Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 29
Filter
1.
SAGE Open Nurs ; 9: 23779608231196843, 2023.
Article in English | MEDLINE | ID: mdl-37675150

ABSTRACT

Introduction: Nurses and respiratory therapists working on the frontline during the pandemic surge were short-staffed and worked extended hours while adding new tasks to already demanding workloads. As the world watched news covering COVID-19's effect, nurses and respiratory therapists lived through the daily stress of treating each patient with care, dignity, and compassion. Limited studies have focused on this population, which is vital to providing care and saving lives; research is needed to understand nurses' and respiratory therapists' experiences during the COVID-19 pandemic. Objective: The study aimed to understand nurses' and respiratory therapists' experiences during the COVID-19 pandemic. Methods: A qualitative descriptive study, informed by naturalistic philosophy, was designed to obtain a detailed account of participants' experiences during the pandemic surge. A purposive sample was recruited and enrolled from the community through professional organizations and snowball sampling from December 2021 to September 2022. Data was analyzed using thematic analysis. Results: Participants were seven registered nurses and six respiratory therapists employed full-time in an intensive care unit, step-down intensive care unit, emergency department, or medical-surgical unit; seven (53.8%) with an associate degree, and six (46.2%) with a bachelor's degree. Eight (66.7%) self-identified as White, one Asian, one non-Hispanic Black, and two Pacific Islanders. The mean age was 40, and 10 (76.9%) were female. Six primary themes emerged: (a) the work-life experience before the COVID-19 pandemic, (b) the work-life experience during the COVID-19 pandemic, (c) the personal life experience during COVID-19, (d) the coping period, (e) the professional role change, and (f) the work and personal life experiences post COVID-19 surge. Conclusion: The knowledge gained from this study can help improve understanding of the professional quality of life, the need for organizational and community support, and for healthcare professionals to seek help and practice self-care to prevent burnout and secondary traumatic stress.

2.
Epileptic Disord ; 25(6): 803-814, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37584596

ABSTRACT

OBJECTIVE: Eslicarbazepine acetate (ESL) is a once-daily oral antiseizure medication. Its safety and tolerability from clinical trials have been mostly confirmed by real-world data. The main purpose of this report is to provide an overview of the safety profile of ESL in the United Kingdom (UK) and Republic of Ireland (ROI). METHODS: Safety data were obtained from the UK and ROI post-marketing sources (October 2009-April 2022) by the marketing authorization holder. All individual reports were included in the Argus Safety™ database. All adverse events (AEs) were coded using MedDRA® version 24.1. Only valid cases (meeting the minimum pharmacovigilance reporting requirements) were included. RESULTS: During 13 years of ESL marketing, with cumulative estimated exposure of 2 210 395 patients-years, 183 reports were received. A total of 402 AEs were reported for the 155 valid reports. The most common reported AEs (≥6% of total reported), per system organ class (SOC), were: nervous system disorders (23.4%), injury, poisoning, and procedural complications (18.9%), general disorders and administration site conditions (12.9%), psychiatric disorders (12.7%) and gastrointestinal disorders (6.7%). The most frequently reported (≥2% of total reported) AEs were: seizure (4.5%), hyponatremia (4.2%), dizziness (2.7%), rash, fatigue (2.5% each), and somnolence (2.0%). Twenty-six percent of events were classified as serious (including six fatal cases). SIGNIFICANCE: The current analysis supports the known safety profile of ESL, as generally well-tolerated with most AEs being non-serious. The most common AEs were considered either expected according to the disease itself or to the reference safety information. ESL continues to be a relevant medication in the treatment of partial (focal-onset) epilepsy, as also confirmed by the 2022 NICE guidelines.


Subject(s)
Anticonvulsants , Dibenzazepines , Humans , Anticonvulsants/adverse effects , Ireland/epidemiology , Dibenzazepines/adverse effects , United Kingdom , Treatment Outcome
3.
J Prim Care Community Health ; 14: 21501319231174810, 2023.
Article in English | MEDLINE | ID: mdl-37306326

ABSTRACT

OBJECTIVE: COVID-19 disproportionally affected Hispanic/Latinx populations exacerbating systemic health inequities. The pilot study aimed to explore barriers to COVID-19 vaccination across Hispanic/Latinx communities in Southern California. METHODS: Cross-sectional survey of 200 participants to identify common barriers to vaccine hesitancy among Hispanics/Latinx individuals in Southern California utilizing a 14-item survey and questionnaire in English and Spanish. RESULTS: Of the 200 participants that completed questionnaires, 37% identified a knowledge deficit, 8% identified misinformation, and 15% identified additional barriers such as awaiting appointments, immigration status, transportation issues, or religious reasons as barriers to not receiving the COVID-19 vaccine. Wald statistics denoted that household members with COVID-19 infection within the past 3 months saw a medical provider within the last year, wearing a mask in public often, and barriers to vaccination (not knowing enough about the vaccine) predicted vaccine. These variables indicated changes in the likelihood of obtaining vaccination. CONCLUSION: The most crucial factor for increasing vaccination rates was directly reaching out to the community and actively conducting surveys to address the barriers and concerns encountered by Hispanic/Latinx participants.


Subject(s)
COVID-19 Vaccines , COVID-19 , Healthcare Disparities , Vaccination , Humans , COVID-19/prevention & control , Cross-Sectional Studies , Hispanic or Latino , Pilot Projects
4.
J Nurs Care Qual ; 38(2): 100-106, 2023.
Article in English | MEDLINE | ID: mdl-36094277

ABSTRACT

BACKGROUND: Falls are the most prevalent adverse event among hospitalized patients. Multilevel risk factors are associated with falls, yet falls continue. PURPOSE: To evaluate the relationship between the Johns Hopkins Fall Risk instrument, patient characteristics, and perception of fall risk. METHODS: The Johns Hopkins Fall Risk score, patient perception of fall risk, and patient characteristics were analyzed among inpatient adults (n = 201) from 5 acute care units in a large southern California medical center. RESULTS: Bivariate analyses revealed that fall risk was inversely associated with participants' confidence in their ability to perform high fall risk behaviors without help and without falling ( P = .018). CONCLUSIONS: Perception of fall risk is a promising new indicator in preventing falls. Patient perception of fall risk may elicit a behavior change to help prevent falls. Increased health care provider awareness of patient perception of fall risk may improve fall risk interventions and prevention programs.


Subject(s)
Inpatients , Perception , Adult , Humans , Risk Assessment , Risk Factors
5.
Oncol Nurs Forum ; 49(6): 595-612, 2022 10 20.
Article in English | MEDLINE | ID: mdl-36413738

ABSTRACT

OBJECTIVES: To examine the effect of oncology nurse navigators (ONNs) on the number of emergency department (ED) visits and hospital admissions (HAs) of adults with cancer post-outpatient chemotherapy. SAMPLE & SETTING: 1,370 patients with cancer between January 1, 2018, and December 31, 2019, in a comprehensive community cancer center in southern California. METHODS & VARIABLES: A descriptive cross-sectional study was conducted using retrospective electronic health records. Primary analysis included bivariate and multiple linear regression to identify correlates of ED visits and HAs in terms of ONN involvement. RESULTS: About 35% of patients had an ED visit or HA. Anemia, dehydration, and pain were common diagnoses. No significant differences were found in ED visits and HAs by ONN group. Medicare and chemotherapy administration location contributed to the likelihood of ED visits; nausea, pain, and pneumonia contributed to the likelihood of HAs. IMPLICATIONS FOR NURSING: ED visits and HAs are not appropriate clinical outcomes to measure ONNs' efficacy. Further research is needed to understand the long-term fiscal and operational outcomes of ONNs.


Subject(s)
Neoplasms , Outpatients , Adult , Aged , Humans , Cross-Sectional Studies , Emergency Service, Hospital , Hospitals , Medicare , Neoplasms/drug therapy , Pain , Retrospective Studies , United States
6.
ACS Catal ; 12(11): 6570-6577, 2022 Jun 03.
Article in English | MEDLINE | ID: mdl-35692250

ABSTRACT

Fluorinases, the only enzymes known to catalyze the transfer of fluorine to an organic molecule, are essential catalysts for the biological synthesis of valuable organofluorines. However, the few fluorinases identified so far have low turnover rates that hamper biotechnological applications. Here, we isolated and characterized putative fluorinases retrieved from systematic in silico mining and identified a nonconventional archaeal enzyme from Methanosaeta sp. that mediates the fastest SN2 fluorination rate reported to date. Furthermore, we demonstrate enhanced production of fluoronucleotides in vivo in a bacterial host engineered with this archaeal fluorinase, paving the way toward synthetic metabolism for efficient biohalogenation.

7.
Environ Microbiol ; 24(11): 5082-5104, 2022 11.
Article in English | MEDLINE | ID: mdl-35726888

ABSTRACT

The presence of mineral fluoride (F- ) in the environment has both a geogenic and anthropogenic origin, and the halide has been described to be toxic in virtually all living organisms. While the evidence gathered in different microbial species supports this notion, a systematic exploration of the effects of F- salts on the metabolism and physiology of environmental bacteria remained underexplored thus far. In this work, we studied and characterized tolerance mechanisms deployed by the model soil bacterium Pseudomonas putida KT2440 against NaF. By adopting systems-level omic approaches, including functional genomics and metabolomics, we gauged the impact of this anion at different regulatory levels under conditions that impair bacterial growth. Several genes involved in halide tolerance were isolated in a genome-wide Tn-Seq screening-among which crcB, encoding an F- -specific exporter, was shown to play the predominant role in detoxification. High-resolution metabolomics, combined with the assessment of intracellular and extracellular pH values and quantitative physiology experiments, underscored the key nodes in central carbon metabolism affected by the presence of F- . Taken together, our results indicate that P. putida undergoes a general, multi-level stress response when challenged with NaF that significantly differs from that caused by other saline stressors. While microbial stress responses to saline and oxidative challenges have been extensively studied and described in the literature, very little is known about the impact of fluoride (F- ) on bacterial physiology and metabolism. This state of affairs contrasts with the fact that F- is more abundant than other halides in the Earth crust (e.g. in some soils, the F- concentration can reach up to 1 mg gsoil -1 ). Understanding the global effects of NaF treatment on bacterial physiology is not only relevant to unveil distinct mechanisms of detoxification but it could also guide microbial engineering approaches for the target incorporation of fluorine into value-added organofluorine molecules. In this regard, the soil bacterium P. putida constitutes an ideal model to explore such scenarios, since this species is particularly known for its high level of stress resistance against a variety of physicochemical perturbations.


Subject(s)
Pseudomonas putida , Pseudomonas putida/metabolism , Fluorides/metabolism , Genomics , Minerals/metabolism , Soil
8.
J Am Assoc Nurse Pract ; 34(6): 827-834, 2022 Jun 01.
Article in English | MEDLINE | ID: mdl-35439215

ABSTRACT

BACKGROUND: Effectively managing pain is a unique challenge for the U.S. military. Chronic pain has a tremendous detrimental impact on mission readiness throughout the Armed Forces. Examining the effects of chronic pain on readiness is critical to understanding and addressing these challenges. PURPOSE: The purpose of this study was to examine the associations of chronic pain and sleep disruption in the context of work performance among active duty military service members. METHODOLOGICAL ORIENTATION: The study design was a cross-sectional observational study that examined associations between patients with chronic pain and sleep disruption, in the context of work performance. RESULTS: One hundred forty-five participants completed the study. Age, depression, sleep, and pain severity were consistently strong predictors of work performance. CONCLUSIONS: Patients performed better with age, whereas those with depression, sleep disruption, and increased pain severity performed poorly. IMPLICATIONS FOR PRACTICE: Research focused on the differences in work performance among age groups may provide a better understanding of coping strategies. Focused depression research can lead to a greater understanding of how mental health affects pain, sleep, and work. The findings of this study open the door to explore multiple approaches that could lead to treatments and preventions for military members living with chronic pain.


Subject(s)
Chronic Pain , Military Personnel , Work Performance , Cross-Sectional Studies , Humans , Military Personnel/psychology , Sleep
9.
Nurs Womens Health ; 26(2): 95-106, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35231418

ABSTRACT

OBJECTIVE: To examine the relationships among depression and anxiety symptomatology, stigma of mental illness, levels of social support, and select demographics among hospitalized women in the postpartum period. DESIGN: Descriptive, cross-sectional, correlational. SETTING: A convenience sample of 105 English-speaking and Spanish-speaking women was recruited and enrolled from a 208-bed free-standing Southern California women's community hospital postpartum unit serving a diverse community. MEASUREMENTS: Data were collected on potential covariates including participants' characteristics, depression and anxiety symptomatology, social support, and stigma. RESULTS: Sixteen participants were classified as high risk for depression or anxiety based on the Edinburgh Postnatal Depression Scale and Generalized Anxiety Disorder-7. Anxiety was significantly associated with all stigma subscales; the strongest association was with Internal Stigma (r = .46, p < .001, moderate effect), followed by Disclosure Stigma (r = .36, p < .001, moderate effect) and External Stigma (r = .30, p = .002, moderate effect). All social support subscales were negatively associated with depression and anxiety; the Friends subscale had the strongest correlations with depression (r = -.27, p = .006, small effect) and anxiety (r = .34, p = .001, moderate effect). Firth (penalized likelihood) logistic regression analysis was conducted to ascertain the effects of study covariates on the likelihood of participants being at risk for postnatal depression or anxiety. The significant factor that increased the odds of participants being in the high-risk group was decreased social support (adjusted OR = 0.46, 95% CI [0.24, 0.76], p = .003). CONCLUSION: These results show the enduring prevalence of postnatal depression and anxiety and the relevance of stigma and social support in aggravating or mitigating symptomatology. There is a need for comprehensive standardized screening to ensure the identification of and referral to treatment for women at risk.


Subject(s)
Depression, Postpartum , Depression , Anxiety/epidemiology , Anxiety Disorders , Cross-Sectional Studies , Depression/epidemiology , Depression, Postpartum/diagnosis , Depression, Postpartum/epidemiology , Female , Humans , Postpartum Period , Social Support
10.
Microb Biotechnol ; 15(5): 1622-1632, 2022 05.
Article in English | MEDLINE | ID: mdl-35084776

ABSTRACT

The fluorinase enzyme represents the only biological mechanism capable of forming stable C-F bonds characterized in nature thus far, offering a biotechnological route to the biosynthesis of value-added organofluorines. The fluorinase is known to operate in a hexameric form, but the consequence(s) of the oligomerization status on the enzyme activity and its catalytic properties remain largely unknown. In this work, this aspect was explored by rationally engineering trimeric fluorinase variants that retained the same catalytic rate as the wild-type enzyme. These results ruled out hexamerization as a requisite for the fluorination activity. The Michaelis constant (KM ) for S-adenosyl-l-methionine, one of the substrates of the fluorinase, increased by two orders of magnitude upon hexamer disruption. Such a shift in S-adenosyl-l-methionine affinity points to a long-range effect of hexamerization on substrate binding - likely decreasing substrate dissociation and release from the active site. A practical application of trimeric fluorinase is illustrated by establishing in vitro fluorometabolite synthesis in a bacterial cell-free system.


Subject(s)
Streptomyces , Bacterial Proteins/metabolism , Methionine , Oxidoreductases/metabolism , S-Adenosylmethionine
11.
Int J Nurs Sci ; 8(4): 418-425, 2021 Oct 10.
Article in English | MEDLINE | ID: mdl-34631992

ABSTRACT

OBJECTIVES: There is extensive literature from various disciplines on self-care, an important aspect of nursing intervention via evaluation and education, but its meaning remains unprecise due to the difficulty integrating the diverse definitions developed over time across disciplines. Therefore, it is vital to clarify the meaning of self-care and formulate the defining attributes, antecedents, and consequences to self-care. METHODS: Walker and Avant's concept analysis approach was used to analyze the concept of self-care. A search of the literature was completed using the databases CINAHL, PubMed, and EBSCOhost for years 1975-2020; literature search included peer-review articles, full-text publications, and available in English. A total of 31 articles were reviewed, and saturation was reached. RESULTS: An extensive review of the literature revealed salient characteristics that reflected the most frequently used terms associated with the concept. Guided by Walker and Avant's method, three defining attributes emerged as common themes: awareness, self-control, and self-reliance. CONCLUSIONS: A clarified definition was identified: the ability to care for oneself through awareness, self-control, and self-reliance in order to achieve, maintain, or promote optimal health and well-being.

12.
Health Equity ; 5(1): 151-159, 2021.
Article in English | MEDLINE | ID: mdl-33937600

ABSTRACT

Purpose: Increasing patient activation facilitates self-management of health, improves health outcomes, and lowers health care expenditures. Extant research notes mixed findings in patient activation by race/ethnicity. The purpose of the study was to examine the relationships among patient activation, select patient characteristics, and glycemic control among Filipino Americans. Methods: A cross-sectional study was conducted with a convenience sample of Filipino Americans (n=191), with a diagnosis of diabetes mellitus type 1 or type 2, recruited from a southern California adult primary care clinic between December 2017 and March 2018. Patient activation, select characteristics, and hemoglobin A1c (HbA1c) levels were assessed. Bivariate and logistic regression analyses were used to identify correlates of glycemic control. The Strengthening the Reporting of Observational studies in Epidemiology (STROBE) checklist was used to develop the study. Results: Participants with HgbA1C≤7.0% reported statistically higher patient activation measure (13 items) (PAM-13) natural log score (mean [M]=60.32, standard deviation [SD]=13.50) compared to those with an HgbA1C>7.0%, M=52.58, SD=10.19, F(1)=11.05, p<0.001. Multivariate logistic regression using age, low-density lipoprotein, and PAM-13 natural log was statistically reliable distinguishing between A1C≤7.0 and A1C>7.0, -2 LogLikehood=1183.23, χ 2(3)=15.44, p<0.001. Conclusions: Patient activation is an important factor in supporting glycemic control. Findings support interventions to target patient activation. Providers are encouraged to use racial/ethnic-centered engagement strategies in resolving health disparity with racial and ethnic minorities to facilitate patient activation and improve health outcomes in patients with diabetes.

13.
Nat Commun ; 11(1): 5045, 2020 10 07.
Article in English | MEDLINE | ID: mdl-33028813

ABSTRACT

Fluorine is a key element in the synthesis of molecules broadly used in medicine, agriculture and materials. Addition of fluorine to organic structures represents a unique strategy for tuning molecular properties, yet this atom is rarely found in Nature and approaches to integrate fluorometabolites into the biochemistry of living cells are scarce. In this work, synthetic gene circuits for organofluorine biosynthesis are implemented in the platform bacterium Pseudomonas putida. By harnessing fluoride-responsive riboswitches and the orthogonal T7 RNA polymerase, biochemical reactions needed for in vivo biofluorination are wired to the presence of fluoride (i.e. circumventing the need of feeding expensive additives). Biosynthesis of fluoronucleotides and fluorosugars in engineered P. putida is demonstrated with mineral fluoride both as only fluorine source (i.e. substrate of the pathway) and as inducer of the synthetic circuit. This approach expands the chemical landscape of cell factories by providing alternative biosynthetic strategies towards fluorinated building-blocks.


Subject(s)
Gene Regulatory Networks , Halogenation/genetics , Metabolic Engineering/methods , Pseudomonas putida/metabolism , Synthetic Biology/methods , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Biosynthetic Pathways/genetics , DNA-Directed RNA Polymerases/genetics , Fluorides/metabolism , Fluorine/metabolism , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , Mutation , Pseudomonas putida/genetics , RNA, Bacterial/genetics , Riboswitch/genetics , Viral Proteins/genetics
15.
Microb Biotechnol ; 13(4): 997-1011, 2020 07.
Article in English | MEDLINE | ID: mdl-32064751

ABSTRACT

In contrast to the current paradigm of using microbial mono-cultures in most biotechnological applications, increasing efforts are being directed towards engineering mixed-species consortia to perform functions that are difficult to programme into individual strains. In this work, we developed a synthetic microbial consortium composed of two genetically engineered microbes, a cyanobacterium (Synechococcus elongatus PCC 7942) and a heterotrophic bacterium (Pseudomonas putida EM173). These microbial species specialize in the co-culture: cyanobacteria fix CO2 through photosynthetic metabolism and secrete sufficient carbohydrates to support the growth and active metabolism of P. putida, which has been engineered to consume sucrose and to degrade the environmental pollutant 2,4-dinitrotoluene (2,4-DNT). By encapsulating S. elongatus within a barium-alginate hydrogel, cyanobacterial cells were protected from the toxic effects of 2,4-DNT, enhancing the performance of the co-culture. The synthetic consortium was able to convert 2,4-DNT with light and CO2 as key inputs, and its catalytic performance was stable over time. Furthermore, cycling this synthetic consortium through low nitrogen medium promoted the sucrose-dependent accumulation of polyhydroxyalkanoate, an added-value biopolymer, in the engineered P. putida strain. Altogether, the synthetic consortium displayed the capacity to remediate the industrial pollutant 2,4-DNT while simultaneously synthesizing biopolymers using light and CO2 as the primary inputs.


Subject(s)
Pseudomonas putida , Biotransformation , Coculture Techniques , Dinitrobenzenes , Pseudomonas putida/genetics , Synechococcus
16.
Microb Biotechnol ; 12(1): 98-124, 2019 01.
Article in English | MEDLINE | ID: mdl-29926529

ABSTRACT

The last few years have witnessed an unprecedented increase in the number of novel bacterial species that hold potential to be used for metabolic engineering. Historically, however, only a handful of bacteria have attained the acceptance and widespread use that are needed to fulfil the needs of industrial bioproduction - and only for the synthesis of very few, structurally simple compounds. One of the reasons for this unfortunate circumstance has been the dearth of tools for targeted genome engineering of bacterial chassis, and, nowadays, synthetic biology is significantly helping to bridge such knowledge gap. Against this background, in this review, we discuss the state of the art in the rational design and construction of robust bacterial chassis for metabolic engineering, presenting key examples of bacterial species that have secured a place in industrial bioproduction. The emergence of novel bacterial chassis is also considered at the light of the unique properties of their physiology and metabolism, and the practical applications in which they are expected to outperform other microbial platforms. Emerging opportunities, essential strategies to enable successful development of industrial phenotypes, and major challenges in the field of bacterial chassis development are also discussed, outlining the solutions that contemporary synthetic biology-guided metabolic engineering offers to tackle these issues.


Subject(s)
Bacteria/genetics , Bacteria/metabolism , Biotechnology/methods , Metabolic Engineering/methods , Biotechnology/trends , Metabolic Engineering/trends , Synthetic Biology/methods
17.
Issues Ment Health Nurs ; 39(10): 840-849, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30277842

ABSTRACT

Post-traumatic stress disorder (PTSD) is an important and often neglected comorbidity of pregnancy; left untreated, it can lead to serious health complications for the mother and developing fetus. Structured interviews were conducted to identify risk factors of PTSD among culturally diverse women with depressive symptomatology receiving perinatal services at community obstetric/gynecologic clinics. Women abused as adults, with two or more instances of trauma, greater trauma severity, insomnia, and low social support were more likely to present perinatal PTSD symptoms. Perinatal PTSD is prevalent and has the potential for chronicity. It is imperative healthcare providers recognize salient risk factors and integrate culturally sensitive screening, appropriate referral, and treatment services for perinatal PTSD.


Subject(s)
Depression/epidemiology , Ethnicity/statistics & numerical data , Pregnancy Complications/epidemiology , Pregnancy Complications/psychology , Stress Disorders, Post-Traumatic/epidemiology , White People/statistics & numerical data , Adolescent , Adult , Cross-Sectional Studies , Female , Humans , Pregnancy , Risk Factors , Socioeconomic Factors , Young Adult
18.
Biotechnol Bioeng ; 115(3): 762-774, 2018 03.
Article in English | MEDLINE | ID: mdl-29131301

ABSTRACT

The soil bacterium Pseudomonas putida KT2440 has gained increasing biotechnological interest due to its ability to tolerate different types of stress. Here, the tolerance of P. putida KT2440 toward eleven toxic chemical compounds was investigated. P. putida was found to be significantly more tolerant toward three of the eleven compounds when compared to Escherichia coli. Increased tolerance was for example found toward p-coumaric acid, an interesting precursor for polymerization with a significant industrial relevance. The tolerance mechanism was therefore investigated using the genome-wide approach, Tn-seq. Libraries containing a large number of miniTn5-Km transposon insertion mutants were grown in the presence and absence of p-coumaric acid, and the enrichment or depletion of mutants was quantified by high-throughput sequencing. Several genes, including the ABC transporter Ttg2ABC and the cytochrome c maturation system (ccm), were identified to play an important role in the tolerance toward p-coumaric acid of this bacterium. Most of the identified genes were involved in membrane stability, suggesting that tolerance toward p-coumaric acid is related to transport and membrane integrity.


Subject(s)
Drug Resistance, Bacterial/genetics , Propionates/pharmacology , Pseudomonas putida , Coumaric Acids , Genome-Wide Association Study , Pseudomonas putida/genetics , Pseudomonas putida/metabolism
19.
Sci Rep ; 7(1): 18055, 2017 12 22.
Article in English | MEDLINE | ID: mdl-29273811

ABSTRACT

Biofilm dispersal is a genetically programmed response enabling bacterial cells to exit the biofilm in response to particular physiological or environmental conditions. In Pseudomonas putida biofilms, nutrient starvation triggers c-di-GMP hydrolysis by phosphodiesterase BifA, releasing inhibition of protease LapG by the c-di-GMP effector protein LapD, and resulting in proteolysis of the adhesin LapA and the subsequent release of biofilm cells. Here we demonstrate that the stringent response, a ubiquitous bacterial stress response, is accountable for relaying the nutrient stress signal to the biofilm dispersal machinery. Mutants lacking elements of the stringent response - (p)ppGpp sythetases [RelA and SpoT] and/or DksA - were defective in biofilm dispersal. Ectopic (p)ppGpp synthesis restored biofilm dispersal in a ∆relA ∆spoT mutant. In vivo gene expression analysis showed that (p)ppGpp positively regulates transcription of bifA, and negatively regulates transcription of lapA and the lapBC, and lapE operons, encoding a LapA-specific secretion system. Further in vivo and in vitro characterization revealed that the PbifA promoter is dependent on the flagellar σ factor FliA, and positively regulated by ppGpp and DksA. Our results indicate that the stringent response stimulates biofilm dispersal under nutrient limitation by coordinately promoting LapA proteolysis and preventing de novo LapA synthesis and secretion.


Subject(s)
Adhesins, Bacterial/metabolism , Biofilms , Pseudomonas putida/metabolism , Stress, Physiological/physiology , Gene Expression Regulation, Bacterial , Promoter Regions, Genetic
20.
Microb Cell Fact ; 15(1): 176, 2016 Oct 13.
Article in English | MEDLINE | ID: mdl-27737709

ABSTRACT

BACKGROUND: Economically viable biobased production of bulk chemicals and biofuels typically requires high product titers. During microbial bioconversion this often leads to product toxicity, and tolerance is therefore a critical element in the engineering of production strains. RESULTS: Here, a systems biology approach was employed to understand the chemical stress response of Escherichia coli, including a genome-wide screen for mutants with increased fitness during chemical stress. Twelve chemicals with significant production potential were selected, consisting of organic solvent-like chemicals (butanol, hydroxy-γ-butyrolactone, 1,4-butanediol, furfural), organic acids (acetate, itaconic acid, levulinic acid, succinic acid), amino acids (serine, threonine) and membrane-intercalating chemicals (decanoic acid, geraniol). The transcriptional response towards these chemicals revealed large overlaps of transcription changes within and between chemical groups, with functions such as energy metabolism, stress response, membrane modification, transporters and iron metabolism being affected. Regulon enrichment analysis identified key regulators likely mediating the transcriptional response, including CRP, RpoS, OmpR, ArcA, Fur and GadX. These regulators, the genes within their regulons and the above mentioned cellular functions therefore constitute potential targets for increasing E. coli chemical tolerance. Fitness determination of genome-wide transposon mutants (Tn-seq) subjected to the same chemical stress identified 294 enriched and 336 depleted mutants and experimental validation revealed up to 60 % increase in mutant growth rates. Mutants enriched in several conditions contained, among others, insertions in genes of the Mar-Sox-Rob regulon as well as transcription and translation related gene functions. CONCLUSIONS: The combination of the transcriptional response and mutant screening provides general targets that can increase tolerance towards not only single, but multiple chemicals.


Subject(s)
Escherichia coli/genetics , Escherichia coli/physiology , Gene Expression Regulation, Bacterial/genetics , Regulon , Stress, Physiological/genetics , 4-Butyrolactone/pharmacology , Biofuels , Butanols/pharmacology , Butylene Glycols/pharmacology , Drug Tolerance/genetics , Escherichia coli/drug effects , Escherichia coli Proteins/genetics , Gene Expression Profiling , Genes, Bacterial , Genome, Bacterial , Mutation , Organic Chemicals/pharmacology , Solvents/pharmacology , Succinates/pharmacology , Systems Biology/methods
SELECTION OF CITATIONS
SEARCH DETAIL
...