bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombination between the
dfrA12
-orfF-
aadA2
Cassette Array and an
aadA1
Gene Cassette Creates a Hybrid Cassette,
aadA8b
Authors: Gestal Alicia M. , Stokes H. W. , Partridge Sally R. , Hall Ruth M. 
Published: October 2005

ABSTRACT

Homologous recombination between closely related gene cassettes, such as
aadA1
and
aadA2
, which are 89% identical, can create hybrid cassettes and hybrids of existing cassette arrays. A new cassette array,
dfrA12
-orfF-
aadA8b
, which was created by such a recombination event occurring within the
aadA2
cassette in the
dfrA12
-orfF-
aadA2
array, has been identified.
Use of an Efflux-Deficient
Streptococcus pneumoniae
Strain Panel To Identify ABC-Class Multidrug Transporters Involved in Intrinsic Resistance to Antimicrobial Agents
Authors: Robertson Gregory T. , Doyle Timothy B. , Lynch A. Simon 
Published: October 2005

ABSTRACT

Thirteen derivatives of the
Streptococcus pneumoniae
TIGR4 strain in which putative drug efflux pumps were genetically inactivated were constructed and characterized. The results indicate that two linked genes encoding the ABC-type transporters SP2073 and SP2075 function together to confer intrinsic resistance to a series of structurally unrelated compounds, including certain fluoroquinolones.
High Prevalence of Glycopeptide Resistance Genes
vanB
,
vanD
, and
vanG
Not Associated with Enterococci in Human Fecal Flora
Authors: Domingo M.-C. , Huletsky A. , Giroux R. , Boissinot K. , Picard F. J. , Lebel P. , Ferraro M. J. , Bergeron M. G. 
Published: October 2005

ABSTRACT

The presence of
Enterococcus
-associated vancomycin resistance genes
vanA
,
vanB
,
vanD
,
vanE
, and
vanG
in rectal swabs was investigated in two hospitals using PCR. All
vanA
genes detected were associated with vancomycin-resistant enterococci (VRE), whereas VRE-associated
vanB
genes were detected in only one hospital (4.7%). However, in both hospitals, high prevalences of
vanB
(6.2 and 2.3%),
vanD
(43.8 and 26.7%), and
vanG
(10.5 and 6.9%) genes not associated with enterococci were found.
Efficacy of Penicillin versus Cefdinir in Eradication of Group A Streptococci and Tonsillar Flora
Authors: Brook Itzhak , Foote Perry A. 
Published: October 2005

ABSTRACT

Core tonsillar cultures were obtained from 40 children with recurrent tonsillitis treated with either penicillin or cefdinir. Group A beta-hemolytic streptococci were isolated from 11 penicillin- and 3 cefdinir-treated (
P
< 0.001) patients. β-Lactamase producers were recovered from 17 penicillin- and 3 cefdinir-treated (
P
< 0.01) patients. Inhibiting alpha-hemolytic streptococci were isolated less often from penicillin-treated patients than from cefdinir-treated patients.
Therapeutic Effects of Bacteriophage Cpl-1 Lysin against
Streptococcus pneumoniae
Endocarditis in Rats
Authors: Entenza J. M. , Loeffler J. M. , Grandgirard D. , Fischetti V. A. , Moreillon P. 
Published: October 2005

ABSTRACT

Cpl-1, a pneumococcal phage lytic enzyme, was tested in rats with experimental endocarditis due to
Streptococcus pneumoniae
WB4. High-dose regimen Cpl-1 eliminated pneumococci from blood within 30 min and decreased bacterial titers in vegetations (>4 log
10
CFU/g) within 2 h. Rapid bacterial lysis induced by Cpl-1 treatment increased cytokine secretion noticeably.
Recovery of Interfering Bacteria in the Nasopharynx following Antimicrobial Therapy of Acute Maxillary Sinusitis with Telithromycin or Amoxicillin-Clavulanate
Authors: Brook Itzhak , Hausfeld Jeffrey N. 
Published: October 2005

ABSTRACT

The effect on the nasopharyngeal flora of 7 days of amoxicillin-clavulanate or 5 days of 800 mg once a day was studied in 50 adults with acute sinusitis. The numbers of potential pathogens and interfering alpha-hemolytic streptococci were equally reduced after both therapies. However, the number of interfering
Prevotella
spp. declined more significantly after amoxicillin-clavulanate treatment.
Effectiveness of Anidulafungin in Eradicating
Candida
Species in Invasive Candidiasis
Authors: Pfaller M. A. , Diekema D. J. , Boyken L. , Messer S. A. , Tendolkar S. , Hollis R. J. , Goldstein B. P. 
Published: October 2005

ABSTRACT

In a phase 2 open-label, dose-ranging study in patients with candidemia, anidulafungin was effective in eradicating
Candida albicans
and other species of
Candida
. The anidulafungin MIC distribution showed that
Candida albicans
and
C. glabrata
were the most susceptible species and
C. parapsilosis
was the least susceptible species.
Multiplex PCR for Simultaneous Detection of Macrolide and Tetracycline Resistance Determinants in Streptococci
Authors: Malhotra-Kumar Surbhi , Lammens Christine , Piessens Jasper , Goossens Herman 
Published: October 2005

ABSTRACT

Resistance to macrolides and tetracyclines is increasing among streptococci and co-occurs as their resistance determinants are carried on the same mobile element. We developed a multiplex PCR to facilitate simultaneous and specific detection of resistance determinants for both macrolides [
erm
(A),
erm
(B), and
mef
(A/E)] and tetracyclines [
tet
(M),
tet
(O),
tet
(K), and
tet
(L)] in streptococci.
New
Mycobacterium avium
Antifolate Shows Synergistic Effect when Used in Combination with Dihydropteroate Synthase Inhibitors
Authors: Suling W. J. , Seitz L. E. , Reynolds R. C. , Barrow W. W. 
Published: October 2005

ABSTRACT

Mycobacterium avium
complex (MAC) is resistant to trimethoprim, an inhibitor of bacterial dihydrofolate reductase (DHFR). A previously identified selective inhibitor of MAC DHFR, SRI-8858, was shown to have synergistic activity in combination with dapsone and sulfamethoxazole, two drugs that inhibit bacterial dihydropteroate synthase.
Shiga Toxin 1 Causes Direct Renal Injury in Rats
Authors: Yamamoto Elise T. , Mizuno Masashi , Nishikawa Kiyotaka , Miyazawa Shinobu , Zhang Lianshan , Matsuo Seiichi , Natori Yasuhiro 
Published: October 2005

ABSTRACT

Infection with Shiga toxin (Stx)-producing
Escherichia coli
has been implicated to cause hemolytic uremic syndrome, which is characterized by histological abnormalities such as microvascular thrombi and tubular cell damage in the kidney. Although Stx is known to be the major virulence factor of the pathogen, it is still unclear whether Stx directly impairs renal cells in vivo to cause such histological changes and deterioration of renal function. To assess the consequence of the direct action of Stx on renal cells, left kidneys of rats were perfused with Stx1 from the renal artery through the renal vein and then revascularized. Kidneys of control animals were perfused with the vehicle alone. On day 1, apoptosis and induction of tumor necrosis factor alpha gene expression were noticed to occur in the medulla of the Stx1-perfused kidneys. On day 3, extensive tubular injuries were observed by light microscopy: aggregated platelets and monocytic infiltrates in both glomeruli and the medullary interstitium were detected by immunostaining. Tubular changes were more extensive on day 9, with areas of infarction seen in the cortex and medulla. These changes were not found to occur in the sham-operated kidneys. No obvious glomerular changes were detected by light microscopy at any time point. When nonperfused right kidneys were removed after the Stx1 perfusion of the left kidneys, the serum creatinine and blood urea nitrogen levels were increased from day 2, and acute renal failure followed on day 3. These results indicate that Stx1 caused glomerular platelet aggregation, tubular damage, and acute deterioration of renal function by acting directly on renal cells.
Disruption of Tight Junctions during Traversal of the Respiratory Epithelium by
Burkholderia cenocepacia
Authors: Kim Jason Y. , Sajjan Umadevi S. , Krasan Graham P. , LiPuma John J. 
Published: October 2005

ABSTRACT

Burkholderia cenocepacia
is an opportunistic bacterial species capable of causing life-threatening respiratory tract infection in persons with cystic fibrosis (CF). Unlike most other pathogens in CF, which typically remain confined to the endobronchial spaces,
B. cenocepacia
can traverse airway epithelium to cause bacteremia and sepsis. The mechanisms by which this occurs, however, are unknown. We examined the transmigration of
B. cenocepacia
through polarized respiratory epithelium. Representatives of three “epidemic” lineages common among CF patients in North America were able to traverse polarized 16HBE14o
−
cells in vitro. Transmigration of bacteria was associated with significant perturbations in epithelial permeability, as measured by a loss of transepithelial electrical resistance and increased flux of bovine serum albumin across the cell layer. Terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling and trypan blue exclusion assays, as well as lactate dehydrogenase levels, did not indicate excessive cytotoxicity or cell death in infected cell layers. Rather, confocal fluorescence microscopy demonstrated the loss of occludin from tight junctions. In contrast, zonula occludens 1 was well preserved along intercellular borders. Western blot analysis showed a shift in the major occludin isoforms from high- to low-phosphorylation states during infection. These observations suggest that
B. cenocepacia
traverses polarized respiratory epithelium by the dephosphorylation and dissociation of occludin from the tight-junction complex.
Cholesterol-Enriched Membrane Microdomains Are Required for Inducing Host Cell Cytoskeleton Rearrangements in Response to Attaching-Effacing
Escherichia coli
Authors: Riff Jason D. , Callahan John W. , Sherman Philip M. 
Published: October 2005

ABSTRACT

The diarrheal pathogens enterohemorrhagic
Escherichia coli
(EHEC) O157:H7 strain CL56 and enteropathogenic
Escherichia coli
(EPEC) O127:H6 strain E2348/69 adhere intimately to epithelial cells through attaching-effacing lesions, which are characterized by rearrangements of the host cytoskeleton, intimate adherence, and destruction of microvilli. These cytoskeletal responses require activation of host signal transduction pathways. Lipid rafts are signaling microdomains enriched in sphingolipid and cholesterol in the plasma membrane. The effect of perturbing plasma membrane cholesterol on bacterial intimate adherence was assessed. Infection of both HEp-2 cells and primary skin fibroblasts with strains CL56 and E2348/69 caused characteristic rearrangements of the cytoskeleton at sites of bacterial adhesion. CL56- and E2348/69-induced cytoskeletal rearrangements were inhibited following cholesterol depletion. Addition of exogenous cholesterol to depleted HEp-2 cells restored cholesterol levels and rescued bacterially induced α-actinin mobilization. Quantitative bacterial adherence assays showed that EPEC adherence to HEp-2 cells was dramatically reduced following cholesterol depletion, whereas the adherence of EHEC remained high. Cytoskeletal rearrangements on skin fibroblasts obtained from children with Niemann-Pick type C disease were markedly reduced. These findings indicate that host membrane cholesterol contained in lipid rafts is necessary for the cytoskeletal rearrangements following infection with attaching-effacing
Escherichia coli
. Differences in initial adherence indicate divergent roles for host membrane cholesterol in the pathogenesis of EHEC and EPEC infections.
Demonstration of Factor H-Like Protein 1 Binding toTreponema denticola, a Pathogen Associated with Periodontal Disease in Humans
Authors: McDowell John V. , Lankford Justin , Stamm Lola , Sadlon Tania , Gordon David L. , Marconi Richard T. 
Published: October 2005

ABSTRACTTreponema denticolais an important contributor to periodontal disease. In this study we investigated the ability ofT. denticolato bind the complement regulatory proteins factor H and factor H-like protein 1 (FHL-1). The binding of these proteins has been demonstrated to facilitate evasion of the alternative complement cascade and/or to play a role in adherence and invasion. Here we demonstrate thatT. denticolaspecifically binds FHL-1 via a 14-kDa, surface-exposed protein that we designated FhbB. Consistent with its FHL-1 binding specificity, FhbB binds only to factor H recombinant fragments spanning short consensus repeats (SCRs) 1 to 7 (H7 construct) and not to SCR constructs spanning SCRs 8 to 15 and 16 to 20. Binding of H7 to FhbB was inhibited by heparin. The specific involvement of SCR 7 in the interaction was demonstrated using an H7 mutant (H7AB) in which specific charged residues in SCR 7 were replaced by alanine. This construct lost FhbB binding ability. Analyses of the ability of FHL-1 bound to the surface ofT. denticolato serve as a cofactor for factor I-mediated cleavage of C3b revealed that C3b is cleaved in an FHL-1/factor I-independent manner, perhaps by an unidentified protease. Based on the data presented here, we hypothesize that the primary function of FHL-1 binding byT. denticolamight be to facilitate adherence to FHL-1 present on anchorage-dependent cells and in the extracellular matrix.
Pathogenesis ofYersinia pestisInfection in BALB/c Mice: Effects on Host Macrophages and Neutrophils
Authors: Lukaszewski Roman A. , Kenny Dermot J. , Taylor Rosa , Rees D. G. Cerys , Hartley M. Gill , Oyston Petra C. F. 
Published: October 2005

ABSTRACTThe pathogenesis of infection withYersinia pestis, the causative agent of plague, was examined following subcutaneous infection of BALB/c mice with a fully virulent strain expressing green fluorescent protein. Plate culturing, flow cytometry, and laser confocal microscopy of spleen homogenates throughout infection revealed three discernible stages of infection. The early phase was characterized by the presence of a small number of intracellular bacteria mostly within CD11b+macrophages and Ly-6G+neutrophils. These bacteria were not viable, as determined by plate culturing of spleen homogenates, until day 2 postinfection. Between days 2 and 4 postinfection, a plateau phase was observed, with bacterial burdens of 103to 104CFU per spleen. Flow cytometric analysis revealed that there was even distribution ofY. pestiswithin both CD11b+macrophage and Ly-6G+neutrophil populations on day 2 postinfection. However, from day 3 postinfection onward, intracellular bacteria were observed exclusively within splenic CD11b+macrophages. The late phase of infection, between days 4 and 5 postinfection, was characterized by a rapid increase in bacterial numbers, as well as escape of bacteria into the extracellular compartment. Annexin V staining of spleens indicated that a large proportion of splenic neutrophils underwent rapid apoptosis on days 1 and 2 postinfection. Fewer macrophages underwent apoptosis during the same period. Our data suggest that during the early stages ofY. pestisinfection, splenic neutrophils are responsible for limiting the growth ofY. pestisand that splenic macrophages provide safe intracellular shelters within whichY. pestisis able to grow and escape during the later stages of infection. This macrophage compliance can be overcome in vitro by stimulation with a combination of gamma interferon and tumor necrosis factor alpha.
Human Airway Epithelial Cells SensePseudomonas aeruginosaInfection via Recognition of Flagellin by Toll-Like Receptor 5
Authors: Zhang Zhe , Louboutin Jean-Pierre , Weiner Daniel J. , Goldberg Joanna B. , Wilson James M. 
Published: October 2005

ABSTRACTPseudomonas aeruginosa, an opportunistic respiratory pathogen that infects the majority of patients with cystic fibrosis, initiates host inflammatory responses through interaction with airway epithelial cells. The Toll-like receptors (TLRs) are a family of pathogen pattern recognition receptors that play key roles in host innate immunity. In this study we aimed to determine whether TLRs mediate the interaction betweenP. aeruginosaand airway epithelial cells. Individual murine TLRs (TLR1 to TLR9) and dual combinations of these TLRs that activate an NF-κB-driven luciferase reporter in response to PAO1 were screened in HEK 293 cells. TLR5, TLR2, a combination of TLR1 and TLR2, or a combination of TLR2 and TLR6 responded to PAO1. AnotherP. aeruginosastrain, strain PAK, activated TLR5 similarly, while the isogenic flagellin-deficient strain PAK/fliCand the flagellum-free bacteriumHaemophilus influenzaefailed to activate TLR5. Reverse transcription-PCR was used to probe the presence of multiple TLRs (including TLR5) in primary human airway epithelial cells (HAECs). Immunostaining with TLR5 antibodies showed that TLR5 was expressed in HAECs and on the apical surface of the human trachea epithelium. In HAECs, PAO1, PAK, andBurkholderia cepacia, but not flagellin-deficient strain PAK/fliCor aB. cepacia fliCmutant, activated the NF-κB reporter. Dominant negative TLR5 specifically blocked the response toP. aeruginosabut not to the response to lipoteichoic acid, a specific ligand of TLR2. We also determined that MyD88, IRAK, TRAF6, and Toll-interacting protein (Tollip), but not TIRAP, were involved in the TLR-mediated response toP. aeruginosain HAECs. These findings demonstrate that the airway epithelial receptor TLR5 sensesP. aeruginosathrough its flagellin protein, which may have an important role in the initiation of the host inflammatory reaction to clear the invading pathogen.
The Role of
Candida albicans NOT5
in Virulence Depends upon Diverse Host Factors In Vivo
Authors: Cheng Shaoji , Clancy Cornelius J. , Checkley Mary Ann , Zhang Zongde , Wozniak Karen L. , Seshan Kalpathi R. , Jia Hong Yan , Fidel Paul , Cole Garry , Nguyen M. Hong 
Published: October 2005

ABSTRACT

We previously identified
Candida albicans
Not5p as an immunogenic protein expressed during oropharyngeal candidiasis (OPC). In this study, we demonstrate that
C. albicans NOT5
reverses the growth defects of a
Saccharomyces cerevisiae not5
mutant strain at 37°C, suggesting that the genes share at least some functional equivalence. We implicate
C. albicans NOT5
in the pathogenesis of disseminated candidiasis (DC) induced by intravenous infection among neutropenic and nonimmunosuppressed mice, as well as in that of OPC in mice immunosuppressed with corticosteroids. We find no role in virulence, however, among neutropenic and corticosteroid-suppressed mice with DC resulting from gastrointestinal translocation, nor do we implicate the gene in vulvovaginal candidiasis among mice in pseudoestrus. These findings suggest that the role of
NOT5
in virulence depends on the specific in vivo environment and is influenced by diverse factors such as tissue site, portal of entry, and the status of host defenses.
NOT5
is necessary for normal adherence to colonic and cervical epithelial cells in vitro, demonstrating that such assays cannot fully replicate disease processes in vivo. Lastly, antibody responses against Not5p do not differ in the sera of patients with OPC, patients with DC, and healthy controls, suggesting that the protein is associated with both commensalism and the pathogenesis of disease.
Immunosuppressive Effects of CCL17 on Pulmonary Antifungal Responses during Pulmonary Invasive Aspergillosis
Authors: Carpenter Kristin J. , Hogaboam Cory M. 
Published: October 2005

ABSTRACTAspergillus fumigatus-sensitized CCR4-deficient (CCR4−/−) mice exhibit an accelerated clearance of conidia during fungal asthma. In the present study, we examined the roles of CCL17 and CCL22, two CCR4 ligands, during pulmonary invasive aspergillosis in neutropenic mice. Kaplan-Meier survival curve analysis revealed that wild-type C57BL/6 (CCR4+/+) mice were significantly protected from the lethal effects ofAspergilluscompared with their wild-type controls following systemic neutralization with anti-CCL17 but not anti-CCL22 antibodies. Systemic neutralization of CCL17 significantly increased whole-lung CCL2 levels. Mouse survival and histological analysis revealed that the receptor mediating the deleterious effects of CCL17 was CCR4 since mice genetically deficit in CCR4 (CCR4−/−) did not develop invasive aspergillosis. Enzyme-linked immunosorbent assay analysis of whole-lung samples at day 2 after conidial challenge in neutrophil-depleted CCR4−/−and CCR4+/+mice revealed that whole-lung IL-12 levels were significantly increased in the CCR4−/−group compared with the wild-type group. Also at day 2 after conidial challenge, significantly greater numbers of CD11c+F4/80+and CD11c+/CD86+but fewer CD3/NK1.1+cells were present in the lungs of CCR4−/−mice compared with their wild-type counterparts. Thus, CCL17-CCR4 interactions dramatically impair the pulmonary antifungal response againstA. fumigatusin neutropenic mice.
Association of Linear Plasmid 28-1 with an Arthritic Phenotype ofBorrelia burgdorferi
Authors: Xu Qilong , Seemanapalli Sunita V. , Lomax Larry , McShan Kristy , Li Xin , Fikrig Erol , Liang Fang Ting 
Published: October 2005

ABSTRACTBorrelia burgdorferi, the Lyme disease spirochete, has a genome comprised of a linear chromosome and up to 21 plasmids. Loss of plasmids is associated with decreased infectivity and pathogenicity. Sixteen transformants were generated by transforming the noninfectious clone 5A13 with the recombinant plasmid pBBE22. The transformants were classified into nine groups based on plasmid content analysis. An infectivity study revealed that all nine transformants examined, each of which represented one of the plasmid patterns, were infectious in mice with severe combined immunodeficiency (SCID) regardless of their genomic compositions. Tissue bacterial quantification revealed that the loss of plasmids significantly reduced the spirochete burden in the heart and joint tissues, not in the skin, suggesting virulence factors may be tissue specific. Four transformants containing lp28-1 induced severe arthritis in SCID mice, in contrast to the five transformants lacking lp28-1. These pathogenicity studies associated lp28-1 with an arthritic phenotype and further studies may identify factors that contribute to arthritic pathology.
Peptidoglycan Recognition Protein 2 (N-Acetylmuramoyl-l-Ala Amidase) Is Induced in Keratinocytes by Bacteria through the p38 Kinase Pathway
Authors: Wang Haitao , Gupta Dipika , Li Xinna , Dziarski Roman 
Published: October 2005

ABSTRACTHuman peptidoglycan recognition protein 2 (PGLYRP2) is anN-acetylmuramoyl-l-alanine amidase that hydrolyzes bacterial peptidoglycan and is constitutively produced in the liver and secreted into the blood. Here we demonstrate that PGLYRP2 was not expressed in healthy human skin and had low expression in the eye. However, upon exposure to gram-positive and gram-negative bacteria or cytokines, PGLYRP2 expression was highly induced in keratinocytes and to a lower level in corneal epithelial cells. Expression of PGLYRP2 was not induced in nonepithelial cells. Exposure of keratinocytes to bacteria induced keratinocyte differentiation and stress response and inhibited activation of signal transduction molecules involved in cell proliferation. Induction of PGLYRP2 expression correlated with expression of differentiation markers (cytokeratins and transglutaminase). Bacteria induced activation of p38 mitogen-activated protein kinase (MAPK) in keratinocytes, which was required for the induction of PGLYRP2 expression, because induction of PGLYRP2 transcription by bacteria was inhibited by SB203580 (a specific inhibitor of p38 MAPK) and by a dominant-negative p38 construct. Induction of PGLYRP2 expression by bacteria (in contrast to expression of human β-defensin-2) was not mediated by Toll-like receptor 2 or 4. PGLYRP2 may function in the skin and the eyes as an inducible scavenger of proinflammatory peptidoglycan.