithelial cells were increased following commensal-mediated CFTR redistribution. These data suggest that commensal microorganisms present in the intestinal lumen can affect the efficiency of serovar Typhi invasion of the intestinal submucosa. This could be a key factor influencing host susceptibility to typhoid fever.