bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extended-Spectrum Cephalosporinases in
Pseudomonas aeruginosa
Authors: Rodríguez-Martínez José-Manuel , Poirel Laurent , Nordmann Patrice 
Published: March 2009

ABSTRACT

The characterization of AmpC-type β-lactamases was performed in a collection of 32 clinical
Pseudomonas aeruginosa
isolates with intermediate susceptibility or resistance to imipenem and ceftazidime. Twenty-one out of those 32 isolates overexpressed AmpC β-lactamase, and the MICs of ceftazidime and imipenem were reduced after cloxacillin addition. Cloning and sequencing identified 10 AmpC β-lactamase variants. Reduced susceptibility to imipenem, ceftazidime, and cefepime was observed only with recombinant
P. aeruginosa
strains expressing an AmpC β-lactamase that had an alanine residue at position 105. The catalytic efficiencies (
k
cat
/

K
m

) of the AmpC variants possessing this residue were increased against oxyiminocephalosporins and imipenem. In addition, we show here that those AmpC variants constitute a favorable background for the in vitro selection of imipenem-resistant strains. This report identified a novel resistance mechanism that may contribute to imipenem resistance in
P. aeruginosa
.
Tetracyclines Modulate Protease-Activated Receptor 2-Mediated Proinflammatory Reactions in Epidermal Keratinocytes
Authors: Ishikawa Chika , Tsuda Tatsuya , Konishi Hiroe , Nakagawa Noboru , Yamanishi Kiyofumi 
Published: March 2009

ABSTRACTIn addition to their antibiotic effects, tetracyclines have anti-inflammatory action that is often beneficial in the control of inflammatory skin disorders. In this study, we examined the effects of tetracycline (TET) and two of its derivatives, doxycycline (DOX) and minocycline (MIN), on the production of interleukin-8 (IL-8) elicited by the activation of protease-activated receptor 2 (PAR2) in normal human epidermal keratinocytes (NHEK). In NHEK, the production of IL-8 stimulated by an agonist peptide of PAR2, SLIGKIV-NH2, at 100 μM was significantly reduced by TET, DOX, or MIN at 5 and 10 μM, concentrations that are noncytotoxic. The tumor necrosis factor alpha (TNF-α)-induced production of IL-8 was synergistically augmented by SLIGKIV-NH2, and that synergistic increase in the production of IL-8 was suppressed by 100 nMPAR2-specific small interfering RNA. It was also suppressed by TET, DOX, or MIN but not by the 14-membered-ring macrolide antibiotics erythromycin, roxithromycin, and clarithromycin, which also have anti-inflammatory activities, at 10 μM. These results suggest that tetracyclines attenuate the PAR2-IL-8 axis in keratinocytes and thereby effectively modulate proinflammatory responses in the skin.
Identification and Characterization of Mefloquine Efficacy against JC Virus In Vitro
Authors: Brickelmaier Margot , Lugovskoy Alexey , Kartikeyan Ramya , Reviriego-Mendoza Marta M. , Allaire Norm , Simon Kenneth , Frisque Richard J. , Gorelik Leonid 
Published: March 2009

ABSTRACTProgressive multifocal leukoencephalopathy (PML) is a rare but frequently fatal disease caused by the uncontrolled replication of JC virus (JCV), a polyomavirus, in the brains of some immunocompromised individuals. Currently, no effective antiviral treatment for this disease has been identified. As a first step in the identification of such therapy, we screened the Spectrum collection of 2,000 approved drugs and biologically active molecules for their anti-JCV activities in an in vitro infection assay. We identified a number of different drugs and compounds that had significant anti-JCV activities at micromolar concentrations and lacked cellular toxicity. Of the compounds with anti-JCV activities, only mefloquine, an antimalarial agent, has been reported to show sufficiently high penetration into the central nervous system such that it would be predicted to achieve efficacious concentrations in the brain. Additional in vitro experiments demonstrated that mefloquine inhibits the viral infection rates of three different JCV isolates, JCV(Mad1), JCV(Mad4), and JCV(M1/SVEΔ), and does so in three different cell types, transformed human glial (SVG-A) cells, primary human fetal glial cells, and primary human astrocytes. Using quantitative PCR to quantify the number of viral copies in cultured cells, we have also shown that mefloquine inhibits viral DNA replication. Finally, we demonstrated that mefloquine does not block viral cell entry; rather, it inhibits viral replication in cells after viral entry. Although no suitable animal model of PML or JCV infection is available for the testing of mefloquine in vivo, our in vitro results, combined with biodistribution data published in the literature, suggest that mefloquine could be an effective therapy for PML.
Conditioning of Uropathogenic
Escherichia coli
for Enhanced Colonization of Host
Authors: Bower Jean M. , Gordon-Raagas Hannah B. , Mulvey Matthew A. 
Published: March 2009

ABSTRACT

While in transit within and between hosts, uropathogenic
Escherichia coli
(UPEC) encounters multiple stresses, including substantial levels of nitric oxide and reactive nitrogen intermediates. Here we show that UPEC, the primary cause of urinary tract infections, can be conditioned to grow at higher rates in the presence of acidified sodium nitrite (ASN), a model system used to generate nitrosative stress. When inoculated into the bladder of a mouse, ASN-conditioned UPEC bacteria are far more likely to establish an infection than nonconditioned bacteria. Microarray analysis of ASN-conditioned bacteria suggests that several NsrR-regulated genes and other stress- and polyamine-responsive factors may be partially responsible for this effect. Compared to K-12 reference strains, most UPEC isolates have increased resistance to ASN, and this resistance can be substantially enhanced by addition of the polyamine cadaverine. Nitrosative stress, as generated by ASN, can stimulate cadaverine synthesis by UPEC, and growth of UPEC in cadaverine-supplemented broth in the absence of ASN can also promote UPEC colonization of the bladder. These results suggest that UPEC interactions with polyamines or stresses such as reactive nitrogen intermediates can in effect reprogram the bacteria, enabling them to better colonize the host.
Listeria monocytogenesσBModulates PrfA-Mediated Virulence Factor Expression
Authors: Ollinger Juliane , Bowen Barbara , Wiedmann Martin , Boor Kathryn J. , Bergholz Teresa M. 
Published: March 2009

ABSTRACTListeria monocytogenesσBand positive regulatory factor A (PrfA) are pleiotropic transcriptional regulators that coregulate a subset of virulence genes. A positive regulatory role for σBinprfAtranscription has been well established; therefore, observations of increased virulence gene expression and hemolytic activity in a ΔsigBstrain initially appeared paradoxical. To test the hypothesis thatL. monocytogenesσBcontributes to a regulatory network critical for appropriate repression as well as induction of virulence gene expression, genome-wide transcript profiling and follow-up quantitative reverse transcriptase PCR (qRT-PCR), reporter fusion, and phenotypic experiments were conducted usingL. monocytogenes prfA*,prfA* ΔsigB, ΔprfA, and ΔprfAΔsigBstrains. Genome-wide transcript profiling and qRT-PCR showed that in the presence of active PrfA (PrfA*), σBis responsible for reduced expression of the PrfA regulon. σB-dependent modulation of PrfA regulon expression reduced the cytotoxic effects of a PrfA* strain in HepG2 cells, highlighting the functional importance of regulatory interactions between PrfA and σB. The emerging model of the role of σBin regulating overall PrfA activity includes a switch from transcriptional activation at the P2prfApromoter (e.g., in extracellular bacteria when PrfA activity is low) to posttranscriptional downregulation of PrfA regulon expression (e.g., in intracellular bacteria when PrfA activity is high).
Staphylococcus aureusSuperantigens Elicit Redundant and Extensive Human Vβ Patterns
Authors: Thomas Damien , Dauwalder Olivier , Brun Virginie , Badiou Cedric , Ferry Tristan , Etienne Jerome , Vandenesch François , Lina Gerard 
Published: March 2009

ABSTRACTStaphylococcus aureuscan produce a wide variety of exotoxins, including toxic shock syndrome toxin 1 (TSST-1), staphylococcal enterotoxins, and staphylococcal enterotoxin-like toxins. These toxins share superantigenic activity. To investigate the β chain (Vβ) specificities of each of these toxins, TSST-1 and all knownS. aureusenterotoxins and enterotoxin-like toxins were produced as recombinant proteins and tested for their ability to induce the selective in vitro expansion of human T cells bearing particular Vβ T-cell receptors (TCR). Although redundancies were observed between the toxins and the Vβ populations, each toxin induced the expansion of distinct Vβ subsets, including enterotoxin H and enterotoxin-like toxin J. Surprisingly, the Vβ signatures were not associated with a specific phylogenic group of toxins. Interestingly, each human Vβ analyzed in this study was stimulated by at least one staphylococcal superantigen, suggesting that the bacterium derives a selective advantage from targeting the entire human TCR Vβ panel.
Protection against Pneumococcal Colonization and Fatal Pneumonia by a Trivalent Conjugate of a Fusion Protein with the Cell Wall Polysaccharide
Authors: Lu Ying-Jie , Forte Sophie , Thompson Claudette M. , Anderson Porter W. , Malley Richard 
Published: March 2009

ABSTRACT

Cell wall polysaccharide (CWPS), pneumolysin, and surface adhesin A (PsaA) are antigens common to virtually all serotypes of
Streptococcus pneumoniae
(pneumococcus), and all have been studied separately for use in protection. Previously we showed that protection against nasopharyngeal (NP) colonization by intranasal vaccination of mice with killed pneumococci is mediated by T
H
17 cells and correlates with interleukin-17A (IL-17A) expression by T cells in vitro; we have also shown that CWPS and other species-common antigens protect against colonization by a similar mechanism. Here we made a fusion protein of PsaA with the pneumolysin nontoxic derivative PdT and then coupled CWPS to the fusion protein, aiming to enhance immune responses to all three antigens. When given intranasally with cholera toxin adjuvant, the fusion conjugate induced higher serum antibody titers and greater priming for IL-17A responses than an equimolar mixture of the three antigens. The conjugate administered intranasally protected mice against experimental NP colonization by a strain of serotype 6B, while mice immunized with the mixture or with bivalent conjugates were not protected. Subcutaneous immunization with the conjugate and alum adjuvant likewise induced higher antibody titers than the mixture, primed for IL-17A responses, and reduced colonization. The conjugate, but not the antigen mixture, fully protected mice from fatal pneumonia caused by a highly virulent serotype 3 strain. Thus, a covalent construct of three antigens common to all serotypes exhibits protection with both mucosal and systemic administration.
How the Microbial World Saved Evolution from the Scylla of Molecular Biology and the Charybdis of the Modern Synthesis
Authors: Woese Carl R. , Goldenfeld Nigel 
Published: March 2009

SUMMARY
In this commentary, we provide a personal overview of the conceptual history of microbiology and molecular biology over the course of the last hundred years, emphasizing the relationship of these fields to the problem of evolution. We argue that despite their apparent success, all three reached an impasse that arose from the influence of dogmatic or overly narrow perspectives. Finally, we describe how recent developments in microbiology are realizing Beijerinck's vision of a field that is fully integrated with molecular biology, microbial ecology, thereby challenging and extending current thinking in evolution.
A Gripping Tale of Ribosomal Frameshifting: Extragenic Suppressors of Frameshift Mutations Spotlight P-Site Realignment
Authors: Atkins John F. , Björk Glenn R. 
Published: March 2009

SUMMARY
Mutants of translation components which compensate for both −1 and +1 frameshift mutations showed the first evidence for framing malleability. Those compensatory mutants isolated in bacteria and yeast with altered tRNA or protein factors are reviewed here and are considered to primarily cause altered P-site realignment and not altered translocation. Though the first sequenced tRNA mutant which suppressed a +1 frameshift mutation had an extra base in its anticodon loop and led to a textbook “yardstick” model in which the number of anticodon bases determines codon size, this model has long been discounted, although not by all. Accordingly, the reviewed data suggest that reading frame maintenance and translocation are two distinct features of the ribosome. None of the −1 tRNA suppressors have anticodon loops with fewer than the standard seven nucleotides. Many of the tRNA mutants potentially affect tRNA bending and/or stability and can be used for functional assays, and one has the conserved C74 of the 3′ CCA substituted. The effect of tRNA modification deficiencies on framing has been particularly informative. The properties of some mutants suggest the use of alternative tRNA anticodon loop stack conformations by individual tRNAs in one translation cycle. The mutant proteins range from defective release factors with delayed decoding of A-site stop codons facilitating P-site frameshifting to altered EF-Tu/EF1α to mutant ribosomal large- and small-subunit proteins L9 and S9. Their study is revealing how mRNA slippage is restrained except where it is programmed to occur and be utilized.
Pivotal Roles of the Outer Membrane Polysaccharide Export and Polysaccharide Copolymerase Protein Families in Export of Extracellular Polysaccharides in Gram-Negative Bacteria
Authors: Cuthbertson Leslie , Mainprize Iain L. , Naismith James H. , Whitfield Chris 
Published: March 2009

SUMMARY
Many bacteria export extracellular polysaccharides (EPS) and capsular polysaccharides (CPS). These polymers exhibit remarkably diverse structures and play important roles in the biology of free-living, commensal, and pathogenic bacteria. EPS and CPS production represents a major challenge because these high-molecular-weight hydrophilic polymers must be assembled and exported in a process spanning the envelope, without compromising the essential barrier properties of the envelope. Emerging evidence points to the existence of molecular scaffolds that perform these critical polymer-trafficking functions. Two major pathways with different polymer biosynthesis strategies are involved in the assembly of most EPS/CPS: the Wzy-dependent and ATP-binding cassette (ABC) transporter-dependent pathways. They converge in an outer membrane export step mediated by a member of the outer membrane auxiliary (OMA) protein family. OMA proteins form outer membrane efflux channels for the polymers, and here we propose the revised name outer membrane polysaccharide export (OPX) proteins. Proteins in the polysaccharide copolymerase (PCP) family have been implicated in several aspects of polymer biogenesis, but there is unequivocal evidence for some systems that PCP and OPX proteins interact to form a trans-envelope scaffold for polymer export. Understanding of the precise functions of the OPX and PCP proteins has been advanced by recent findings from biochemistry and structural biology approaches and by parallel studies of other macromolecular trafficking events. Phylogenetic analyses reported here also contribute important new insight into the distribution, structural relationships, and function of the OPX and PCP proteins. This review is intended as an update on progress in this important area of microbial cell biology.
Biochemical Features and Functional Implications of the RNA-Based T-Box Regulatory Mechanism
Authors: Gutiérrez-Preciado Ana , Henkin Tina M. , Grundy Frank J. , Yanofsky Charles , Merino Enrique 
Published: March 2009

SUMMARY
The T-box mechanism is a common regulatory strategy used for modulating the expression of genes of amino acid metabolism-related operons in gram-positive bacteria, especially members of the Firmicutes. T-box regulation is usually based on a transcription attenuation mechanism in which an interaction between a specific uncharged tRNA and the 5′ region of the transcript stabilizes an antiterminator structure in preference to a terminator structure, thereby preventing transcription termination. Although single T-box regulatory elements are common, double or triple T-box arrangements are also observed, expanding the regulatory range of these elements. In the present study, we predict the functional implications of T-box regulation in genes encoding aminoacyl-tRNA synthetases, proteins of amino acid biosynthetic pathways, transporters, and regulatory proteins. We also consider the global impact of the use of this regulatory mechanism on cell physiology. Novel biochemical relationships between regulated genes and their corresponding metabolic pathways were revealed. Some of the genes identified, such as the quorum-sensing gene luxS, in members of the Lactobacillaceae were not previously predicted to be regulated by the T-box mechanism. Our analyses also predict an imbalance in tRNA sensing during the regulation of operons containing multiple aminoacyl-tRNA synthetase genes or biosynthetic genes involved in pathways common to more than one amino acid. Based on the distribution of T-box regulatory elements, we propose that this regulatory mechanism originated in a common ancestor of members of the Firmicutes, Chloroflexi, Deinococcus-Thermus group, and Actinobacteria and was transferred into the Deltaproteobacteria by horizontal gene transfer.
Environmental Proteomics: a Paradigm Shift in Characterizing Microbial Activities at the Molecular Level
Authors: Keller Martin , Hettich Robert 
Published: March 2009

SUMMARY
The increase in sequencing capacity led to a new wave of metagenomic projects, enabling and setting the prerequisite for the application of environmental proteomics technologies. This review describes the current status of environmental proteomics. It describes sample preparation as well as the two major technologies applied within this field: two-dimensional electrophoresis-based environmental proteomics and liquid chromatography-mass spectrometry-based environmental proteomics. It also highlights current publications and describes major scientific findings. The review closes with a discussion of critical improvements in the area of integrating experimental mass spectrometry technologies with bioinformatics as well as improved sample handling.
Eukaryotic Translesion Polymerases and Their Roles and Regulation in DNA Damage Tolerance
Authors: Waters Lauren S. , Minesinger Brenda K. , Wiltrout Mary Ellen , D'Souza Sanjay , Woodruff Rachel V. , Walker Graham C. 
Published: March 2009

SUMMARYDNA repair and DNA damage tolerance machineries are crucial to overcome the vast array of DNA damage that a cell encounters during its lifetime. In this review, we summarize the current state of knowledge about the eukaryotic DNA damage tolerance pathway translesion synthesis (TLS), a process in which specialized DNA polymerases replicate across from DNA lesions. TLS aids in resistance to DNA damage, presumably by restarting stalled replication forks or filling in gaps that remain in the genome due to the presence of DNA lesions. One consequence of this process is the potential risk of introducing mutations. Given the role of these translesion polymerases in mutagenesis, we discuss the significant regulatory mechanisms that control the five known eukaryotic translesion polymerases: Rev1, Pol ζ, Pol κ, Pol η, and Pol ι.
Incidence rates of surgically treated idiopathic carpal tunnel syndrome in blue- and white-collar workers and housewives in Tuscany, Italy
Authors: Mattioli S , Baldasseroni A , Curti S , Cooke R M T , Mandes A , Zanardi F , Farioli A , Buiatti E , Campo G , Violante F S 
Published: March 2009

Objectives:Rates of surgically treated carpal tunnel syndrome (CTS) among blue- and white-collar workers and housewives in the general population were compared.Methods:Surgically treated cases of idiopathic CTS were investigated among 25–59-year-old residents of Tuscany, Italy, during 1997–2000, based on obligatory discharge records from all Italian public/private hospitals, archived according to residence on Tuscany’s regional database. Population data were extracted from the 2001 census.Results:After excluding repeat admissions, 8801 eligible cases were identified. Age-standardised rates (per 100 000 person-years) of surgical CTS were: “blue-collar women”, 367.8; “white-collar women”, 88.1; “housewives”, 334.5; “blue-collar men”, 73.5; and “white-collar men”, 15.3. Compared with reference categories (same-sex white-collar workers): female blue-collar workers experienced a 4.2-fold higher standardised rate; housewives, a 3.8-fold excess; and male blue-collar workers, a 4.8-fold excess (all p<0.001). Male and female blue-collar workers showed approximately three to sevenfold higher age-specific rates compared to their white-collar counterparts (all p<0.001). Housewives’ rates were similar to those of blue-collar female workers up to 40–44 years of age, after which they were significantly lower (p<0.002). At all ages, housewives’ rates were much higher (p<0.001) than those of white-collar women.Conclusions:Surgically treated CTS was three to seven times more common (depending on age/gender) in blue-collar than in white-collar workers, which is difficult to explain by differences in body weight or other individual factors. Thus, occupational risk factors seem relevant throughout working life. The high rates for full-time housewives suggest that domestic chores should be investigated as a possible risk factor for CTS.
Mortality among British asbestos workers undergoing regular medical examinations (1971–2005)
Authors: Harding A-H , Darnton A , Wegerdt J , McElvenny D 
Published: March 2009

Objectives:The Great Britain Asbestos Survey was established to monitor mortality among workers covered by regulations to control occupational exposure to asbestos. This study updates the estimated burden of asbestos-related mortality in the cohort, and identifies risk factors associated with mortality.Methods:From 1971, workers were recruited during initially voluntary and later statutory medical examinations. A brief questionnaire was completed during the medical, and participants were flagged for death registrations. Standardised mortality ratios (SMRs) and proportional mortality ratios (PMRs) were calculated for deaths occurring before 2006. Poisson regression analyses were undertaken for diseases with significant excess mortality.Results:There were 15 496 deaths among 98 117 workers followed-up for 1 779 580 person-years. The SMR for all cause mortality was 141 (95% CI 139 to 143) and for all malignant neoplasms 163 (95% CI 159 to 167). The SMRs for cancers of the stomach (166), lung (187), peritoneum (3730) and pleura (968), mesothelioma (513), cerebrovascular disease (164) and asbestosis (5594) were statistically significantly elevated, as were the corresponding PMRs. In age and sex adjusted analysis, birth cohort, age at first exposure, year of first exposure, duration of exposure, latency and job type were associated with the relative risk of lung, pleural and peritoneal cancers, asbestosis and mesothelioma mortality.Conclusions:Known associations between asbestos exposure and mortality from lung, peritoneal and pleural cancers, mesothelioma and asbestosis were confirmed, and evidence of associations with stroke and stomach cancer mortality was observed. Limited evidence suggested that asbestos-related disease risk may be lower among those first exposed in more recent times.