bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inactivation of Plasmepsins 2 and 3 Sensitizes Plasmodium falciparum to the Antimalarial Drug Piperaquine
Authors: Mukherjee Angana , Gagnon Dominic , Wirth Dyann F. , Richard Dave 
Published: February 2018

ABSTRACT

Dihydroartemisinin-piperaquine (DHA-PPQ), the current frontline artemisinin combination therapy used to treat
Plasmodium falciparum
malaria in multiple Southeast Asian countries, is now increasingly failing in Cambodia, where artemisinin resistance is nearly fixed, which suggests that PPQ resistance has emerged and is spreading rapidly in the Greater Mekong Subregion. Recent reports have shown that amplification of the genes encoding plasmepsins 2 and 3 is a molecular marker of PPQ resistance; however, whether these enzymes play a role in the mechanism of resistance is currently unknown. We show here that inactivating the genes encoding plasmepsin 2 or 3 individually in
P. falciparum
reference strain 3D7 results in hypersusceptibility to PPQ. Interestingly, no significant differences in the susceptibility to other antimalarials were observed, which suggests specific roles of plasmepsins 2 and 3 in PPQ susceptibility. The piperaquine hyper-sensitivity of the plasmepsin-2-and-3-inactivated lines provides direct evidence that these enzymes modulate parasite susceptibility to PPQ in the context of a single copy of
PfMDR1
and independent of Kelch13 mutations conferring artemisinin resistance.
Metagenomics Reveals the Impact of Wastewater Treatment Plants on the Dispersal of Microorganisms and Genes in Aquatic Sediments
Authors: Chu Binh T. T. , Petrovich Morgan L. , Chaudhary Adit , Wright Dorothy , Murphy Brian , Wells George , Poretsky Rachel 
Published: February 2018

ABSTRACT

Wastewater treatment plants (WWTPs) release treated effluent containing mobile genetic elements (MGEs), antibiotic resistance genes (ARGs), and microorganisms into the environment, yet little is known about their influence on nearby microbial communities and the retention of these factors in receiving water bodies. Our research aimed to characterize the genes and organisms from two different WWTPs that discharge into Lake Michigan, as well as from surrounding lake sediments to determine the dispersal and fate of these factors with respect to distance from the effluent outfall. Shotgun metagenomics coupled to distance-decay analyses showed a higher abundance of genes identical to those in WWTP effluent genes in sediments closer to outfall sites than in sediments farther away, indicating their possible WWTP origin. We also found genes attributed to organisms, such as those belonging to
Helicobacteraceae
,
Legionellaceae
,
Moraxellaceae
, and
Neisseriaceae
, in effluent from both WWTPs and decreasing in abundance in lake sediments with increased distance from WWTPs. Moreover, our results showed that the WWTPs likely influence the ARG composition in lake sediments close to the effluent discharge. Many of these ARGs were located on MGEs in both the effluent and sediment samples, indicating a relatively broad propensity for horizontal gene transfer (HGT). Our approach allowed us to specifically link genes to organisms and their genetic context, providing insight into WWTP impacts on natural microbial communities. Overall, our results suggest a substantial influence of wastewater effluent on gene content and microbial community structure in the sediments of receiving water bodies.

IMPORTANCE
Wastewater treatment plants (WWTPs) release their effluent into aquatic environments. Although treated, effluent retains many genes and microorganisms that have the potential to influence the receiving water in ways that are poorly understood. Here, we tracked the genetic footprint, including genes specific to antibiotic resistance and mobile genetic elements and their associated organisms, from WWTPs to lake sediments. Our work is novel in that we used metagenomic data sets to comprehensively evaluate total gene content and the genetic and taxonomic context of specific genes in environmental samples putatively impacted by WWTP inputs. Based on two different WWTPs with different treatment processes, our findings point to an influence of WWTPs on the presence, abundance, and composition of these factors in the environment.
Enteric Viruses in Surface Waters from Argentina: Molecular and Viable-Virus Detection
Authors: Masachessi G. , Pisano M. B. , Prez V. E. , Martínez L. C. , Michelena J. F. , Martínez-Wassaf M. , Giordano M. O. , Isa M. B. , Pavan J. V. , Welter A. , Nates S. V. , Ré V. 
Published: February 2018

ABSTRACT
Water resources contaminated with wastewater are an important source for the dissemination of enteric viruses with an impact on the health of the population. The aim of the study was to assess the viral contamination of freshwater from a dam in Argentina by using infectious enterovirus detection, viral RNA amplification, and a genetic characterization of five enteric viruses associated with diarrhea and hepatitis. Enterovirus infectivity (iEV) was evaluated by cell culture and direct immunofluorescence. The detection of the viral genome of rotavirus (RV), human astrovirus (HAstV), norovirus (NoV), hepatitis A virus (HAV), and hepatitis E virus (HEV) was performed by reverse transcriptase PCR (RT-PCR). A total of 48 water samples from 4 monitoring points on the body of the dam from January to December 2012 and 66 water samples from 3 tourist beaches on the edge of the dam from October 2013 to October 2015 were collected monthly. During the first period, the overall viral frequency detection was 52.1% for group A RV, 50% for HAstV, 60.4% for NoV, 22.9% for HAV, 2.1% for HEV, and 64.6% for iEV. The overall frequency detection for the second sampling was 18.2% for RV and HAstV, 31.8% for NoV, 7.57% for HEV, and 66.7% for iEV. There was no detection of HAV during this period. The genotypes and genogroups detected through the study correlated with the most common genomic variants associated with human gastrointestinal and hepatitis illnesses. The results obtained could alert the health systems and environmental sanitation to make decisions for viral control and prevention in our environment.

IMPORTANCE
The study shows the impact of anthropic contamination of one of the most important tourist water resources in Argentina. This course of recreational water would be a favorable scenario for infection, as well as a reservoir for the enteric viruses, creating a risk for the population exposed to these waters. The results obtained could alert the health systems and environmental sanitation to make decisions for the control and prevention of viral diseases in this environment.
Staphylococcal Osteomyelitis: Disease Progression, Treatment Challenges, and Future Directions
Authors: Kavanagh Nicola , Ryan Emily J. , Widaa Amro , Sexton Gillian , Fennell Jerome , O'Rourke Sadhbh , Cahill Kevin C. , Kearney Cathal J. , O'Brien Fergal J. , Kerrigan Steven W. 
Published: February 2018

SUMMARY

Osteomyelitis is an inflammatory bone disease that is caused by an infecting microorganism and leads to progressive bone destruction and loss. The most common causative species are the usually commensal staphylococci, with
Staphylococcus aureus
and
Staphylococcus epidermidis
responsible for the majority of cases. Staphylococcal infections are becoming an increasing global concern, partially due to the resistance mechanisms developed by staphylococci to evade the host immune system and antibiotic treatment. In addition to the ability of staphylococci to withstand treatment, surgical intervention in an effort to remove necrotic and infected bone further exacerbates patient impairment. Despite the advances in current health care, osteomyelitis is now a major clinical challenge, with recurrent and persistent infections occurring in approximately 40% of patients. This review aims to provide information about staphylococcus-induced bone infection, covering the clinical presentation and diagnosis of osteomyelitis, pathophysiology and complications of osteomyelitis, and future avenues that are being explored to treat osteomyelitis.
Virulence of the Melioidosis Pathogen Burkholderia pseudomallei Requires the Oxidoreductase Membrane Protein DsbB
Authors: McMahon Róisín M. , Ireland Philip M. , Sarovich Derek S. , Petit Guillaume , Jenkins Christopher H. , Sarkar-Tyson Mitali , Currie Bart J. , Martin Jennifer L. 
Published: February 2018

ABSTRACT

The naturally antibiotic-resistant bacterium
Burkholderia pseudomallei
is the causative agent of melioidosis, a disease with stubbornly high mortality and a complex, protracted treatment regimen. The worldwide incidence of melioidosis is likely grossly underreported, though it is known to be highly endemic in northern Australia and Southeast Asia. Bacterial disulfide bond (DSB) proteins catalyze the oxidative folding and isomerization of disulfide bonds in substrate proteins. In the present study, we demonstrate that
B. pseudomallei
membrane protein disulfide bond protein B (BpsDsbB) forms a functional redox relay with the previously characterized virulence mediator
B. pseudomallei
disulfide bond protein A (BpsDsbA). Genomic analysis of diverse
B. pseudomallei
clinical isolates demonstrated that
dsbB
is a highly conserved core gene. Critically, we show that DsbB is required for virulence in
B. pseudomallei
. A panel of
B. pseudomallei
dsbB
deletion strains (K96243, 576, MSHR2511, MSHR0305b, and MSHR5858) were phenotypically diverse according to the results of
in vitro
assays that assess hallmarks of virulence. Irrespective of their
in vitro
virulence phenotypes, two deletion strains were attenuated in a BALB/c mouse model of infection. A crystal structure of a DsbB-derived peptide complexed with BpsDsbA provides the first molecular characterization of their interaction. This work contributes to our broader understanding of DSB redox biology and will support the design of antimicrobial drugs active against this important family of bacterial virulence targets.
Reduction of Spermidine Content Resulting from Inactivation of Two Arginine Decarboxylases Increases Biofilm Formation in Synechocystis sp. Strain PCC 6803
Authors: Kera Kota , Nagayama Tatsuya , Nanatani Kei , Saeki-Yamoto Chika , Tominaga Akira , Souma Satoshi , Miura Nozomi , Takeda Kota , Kayamori Syunsuke , Ando Eiji , Higashi Kyohei , Igarashi Kazuei , Uozumi Nobuyuki 
Published: February 2018

ABSTRACT

The phototropic bacterium
Synechocystis
sp. strain PCC 6803 is able to adapt its morphology in order to survive in a wide range of harsh environments. Under conditions of high salinity, planktonic cells formed cell aggregates in culture. Further observations using crystal violet staining, confocal laser scanning microscopy, and field emission-scanning electron microscopy confirmed that these aggregates were
Synechocystis
biofilms. Polyamines have been implicated in playing a role in biofilm formation, and during salt stress the content of spermidine, the major polyamine in
Synechocystis
, was reduced. Two putative arginine decarboxylases, Adc1 and Adc2, in
Synechocystis
were heterologously expressed in
Escherichia coli
and purified. Adc2 had high arginine decarboxylase activity, whereas Adc1 was much less active. Disruption of the
adc
genes in
Synechocystis
resulted in decreased spermidine content and formation of biofilms even under nonstress conditions. Based on the characterization of the
adc
mutants, Adc2 was the major arginine decarboxylase whose activity led to inhibition of biofilm formation, and Adc1 contributed only minimally to the process of polyamine synthesis. Taken together, in
Synechocystis
the shift from planktonic lifestyle to biofilm formation was correlated with a decrease in intracellular polyamine content, which is the inverse relationship of what was previously reported in heterotroph bacteria.

IMPORTANCE
There are many reports concerning biofilm formation in heterotrophic bacteria. In contrast, studies on biofilm formation in cyanobacteria are scarce. Here, we report on the induction of biofilm formation by salt stress in the model phototrophic bacterium
Synechocystis
sp. strain PCC 6803. Two arginine decarboxylases (Adc1 and Adc2) possess function in the polyamine synthesis pathway. Inactivation of the
adc1
and
adc2
genes leads to biofilm formation even in the absence of salt. The shift from planktonic culture to biofilm formation is regulated by a decrease in spermidine content in
Synechocystis
. This negative correlation between biofilm formation and polyamine content, which is the opposite of the relationship reported in other bacteria, is important not only in autotrophic but also in heterotrophic bacteria.
Identification of Streptococcus gallolyticus subsp. gallolyticus (Biotype I) Competence-Stimulating Peptide Pheromone
Authors: Harrington Anthony , Tal-Gan Yftah 
Published: February 2018

ABSTRACT

Streptococcus gallolyticus
subsp.
gallolyticus
, a member of the group D streptococci, is normally found in the bovine rumen and human gut. It is an opportunistic pathogen that was recently determined to be a bacterial driver of colorectal cancer, in addition to causing other diseases, such as infective endocarditis, bacteremia, neonatal meningitis, and septicemia. As an emerging pathogen, not much is known about this bacterium, its virulence mechanisms, or its virulence regulatory pathways. Previous studies suggest that
S. gallolyticus
subsp.
gallolyticus
uses a ComRS pathway, one of many
Streptococcus
quorum-sensing circuitries, for competence. However, thus far, the ubiquitous ComABCDE pathway has not been studied, nor has its regulatory role in
S. gallolyticus
subsp.
gallolyticus
. We therefore sought to study the
S. gallolyticus
subsp.
gallolyticus
ComABCDE quorum-sensing pathway and have identified its peptide pheromone, which is termed the competence-stimulating peptide (CSP). We further determined that this peptide regulates the production of bacteriocin-like inhibitory substances (BLISs), a phenotype that has been linked with the ComABCDE pathway in both
Streptococcus pneumoniae
and
Streptococcus mutans
. Our data show that
S. gallolyticus
subsp.
gallolyticus
TX20005 produces a 21-mer CSP signal, which differs from CSP signals of other
Streptococcus
species in that its active form begins three residues after the double-glycine leader signal of the ComC precursor peptide. Additionally, our data suggest that this peptide might not be related to competence induction, as opposed to CSP signaling peptides in other
Streptococcus
species. This study provides the first evidence that
S. gallolyticus
subsp.
gallolyticus
utilizes quorum sensing to eliminate competitors, presenting a potential pathway to target this emerging human pathogen.

IMPORTANCE
Streptococcus gallolyticus
subsp.
gallolyticus
is an emerging human pathogen known as a causative agent of infective endocarditis, and recently, of colorectal cancer. In this work, we revealed a functional quorum-sensing circuitry in
S. gallolyticus
subsp.
gallolyticus
, including the identification of the central signaling peptide pheromone, competence-stimulating peptide (CSP), and the regulatory role of this circuitry in the production of bacteriocin-like inhibitory substances (BLISs). This work uncovered a mechanism by which this bacterium outcompetes other bacterial species and thus provides a potential tool to study this opportunistic pathogen.
Expression of Pyridoxal 5′-Phosphate-Independent Racemases Can Reduce 2-Aminoacrylate Stress in Salmonella enterica
Authors: Hodge-Hanson Kelsey M. , Zoino Allison , Downs Diana M. 
Published: February 2018

ABSTRACT

The RidA protein (PF01042) from
Salmonella enterica
is a deaminase that quenches 2-aminoacrylate (2AA) and other reactive metabolites. In the absence of RidA, 2AA accumulates, damages cellular enzymes, and compromises the metabolic network.
In vitro
, RidA homologs from all domains of life deaminate 2AA, and RidA proteins from plants, bacteria, yeast, and humans complement the mutant phenotype of a
ridA
mutant strain of
S. enterica
. In the present study, a methanogenic archaeon,
Methanococcus maripaludis
S2, was used to probe alternative mechanisms to restore metabolic balance.
M. maripaludis
MMP0739, which is annotated as an aspartate/glutamate racemase, complemented a
ridA
mutant strain and reduced the intracellular 2AA burden. The aspartate/glutamate racemase YgeA from
Escherichia coli
or
S. enterica
, when provided in
trans
, similarly restored wild-type growth to a
ridA
mutant. These results uncovered a new mechanism to ameliorate metabolic stress, and they suggest that direct quenching by RidA is not the only strategy to quench 2AA.

IMPORTANCE
2-Aminoacrylate is an endogenously generated reactive metabolite that can damage cellular enzymes if not directly quenched by the conserved deaminase RidA. This study used an archaeon to identify a RidA-independent mechanism to prevent metabolic stress caused by 2AA. The data suggest that a gene product annotated as an aspartate/glutamate racemase (MMP0739) produces a metabolite that can quench 2AA, expanding our understanding of strategies available to quench reactive metabolites.
Lactic Acid Downregulates Viral MicroRNA To Promote Epstein-Barr Virus-Immortalized B Lymphoblastic Cell Adhesion and Growth
Authors: Mo Xiaohui , Wei Fang , Tong Yin , Ding Ling , Zhu Qing , Du Shujuan , Tan Fei , Zhu Caixia , Wang Yuyan , Yu Qian , Liu Yeqiang , Robertson Erle S. , Yuan Zhenghong , Cai Qiliang 
Published: February 2018

ABSTRACT

High plasma lactate is associated with poor prognosis of many malignancies, but its role in virally mediated cancer progression and underlying molecular mechanisms are unclear. Epstein-Barr virus (EBV), the first human oncogenic virus, causes several cancers, including B-cell lymphoma. Here, we report that lactate dehydrogenase A (LDH-A) expression and lactate production are elevated in EBV-immortalized B lymphoblastic cells, and lactic acid (LA; acidic lactate) at low concentration triggers EBV-infected B-cell adhesion, morphological changes, and proliferation
in vitro
and
in vivo
. Moreover, LA-induced responses of EBV-infected B cells uniquely occurs in viral latency type III, and it is dramatically associated with the inhibition of global viral microRNAs, particularly the miR-BHRF1 cluster, and the high expression of
SMAD3
,
JUN
, and
COL1A
genes. The introduction of miR-BHRF1-1 blocks the LA-induced effects of EBV-infected B cells. Thus, this may be a novel mechanism to explain EBV-immortalized B lymphoblastic cell malignancy in an LA microenvironment.

IMPORTANCE
The tumor microenvironment is complicated, and lactate, which is created by cell metabolism, contributes to an acidic microenvironment that facilitates cancer progression. However, how LA operates in virus-associated cancers is unclear. Thus, we studied how EBV (the first tumor virus identified in humans; it is associated with many cancers) upregulates the expression of LDH-A and lactate production in B lymphoma cells. Elevated LA induces adhesion and the growth of EBV-infected B cells by inhibiting viral microRNA transcription. Thus, we offer a novel understanding of how EBV utilizes an acidic microenvironment to promote cancer development.
Health professionals’ and coroners’ views on less invasive perinatal and paediatric autopsy: a qualitative study
Authors: Lewis Celine , Hill Melissa , Arthurs Owen J , Hutchinson John C , Chitty Lyn S , Sebire Neil 
Published: February 2018

ObjectiveTo assess health professionals’ and coroners’ attitudes towards non-minimally and minimally invasive autopsy in the perinatal and paediatric setting.MethodsA qualitative study using semistructured interviews. Data were analysed thematically.ResultsTwenty-five health professionals (including perinatal/paediatric pathologists and anatomical pathology technologists, obstetricians, fetal medicine consultants and bereavement midwives, intensive care consultants and family liaison nurses, a consultant neonatologist and a paediatric radiologist) and four coroners participated. Participants viewed less invasive methods of autopsy as a positive development in prenatal and paediatric care that could increase autopsy rates. Several procedural and psychological benefits were highlighted including improved diagnostic accuracy in some circumstances, potential for faster turnaround times, parental familiarity with imaging and laparoscopic approaches, and benefits to parents and faith groups who object to invasive approaches. Concerns around the limitations of the technology such not reaching the same levels of certainty as full autopsy, unsuitability of imaging in certain circumstances, the potential for missing a diagnosis (or misdiagnosis) and de-skilling the workforce were identified. Finally, a number of implementation issues were raised including skills and training requirements for pathologists and radiologists, access to scanning equipment, required computational infrastructure, need for a multidisciplinary approach to interpret results, cost implications, equity of access and acceptance from health professionals and hospital managers.ConclusionHealth professionals and coroners viewed less invasive autopsy as a positive development in perinatal and paediatric care. However, to inform implementation a detailed health economic analysis and further exploration of parental views, particularly in different religious groups, are required.
Yellow (577 nm) micropulse laser versus half-dose verteporfin photodynamic therapy in eyes with chronic central serous chorioretinopathy: results of the Pan-American Collaborative Retina Study (PACORES) Group
Authors: Roca Jose A , Wu Lihteh , Fromow-Guerra Jans , Rodríguez Francisco J , Berrocal Maria H , Rojas Sergio , Lima Luiz H , Gallego-Pinazo Roberto , Chhablani Jay , Arevalo J Fernando , Lozano-Rechy David , Serrano Martin 
Published: February 2018

PurposeTo compare the functional and anatomical outcomes of eyes with chronic central serous chorioretinopathy treated with yellow micropulse (MP) laser versus half-dose verteporfin photodynamic therapy (PDT).MethodsThis is a multicentre, retrospective comparative study of 92 eyes treated with yellow MP laser (duty cycle of 5%, zero spacing between spots, spot size varied from 100 to 200 µm, power varied from 320 to 660 mW, and the pulse burst duration was 200 ms) and 67 eyes treated with PDT (half-dose verteporfin (3 mg/m2) infused over 10 min), followed by laser activation for 83 s. Spot sizes varied from 400 to 2000 µm.ResultsIn the MP group, at 12 months of follow-up, the mean best corrected visual acuity (BCVA) improved from the logarithm of the minimum angle of resolution (logMAR) of 0.41±0.27 at baseline to 0.21±0.26 (P<0.0001), 48.9% (45/92) of eyes had an improvement of ≥3 lines of BCVA from baseline, 48.9% (45/92) of eyes remained within 2 lines of baseline BCVA, and only 2.2% (2/92) of eyes lost ≥3 lines of BCVA from baseline. In the PDT group, at 12 months of follow-up, the mean BCVA changed from logMAR of 0.50±0.34 at baseline to 0.47±0.34 (P=0.89), 19% (13/67) of eyes had an improvement of ≥3 lines of BCVA from baseline, 73% (49/67) of eyes remained within 2 lines of baseline BCVA, and 7% (5/67) of eyes lost ≥3 lines of BCVA from baseline. There were no adverse events attributable to the yellow MP laser treatment. One eye in the PDT group developed choroidal neovascularisation, which was treated with three intravitreal bevacizumab injections.ConclusionsBoth PDT and MP are effective in restoring the macular anatomy. In places where PDT is not available, yellow MP laser may be an adequate treatment alternative.