bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitogenic Effect ofBartonella bacilliformison Human Vascular Endothelial Cells and Involvement of GroEL
Authors: Minnick Michael F. , Smitherman Laura S. , Samuels D. Scott 
Published: November 2003

ABSTRACTBartonellae are bacterial pathogens for a wide variety of mammals. In humans, bartonellosis can result in angioproliferative lesions that are potentially life threatening to the patient, including bacillary angiomatosis, bacillary peliosis, and verruga peruana. The results of this study show thatBartonella bacilliformis, the agent of Oroya fever and verruga peruana, produces a proteinaceous mitogen for human vascular endothelial cells (HUVECs) that acts in a dose-dependent fashion in vitro with maximal activity at ≥72 h of exposure and results in a 6- to 20-fold increase in cell numbers relative to controls. The mitogen increases bromodeoxyuridine (BrdU) incorporation into HUVECs by almost twofold relative to controls. The mitogen is sensitive to heat and trypsin but is not affected by the lipopolysaccharide inhibitor polymyxin B. The mitogen does not affect caspase 3 activity in HUVECs undergoing serum starvation-induced apoptosis. TheBartonellamitogen was found in bacterial culture supernatants, the soluble cell lysate fraction, and, to a lesser degree, in insoluble cell fractions of the bacterium. In contrast, soluble cell lysate fractions from closely relatedB. henselae, although possessing significant mitogenicity for HUVECs, resulted in only about a twofold increase in cell numbers. Biochemical and immunological analyses identified GroEL as a participant in the observed HUVEC mitogenicity. AB. bacilliformisstrain containing the intactgroES-groELoperon on a multicopy plasmid was generated and used to demonstrate a correlation between HUVEC mitogenicity and GroEL levels in the lysate (r2= 0.85). Antiserum to GroEL significantly inhibited mitogenicity of the lysate. Data also show that GroEL is located in the soluble and insoluble fractions (including inner and outer membranes) of the cell and is actively secreted byB. bacilliformis.
Synergism ofGamma Interferon and Interleukin-5 in the Control of MurineFilariasis
Authors: Saeftel Michael , Arndt Manuela , Specht Sabine , Volkmann Lars , Hoerauf Achim 
Published: November 2003

ABSTRACTThere has been a prevailing perception that Th1 and Th2 immune responses induce antagonistic immune effector mechanisms during an infection. We investigated the role of the Th1 cytokine gamma interferon (IFN-γ) and the Th2 cytokine interleukin-5 (IL-5) in murine filariasis infections with the rodent filarial nematodeLitomosoides sigmodontiswith regard to immune responses to the parasite. Earlier data showed an important role for IL-5 and IFN-γ in effective immune responses to filarial infection. Therefore, in this study it was asked whether IL-5 and IFN-γ act synergistically or antagonistically. Indeed, IL-5 as well as IFN-γ knockout (KO) mice show a higher worm load than the wild-type controls. IFN-γ/IL-5 double-KO mice had a significantly higher worm load than any of the single-KO mice, suggesting a synergism between IFN-γ and IL-5 in controlling worm infection. Neutrophils are known to play an important role for the containment and encapsulation process of the worms. In infected IFN-γ KO, IL-5 KO, and IFN-γ/IL-5 double-KO mice, neutrophils were significantly reduced in chemotactic activity levels compared to controls. In addition, the level of phagocytosis activity of neutrophils from IFN-γ/IL-5 double-KO mice was further decreased in comparison to that of the single-KO mice. Levels of tumor necrosis factor alpha, which is an important factor for neutrophil activation, were found to be reduced in macrophages from KO mice. In conclusion, these results argue for immune effector mechanisms in murine filarial infection that are dependent on both IFN-γ and IL-5. Synergistic effects of the two cytokines may be mediated, at least in part, by neutrophils for the control of adult worms.
Removal of
Wolbachia
from
Brugia pahangi
Is Closely Linked to Worm Death and Fecundity but Does Not Result in Altered Lymphatic Lesion Formation in Mongolian Gerbils (
Meriones unguiculatus
)
Authors: Chirgwin Sharon R. , Coleman Sharon U. , Porthouse Kristina H. , Nowling Jena M. , Punkosdy George A. , Klei Thomas R. 
Published: November 2003

ABSTRACT

Approximately 30 years ago, researchers reported intracellular bacteria in filarial nematodes. These bacteria are relatives of the arthropod symbiont
Wolbachia
and occur in many filarial nematodes, including
Brugia pahangi
and
Brugia malayi. Wolbachia
bacteria have been implicated in a variety of roles, including filaria development and fecundity and the pathogenesis of lymphatic lesions associated with filarial infections. However, the role of the bacteria in worm biology or filarial disease is still not clear. The present experiments support previous data showing that tetracycline eliminates or reduces
Wolbachia
bacteria in
B. pahangi
in vivo. The elimination of
Wolbachia
was closely linked to a reduction in female fecundity and the viability of both sexes, suggesting that the killing of
Wolbachia
is detrimental to
B. pahangi
. The gerbils treated with tetracycline showed reduced levels of interleukin-4 (IL-4) and IL-5 mRNA in renal lymph nodes and spleens compared with the levels in
B. pahangi
-infected gerbils not treated with tetracycline. However, similar findings were noted in
B. pahangi
-infected gerbils treated with ivermectin, suggesting that the loss of circulating microfilariae, not the reduction of
Wolbachia
bacteria, was associated with the altered cytokine profile. Despite the change in T-cell cytokines, there was no difference in the sizes of renal lymph nodes isolated from gerbils in each treatment group. Furthermore, the numbers, sizes, or cellular compositions of granulomas examined in the lymphatics or renal lymph nodes did not differ with treatment. These data suggest that
Wolbachia
may not play a primary role in the formation of lymphatic lesions in gerbils chronically infected with
B. pahangi
.
Effect ofMycobacterium bovisBCG Vaccinationon Mycobacterium-Specific Cellular Proliferation and TumorNecrosis Factor Alpha Production from Distinct Guinea PigLeukocytePopulations
Authors: Lasco Todd M. , Yamamoto Toshiko , Yoshimura Teizo , Allen Shannon Sedberry , Cassone Lynne , McMurray David N. 
Published: November 2003

ABSTRACTIn this study, we focused on three leukocyte-rich guinea pig cell populations, bronchoalveolar lavage (BAL) cells, resident peritoneal cells (PC), and splenocytes (SPC). BAL cells, SPC, and PC were stimulated either with live attenuatedMycobacterium tuberculosisH37Ra or with live or heat-killed virulentM. tuberculosisH37Rv (multiplicity of infection of 1:100). Each cell population was determined to proliferate in response to heat-killed virulent H37Rv, whereas no measurable proliferative response could be detected upon stimulation with live mycobacteria. Additionally, this proliferative capacity (in SPC and PC populations) was significantly enhanced upon prior vaccination withMycobacterium bovisBCG. Accordingly, in a parallel set of experiments we found a strong positive correlation between production of antigen-specific bioactive tumor necrosis factor alpha (TNF-α) and prior vaccination with BCG. A nonspecific stimulus, lipopolysaccharide, failed to induce this effect on BAL cells, SPC, and PC. These results showed that production of bioactive TNF-α from mycobacterium-stimulated guinea pig cell cultures positively correlates with the vaccination status of the host and with the virulence of the mycobacterial strain.
Characterization of an Extracellular Virulence FactorMade by Group A
Streptococcus
with Homology to the
Listeria monocytogenes
Internalin Family ofProteins
Authors: Reid Sean D. , Montgomery Alison G. , Voyich Jovanka M. , DeLeo Frank R. , Lei Benfang , Ireland Robin M. , Green Nicole M. , Liu Mengyao , Lukomski Slawomir , Musser James M. 
Published: November 2003

ABSTRACT

Leucine-rich
repeats (LRR) characterize a diverse array of proteins and function to
provide a versatile framework for protein-protein interactions.
Importantly, each of the bacterial LRR proteins that have been well
described, including those of
Listeria monocytogenes
,
Yersinia pestis
, and
Shigella flexneri
, have been
implicated in virulence. Here we describe an 87.4-kDa group A
Streptococcus
(GAS) protein (designated Slr, for streptococcal
leucine-rich) containing 10 1/2 sequential units of a 22-amino-acid
C-terminal LRR homologous to the LRR of the
L. monocytogenes
internalin family of proteins. In addition to the LRR domain,
slr
encodes a gram-positive signal secretion sequence
characteristic of a lipoprotein and a putative N-terminal domain with a
repeated histidine triad motif (HxxHxH). Real-time reverse
transcriptase PCR assays indicated that
slr
is transcribed
abundantly in vitro in the exponential phase of growth. Flow cytometry
confirmed that Slr was attached to the GAS cell surface. Western
immunoblot analysis of sera obtained from 80 patients with invasive
infections, noninvasive soft tissue infections, pharyngitis, and
rheumatic fever indicated that Slr is produced in vivo. An isogenic
mutant strain lacking
slr
was significantly less virulent in
an intraperitoneal mouse model of GAS infection and was significantly
more susceptible to phagocytosis by human polymorphonuclear leukocytes.
These studies characterize the first GAS LRR protein as an
extracellular virulence factor that contributes to pathogenesis and may
participate in evasion of the innate host
defense.
β-1,2- and α-1,2-LinkedOligomannosides Mediate Adherence of
Candida albicans
Blastospores to Human Enterocytes InVitro
Authors: Dalle Fredéric , Jouault Thierry , Trinel Pierre André , Esnault Jacques , Mallet Jean Maurice , d'Athis Philippe , Poulain Daniel , Bonnin Alain 
Published: November 2003

ABSTRACT

Candida
albicans
is a commensal dimorphic yeast of the digestive tract
that causes hematogenously disseminated infections in immunocompromised
individuals. Endogenous invasive candidiasis develops from
C.
albicans
adhering to the intestinal epithelium. Adherence is
mediated by the cell wall surface, a domain composed essentially of
mannopyranosyl residues bound to proteins, the N-linked moiety of which
comprises sequences of α-1,2- and β-1,2-linked mannose
residues. β-1,2-linked mannosides are also associated with a
glycolipid, phospholipomannan, at the
C. albicans
surface. In
order to determine the roles of β-1,2 and α-1,2
oligomannosides in the
C. albicans
-enterocyte interaction, we
developed a model of adhesion of
C. albicans
VW32 blastospores
to the apical regions of differentiated Caco-2 cells. Preincubation of
yeasts with monoclonal antibodies (MAbs) specific for α-1,2 andβ
-1,2 mannan epitopes resulted in a dose-dependent decrease in
adhesion (50% of the control with a 60-μg/ml MAb
concentration). In competitive assays β-1,2 and α-1,2
tetramannosides were the most potent carbohydrate inhibitors, with
50% inhibitory concentrations of 2.58 and 6.99 mM, respectively.
Immunolocalization on infected monolayers with MAbs specific forα
-1,2 and β-1,2 oligomannosides showed that these
epitopes were shed from the yeast to the enterocyte surface. Taken
together, our data indicate that α-1,2 and β-1,2
oligomannosides are involved in the
C. albicans
-enterocyte
interaction and participate in the adhesion of the yeasts to the
mucosal
surface.
Phenotypic Switching and Mating Type Switching of
Candida glabrata
at Sites ofColonization
Authors: Brockert Paula J. , Lachke Salil A. , Srikantha Thyagarajan , Pujol Claude , Galask Rudolph , Soll David R. 
Published: November 2003

ABSTRACT

Candida
glabrata
switches spontaneously at high frequency among the
following four graded phenotypes discriminated on agar containing 1 mM
CuSO
4
: white, light brown, dark brown (DB), and very dark
brown.
C. glabrata
also contains three mating type loci with a
configuration similar to that of the
Saccharomyces cerevisiae
mating type cassette system, suggesting it may also undergo cassette
switching at the expression locus
MTL1
. To analyze both
reversible, high-frequency phenotypic switching and mating type
switching at sites of colonization, primary samples from the oral
cavities and vaginal canals of three patients suffering from
C.
glabrata
vaginitis were clonally plated on agar containing
CuSO
4
. It was demonstrated that (i) in each vaginitis
patient, there was only one colonizing strain; (ii) an individual could
have vaginal colonization without oral colonization; (iii) phenotypic
switching occurred at sites of colonization; (iv) the DB phenotype
predominated at the site of infection in all three patients; (v)
genetically unrelated strains switched in similar, but not identical,
fashions and caused vaginal infection; (vi) different switch phenotypes
of the same strain could simultaneously dominate different body
locations in the same host; (vii) pathogenesis could be caused by cells
in different mating type classes; and (viii) mating type switching
demonstrated at both the genetic and transcription levels occurred in
one
host.
Recruitment of Complement Factor H-Like Protein 1 Promotes Intracellular Invasion by Group A Streptococci
Authors: Pandiripally Vinod , Wei Lin , Skerka Christine , Zipfel Peter F. , Cue David 
Published: November 2003

ABSTRACTNumerous microbial pathogens exploit complement regulatory proteins such as factor H (FH) and factor H-like protein 1 (FHL-1) for immune evasion. Fba is an FHL-1 and FH binding protein expressed on the surface of the human pathogenic bacterium,Streptococcus pyogenes, a common agent of pharyngeal, skin, and soft-tissue infections. In the present study, we demonstrate that Fba and FHL-1 work in concert to promote invasion of epithelial cells byS. pyogenes. Fba fragments were expressed as recombinant proteins and assayed for binding of FHL-1 and FH by Western blotting, enzyme-linked immunosorbent assay, and surface plasmon resonance. A binding site for FHL-1 and FH was localized to the N-terminal half of Fba, a region predicted to contain a coiled-coil domain. Deletion of this coiled-coil domain greatly reduced FHL-1 and FH binding. PepSpot analyses identified a 16-amino-acid segment of Fba which overlaps the coiled-coil domain that binds both FHL-1 and FH. To localize the Fba binding site in FHL-1 and FH, surface plasmon resonance was used to assess the interactions between the streptococcal protein and a series of recombinant FH deletion constructs. The Fba binding site was localized to short consensus repeat 7 (SCR 7), a domain common to FHL-1 and FH. SCR 7 contains a heparin binding site, and heparin was found to inhibit FHL-1 binding to Fba. FHL-1 promoted entry of Fba+group A streptococci into epithelial cells in a dose-dependent manner but did not affect invasion by an isogenicfbamutant. To our knowledge, this is the first report of a bacterial pathogen exploiting a soluble complement regulatory protein for entry into host cells.
Comparative Analysis of
Salmonella enterica
Serovar Typhimurium Biofilm Formation on Gallstones and on Glass
Authors: Prouty A. M. , Gunn J. S. 
Published: November 2003

ABSTRACT
In this study, the roles of global regulators, motility, lipopolysaccharide, and exopolysaccharides were further characterized with respect to biofilm formation on both gallstones and glass surfaces. These studies show the complex nature of biofilms and demonstrate that characteristics observed for each biofilm are unique to the particular culture condition.
Interleukin-10 and Pathogenesis of Murine Ocular Toxoplasmosis
Authors: Lu Fangli , Huang Shiguang , Kasper Lloyd H. 
Published: November 2003

ABSTRACTTo understand the role of interleukin-10 (IL-10) in ocular toxoplasmosis, we compared C57BL/6 (B6) and BALB/c background mice lacking a functional IL-10 gene (IL-10−/−) and B6 transgenic mice expressing IL-10 under the control of the IL-2 promoter. Increased cellular infiltration and necrosis were observed in the eye tissue of IL-10−/−mice of both the B6 and BALB/c backgrounds with associated changes in the levels of cytokines in serum. In contrast, there was no evidence of necrosis in the eye tissue from IL-10 transgenic mice following parasite exposure. Our results demonstrate that IL-10 is important in the regulation of inflammation during acute ocular toxoplasmosis.
Role of Urease Enzymes in Stability of a 10-Species Oral Biofilm Consortium Cultivated in a Constant-Depth Film Fermenter
Authors: Shu Man , Browngardt Christopher M. , Chen Yi-Ywan M. , Burne Robert A. 
Published: November 2003

ABSTRACT
Using a 10-species oral biofilm consortium and defined mutants, we show that high-level capacity to generate ammonia from a common salivary substrate is needed to maintain community diversity. This model appears to be suitable for the study of the effects of individual genetic determinants on the ecology of oral biofilms.
The Activation of Bovine Plasminogen by PauA Is Not Required for Virulence ofStreptococcus uberis
Authors: Ward Philip N. , Field Terence R. , Rapier Christopher D. , Leigh James A. 
Published: November 2003

ABSTRACTA mutant ofStreptococcus uberiscarrying a single copy of ISS1withinpauAwas unable to activate bovine plasminogen. Contrary to a hypothesis postulated previously, this mutation did not alter the ability of the bacterium to grow in milk or to infect the lactating bovine mammary gland.
Lipopolysaccharidefrom the Periodontal PathogenPorphyromonas gingivalisPrevents Apoptosis of HL60-Derived Neutrophils InVitro
Authors: Murray D. A , Wilton J. M. A. 
Published: November 2003

ABSTRACTLipopolysaccharide (LPS) fromPorphyromonas gingivalisprevented apoptosis of HL60-derived neutrophils, which could not be restored upon the addition of interleukin-10. Signaling ofP. gingivalisLPS through Toll-like receptor 2 (TLR2), not TLR4, may account for the inhibiting effect ofP. gingivalisLPS on apoptosis and provide a mechanism for the development of destructive periodontal inflammation.
Antibody Prophylaxis and Therapy against West NileVirus Infection in Wild-Type and ImmunodeficientMice
Authors: Engle Michael J. , Diamond Michael S. 
Published: November 2003

ABSTRACTWest Nile virus (WNV) is a mosquito-borneFlavivirusthat causes encephalitis in a subset of susceptible humans. Current treatment for WNV infections is supportive, and no specific therapy or vaccine is available. In this study, we directly tested the prophylactic and therapeutic efficacy of polyclonal antibodies against WNV. Passive administration of human gamma globulin or mouse serum prior to WNV infection protected congenic wild-type, B-cell-deficient (μMT), and T- and B-cell-deficient (RAG1) C57BL/6J mice. Notably, no increased mortality due to immune enhancement was observed. Although immune antibody completely prevented morbidity and mortality in wild-type mice, its effect was not durable in immunocompromised mice: many μMT andRAG1mice eventually succumbed to infection. Thus, antibody by itself did not completely eliminate viral reservoirs in host tissues, consistent with an intact cellular immune response being required for viral clearance. In therapeutic postexposure studies, human gamma globulin partially protected against WNV-induced mortality. In μMT mice, therapy had to be initiated within 2 days of infection to gain a survival benefit, whereas in the wild-type mice, therapy even 5 days after infection reduced mortality. This time point is significant because between days 4 and 5, WNV was detected in the brains of infected mice. Thus, passive transfer of immune antibody improves clinical outcome even after WNV has disseminated into the central nervous system.
Effects of a Single Amino Acid Substitution within thep2 Region of Human Immunodeficiency Virus Type 1 on Packagingof Spliced ViralRNA
Authors: Russell Rodney S. , Roldan Ariel , Detorio Mervi , Hu Jing , Wainberg Mark A. , Liang Chen 
Published: November 2003

ABSTRACT
Human
immunodeficiency virus type 1 encapsidates two copies of viral genomic
RNA in the form of a dimer. The dimerization process initiates via a
6-nucleotide palindrome that constitutes the loop of a viral RNA
stem-loop structure (i.e., stem loop 1 [SL1], also termed the
dimerization initiation site [DIS]) located within the
5′ untranslated region of the viral genome. We have now shown
that deletion of the entire DIS sequence virtually eliminated viral
replication but that this impairment was overcome by four second-site
mutations located within the matrix (MA), capsid (CA), p2, and
nucleocapsid (NC) regions of Gag. Interestingly, defective viral RNA
dimerization caused by the ΔDIS deletion was not significantly
corrected by these compensatory mutations, which did, however, allow
the mutated viruses to package wild-type levels of this DIS-deleted
viral RNA while excluding spliced viral RNA from encapsidation. Further
studies demonstrated that the compensatory mutation T12I located within
p2, termed MP2, sufficed to prevent spliced viral RNA from being
packaged into the ΔDIS virus. Consistently, theΔ
DIS-MP2 virus displayed significantly higher levels of
infectiousness than did the ΔDIS virus. The importance of
position T12 in p2 was further demonstrated by the identification of
four point mutations,T12D, T12E, T12G, and T12P, that resulted in
encapsidation of spliced viral RNA at significant levels. Taken
together, our data demonstrate that selective packaging of viral
genomic RNA is influenced by the MP2 mutation and that this represents
a major mechanism for rescue of viruses containing the ΔDIS
deletion.
Role of Nonstructural Proteins 3A and 3B in Host Rangeand Pathogenicity of Foot-and-Mouth DiseaseVirus
Authors: Pacheco Juan M. , Henry Tina M. , O'Donnell Vivian K. , Gregory Jason B. , Mason Peter W. 
Published: November 2003

ABSTRACT

The
genome of foot-and-mouth disease virus (FMDV) differs from that of
other picornaviruses in that it encodes a larger 3A protein
(>50% longer than poliovirus 3A), as well as three
copies of protein 3B (also known as VPg). Previous studies have shown
that a deletion of amino acids 93 to 102 of the 153-codon 3A protein is
associated with an inability of a Taiwanese strain of FMDV (O/TAW/97)
to cause disease in bovines. Recently, an Asian virus with a second 3A
deletion (amino acids 133 to 143) has also been detected (N.
J. Knowles et al., J. Virol.
75:
1551-1556, 2001).
Genetically engineered viruses harboring the amino acids 93 to 102 or
133 to 143 grew well in porcine cells but replicated poorly in bovine
cells, whereas a genetically engineered derivative of the O/TAW/97
virus expressing a full-length 3A (strain A12) grew well in both cell
types. Interestingly, a virus with a deletion spanning amino acid 93 to
144 also grew well in porcine cells and caused disease in swine.
Further, genetically engineered viruses containing only a single copy
of VPg were readily recovered with the full-length 3A, the deleted 3A
(amino acids 93 to 102), or the “super” deleted forms
of 3A (missing amino acids 93 to 144). All of the single-VPg viruses
were attenuated in porcine cells and replicated poorly in bovine cells.
The single-VPg viruses produced a mild disease in swine, indicating
that the VPg copy number is an important determinant of host range and
virulence. The association of VPg copy number with increased virulence
in vivo may help to explain why all naturally occurring FMDVs have
retained three copies of
VPg.