bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variable Tick Protein in Two Genomic Groups of the Relapsing Fever Spirochete
Borrelia hermsii
in Western North America
Authors: Porcella Stephen F. , Raffel Sandra J. , Anderson Donald E. , Gilk Stacey D. , Bono James L. , Schrumpf Merry E. , Schwan Tom G. 
Published: September 2005

ABSTRACT

Borrelia hermsii
is the primary cause of tick-borne relapsing fever in North America. When its tick vector,
Ornithodoros hermsi
, acquires these spirochetes from the blood of an infected mammal, the bacteria switch their outer surface from one of many bloodstream variable major proteins (Vmps) to a unique protein, Vtp (Vsp33). Vtp may be critical for successful tick transmission of
B. hermsii
; however, the gene encoding this protein has been described previously in only one isolate. Here we identified and sequenced the
vtp
gene in 31 isolates of
B. hermsii
collected over 40 years from localities throughout much of its known geographic distribution. Seven major Vtp types were found. Little or no sequence variation existed within types, but between them significant variation was observed, similar to the pattern of diversity described for the outer surface protein C (OspC) gene in Lyme disease spirochetes. The pattern of sequence relatedness among the Vtp types was incongruent in two branches compared to two genomic groups identified among the isolates by multilocus sequence typing of the
16S rRNA
,
flaB
,
gyrB
, and
glpQ
genes. Therefore, both horizontal transfer and recombination within and between the two genomic groups were responsible for some of the variation observed in the
vtp
gene.
O. hermsi
ticks were capable of transmitting spirochetes in the newly identified genomic group. Therefore, given the longevity of the tick vector and persistent infection of spirochetes in ticks, these arthropods rather than mammals may be the likely host where the exchange of spirochetal DNA occurs.
Plasmodium bergheiResists Killing by Reactive Oxygen Species
Authors: Sobolewski Peter , Gramaglia Irene , Frangos John A. , Intaglietta Marcos , van der Heyde Henri 
Published: September 2005

ABSTRACTReactive oxygen species (ROS) are widely believed to kill malarial parasites. C57BL/6 mice injected withP. bergheiinocula incubated with supraphysiological doses of NO (≤150 μM) or with peroxynitrite (220 μM), however, exhibited parasitemia similar to that seen with those given control inocula, and there was no difference in disease development. Only treatment of inocula with NO doses nearing saturation (≥1.2 mM) resulted in no detectable parasitemia in the recipients; flow cytometric analysis with a vital dye (hydroethidine) indicated that 1.5 mM NO lysed the erythrocytes rather than killing the parasites. The hemoglobin level in the inocula was about 8 μM; the hemoglobin was mainly oxyhemoglobin (oxyHb) (96%), which was converted to methemoglobin (>95%) after treatment with 150 μM NO. The concentrations of 150 μM of NO and 220 μM of peroxynitrite were far in excess of the hemoglobin concentration (∼8 μM), and yet no parasite killing was detected. We therefore conclude that hemoglobin protectsPlasmodiumparasites from ROS, but the parasite likely possesses intrinsic defense mechanisms against ROS.
Isocitrate Lyase Activity Is Required for Virulence of the Intracellular Pathogen
Rhodococcus equi
Authors: Wall Daniel M. , Duffy Pamela S. , DuPont Chris , Prescott John F. , Meijer Wim G. 
Published: September 2005

ABSTRACT

Rhodococcus equi
is an important pathogen of foals, causing severe pyogranulomatous pneumonia. Virulent
R. equi
strains grow within macrophages, a process which remains poorly characterized. A potential source of carbon for intramacrophage
R. equi
is membrane lipid-derived fatty acids, which following β oxidation are assimilated via the glyoxylate bypass. To assess the importance of isocitrate lyase, the first enzyme of the glyoxylate bypass, in virulence of a foal isolate of
R. equi
, a mutant was constructed by a strategy of single homologous recombination using a suicide plasmid containing an internal fragment of the
R. equi aceA
gene encoding isocitrate lyase. Complementation of the resulting mutant with
aceA
showed that the mutant was specific for this gene. Assessment of virulence in a mouse macrophage cell line showed that the mutant was killed, in contrast to the parent strain. Studies in the liver of intravenously infected mice showed enhanced clearance of the mutant. When four 3-week-old foals were infected intrabronchially, the
aceA
mutant was completely attenuated, in contrast to the parent strain. In conclusion, the
aceA
gene was shown to be essential for virulence of
R. equi
, suggesting that membrane lipids may be an important source of carbon for phagocytosed
R. equi.
Keratinocyte Production of Cathelicidin Provides Direct Activity against Bacterial Skin Pathogens
Authors: Braff Marissa H. , Zaiou Mohamed , Fierer Joshua , Nizet Victor , Gallo Richard L. 
Published: September 2005

ABSTRACT

Immune defense at an interface with the external environment reflects the functions of physical and chemical barriers provided by epithelial and immune cells. Resident epithelial cells, such as keratinocytes, produce numerous peptides with direct antimicrobial activity but also provide a physical barrier against invading pathogens and signal the recruitment of circulating immune cells, such as neutrophils. Antimicrobial peptides such as cathelicidin are produced constitutively by neutrophils and are inducible in keratinocytes in response to infection. The multiplicity of antimicrobial peptides and their cellular sources has resulted in an incomplete understanding of the role of cathelicidin production by epithelial cells in cutaneous immune defense. Therefore, this study sought to evaluate keratinocyte antimicrobial activity and the potential contribution of keratinocyte cathelicidin to host protection against two leading human skin pathogens. Wild-type mice and those with a targeted deletion of the cathelicidin gene,
Cnlp
, were rendered neutropenic prior to cutaneous infection. Interestingly,
Cnlp
-deficient mice remained more susceptible to group A streptococcus infection than mice with
Cnlp
intact, suggesting the involvement of epithelial cell-derived cathelicidin in host immune defense. Keratinocytes were then isolated in culture and found to inhibit the growth of
Staphylococcus aureus
, an effect that was partially dependent on their ability to synthesize and activate cathelicidin. Further, lentivirus-mediated delivery of activated human cathelicidin enhanced keratinocyte antimicrobial activity. Combined, these data illustrate the potential contribution of keratinocyte cathelicidin to the innate immune defense of skin against bacterial pathogens and highlight the need to consider epithelial antimicrobial function in the diagnosis and therapy of skin infection.
Effect of Deletion or Overexpression of the 19-Kilodalton Lipoprotein Rv3763 on the Innate Response to
Mycobacterium tuberculosis
Authors: Stewart Graham R. , Wilkinson Katalin A. , Newton Sandra M. , Sullivan Susan M. , Neyrolles Olivier , Wain John R. , Patel Janisha , Pool Kara-Lee , Young Douglas B. , Wilkinson Robert J. 
Published: September 2005

ABSTRACT

The 19-kDa lipoprotein of
Mycobacterium tuberculosis
is an important target of the innate immune response. To investigate the immune biology of this antigen in the context of the whole bacillus, we derived a recombinant
M. tuberculosis
H37Rv that lacked the 19-kDa-lipoprotein gene (Δ19) and complemented this strain by reintroduction of the 19-kDa-lipoprotein gene on a multicopy vector to produce Δ19::pSMT181. The Δ19 strain multiplied less well than Δ19::pSMT181 in human monocyte-derived macrophages (MDM) (
P
= 0.039). Surface expression of major histocompatibility complex class II molecules was reduced in phagocytes infected with
M. tuberculosis
; this effect was not seen in cells infected with Δ19. Δ19 induced lower interleukin 1β (IL-1β) secretion from monocytes and MDM. Overexpression of the 19-kDa protein increased IL-1β, IL-12p40, and tumor necrosis factor alpha secretion irrespective of phagocyte maturity. These data support reports that the 19-kDa lipoprotein has pleiotropic effects on the interaction of
M. tuberculosis
with phagocytes. However, this analysis indicates that in the context of the whole bacillus, the 19-kDa lipoprotein is only one of a number of molecules that mediate the innate response to
M. tuberculosis
.
Antibody Profiles Characteristic ofMycobacterium tuberculosisInfection State
Authors: Davidow Amy , Kanaujia Ganga V. , Shi Lanbo , Kaviar Justin , Guo XuDong , Sung Nackmoon , Kaplan Gilla , Menzies Dick , Gennaro Maria L. 
Published: September 2005

ABSTRACTThe relationship between specific antibody profiles and tuberculosis (TB) state was investigated by measuring serum antibody levels to sixMycobacterium tuberculosisantigens in human subjects grouped into four diagnostic categories: active disease, inactive (past) tuberculosis, latent infection without radiographic chest abnormalities, and infection free. Statistical data analyses showed that the latter two groups were serologically indistinguishable and that active tuberculosis and inactive tuberculosis were characterized by different antibody profiles. Antibodies to the 38-kDa antigen, alanine dehydrogenase, and Rv2626c were associated with active TB, while antibodies to the 16-kDa antigen, ferredoxin A, and ESAT-6 were associated with inactive TB. Thus, the targets of the immune response vary with tuberculosis state. The correlation between bacterial antigen production and infection stage was investigated in mice infected withM. tuberculosisby bacterial transcription profiling. It was found that levels of transcripts encoding the sixM. tuberculosisantigens varied during infection. Together, the data indicate that antigen composition of tubercle bacilli varies with stage of infection and that immunoprofiling can distinguish between tuberculosis states.
Colonization of the Cecal Mucosa by
Helicobacter hepaticus
Impacts the Diversity of the Indigenous Microbiota
Authors: Kuehl Carole J. , Wood Heather D. , Marsh Terence L. , Schmidt Thomas M. , Young Vincent B. 
Published: September 2005

ABSTRACT

Establishment of mucosal and/or luminal colonization is the first step in the pathogenesis of many gastrointestinal bacterial pathogens. The pathogen must be able to establish itself in the face of competition from the complex microbial community that is already in place. We used culture-independent methods to monitor the colonization of the cecal mucosa of
Helicobacter
-free mice following experimental infection with the pathogen
Helicobacter hepaticus
. Two days after infection,
H. hepaticus
comprised a minor component of the mucosa-associated microbiota, but within 14 days, it became the dominant member of the community. Colonization of the mucosa by
H. hepaticus
was associated with a decrease in the overall diversity of the microbial community, in large part due to changes in evenness resulting from the relative dominance of
H. hepaticus
as a member of the community. Our results demonstrate that invasion of the complex gastrointestinal microbial community by a pathogenic microorganism causes reproducible and significant disturbances in the community structure. The use of non-culture-based methods to monitor these changes should lead to a greater understanding of the ecological principles that govern pathogen invasion and may lead to novel methods for the prevention and control of gastrointestinal pathogens.
Poly-
N
-Acetylglucosamine Production in
Staphylococcus aureus
Is Essential for Virulence in Murine Models of Systemic Infection
Authors: Kropec Andrea , Maira-Litran Tomas , Jefferson Kimberly K. , Grout Martha , Cramton Sarah E. , Götz Friedrich , Goldmann Donald A. , Pier Gerald B. 
Published: September 2005

ABSTRACT

The contribution of the
Staphylococcus aureus
surface polysaccharide poly-
N
-acetylglucosamine (PNAG) to virulence was evaluated in three mouse models of systemic infection: bacteremia, renal abscess formation, and lethality following high-dose intraperitoneal (i.p.) infection. Deletion of the intercellular adhesin (
ica
) locus that encodes the biosynthetic enzymes for PNAG production in
S. aureus
strains Mn8, Newman, and NCTC 10833 resulted in mutant strains with significantly reduced abilities to maintain bacterial levels in blood following intravenous or i.p. injection, to spread systemically to the kidneys following i.p. injection, or to induce a moribund/lethal state following i.p. infection. In the bacteremia model, neither growth phase nor growth medium used to prepare the
S. aureus
inoculum affected the conclusion that PNAG production was needed for full virulence. As the SarA regulatory protein has been shown to affect
ica
transcription, PNAG synthesis, and biofilm formation, we also evaluated
S. aureus
strains Mn8 and 10833 deleted for the
sarA
gene in the renal infection model. A decrease in PNAG production was seen in
sarA
mutants using immunoblots of cell surface extracts but was insufficient to reduce the virulence of
sarA
-deleted strains in this model.
S. aureus
strains deleted for the
ica
genes were much more susceptible to antibody-independent opsonic killing involving human peripheral blood leukocytes and rabbit complement. Thus, PNAG confers on
S. aureus
resistance to killing mediated by these innate host immune mediators. Overall, PNAG production by
S. aureus
appears to be a critical virulence factor as assessed in murine models of systemic infection.
Expression Library Immunization Confers Protection against
Mycobacterium avium
subsp.
paratuberculosis
Infection
Authors: Huntley J. F. , Stabel J. R. , Paustian M. L. , Reinhardt T. A. , Bannantine J. P. 
Published: September 2005

ABSTRACT

Currently, paratuberculosis vaccines are comprised of crude whole-cell preparations of
Mycobacterium avium
subsp.
paratuberculosis
. Although effective in reducing clinical disease and fecal shedding, these vaccines have severe disadvantages as well, including seroconversion of vaccinated animals and granulomatous lesions at the site of vaccination. DNA vaccines can offer an alternative approach that may be safer and elicit more protective responses. In an effort to identify protective
M. avium
subsp.
paratuberculosis
sequences, a genomic DNA expression library was generated and subdivided into pools of clones (∼1,500 clones/pool). The clone pools were evaluated to determine DNA vaccine efficacy by immunizing mice via gene gun delivery and challenging them with live, virulent
M. avium
subsp.
paratuberculosis
. Four clone pools resulted in a significant reduction in the amount of
M. avium
subsp.
paratuberculosis
recovered from mouse tissues compared to mice immunized with other clone pools and nonvaccinated, infected control mice. One of the protective clone pools was further partitioned into 10 clone arrays of 108 clones each, and four clone arrays provided significant protection from both spleen and mesenteric lymph node colonization by
M. avium
subsp.
paratuberculosis
. The nucleotide sequence of each clone present in the protective pools was determined, and coding region functions were predicted by computer analysis. Comparison of the protective clone array sequences implicated 26 antigens that may be responsible for protection in mice. This study is the first study to demonstrate protection against
M. avium
subsp.
paratuberculosis
infection with expression library immunization.
LPXTG Protein InlJ, a Newly Identified Internalin Involved in
Listeria monocytogenes
Virulence
Authors: Sabet Christophe , Lecuit Marc , Cabanes Didier , Cossart Pascale , Bierne Hélène 
Published: September 2005

ABSTRACT

Listeria monocytogenes
expresses surface proteins covalently anchored to the peptidoglycan by sortase enzymes. Inactivation of
srtA
attenuates
Listeria
virulence in mice (H. Bierne, S. K. Mazmanian, M. Trost, M. G. Pucciarelli, G. Liu, P. Dehoux, L. Jansch, F. Garcia-del Portillo, O. Schneewind, and P. Cossart, Mol. Microbiol.
43:
869-881, 2002). We show here that an
srtA
mutant is more attenuated than an internalin mutant in orally infected guinea pigs and transgenic mice expressing human E-cadherin (hEcad mice), indicating the involvement of other SrtA substrates, LPXTG proteins, in food-borne listeriosis. Data recently generated with a listerial DNA macroarray identified two LPXTG protein-encoding genes present in the genomes of
L. monocytogenes
strains and absent from all other
Listeria
species,
inlI
(lmo0333) and
inlJ
(lmo2821). They also revealed two other LPXTG protein-encoding genes, ORF29 and ORF2568, present only in a subclass of
L. monocytogenes
serovars, including the epidemic serovar 4b. We report here that an
inlJ
deletion mutant, in contrast to
inlI
and ORF29 mutants, is significantly attenuated in virulence after intravenous infection of mice or oral inoculation of hEcad mice. Interestingly, a ΔORF2568 strain showed a slight increase in virulence.
inlJ
encodes a leucine-rich repeat (LRR) protein that is structurally related to the listerial invasion factor internalin. However, the consensus sequence of the InlJ LRR defines a novel subfamily of cysteine-containing LRRs in bacteria. In conclusion, this postgenomic approach identified InlJ as a new virulence factor among the proteins belonging to the internalin family in
L. monocytogenes
.
Role of B Cells in Vaccine-Induced Immunity against Coccidioidomycosis
Authors: Magee D. Mitchell , Friedberg Rhonda L. , Woitaske Melanie D. , Johnston Stephen Albert , Cox Rebecca A. 
Published: September 2005

ABSTRACTWe investigated secondary immunity against coccidioidomycosis by using gene expression microarrays. Surprisingly, a high percentage of B-cell-related genes were associated with protective immunity. A functional confirmation of the importance of B cells against coccidioidomycosis was achieved by demonstrating that vaccination was not fully protective in B-cell-deficient MuMT mice.
Lethal Infection of C3H/HeJ and C3H/SCID Mice with an Isolate of
Leptospira interrogans
Serovar Copenhageni
Authors: Nally Jarlath E. , Fishbein Michael C. , Blanco David R. , Lovett Michael A. 
Published: September 2005

ABSTRACT

Leptospira interrogans
serovar Copenhageni strain RJ16441, a blood isolate from humans with the severe pulmonary form of leptospirosis, has previously been shown to cause fatal pulmonary hemorrhage in guinea pigs and asymptomatic chronic renal tubular colonization with urinary shedding in rats. In this study, RJ16441 caused lethal infection of both C3H/HeJ and C3H/SCID mice, but no hemorrhagic phenomena were observed.
Induction of
SAP7
Correlates with Virulence in an Intravenous Infection Model of Candidiasis but Not in a Vaginal Infection Model in Mice
Authors: Taylor Brad N. , Hannemann Holger , Sehnal Miriam , Biesemeier Antje , Schweizer Anja , Röllinghoff Martin , Schröppel Klaus 
Published: September 2005

ABSTRACT

SAP7
of
Candida albicans
is induced after vaginal infection of mice. Conversely, virulence during vaginal infection was not affected in a Δ
sap7/
Δ
sap7
mutant strain. Only a partial virulence phenotype was detectable after intravenous injection. In conclusion,
SAP7
expression does not correlate with
C. albicans
virulence in mice.
COMPOSITION DEPENDENCE OF THE POSITRON ANNIHILATION INZn1-xBexSe
Authors: BENKABOU F. 
Published: September 2005

In order to clarify the electronic and optical properties of wide-energy gap zinc-blende structure ZnSe , BeSe and their alloys, a simple pseudo-potential scheme (EPM), within an affective potential the virtual crystal approximation (VCA) which incorporates compositional disorder as an effective potential are presented.Angular correlation of positron annihilation radiation (ACPAR) along different crystallographic directions in Zn1-xBexSe are calculated. We observe that the electron-positron momentum density increases rapidly with increasing Beryllium content.
[11C]Methionine Positron Emission Tomography and Survival in Patients with Bone and Soft Tissue Sarcomas Treated by Carbon Ion Radiotherapy
Authors: Zhang Hong , Yoshikawa Kyosan , Tamura Katsumi , Tomemori Takashi , Sagou Kenji , Tian Mei , Kandatsu Susumu , Kamada Tadashi , Tsuji Hiroshi , Suhara Tetsuya , Suzuki Kazutoshi , Tanada Shuji , Tsujii Hirohiko 
Published: September 2005

Abstract
Purpose: The development of the novel carbon ion radiotherapy (CIRT) in the treatment of refractory cancers has resulted in the need for a way to accurately evaluate patient prognosis. We evaluated whether l-[methyl-11C]-methionine (MET) uptake and its change after CIRT were the early survival predictors in patients with unresectable bone and soft tissue sarcomas.
Experimental Design: MET positron emission tomography was prospectively performed in 62 patients with unresectable bone and soft tissue sarcomas before and within 1 month after CIRT. Tumor MET uptake was measured with the semiquantitative tumor:nontumor ratio (T/N ratio). The MET uptake in the tumor and relevant clinical parameters were entered into univariate and multivariate survival analysis.
Results: The overall median survival time was 20 months. Patients with a baseline T/N ratio of ≤6 had a significant better survival than patients with a baseline T/N ratio &gt;6 (2-year survival rate: 69.4% versus 32.3%; P = 0.01). Patients with a post-CIRT ratio of ≤4.4 had a better survival than that with a post-CIRT ratio &gt;4.4 (2-year survival rate: 63.7% versus 41.3%; P = 0.01). A significant higher survival rate was observed in patients with post-therapeutic MET uptake change of &gt;30% than patients in lower change group (2-year survival rate: 74.6% versus 41.6%; P = 0.049). The multivariate analysis showed that both baseline and post-CIRT T/N ratio were statistically significant independent predictors of patient survival. Tumors with larger T/N ratio had a significantly poorer prognosis.
Conclusions: MET uptake as measured by either baseline or post-CIRT T/N ratio was an independent predictor of survival in patients with bone and soft tissue sarcomas treated by carbon ion radiotherapy, whereas post-therapeutic MET uptake change might have potential value for the same purpose.