bluuebunny/crossref_metadata_2025_split huggingface dataset:
Roxithromycin Favorably Modifies the Initial Phase of Resistance against Infection with Macrolide-Resistant
Streptococcus pneumoniae
in a Murine Pneumonia Model
Authors: Yasuda Yasuki , Kasahara Kei , Mizuno Fumiko , Nishi Kazuyuki , Mikasa Keiichi , Kita Eiji 
Published: March 2007

ABSTRACT

Sub-MIC levels of macrolides down-regulate bacterial virulence factors and suppress inflammatory processes. The ability of macrolides to reduce the production of pneumolysin has been shown to explain the discrepancy between in vitro resistance and outcomes with macrolides against macrolide-resistant
Streptococcus pneumoniae
. In this study, we determined whether the ability of macrolides to regulate inflammatory processes is beneficial for innate resistance to macrolide-resistant pneumococci in a murine pneumonia model. Among the macrolides tested, only roxithromycin did not affect in vitro pneumococcal virulence factors at sub-MIC levels. Roxithromycin (1.25 to 10 mg/kg of body weight/day) was administered to mice by oral gavage for 3 days before infection with a resistant strain of
S. pneumoniae
. We evaluated the efficacy of the treatment by determining mouse survival curves and by measuring bacterial burdens and several inflammatory parameters in the airways. Pneumolysin and PspA in infected lungs were examined by Western blot assay. Roxithromycin at doses of ≥5 mg/kg/day increased the median survival time and retarded bacteremia without suppressing the production of pneumolysin and PspA in infected lungs. This treatment reduced matrix metalloproteinase-7 expression and activation and keratinocyte-derived chemokine production in the lungs, while it increased mononuclear cell responses in the lungs, with enhanced bacterial clearance. Concentrations of roxithromycin in plasma and tissues were below the MICs for the inoculated strain during infection. The treatment also reduced inflammatory responses to killed pneumococci in the lungs. These results suggest that the modification by roxithromycin of airway inflammatory responses, including those of matrix metalloproteinase-7 and phagocytes, is beneficial for initial resistance to macrolide-resistant pneumococci.
In Vitro Activities of Isepamicin, Other Aminoglycosides, and Capreomycin against Clinical Isolates of Rapidly Growing Mycobacteria in Taiwan
Authors: Shen Gwan-Han , Wu Bo-Da , Wu Kun-Ming , Chen Jiann-Hwa 
Published: March 2007

ABSTRACT

The in vitro activities of isepamicin against 117
Mycobacteria abscessus
, 48
Mycobacterium fortuitum
, and 20
Mycobacterium chelonae
isolates were evaluated by a microdilution test. Isepamicin MIC
90
s were ≤16 μg/ml for the three species. Isepamicin was as active as amikacin and kanamycin and more active than tobramycin, capreomycin, gentamicin, and streptomycin.
The Salmochelin Siderophore Receptor IroN Contributes to Invasion of Urothelial Cells by Extraintestinal Pathogenic
Escherichia coli
In Vitro
Authors: Feldmann Friederike , Sorsa Liisa Johanna , Hildinger Kirsten , Schubert Sören 
Published: March 2007

ABSTRACT

Extraintestinal pathogenic
Escherichia coli
(ExPEC) strains possess several siderophore-dependent iron uptake systems. In this study we demonstrated that the salmochelin siderophore receptor IroN is involved in the invasion of urothelial cells by ExPEC in vitro. Thus, IroN may play a dual role in the establishment of urinary tract infections, displaying an iron uptake receptor as well as an internalization factor.
Host Cell Responses to
Chlamydia pneumoniae
in Gamma Interferon-Induced Persistence Overlap Those of Productive Infection and Are Linked to Genes Involved in Apoptosis, Cell Cycle, and Metabolism
Authors: Eickhoff Meike , Thalmann Jessica , Hess Simone , Martin Myriam , Laue Thomas , Kruppa Joachim , Brandes Gudrun , Klos Andreas 
Published: March 2007

ABSTRACT

The respiratory pathogen
Chlamydia
(
Chlamydophila
)
pneumoniae
is associated with chronic diseases, including atherosclerosis and giant-cell arteritis, which are accompanied by the occurrence of these obligate intracellular bacteria in blood vessels. There,
C. pneumoniae
seems to be present in a persistent state. Persistence is characterized by modified bacterial metabolism and morphology, as well as a reversible arrest of chlamydial development. In cell culture, this persistent state can be induced by gamma interferon (IFN-γ). To elucidate this long-term interaction between chlamydiae and their host cells, microarray screening on epithelial HeLa cells was performed. Transcription of persistently (and productively) infected cells was compared with that of mock-infected cells. Sixty-six host cell genes were regulated at 24 h and/or 96 h of IFN-γ-induced persistence. Subsequently, a set of 17 human host cell genes related to apoptosis, cell cycle, or metabolism was identified as permanently up- or down-regulated by real-time PCR. Some of these chlamydia-dependent host cell responses were diminished or even absent in the presence of rifampin. However, other expression patterns were not altered by the inhibition of bacterial RNA polymerase, suggesting two different modes of host cell activation. Thus, in the IFN-γ model, the persisting bacteria cause long-lasting changes in the expression of genes coding for functionally important proteins. They might be potential drug targets for the treatment of persistent
C. pneumoniae
infections.
Relaxed Cleavage Specificity of an Immunoglobulin A1 Protease from
Neisseria meningitidis
Authors: Vitovski Srdjan , Sayers Jon R. 
Published: March 2007

ABSTRACT

Respiratory pathogens, such as
Neisseria meningitidis
, secrete site-specific proteases able to cleave human immunoglobulin A1 (IgA1), the first line of defense at mucosal membranes. Bacterial isolates show wide variability in IgA1 protease activity, and those isolated from patients with clinical infection possess the highest levels of activity. A feature of this enzyme is the self-cleavage required for secretion of the mature extracellular form. Known cleavage targets contain a proline-rich consensus recognition sequence, Pro-Pro-Ser-Pro, residing in the variable linker region that connects the protease and translocator domains. Here, we report the sequence of the NMB IgA1 protease and the unexpected self-cleavage and subsequent extracellular release of mature IgA1 protease from mutants lacking the previously defined consensus cleavage site. We investigated the possible link between enzyme secretion and variability in the linker sequence segment using site-directed mutagenesis and linker domain swapping to construct mutated and chimeric forms of the IgA1 protease from
N. meningitidis
strain NMB. The observed change in secreted activity levels compared to the wild-type clone indicated that the precise amino acid sequence of the intervening region, between mature IgA1 protease and the β-core translocator domain, influences the efficacy of autoproteolytic processing. The broader specificity uncovered for the NMB IgA1 protease suggests that it could cleave a far wider range of human proteins than previously appreciated.
Microevolution and Patterns of Dissemination of the JP2 Clone of
Aggregatibacter
(
Actinobacillus
)
actinomycetemcomitans
Authors: Haubek Dorte , Poulsen Knud , Kilian Mogens 
Published: March 2007

ABSTRACT

The natural history, microevolution, and patterns of interindividual transmission and global dissemination of the JP2 clone of
Aggregatibacter
(
Actinobacillus
)
actinomycetemcomitans
were studied by population genetic analysis. The JP2 clone is strongly associated with aggressive periodontitis in adolescents of African descent and differs from other clones of the species by several genetic peculiarities, including a 530-bp deletion in the promoter region of the leukotoxin gene operon, which results in increased leukotoxic activity. Multilocus sequence analysis of 82
A. actinomycetemcomitans
strains, 66 of which were JP2 clone strains collected over a period of more than 20 years, confirmed that there is a clonal population structure with evolutionary lineages corresponding to serotypes. Although genetically highly conserved, as shown by alignment of sequences of eight housekeeping genes, strains belonging to the JP2 clone had a number of point mutations, particularly in the pseudogenes
hbpA
and
tbpA
. Characteristic mutations allowed isolates from individuals from the Mediterranean area and from West Africa, including the Cape Verde Islands, to be distinguished. The patterns of mutations indicate that the JP2 clone initially emerged as a distinct genotype in the Mediterranean part of Africa approximately 2,400 years ago and subsequently spread to West Africa, from which it was transferred to the American continents during the transatlantic slave trade. The sustained exclusive colonization of individuals of African descent despite geographical separation for centuries suggests that the JP2 clone has a distinct host tropism. The colonization of family members by JP2 clone strains with unique point mutations provides strong evidence that there is intrafamilial transmission and suggests that dissemination of the JP2 clone is restricted to close contacts.
Wild-Type and Interleukin-10-Deficient Regulatory T Cells Reduce Effector T-Cell-Mediated Gastroduodenitis in Rag2−/−Mice, but Only Wild-Type Regulatory T Cells SuppressHelicobacter pyloriGastritis
Authors: Lee Chung-Wei , Rao Varada P. , Rogers Arlin B. , Ge Zhongming , Erdman Susan E. , Whary Mark T. , Fox James G. 
Published: March 2007

ABSTRACTCD4+CD45RBhiCD25−effector T cells (TE) promoteHelicobacter pylorigastritis in mice, and CD4+CD45RBloCD25+regulatory T cells (TR) are anti-inflammatory. Using adoptive transfer intoH. pylori-infected Rag2−/−mice, we evaluated effects of wild-type (wt) C57BL/6 or congenic interleukin-10-deficient (IL-10−/−) TRcells on gastritis, gastric cytokines, andH. pyloricolonization. Infected Rag2−/−mice colonized in the corpus and antrum with 105to 106H. pyloriCFU/gram without associated gastritis. TEcell transfer caused morbidity and anH. pylori-independent pangastritis and duodenitis (gastroduodenitis) associated with increased expression of gamma interferon (IFN-γ) and tumor necrosis factor alpha. TEcell transfer toH. pylori-infected mice led to additive corpus gastritis associated with inflammatory cytokine expression and reduced colonization. wt TRcells reduced morbidity,H. pyloricorpus gastritis, gastroduodenitis, and inflammatory cytokine expression and reversed the decline inH. pyloricolonization attributable to TEcells. Although less effective than wt TRcells, IL-10−/−TRcells also reduced morbidity and gastroduodenitis but did not reduceH. pyloricorpus gastritis or impact TEcell inhibition of colonization. Gastric tissues from mice receiving wt TRcells expressed higher levels of Foxp3 compared to recipients of IL-10−/−TRcells, consistent with lower regulatory activity of IL-10−/−TRcells. These results demonstrate that wt TRcells suppressed TE-cell-mediatedH. pylori-independent gastroduodenitis andH. pylori-dependent corpus gastritis more effectively than IL-10−/−TRcells. Compartmental differences in TE-cell- andH. pylori-mediated inflammation and in regulatory effects between wt TRand IL-10−/−TRcells suggest that IL-10 expression by wt TRcells is important to regulatory suppression of gastric inflammation.
Deficiencies of Myeloid Differentiation Factor 88, Toll-Like Receptor 2 (TLR2), or TLR4 Produce Specific Defects in Macrophage Cytokine Secretion Induced byHelicobacter pylori
Authors: Obonyo Marygorret , Sabet Mojgan , Cole Sheri P. , Ebmeyer Joerg , Uematsu Satoshi , Akira Shizuo , Guiney Donald G. 
Published: March 2007

ABSTRACTHelicobacter pyloriis a gram-negative microaerophilic bacterium that colonizes the gastric mucosa, leading to disease conditions ranging from gastritis to cancer. Toll-like receptors (TLRs) play a central role in innate immunity by their recognition of conserved molecular patterns on bacteria, fungi, and viruses. Upon recognition of microbial components, these TLRs associate with several adaptor molecules, including myeloid differentiation factor 88 (MyD88). To investigate the contribution of the innate immune system toH. pyloriinfection, bone marrow-derived macrophages from mice deficient in TLR2, TLR4, TLR9, and MyD88 were infected withH. pyloriSS1 and SD4 for 24 or 48 h. We demonstrate that MyD88 was essential forH. pyloriinduction of all cytokines investigated except alpha interferon (IFN-α). The secretion of IFN-α was substantially increased from cells deficient in MyD88.H. pyloriinduced interleukin-12 (IL-12) and IL-10 through TLR4/MyD88 signaling. In addition,H. pyloriinduced less IL-6 and IL-1β in TLR2-deleted macrophages, suggesting that the MyD88 pathway activated by TLR2 stimulation is responsible forH. pyloriinduction of the host proinflammatory response (IL-6 and IL-1β). These observations are important in light of a recent report on IL-6 and IL-1β playing a role in the development ofH. pylori-related gastric cancer. In conclusion, our study demonstrates thatH. pyloriactivates TLR2 and TLR4, leading to the secretion of distinct cytokines by macrophages.
The ChrA-ChrS and HrrA-HrrS Signal Transduction Systems Are Required for Activation of the
hmuO
Promoter and Repression of the
hemA
Promoter in
Corynebacterium diphtheriae
Authors: Bibb Lori A. , Kunkle Carey A. , Schmitt Michael P. 
Published: March 2007

ABSTRACT

Transcription of the
Corynebacterium diphtheriae hmuO
gene, which encodes a heme oxygenase involved in heme iron utilization, is activated in a heme- or hemoglobin-dependent manner in part by the two-component system ChrA-ChrS. Mutation of either the
chrA
or the
chrS
gene resulted in a marked reduction of hemoglobin-dependent activation at the
hmuO
promoter in
C. diphtheriae
; however, it was observed that significant levels of hemoglobin-dependent expression were maintained in the mutants, suggesting that an additional activator is involved in regulation. A BLAST search of the
C. diphtheriae
genome sequence revealed a second two-component system, encoded by DIP2268 and DIP2267, that shares similarity with ChrS and ChrA, respectively; we have designated these genes
hrrS
(DIP2268) and
hrrA
(DIP2267). Analysis of
hmuO
promoter expression demonstrated that hemoglobin-dependent activity was fully abolished in strains from which both the
chrA
-
chrS
and the
hrrA
-
hrrS
two-component systems were deleted. Similarly, deletion of the sensor kinase genes
chrS
and
hrrS
or the genes encoding both of the response regulators
chrA
and
hrrA
also eliminated hemoglobin-dependent activation at the
hmuO
promoter. We also show that the regulators ChrA-ChrS and HrrA-HrrS are involved in the hemoglobin-dependent repression of the promoter upstream of
hemA
, which encodes a heme biosynthesis enzyme. Evidence for cross talk between the ChrA-ChrS and HrrA-HrrS systems is presented. In conclusion, these findings demonstrate that the ChrA-ChrS and HrrA-HrrS regulatory systems are critical for full hemoglobin-dependent activation at the
hmuO
promoter and also suggest that these two-component systems are involved in the complex mechanism of the regulation of heme homeostasis in
C. diphtheriae
.
A Genetic Screen forMycobacterium tuberculosisMutants Defective for Phagosome Maturation Arrest Identifies Components of the ESX-1 Secretion System
Authors: MacGurn Jason A. , Cox Jeffery S. 
Published: March 2007

ABSTRACTAfter phagocytosis, the intracellular pathogenMycobacterium tuberculosisarrests the progression of the nascent phagosome into a phagolysosome, allowing for replication in a compartment that resembles early endosomes. To better understand the molecular mechanisms that govern phagosome maturation arrest, we performed a visual screen on a set ofM. tuberculosismutants specifically attenuated for growth in mice to identify strains that failed to arrest phagosome maturation and trafficked to late phagosomal compartments. We identified 10 such mutants that could be partitioned into two classes based on the kinetics of trafficking. Importantly, four of these mutants harbor mutations in genes that encode components of the ESX-1 secretion system, a pathway critical forM. tuberculosisvirulence. Although ESX-1 is required, the known ESX-1 secreted proteins are dispensable for phagosome maturation arrest, suggesting that a novel effector required for phagosome maturation arrest is secreted by ESX-1. Other mutants identified in this screen had mutations in genes involved in lipid synthesis and secretion and in molybdopterin biosynthesis, as well as in genes with unknown functions. Most of these trafficking mutants exhibited a corresponding growth defect during macrophage infection, but two mutants grew like wild-typeM. tuberculosisduring macrophage infection. Our results support the emerging consensus that multiple factors fromM. tuberculosis, including the ESX-1 secretion system, are involved in modulating trafficking within the host.
A canonical FtsZ protein in Verrucomicrobium spinosum, a member of the Bacterial phylum Verrucomicrobia that also includes tubulin-producing Prosthecobacter species
Authors: Yee Benjamin , Lafi Feras F , Oakley Brian , Staley James T , Fuerst John A 
Published: March 2007

Abstract

Background
The origin and evolution of the homologous GTP-binding cytoskeletal proteins FtsZ typical of Bacteria and tubulin characteristic of eukaryotes is a major question in molecular evolutionary biology. Both FtsZ and tubulin are central to key cell biology processes – bacterial septation and cell division in the case of FtsZ and in the case of tubulins the function of microtubules necessary for mitosis and other key cytoskeleton-dependent processes in eukaryotes. The origin of tubulin in particular is of significance to models for eukaryote origins. Most members of domain Bacteria possess FtsZ, but bacteria in genus Prosthecobacter of the phylum Verrucomicrobia form a key exception, possessing tubulin homologs BtubA and BtubB. It is therefore of interest to know whether other members of phylum Verrucomicrobia possess FtsZ or tubulin as their FtsZ-tubulin gene family representative.

Results

Verrucomicrobium spinosum, a member of Phylum Verrucomicrobia of domain Bacteria, has been found to possess a gene for a protein homologous to the cytoskeletal protein FtsZ. The deduced amino acid sequence has sequence signatures and predicted secondary structure characteristic for FtsZ rather than tubulin, but phylogenetic trees and sequence analysis indicate that it is divergent from all other known FtsZ sequences in members of domain Bacteria. The FtsZ gene of V. spinosum is located within a dcw gene cluster exhibiting gene order conservation known to contribute to the divisome in other Bacteria and comparable to these clusters in other Bacteria, suggesting a similar functional role.

Conclusion

Verrucomicrobium spinosum has been found to possess a gene for a protein homologous to the cytoskeletal protein FtsZ. The results suggest the functional as well as structural homology of the V. spinosum FtsZ to the FtsZs of other Bacteria implying its involvement in cell septum formation during division. Thus, both bacteria-like FtsZ and eukaryote-like tubulin cytoskeletal homologs occur in different species of the phylum Verrucomicrobia of domain Bacteria, a result with potential major implications for understanding evolution of tubulin-like cytoskeletal proteins and the origin of eukaryote tubulins.
Genome analysis of DNA repair genes in the alpha proteobacterium Caulobacter crescentus
Authors: Martins-Pinheiro Marinalva , Marques Regina CP , Menck Carlos FM 
Published: March 2007

Abstract

Background
The integrity of DNA molecules is fundamental for maintaining life. The DNA repair proteins protect organisms against genetic damage, by removal of DNA lesions or helping to tolerate them. DNA repair genes are best known from the gamma-proteobacterium Escherichia coli, which is the most understood bacterial model. However, genome sequencing raises questions regarding uniformity and ubiquity of these DNA repair genes and pathways, reinforcing the need for identifying genes and proteins, which may respond to DNA damage in other bacteria.

Results
In this study, we employed a bioinformatic approach, to analyse and describe the open reading frames potentially related to DNA repair from the genome of the alpha-proteobacterium Caulobacter crescentus. This was performed by comparison with known DNA repair related genes found in public databases. As expected, although C. crescentus and E. coli bacteria belong to separate phylogenetic groups, many of their DNA repair genes are very similar. However, some important DNA repair genes are absent in the C. crescentus genome and other interesting functionally related gene duplications are present, which do not occur in E. coli. These include DNA ligases, exonuclease III (xthA), endonuclease III (nth), O6-methylguanine-DNA methyltransferase (ada gene), photolyase-like genes, and uracil-DNA-glycosylases. On the other hand, the genes imuA and imuB, which are involved in DNA damage induced mutagenesis, have recently been described in C. crescentus, but are absent in E. coli. Particularly interesting are the potential atypical phylogeny of one of the photolyase genes in alpha-proteobacteria, indicating an origin by horizontal transfer, and the duplication of the Ada orthologs, which have diverse structural configurations, including one that is still unique for C. crescentus.

Conclusion
The absence and the presence of certain genes are discussed and predictions are made considering the particular aspects of the C. crescentus among other known DNA repair pathways. The observed differences enlarge what is known for DNA repair in the Bacterial world, and provide a useful framework for further experimental studies in this organism.
Equity in health services use and intensity of use in Canada
Authors: Asada Yukiko , Kephart George 
Published: March 2007

Abstract
Background
The Canadian health care system has striven to remove financial or other barriers to access to medically necessary health care services since the establishment of the Canada Health Act 20 years ago. Evidence has been conflicting as to what extent the Canadian health care system has met this goal of equitable access. The objective of this study was to examine whether and where socioeconomic inequities in health care utilization occur in Canada.

Methods
We used a nationally representative cross-sectional survey, the 2000/01 Canadian Community Health Survey, which provides a large sample size (about 110,000) and permits more comprehensive adjustment for need indicators than previous studies. We separately examined general practitioner, specialist, and hospital services using two-part hurdle models: use versus non-use by logistic regression, and the intensity of use among users by zero-truncated negative binomial regression.

Results
We found that lower income was associated with less contact with general practitioners, but among those who had contact, lower income and education were associated with greater intensity of use of general practitioners. Both lower income and education were associated with less contact with specialists, but there was no statistically significant relationship between these socioeconomic variables and intensity of specialist use among the users. Neither income nor education was statistically significantly associated with use or intensity of use of hospitals.

Conclusion
Our study unveiled possible socioeconomic inequities in the use of health care services in Canada.