bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activities of Doripenem (S-4661) against Drug-Resistant Clinical Pathogens
Authors: Jones Ronald N. , Huynh Holly K. , Biedenbach Douglas J. 
Published: July 2004

ABSTRACT

Doripenem (formerly S-4661), a new 1-β-methyl carbapenem, was challenged with a worldwide collection of 394 drug-refractory isolates. For endemic extended-spectrum β-lactamase- and stably derepressed AmpC-producing enteric bacilli, the doripenem MICs at which 90% of the isolates were inhibited (MIC
90
s) were 0.03 to 0.5 μg/ml, generally lower than those of comparator carbapenems. A greater proportion of strains among carbapenem-resistant nonfermentative gram-negative bacilli were inhibited by doripenem at ≤4 μg/ml, and doripenem was the most active carbapenem (MIC
90
, 1 to 4 μg/ml) against penicillin-resistant streptococci.
Lack of Evidence that DNA in Antibiotic Preparations Is a Source of Antibiotic Resistance Genes in Bacteria from Animal or Human Sources
Authors: Lau Susanna K. P. , Woo Patrick C. Y. , To Amanda P. C. , Lau Alexson T. K. , Yuen Kwok-yung 
Published: July 2004

ABSTRACT
Although DNA encoding antibiotic resistance has been discovered in antibiotic preparations, its significance for the development of antibiotic resistance in bacteria is unknown. No phylogenetic evidence was obtained for recent horizontal transfer of antibiotic resistance genes from antibiotic-producing organisms to bacteria from human or animal sources.
Effect of pH on the In Vitro Activities of Amphotericin B, Itraconazole, and Flucytosine against
Aspergillus
Isolates
Authors: Te Dorsthorst D. T. A. , Mouton J. W. , van den Beukel C. J. P. , van der Lee H. A. L. , Meis J. F. G. M. , Verweij P. E. 
Published: July 2004

ABSTRACT

The in vitro susceptibilities of 21
Aspergillus
isolates were tested against three antifungal agents in RPMI 1640 and yeast nitrogen base at pH 5.0 and 7.0 by a broth microdilution format of the NCCLS method. The MICs of amphotericin B and itraconazole were higher, while those of flucytosine were lower, at pH 5.0 than at pH 7.0. The poor correlation between in vitro results and clinical outcome could be due to a difference in pH between the in vitro susceptibility test and at the site of infection.
In Vitro Activities of the Newer Quinolones Garenoxacin, Gatifloxacin, and Gemifloxacin against Human Mycoplasmas
Authors: Pereyre S. , Renaudin H. , Bébéar C. , Bébéar C. M. 
Published: July 2004

ABSTRACT
The activities of garenoxacin, gatifloxacin, and gemifloxacin were compared with those of four fluoroquinolones against human mycoplasmas and ureaplasmas, including fluoroquinolone-resistant genetically characterized strains. Garenoxacin exhibited the highest activity, followed by gemifloxacin, moxifloxacin, and gatifloxacin. The minimal bactericidal activities of these three compounds were lower than those of the four fluoroquinolones.
Rv2686c-Rv2687c-Rv2688c, an ABC Fluoroquinolone Efflux Pump in
Mycobacterium tuberculosis
Authors: Pasca Maria Rosalia , Guglierame Paola , Arcesi Fabio , Bellinzoni Marco , De Rossi Edda , Riccardi Giovanna 
Published: July 2004

ABSTRACT

The
Mycobacterium tuberculosis
Rv2686c-Rv2687c-Rv2688c operon, encoding an ABC transporter, conferred resistance to ciprofloxacin and, to a lesser extent, norfloxacin, moxifloxacin, and sparfloxacin to
Mycobacterium smegmatis
. The resistance level decreased in the presence of the efflux pump inhibitors reserpine, carbonyl cyanide
m
-chlorophenylhydrazone, and verapamil. Energy-dependent efflux of ciprofloxacin from
M. smegmatis
cells containing the Rv2686c-Rv2687c-Rv2688c operon was observed.
Extended-Spectrum-Cephalosporin Resistance in
Salmonella enterica
Isolates of Animal Origin
Authors: Gray Jeffrey T. , Hungerford Laura L. , Fedorka-Cray Paula J. , Headrick Marcia L. 
Published: July 2004

ABSTRACT

A total of 112 out of 5,709
Salmonella enterica
isolates from domestic animal species exhibited decreased susceptibilities to ceftiofur and ceftriaxone, and each possessed the
bla
CMY
gene. Ten
Salmonella
serotypes were significantly more likely to include resistant isolates. Isolates from turkeys, horses, cats, and dogs were significantly more likely to include resistant isolates.
High Prevalence of the
ermB
Gene among Erythromycin-Resistant
Streptococcus pneumoniae
Isolates in Germany during the Winter of 2000-2001 and In Vitro Activity of Telithromycin
Authors: Kresken Michael , Henrichfreise Beate , Bagel Simone , Brauers Johannes , Wiedemann Bernd 
Published: July 2004

ABSTRACT

Of 595 isolates of
Streptococcus pneumoniae
from outpatients with respiratory tract infections, collected from 17 microbiology laboratories, 14.1% were resistant to erythromycin. Eighty-three erythromycin-resistant isolates were genetically analyzed, 83.1% of which harbored the
ermB
gene. Only four isolates (4.8%) harbored the
mefA
gene. Telithromycin exhibited potent activity against all isolates.
Role of β-Lactamases and Porins in Resistance to Ertapenem and Other β-Lactams in
Klebsiella pneumoniae
Authors: Jacoby George A. , Mills Debra M. , Chow Nancy 
Published: July 2004

ABSTRACT

High-level resistance to ertapenem was produced by β-lactamases of groups 1, 2f, and 3 in a strain of
Klebsiella pneumoniae
deficient in Omp35 and Omp36. From a wild-type strain producing ACT-1 β-lactamase, ertapenem-resistant mutants for which the ertapenem MICs were up to 128 μg/ml and expression of outer membrane proteins was diminished could be selected.
α
1
-Antitrypsin Binds to and Interferes with Functionality of EspB from Atypical and Typical Enteropathogenic
Escherichia coli
Strains
Authors: Knappstein Sabine , Ide Tina , Schmidt M. Alexander , Heusipp Gerhard 
Published: July 2004

ABSTRACT

Enteropathogenic
Escherichia coli
(EPEC), including diffusely adhering atypical
E. coli
, strains use a type III secretion system to deliver effector proteins into the membrane and cytoplasm of infected cells. The
E. coli
secreted proteins A, B, and D (EspA, EspB, and EspD) are required for the formation of the characteristic attaching and effacing (A/E) lesions. EspB and EspD are thought to form a translocation pore in the host cell membrane through which effector proteins are injected into the host cytosol. Besides its function in pore formation, EspB has been found in the cytosol and implicated to function as an effector protein. We screened for putative host cell proteins interacting with EspB of atypical EPEC strains and identified α
1
-antitrypsin (AAT) as a binding partner for EspB. AAT binds to EspB in pull-down and overlay experiments and also to EspD in overlay experiments. In agreement with the role of EspB and EspD in pore formation, EPEC-mediated hemolysis of red blood cells is strongly reduced by AAT in a concentration-dependent manner, indicating that AAT interferes with type III secretion by inhibiting the formation of the translocation pore. This is further supported by a decreased actin polymerization after infection of HeLa or CaCo-2 cells with EPEC in the presence of physiologically relevant concentrations of AAT. In this study, we identify AAT as a new binding partner for EspB and EspD, suggesting a previously unappreciated role for AAT in host cell defense against EPEC infections and potentially also against other bacterial pathogens.
Long-Term Multiepitopic Cytotoxic-T-Lymphocyte Responses Induced in Chimpanzees by Combinations ofPlasmodium falciparumLiver-Stage Peptides and Lipopeptides
Authors: BenMohamed Lbachir , Thomas Alan , Druilhe Pierre 
Published: July 2004

ABSTRACTPreclinical immunogenicity studies of 12 malaria peptides, selected from fourPlasmodium falciparumantigens (Ags), namely, LSA1, LSA3, SALSA, and STARP, that are expressed at the pre-erythrocytic (sporozoite and liver) stages of the human parasite were carried out in chimpanzees. To strengthen their immunogenicity, six of these synthetic peptides were modified by the C-terminal addition of a single palmitoyl chain (lipopeptides) and delivered without adjuvant, whereas the remaining six unmodified peptides were emulsified and delivered by using Montanide ISA51 adjuvant. We have previously reported that these peptides and lipopeptides induce high B-cell and CD4+-T-helper responses in chimpanzees. In this report, we show their ability to induce multiepitopic and long-lasting antigen-specific CD8+cytotoxic-T-lymphocyte (CTL) responses. The magnitude, consistency, and memory of CTL responses generated by LSA3 peptides point to the strong immunogenicity of this liver-stage Ag. These findings support the screening strategy used to select the fourP. falciparumpre-erythrocytic Ags and emphasize their valuable immunogenic properties. The successful immunization of nonhuman primates with combinations of corresponding peptides in a mineral oil emulsion (ISA51) and lipopeptides in saline provide a vaccine formulation that can be tested in humans.
Potential Involvement of Gelatinases and Their Inhibitors inMannheimia haemolyticaPneumonia in Cattle
Authors: Starr Amanda E. , Dan Tonima , Minhas Kanwal , Shewen Patricia E. , Coomber Brenda L. 
Published: July 2004

ABSTRACTMannheimia haemolyticainfection of the lower respiratory tract of cattle results in a bronchofibrinous pneumonia characterized by massive cellular influx and lung tissue remodeling and scarring. Since altered levels of gelatinases and their inhibitors have been detected in a variety of inflammatory conditions and are associated with tissue remodeling, we examined the presence of gelatinases in lesional and nonlesional lung tissue obtained from calves experimentally infected withM. haemolytica. Lesional tissue had elevated levels of progelatinase A and B and active gelatinase A and B when compared with nonlesional tissue obtained from the same lung lobe. In vitro,M. haemolyticaproducts stimulated production of gelatinase B, but not its activation, by bovine monocytes. Alveolar macrophages showed constitutive production of gelatinase B but no change in response toM. haemolyticaproducts. Bovine neutrophils exposed toM. haemolyticaproducts also released gelatinase B, and there was a significant increase in the activated form of this enzyme. These effects were virtually identical when recombinantO-sialoglycoprotease was used to stimulate these cells.M. haemolyticaproducts also enhanced the expression by bovine monocytes and alveolar macrophages of the tissue inhibitor of metalloproteinase 1. Our results provide evidence that matrix metalloproteinases are activated in lung lesions from cattle with shipping fever and thatM. haemolyticavirulence products induce production, release, and especially activation of gelatinase B by bovine inflammatory cells in vitro.
Induction of Maturation and Cytokine Release of Human Dendritic Cells byHelicobacter pylori
Authors: Kranzer Katharina , Eckhardt Alexander , Aigner Michael , Knoll Gertrud , Deml Ludwig , Speth Cornelia , Lehn Norbert , Rehli Michael , Schneider-Brachert Wulf 
Published: July 2004

ABSTRACTHelicobacter pyloricauses a persistent infection in the human stomach, which can result in chronic gastritis and peptic ulcer disease. Despite an intensive proinflammatory response, the immune system is not able to clear the organism. However, the immune escape mechanisms of this common bacterium are not well understood. We investigated the interaction betweenH. pyloriand human dendritic cells. Dendritic cells (DCs) are potent antigen-presenting cells and important mediators between the innate and acquired immune system. Stimulation of DCs with different concentrations ofH. pylorifor 8, 24, 48, and 72 h resulted in dose-dependent interleukin-6 (IL-6), IL-8, IL-10 and IL-12 production. Lipopolysaccharide (LPS) fromEscherichia coli, a known DC maturation agent, was used as a positive control. The cytokine release after stimulation with LPS was comparable to that induced byH. pyloriexcept for IL-12. After LPS stimulation IL-12 was only moderately released compared to the large amounts of IL-12 induced byH. pylori. We further investigated the potential ofH. pylorito induce maturation of DCs. Fluorescence-activated cell sorting analysis of cell surface expression of maturation marker molecules such as CD80, CD83, CD86, and HLA-DR revealed equal upregulation after stimulation withH. pylorior LPS. We found no significant differences betweenH. pyloriseropositive and seronegative donors of DCs with regard to cytokine release and upregulation of surface molecules. These data clearly demonstrate thatH. pyloriinduces a strong activation and maturation of human immature DCs.
CD4+Th1 Cells Induced by Dendritic Cell-Based Immunotherapy in Mice Chronically Infected withLeishmania amazonensisDo Not Promote Healing
Authors: Vanloubbeeck Yannick F. , Ramer Amanda E. , Jie Fei , Jones Douglas E. 
Published: July 2004

ABSTRACTThe susceptibility of mice toLeishmania amazonensisinfection is thought to result from an inability to develop a Th1 response. Our data show that the low levels of gamma interferon (IFN-γ) produced by the draining lymph node (DLN) cells of chronically infected mice could be enhanced in vitro and in vivo withL. amazonensisantigen-pulsed bone marrow-derived dendritic cells (BM-DC) and the Th1-promoting cytokine interleukin-12 (IL-12). Given intralesionally to chronically infected mice, this treatment induced the upregulation of mRNA levels for IFN-γ, the transcription factor T-box expressed in T cells, and IL-12 receptor β2 in CD4+T cells from the DLN and an increase in parasite-specific immunoglobulin G2a in the serum. However, this Th1 response was not associated with healing, and the antigen-specific enhancement of IFN-γ production remained impaired in the DLN. However, addition of IL-12 to the in vitro recall response was able to recover this defect, suggesting that antigen-presenting cell-derived IL-12 production may be limited in infected mice. This was supported by the fact thatL. amazonensisamastigotes limited the production of IL-12p40 from BM-DC in vitro. Altogether, our data indicate that the immune response of mice chronically infected withL. amazonensiscan be enhanced towards a Th1 phenotype but that the presence of Th1 CD4+T cells does not promote healing. This suggests that the phenotype of the CD4+T cells may not always be indicative of protection toL. amazonensisinfection. Furthermore, our data support growing evidence that antigen-presenting cell function, such as IL-12 production, may limit the immune response inL. amazonensis-infected mice.
Production of the Subdomains of the
Plasmodium falciparum
Apical Membrane Antigen 1 Ectodomain and Analysis of the Immune Response
Authors: Lalitha P. V. , Ware Lisa A. , Barbosa Arnoldo , Dutta Sheetij , Moch J. Kathleen , Haynes J. David , Fileta Bader B. , White Charles E. , Lanar David E. 
Published: July 2004

ABSTRACT

The apical membrane antigen 1 of
Plasmodium falciparum
is one of the leading candidate antigens being developed as a vaccine to prevent malaria. This merozoite transmembrane protein has an ectodomain that can be divided into three subdomains (D I, D II, and D III). We have previously expressed a major portion of this ectodomain and have shown that it can induce antibodies that prevent merozoite invasion into red blood cells in an in vitro growth and invasion assay. To analyze the antibody responses directed against the individual subdomains, we constructed six different genes that express each of the domains separately (D I, D II, or D III) or in combination with another domain (D I+II, D II+III, or D I+III). These proteins were purified and used to immunize rabbits to raise construct-specific antibodies. We demonstrated that D I+II induced a significant amount of the growth-inhibitory antibodies active in the growth and invasion assay.
A Specific Genomic Location within the
icm
/
dot
Pathogenesis Region of Different
Legionella
Species Encodes Functionally Similar but Nonhomologous Virulence Proteins
Authors: Feldman Michal , Segal Gil 
Published: July 2004

ABSTRACT

Legionella pneumophila
, the major causative agent of Legionnaires' disease, is a facultative intracellular pathogen that grows within human macrophages and amoebae. Intracellular growth involves the formation of a replicative phagosome that requires the Icm/Dot type IV secretion system. Part of the
icm
/
dot
region in
L. pneumophila
contains the
icmTSRQPO
genes. The proteins encoded by the
icmR
and
icmQ
genes were shown to exhibit a chaperone-substrate relationship. Analysis of this region from other pathogenic
Legionella
species, i.e.,
L. micdadei
and
L. longbeachae
, indicated that the overall organization of this region is highly conserved, but it was found to contain a favorable site for gene variation. In the place where the
icmR
gene was expected to be located, other open reading frames that are nonhomologous to each other or to any entry in the GenBank database were found (
migAB
in
L. micdadei
and
ligB
in
L. longbeachae
). Examination of these unique genes revealed an outstanding phenomenon; by use of interspecies complementation, the
icmR
,
migB
, and
ligB
gene products were found to be functionally similar. In addition, the function of these proteins was usually dependent on the presence of the corresponding IcmQ proteins. Moreover, each of these proteins (IcmR, LigB, and MigB) was found to interact with the corresponding IcmQ proteins, and the genes encoding these proteins were found to be regulated by CpxR. This study reveals new evidence of gene variation occurring in the same genomic location within the
icm
/
dot
locus in various
Legionella
species. The genes found at this site were shown to be similarly regulated and to encode species-specific, nonhomologous, but functionally similar proteins.
Expression of the LspA1 and LspA2 Proteins by
Haemophilus ducreyi
Is Required for Virulence in Human Volunteers
Authors: Janowicz Diane M. , Fortney Kate R. , Katz Barry P. , Latimer Jo L. , Deng Kaiping , Hansen Eric J. , Spinola Stanley M. 
Published: July 2004

ABSTRACT

Haemophilus ducreyi
colocalizes with polymorphonuclear leukocytes and macrophages and evades phagocytosis during experimental infection of human volunteers.
H. ducreyi
contains two genes,
lspA1
and
lspA2
, which encode predicted proteins of 456 and 543 kDa, respectively. Compared to its wild-type parent, an
lspA1 lspA2
double mutant does not inhibit phagocytosis by macrophage and myelocytic cell lines in vitro and is attenuated in an experimental rabbit model of chancroid. To test whether expression of LspA1 and LspA2 was necessary for virulence in humans, six volunteers were experimentally infected. Each volunteer was inoculated with three doses (ranging from 85 to 112 CFU) of the parent (35000HP) in one arm and three doses (ranging from 60 to 822 CFU) of the mutant (35000HPΩ12) in the other arm. The papule formation rates were 88% (95% confidence interval [95% CI], 76.8 to 99.9%) at 18 parent sites and 72% (95% CI, 44.4 to 99.9%) at 18 mutant sites (
P
= 0.19). However, papules were significantly smaller at mutant sites (mean size, 24.8 mm
2
) than at parent sites (mean size, 39.1 mm
2
) 24 h after inoculation (
P
= 0.0002). The pustule formation rates were 44% (95% CI, 5.8 to 77.6%) at parent sites and 0% (95% CI, 0 to 39.4%) at mutant sites (
P
= 0.009). With the caveat that biosafety regulations preclude testing of a complemented mutant in human subjects, these results indicate that expression of LspA1 and LspA2 facilitates the ability of
H. ducreyi
to initiate disease and to progress to pustule formation in humans.
Protection against Pneumococcal Pneumonia in Mice by Monoclonal Antibodies to Pneumolysin
Authors: García-Suárez María del Mar , Cima-Cabal María Dolores , Flórez Noelia , García Pilar , Cernuda-Cernuda Rafael , Astudillo Aurora , Vázquez Fernando , De Los Toyos Juan R. , Méndez F. Javier 
Published: July 2004

ABSTRACT

Pneumolysin (PLY) is an important virulence factor of
Streptococcus pneumoniae
. We examined the ability of three murine monoclonal antibodies (MAbs) to PLY (PLY-4, PLY-5, and PLY-7) to affect the course of pneumococcal pneumonia in mice. The intravenous administration of antibodies PLY-4 and PLY-7 protected the mice from the lethal effect of the purified toxin. Mice treated with PLY-4 before intranasal inoculation of
S. pneumoniae
type 2 survived longer (median survival time, 100 h) than did untreated animals (median survival time, 60 h) (
P
< 0.0001). The median survival time for mice treated with a combination of PLY-4 and PLY-7 was 130 h, significantly longer than that for mice given isotype-matched indifferent MAbs (
P
= 0.0288) or nontreated mice (
P
= 0.0002). The median survival time for mice treated with a combination of three MAbs was significantly longer (>480 h) than that for mice treated with PLY-5 (48 h;
P
< 0.0001), PLY-7 (78 h;
P
= 0.0007), or PLY-4 (100 h;
P
= 0.0443) alone. Similarly, the survival rate for mice treated with three MAbs (10 of 20 mice) was significantly higher than the survival rate obtained with PLY-5 (1 of 20;
P
= 0.0033), PLY-4 (2 of 20;
P
= 0.0138), or PLY-7 (3 of 20;
P
= 0.0407) alone. These results suggest that anti-PLY MAbs act with a synergistic effect. Furthermore, MAb administration was associated with a significant decrease in bacterial lung colonization and lower frequencies of bacteremia and tissue injury with respect to the results for the control groups.
Icm/Dot-Independent Entry of
Legionella pneumophila
into Amoeba and Macrophage Hosts
Authors: Bandyopadhyay Purnima , Xiao Huifang , Coleman Hope A. , Price-Whelan Alexa , Steinman Howard M. 
Published: July 2004

ABSTRACT

Legionella pneumophila
, the causative agent of Legionnaires' disease, expresses a type IVB secretion apparatus that translocates bacterial proteins into amoeba and macrophage hosts. When stationary-phase cultures are used to infect hosts, the type IVB apparatus encoded by the
icm
/
dot
genes is required for entry, delay of phagosome-lysosome fusion, and intracellular multiplication within host cells. Null mutants with mutations in
icm
/
dot
genes are defective in these phenotypes. Here a new model is described in which hosts are infected with stationary-phase cultures that have been incubated overnight in pH 6.5 buffer. This model is called Ers treatment because it enhances the resistance to acid, hydrogen peroxide, and antibiotic stress beyond that of stationary-phase cultures. Following Ers treatment entry into amoeba and macrophage hosts does not require
dotA
, which is essential for
Legionella
virulence phenotypes when hosts are infected with stationary-phase cultures,
dotB
,
icmF
,
icmV
, or
icmX
. Defective host entry is also suppressed for null mutants with mutations in the KatA and KatB catalase-peroxidase enzymes, which are required for proper intracellular growth in amoeba and macrophage hosts. Ers treatment-induced suppression of defective entry is not associated with increased bacterial adhesion to host cells or with morphological changes in the bacterial envelope but is dependent on protein expression during Ers treatment. By using proteomic analysis, Ers treatment was shown to induce a protein predicted to contain eight tetratricopeptide repeats, a motif previously implicated in enhanced entry of
L. pneumophila
. Characterization of Ers treatment-dependent changes in expression is proposed as an avenue for identifying
icm
/
dot
-independent factors that function in the entry of
Legionella
into amoeba and macrophage hosts.