The potential benefits of producing gene transfer agents (GTAs) have long been speculated. A new study in PLOS Biology shows that DNA transfer by these phage-like elements allows cells with DNA ...damage to perform DNA repair and survive.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) is a bacterial second messenger that affects diverse processes in different bacteria, including the cell cycle, motility, and biofilm ...formation. Its cellular levels are controlled by the opposing activities of two types of enzymes, with synthesis by diguanylate cyclases containing a GGDEF domain and degradation by phosphodiesterases containing either an HD-GYP or an EAL domain. These enzymes are ubiquitous in bacteria with up to 50 encoded in some genomes, the specific functions of which are mostly unknown.
We used comparative analyses to identify genomic patterns among genes encoding proteins with GGDEF, EAL, and HD-GYP domains in five orders of the class Alphaproteobacteria. GGDEF-containing sequences and GGDEF-EAL hybrids were the most abundant and had the highest diversity of co-occurring auxiliary domains while EAL and HD-GYP containing sequences were less abundant and less diverse with respect to auxiliary domains. There were striking patterns in the chromosomal localizations of the genes found in two of the orders. The Rhodobacterales' EAL-encoding genes and Rhizobiales' GGDEF-EAL-encoding genes showed opposing patterns of distribution compared to the GGDEF-encoding genes. In the Rhodobacterales, the GGDEF-encoding genes showed a tri-modal distribution with peaks mid-way between the origin (ori) and terminus (ter) of replication and at ter while the EAL-encoding genes peaked near ori. The patterns were more complex in the Rhizobiales, but the GGDEF-encoding genes were biased for localization near ter.
The observed patterns in the chromosomal localizations of these genes suggest a coupling of synthesis and hydrolysis of c-di-GMP with the cell cycle. Moreover, the higher proportions and diversities of auxiliary domains associated with GGDEF domains and GGDEF-EAL hybrids compared to EAL or HD-GYP domains could indicate that more stimuli affect synthesis compared to hydrolysis of c-di-GMP.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Due to the bleeding risk of full-dose systemic thrombolysis and the lack of major trials focusing on the clinical benefits of catheter-directed treatment, heparin antiocoagulation remains the ...standard of care for patients with intermediate-high-risk pulmonary embolism (PE).
The Higher-Risk Pulmonary Embolism Thrombolysis (HI-PEITHO) study (ClinicalTrials.gov Identifier: NCT04790370) is a multinational multicenter randomized controlled parallel-group comparison trial. Patients with: (1) confirmed acute PE; (2) evidence of right ventricular (RV) dysfunction on imaging; (3) a positive cardiac troponin test; and (4) clinical criteria indicating an elevated risk of early death or imminent hemodynamic collapse, will be randomized 1:1 to treatment with a standardized protocol of ultrasound-facilitated catheter-directed thrombolysis plus anticoagulation, vs anticoagulation alone. The primary outcome is a composite of PE-related mortality, cardiorespiratory decompensation or collapse, or non-fatal symptomatic and objectively confirmed PE recurrence, within 7 days of randomization. Further assessments cover, apart from bleeding complications, a broad spectrum of functional and patient-reported outcomes including quality of life indicators, functional status and the utilization of health care resources over a 12-month follow-up period. The trial plans to include 406 patients, but the adaptive design permits a sample size increase depending on the results of the predefined interim analysis. As of May 11, 2022, 27 subjects have been enrolled. The trial is funded by Boston Scientific Corporation and through collaborative research agreements with University of Mainz and The PERT Consortium.
Regardless of the outcome, HI-PEITHO will establish the first-line treatment in intermediate-high risk PE patients with imminent hemodynamic collapse. The trial is expected to inform international guidelines and set the standard for evaluation of catheter-directed reperfusion options in the future.
Antimicrobial resistance (AMR) is an ever-present threat to the treatment of infectious diseases. However, the potential relevance of this phenomenon in environmental reservoirs still raises many ...questions. Detection of antimicrobial-resistant bacteria in the environment is a critical aspect for understanding the prevalence of resistance outside of clinical settings, as detection in the environment indicates that resistance is likely already widespread. We isolated antimicrobial-resistant
from three urban waterbodies over a 15-month time series, determined their antimicrobial susceptibilities, investigated their population structure, and identified genetic determinants of resistance. We found that
populations at each site were composed of different dominant phylotypes and showed distinct patterns of antimicrobial and multidrug resistance, despite close geographic proximity. Many strains that were genome-sequenced belonged to sequence types of international concern, particularly the ST131 clonal complex. We found widespread resistance to clinically important antimicrobials such as amoxicillin, cefotaxime, and ciprofloxacin, but found that all strains were susceptible to amikacin and the last-line antimicrobials meropenem and fosfomycin. Resistance was most often due to acquirable antimicrobial resistance genes, while chromosomal mutations in
,
, and
conferred resistance to quinolones. Whole-genome analysis of a subset of strains further revealed the diversity of the population of
present, with a wide array of AMR and virulence genes identified, many of which were present on the chromosome, including
. Finally, we determined that environmental persistence, transmission between sites, most likely mediated by wild birds, and transfer of mobile genetic elements likely contributed significantly to the patterns observed.IMPORTANCEA One Health perspective is crucial to understand the extent of antimicrobial resistance (AMR) globally, and investigation of AMR in the environment has been increasing in recent years. However, most studies have focused on waterways that are directly polluted by sewage, industrial manufacturing, or agricultural activities. Therefore, there remains a lack of knowledge about more natural, less overtly impacted environments. Through phenotypic and genotypic investigation of AMR in
, this study adds to our understanding of the extent and patterns of resistance in these types of environments, including over a time series, and showed that complex biotic and abiotic factors contribute to the patterns observed. Our study further emphasizes the importance of incorporating the surveillance of microbes in freshwater environments in order to better comprehend potential risks for both human and animal health and how the environment may serve as a sentinel for potential future clinical infections.
The distribution and quality of water resources vary dramatically across Canada, and human impacts such as land-use and climate changes are exacerbating uncertainties in water supply and security. At ...the national level, Canada has no enforceable standards for safe drinking water and no comprehensive water-monitoring program to provide detailed, timely reporting on the state of water resources. To provide Canada's first national assessment of lake health, the NSERC Canadian Lake Pulse Network was launched in 2016 as an academic-government research partnership. LakePulse uses traditional approaches for limnological monitoring as well as state-of-the-art methods in the fields of genomics, emerging contaminants, greenhouse gases, invasive pathogens, paleolimnology, spatial modelling, statistical analysis, and remote sensing. A coordinated sampling program of about 680 lakes together with historical archives and a geomatics analysis of over 80,000 lake watersheds are used to examine the extent to which lakes are being altered now and in the future, and how this impacts aquatic ecosystem services of societal importance. Herein we review the network context, objectives and methods.
Display omitted
•About 90% of Canada's municipal drinking water supplies are from surface waters.•An academic-government group is providing the first national review of lake health.•Over 100 variables were sampled at about 680 lakes across Canada.•Topics range from greenhouse gases to emerging contaminants to invasive pathogens.•The impacts of land-use and climate changes on lake health are also studied.
Abstract
We describe 3 instances of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission despite medical masks and eye protection, including transmission despite the source ...person being masked, transmission despite the exposed person being masked, and transmission despite both parties being masked. Whole genome sequencing confirmed perfect homology between source and exposed persons’ viruses in all cases.
Bis-(3′–5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) is an important intracellular signaling molecule that affects diverse physiological processes in bacteria. The intracellular levels of ...c-di-GMP are controlled by proteins acting as diguanylate cyclase (DGC) and phosphodiesterase (PDE) enzymes that synthesize and degrade c-di-GMP, respectively. In the alphaproteobacterium Rhodobacter capsulatus, flagellar motility and gene exchange via production of the gene transfer agent RcGTA are regulated by c-di-GMP. One of the R. capsulatus proteins involved in this regulation is Rcc00620, which contains an N-terminal two-component system response regulator receiver (REC) domain and C-terminal DGC and PDE domains. We demonstrate that the enzymatic activity of Rcc00620 is regulated through the phosphorylation status of its REC domain, which is controlled by a cognate histidine kinase protein, Rcc00621. In this system, the phosphorylated form of Rcc00620 is active as a PDE enzyme and stimulates gene transfer and motility. In addition, we discovered that the rcc00620 and rcc00621 genes are present in only one lineage within the genus Rhodobacter and were acquired via horizontal gene transfer from a distantly related alphaproteobacterium in the order Sphingomonadales. Therefore, a horizontally acquired regulatory system regulates gene transfer in the recipient organism.
Display omitted
•A two-component system (TCS) was characterized in Rhodobacter capsulatus.•In this TCS, Rcc00620 is phosphorylated by Rcc00621.•Rcc00620 ~ P degrades c-di-GMP and stimulates gene transfer and motility.•The TCS was acquired by horizontal gene transfer (HGT) from a distant bacterium.•A TCS acquired by HGT is active and regulates gene transfer in the new location.
Past research has confirmed the utility of environmental variables, and perceptions of religious pressure (RP) in particular, in predicting faith maturity and religious schema scores for participants ...from Christian environments. Whether environmental variables predict religious development and whether religious development, in turn, leads to greater well-being for individuals from broader environments remain unknown. Utilizing participants from both Christian and non-Christian environments, the current study measures religious development variables that were constructed based on self-determination theory (SDT). We used structural equation modeling (SEM) to evaluate our hypothesis that religious pressures RP and autonomy supportive environment (ASE) are antecedents to religious/spiritual relatedness (R/S-R) and self-mastery (R/S-S), which in turn lead to greater well-being, as determined by the presence of meaning in life (MIL). Results indicate that both environmental variables of RP and ASE predicted higher scores on religious/spiritual relatedness and self-mastery, and this led to self-reports of greater well-being for both samples. Therefore, members of the broader religious environment of Christianity responded to RP similarly, implying that certain commonalities may shape Christians’ cognitions around obedience to God and authority across settings, although this result should be interpreted with caution. Further implications of these findings are explored and recommendations for future research provided.
Diverse prokaryotes produce gene transfer agents (GTAs), which are bacteriophage-like particles that exclusively package pieces of the producing cell's genome and transfer them to other cells. There ...are clear evolutionary connections between GTAs and phages, but GTAs have properties that lead us to suggest they are more than simply defective phages and instead provide a selective advantage for the producing organisms. The five types of currently known GTAs are genetically distinct, indicating multiple instances of convergent evolution. GTA production can be regulated by the producing organism and coordinated to coincide with development of the capability to receive DNA from GTAs. Recent discoveries of the genetic basis of GTA production in the bacterium
Rhodobacter capsulatus
and characterization of novel phages that possess homologs of this GTA's structural and regulatory genes have provided important new connections among these elements and highlight the tangled evolutionary relationships within the phageome.
PDF
