bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mycobacterium tuberculosis Arylamine
N
-Acetyltransferase Acetylates and Thus Inactivates
para
-Aminosalicylic Acid
Authors: Wang Xude , Yang Shanshan , Gu Jing , Deng Jiaoyu 
Published: September 2016

ABSTRACT

Mycobacterium tuberculosis
arylamine
N
-acetyltransferase (TBNAT) is able to acetylate
para
-aminosalicylic acid (PAS) both
in vitro
and
in vivo
as determined by high-performance liquid chromatography (HPLC) and electrospray ionization-mass spectrometry (ESI-MS) techniques. The antituberculosis activity of the acetylated PAS is significantly reduced. As a result, overexpression of TBNAT in
M. tuberculosis
results in PAS resistance, as determined by MIC tests and drug exposure experiments. Taken together, our results suggest that TBNAT from
M. tuberculosis
is able to inactivate PAS by acetylating the compound.
Population Pharmacokinetics and Pharmacodynamics Modeling To Optimize Dosage Regimens of Sulbactam in Critically Ill Patients with Severe Sepsis Caused by Acinetobacter baumannii
Authors: Jaruratanasirikul Sutep , Wongpoowarak Wibul , Wattanavijitkul Thitima , Sukarnjanaset Waroonrat , Samaeng Maseetoh , Nawakitrangsan Monchana , Ingviya Natnicha 
Published: September 2016

ABSTRACT

Sulbactam is being considered as an alternative concomitant medication with other effective antibiotics for the treatment of multidrug-resistant (MDR)
Acinetobacter baumannii
infections. Pathophysiological changes in critically ill patients with severe sepsis, resulting in altered pharmacokinetic (PK) patterns for antibiotics, are important factors in determining therapeutic success. The aims of this study were (i) to examine the population PK parameters and (ii) to assess the probability of target attainment (PTA) for sulbactam in patients with severe sepsis caused by
A. baumannii
. PK studies were carried out following administration of 2 g of sulbactam every 12 h on the 4th day of drug administration in 27 patients, and a Monte Carlo simulation was performed to determine the PTA of achieving 40% exposure time during which the plasma drug concentration remained above the MIC (
T
>MIC
) and 60%
T
>MIC
. The central and peripheral volumes of distribution were 14.56 and 9.55 liters, respectively, and total clearances of sulbactam were 2.26 liters/h and 7.64 liters/h in patients aged >65 years and ≤65 years, respectively. The high PTAs (≥90%) for targets of 40%
T
>
MIC
and 60%
T
>
MIC
with a MIC of 4 μg/ml were observed when sulbactam was administered by a 4-h infusion of 1 g every 12 h and 1 g every 8 h, respectively. Sulbactam would be an alternative antibiotic option to coadminister with colistin for the treatment of infections caused by MDR
A. baumannii
. However, for pathogens with MICs of >4 μg/ml, higher dosage regimens of sulbactam are required.
The Bacterial Second Messenger Cyclic di-GMP Regulates Brucella Pathogenesis and Leads to Altered Host Immune Response
Authors: Khan Mike , Harms Jerome S. , Marim Fernanda M. , Armon Leah , Hall Cherisse L. , Liu Yi-Ping , Banai Menachem , Oliveira Sergio C. , Splitter Gary A. , Smith Judith A. 
Published: September 2016

ABSTRACT

Brucella
species are facultative intracellular bacteria that cause brucellosis, a chronic debilitating disease significantly impacting global health and prosperity. Much remains to be learned about how
Brucella
spp. succeed in sabotaging immune host cells and how
Brucella
spp. respond to environmental challenges. Multiple types of bacteria employ the prokaryotic second messenger cyclic di-GMP (c-di-GMP) to coordinate responses to shifting environments. To determine the role of c-di-GMP in
Brucella
physiology and in shaping host-
Brucella
interactions, we utilized c-di-GMP regulatory enzyme deletion mutants. Our results show that a Δ
bpdA
phosphodiesterase mutant producing excess c-di-GMP displays marked attenuation
in vitro
and
in vivo
during later infections. Although c-di-GMP is known to stimulate the innate sensor STING, surprisingly, the Δ
bpdA
mutant induced a weaker host immune response than did wild-type
Brucella
or the low-c-di-GMP guanylate cyclase Δ
cgsB
mutant. Proteomics analysis revealed that c-di-GMP regulates several processes critical for virulence, including cell wall and biofilm formation, nutrient acquisition, and the type IV secretion system. Finally, Δ
bpdA
mutants exhibited altered morphology and were hypersensitive to nutrient-limiting conditions. In summary, our results indicate a vital role for c-di-GMP in allowing
Brucella
to successfully navigate stressful and shifting environments to establish intracellular infection.
Impact of Moderate Temperature Changes on Neisseria meningitidis Adhesion Phenotypes and Proteome
Authors: Lappann Martin , Otto Andreas , Brauer Madita , Becher Dörte , Vogel Ulrich , Johswich Kay 
Published: September 2016

ABSTRACT

Neisseria meningitidis
, the meningococcus, bears the potential to cause life-threatening invasive diseases, but it usually colonizes the nasopharynx without causing any symptoms. Within the nasopharynx,
Neisseria meningitidis
must face temperature changes depending on the ambient air temperature. Indeed, the nasopharyngeal temperature can be substantially lower than 37°C, the temperature commonly used in experimental settings. Here, we compared the levels of meningococcal biofilm formation, autoaggregation, and cellular adherence at 32°C and 37°C and found a clear increase in all these phenotypes at 32°C suggestive of a stronger
in vivo
colonization capability at this temperature. A comparative proteome analysis approach revealed differential protein expression levels between 32°C and 37°C, predominantly affecting the bacterial envelope. A total of 375 proteins were detected. Use of database annotation or the PSORTb algorithm predicted 49 of those proteins to be localized in the outer membrane, 21 in either the inner or outer membrane, 35 in the periplasm, 56 in the inner membrane, and 208 in the cytosol; for 6 proteins, no annotation or prediction was available. Temperature-dependent regulation of protein expression was seen particularly in the periplasm as well as in the outer and inner membranes.
N
eisserial
h
eparin
b
inding
a
ntigen (NHBA), NMB1030, and adhesin complex protein (ACP) showed the strongest upregulation at 32°C and were partially responsible for the observed temperature-dependent phenotypes. Screening of different global regulators of
Neisseria meningitidis
suggested that the extracytoplasmic sigma factor σ
E
might be involved in temperature-dependent biofilm formation. In conclusion, subtle temperature changes trigger adaptation events promoting mucosal colonization by meningococci.
Treatment with Cestode Parasite Antigens Results in Recruitment of CCR2
+
Myeloid Cells, the Adoptive Transfer of Which Ameliorates Colitis
Authors: Reyes José L. , Lopes Fernando , Leung Gabriella , Mancini Nicole L. , Matisz Chelsea E. , Wang Arthur , Thomson Emma A. , Graves Nicholas , Gilleard John , McKay Derek M. 
Published: September 2016

ABSTRACT

Awareness of the immunological underpinnings of host-parasite interactions may reveal immune signaling pathways that could be used to treat inflammatory disease in humans. Previously we showed that infection with the rat tapeworm,
Hymenolepis diminuta
, used as a model helminth, or systemic delivery of worm antigen (HdAg) significantly reduced the severity of dinitrobenzene sulfonic acid (DNBS)-induced colitis in mice. Extending these analyses, intraperitoneal injection of HdAg dose-dependently suppressed dextran sodium sulfate (DSS)-induced colitis, and this was paralleled by reduced gamma interferon (IFN-γ), interleukin-17 (IL-17), and tumor necrosis factor alpha (TNF-α) production and increased IL-10 production from mitogen-activated splenocytes. Treatment with HdAg resulted in a CCR2-dependent recruitment of CDllb
+
F4/80
+
Ly6C
hi
Gr-1
lo
monocyte-like cells into the peritoneum 24 h later that were predominantly programmed death ligand 1 (PD-L1) positive and CXCR2 negative.
In vitro
assays indicated that these cells were unable to suppress T cell proliferation but enhanced IL-10 and IL-4 production from activated T cells. Adoptive transfer of the HdAg-recruited monocytic cells into naive mice blocked DSS-induced colitis. These findings add to the variety of means by which treatment with parasitic helminth-derived antigens can ameliorate concomitant disease. A precise understanding of the mechanism(s) of action of HdAg and other helminth-derived antigens (and a parallel consideration of putative side effects) may lead to the development of novel therapies for human idiopathic disorders such as inflammatory bowel disease.
Uptake and Metabolism of Antibiotics Roseoflavin and 8-Demethyl-8-Aminoriboflavin in Riboflavin-Auxotrophic Listeria monocytogenes
Authors: Matern Andreas , Pedrolli Danielle , Großhennig Stephanie , Johansson Jörgen , Mack Matthias 
Published: September 2016

ABSTRACT

The riboflavin analogs roseoflavin (RoF) and 8-demethyl-8-aminoriboflavin (AF) are produced by the bacteria
Streptomyces davawensis
and
Streptomyces cinnabarinus
. Riboflavin analogs have the potential to be used as broad-spectrum antibiotics, and we therefore studied the metabolism of riboflavin (vitamin B
2
), RoF, and AF in the human pathogen
Listeria monocytogenes
, a bacterium which is a riboflavin auxotroph. We show that the
L. monocytogenes
protein Lmo1945 is responsible for the uptake of riboflavin, RoF, and AF. Following import, these flavins are phosphorylated/adenylylated by the bifunctional flavokinase/flavin adenine dinucleotide (FAD) synthetase Lmo1329 and adenylylated by the unique FAD synthetase Lmo0728, the first monofunctional FAD synthetase to be described in bacteria. Lmo1329 generates the cofactors flavin mononucleotide (FMN) and FAD, whereas Lmo0728 produces FAD only. The combined activities of Lmo1329 and Lmo0728 are responsible for the intracellular formation of the toxic cofactor analogs roseoflavin mononucleotide (RoFMN), roseoflavin adenine dinucleotide (RoFAD), 8-demethyl-8-aminoriboflavin mononucleotide (AFMN), and 8-demethyl-8-aminoriboflavin adenine dinucleotide (AFAD).
In vivo
reporter gene assays and
in vitro
transcription/translation experiments show that the
L. monocytogenes
FMN riboswitch Rli96, which controls expression of the riboflavin transport gene
lmo1945
, is negatively affected by riboflavin/FMN and RoF/RoFMN but not by AF/AFMN. Treatment of
L. monocytogenes
with RoF or AF leads to drastically reduced FMN/FAD levels. We suggest that the reduced flavin cofactor levels in combination with concomitant synthesis of inactive cofactor analogs (RoFMN, RoFAD, AFMN, and AFAD) explain why RoF and AF contribute to antibiotic activity in
L. monocytogenes
.

IMPORTANCE
The riboflavin analogs roseoflavin (RoF) and 8-demethyl-8-aminoriboflavin (AF) are small molecules which are produced by
Streptomyces davawensis
and
Streptomyces cinnabarinus
. RoF and AF were reported to have antibacterial activity, and we studied how these compounds are metabolized by the human bacterial pathogen
Listeria monocytogenes
. We found that the
L. monocytogenes
protein Lmo1945 mediates uptake of AF and RoF and that the combined activities of the enzymes Lmo1329 and Lmo0728 are responsible for the conversion of AF and RoF to toxic cofactor analogs. Comparative studies with RoF and AF (a weaker antibiotic) suggest that the reduction in FMN/FAD levels and the formation of inactive FMN/FAD analogs explain to a large extent the antibiotic activity of AF and RoF.
Implementation and Data Analysis of Tn-seq, Whole-Genome Resequencing, and Single-Molecule Real-Time Sequencing for Bacterial Genetics
Authors: Burby Peter E. , Nye Taylor M. , Schroeder Jeremy W. , Simmons Lyle A. 
Published: September 2016

ABSTRACTFew discoveries have been more transformative to the biological sciences than the development of DNA sequencing technologies. The rapid advancement of sequencing and bioinformatics tools has revolutionized bacterial genetics, deepening our understanding of model and clinically relevant organisms. Although application of newer sequencing technologies to studies in bacterial genetics is increasing, the implementation of DNA sequencing technologies and development of the bioinformatics tools required for analyzing the large data sets generated remain a challenge for many. In this minireview, we have chosen to summarize three sequencing approaches that are particularly useful for bacterial genetics. We provide resources for scientists new to and interested in their application. Here, we discuss the analysis of data from transposon mutagenesis followed by deep sequencing (Tn-seq) to determine gene disruptions differentially represented in a mutant population and Illumina sequencing for identification of suppressor or other mutations, and we summarize single-molecule real-time (SMRT) sequencing forde novogenome assembly and the use of the output data for detection of DNA base modifications.
A Personal View of How Paleomicrobiology Aids Our Understanding of the Role of Lice in Plague Pandemics
Authors: Raoult Didier 
Published: September 2016

ABSTRACT

We have been involved in the field of paleomicrobiology since 1998, when we used dental pulp to identify
Yersinia pestis
as the causative agent of the great plague of Marseille (1720). We recently designed a specific technique, “suicide PCR,” that can prevent contamination. A controversy arose between two teams, with one claiming that DNA must be altered to amplify it and the other group claiming that demographic data did not support the role of
Y. pestis
in the Black Death (i.e., the great plague of the Middle Ages). These controversies led us to evaluate other epidemiological models and to propose the body louse as the vector of this pandemic. This proposal was substantiated by experimental models, the recovery of
Y. pestis
from lice in the Congo, and the identification of epidemics involving both
Y. pestis
and
Bartonella quintana
(the agent of trench fever, transmitted by the body louse) in ancient corpses from mass graves. Paleomicrobiology has led to a re-evaluation of plague pandemics.
The History of Epidemic Typhus
Authors: Angelakis Emmanouil , Bechah Yassina , Raoult Didier 
Published: September 2016

ABSTRACT

Epidemic typhus caused by
Rickettsia prowazekii
is one of the oldest pestilential diseases of humankind. The disease is transmitted to human beings by the body louse
Pediculus humanus corporis
and is still considered a major threat by public health authorities, despite the efficacy of antibiotics, because poor sanitary conditions are conducive to louse proliferation. Epidemic typhus has accompanied disasters that impact humanity and has arguably determined the outcome of more wars than have soldiers and generals. The detection, identification, and characterization of microorganisms in ancient remains by paleomicrobiology has permitted the diagnosis of past epidemic typhus outbreaks through the detection of
R. prowazekii
. Various techniques, including microscopy and immunodetection, can be used in paleomicrobiology, but most of the data have been obtained by using PCR-based molecular techniques on dental pulp samples. Paleomicrobiology enabled the identification of the first outbreak of epidemic typhus in the 18th century in the context of a pan-European great war in the city of Douai, France, and supported the hypothesis that typhus was imported into Europe by Spanish soldiers returning from America.
R. prowazekii
was also detected in the remains of soldiers of Napoleon’s Grand Army in Vilnius, Lithuania, which indicates that Napoleon’s soldiers had epidemic typhus. The purpose of this article is to underscore the modern comprehension of clinical epidemic typhus, focus on the historical relationships of the disease, and examine the use of paleomicrobiology in the detection of past epidemic typhus outbreaks.
Past Intestinal Parasites
Authors: Le Bailly Matthieu , Araújo† Adauto 
Published: September 2016

ABSTRACTThis chapter aims to provide some key points for researchers interested in the study of ancient gastrointestinal parasites. These few pages are dedicated to my colleague and friend, Prof. Adauto Araújo (1951-2015), who participated in the writing of this chapter. His huge efforts in paleoparasitology contributed to the development and promotion of the discipline during more than 30 years.
Demographic Patterns Distinctive of Epidemic Cemeteries in Archaeological Samples
Authors: Castex Dominique , Kacki Sacha 
Published: September 2016

ABSTRACTThe analysis of biological parameters such as age and sex is particularly relevant to the interpretation of ancient skeletal assemblages related to abrupt mortality crises, and more particularly epidemics. In such a context, the mechanisms of selection within a population or part of a population differ according to the pathogen involved. They may also vary depending on the period and location in which the population lived. Here, we illustrate the specificity of plague mortality through the study of several European burial sites contemporary with the first and second plague pandemics. The paleodemographic patterns obtained for different plague outbreaks from the 6th to the 16th centuries reveal some constant features over time and space as well as some differences that suggest a possible evolution in the epidemiological characteristics of the disease.
Paleomicrobiology Data: Authentification and Interpretation
Authors: Drancourt Michel 
Published: September 2016

ABSTRACT
The authenticity of some of the very first works in the field of paleopathology has been questioned, and standards have been progressively established for the experiments and the interpretation of data. Whereas most problems initially arose from the contamination of ancient specimens with modern human DNA, the situation is different in the field of paleomicrobiology, in which the risk for contamination is well-known and adequately managed by any laboratory team with expertise in the routine diagnosis of modern-day infections. Indeed, the exploration of ancient microbiota and pathogens is best done by such laboratory teams, with research directed toward the discovery and implementation of new techniques and the interpretation of data.
Cardiorespiratory fitness cut points to avoid cardiovascular disease risk in children and adolescents; what level of fitness should raise a red flag? A systematic review and meta-analysis
Authors: Ruiz Jonatan R , Cavero-Redondo Ivan , Ortega Francisco B , Welk Gregory J , Andersen Lars B , Martinez-Vizcaino Vicente 
Published: September 2016

BackgroundPoor cardiorespiratory fitness is associated with cardiovascular disease risk factors.AimTo perform a systematic review and meta-analysis of the relationship between poor cardiorespiratory fitness and cardiovascular disease risk in children and adolescents.MethodsSystematic literature search (1980 to 11 April 2015) for studies that determined a cardiorespiratory fitness cut point that predicted cardiovascular disease risk in children and adolescents.ResultsWe identified 7 studies that included 9280 children and adolescents (49% girls) aged 8–19 years from 14 countries. Cardiovascular disease risk was already present in boys (6–39%) and girls (6–86%). Boys with low fitness (<41.8 mL/kg/min) had a 5.7 times greater likelihood of having cardiovascular disease risk (95% CI 4.8 to 6.7). The comparable diagnostic OR for girls with low fitness (<34.6 mL/kg/min) was 3.6 (95% CI 3.0 to 4.3). The 95% confidence region of cardiorespiratory fitness associated with low cardiovascular disease risk ranges, 41.8–47.0 mL/kg/min in boys (eg, stages 6–8 for a boy aged 15 years) and 34.6–39.5 mL/kg/min in girls (eg, stages 3–5 for a girl aged 15 years). The cardiorespiratory fitness cut point to avoid cardiovascular disease risk ranged 41.8 mL/kg/min in boys and was 34.6 mL/kg/min in girls.SummaryFitness levels below 42 and 35 mL/kg/min for boys and girls, respectively, should raise a red flag. These translate to 6 and 3 stages on the shuttle run test for a boy and a girl, both aged 15 years, respectively. These cut points identify children and adolescents who may benefit from primary and secondary cardiovascular prevention programming.
Burden assessment of podoconiosis in Wayu Tuka woreda, east Wollega zone, western Ethiopia: a community-based cross-sectional study
Authors: Bekele Kenate , Deribe Kebede , Amberbir Tsige , Tadele Geleta , Davey Gail , Samuel Abdi 
Published: September 2016

ObjectivePodoconiosis is a neglected tropical disease characterised by a slowly progressive swelling of the foot and lower leg. It is prevalent among subsistence barefoot farmers who live and work in highland areas of the tropics. This study was conducted in Wayu Tuka ‘woreda’ (district), western Ethiopia to determine the prevalence of podoconiosis and assess factors associated with acute adenolymphangitis (ALA) episodes.Methods and analysisA two phase, community-based cross-sectional study was conducted between January and March 2015. First, all households in the district were surveyed to determine the prevalence of podoconiosis. This was followed by a second phase in which 366 people with podoconiosis from four randomly selected ‘kebeles’ (subdistricts) were assessed for clinical features of the disease, shoe-wearing habits, personal hygiene, social stigma and functional impairment. Data entered into Epi DATA were then exported to SPSS. Logistic regression analysis was conducted to identify factors associated with ALA.ResultsPrevalence of podoconiosis in the population was 3.05% (1197/39 256) (95% CI 2.9% to 3.2%). The prevalence was significantly higher among women than men (3.67% vs 2.4%). Most (92.2%) people with podoconiosis were in the economically active age group (15–64 years) in the first phase survey. Of participants in the second phase of the study, 43% had stage 2 disease and 38.1% had ‘moss’-like skin changes. On average, people with podoconiosis had 23.3 episodes of ALA/year and each person with podoconiosis lost 149.5 days of activity/year. Never walking barefoot and daily foot washing were both associated with decreased odds of ALA (AOR=0.23; 95% CI 0.06 to 0.80 and 0.09; 95% CI 0.01 to 0.75, respectively).ConclusionsA relatively high prevalence of podoconiosis, frequent ALA episodes and considerable decreases in daily activities were identified in this district. Footwear use and daily foot hygiene were associated with decreased odds of ALA. We recommend prevention and morbidity management interventions to address this developmental challenge.