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1.
EMBO J ; 41(13): e110352, 2022 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-35620914

RESUMEN

Beyond its role in cellular homeostasis, autophagy plays anti- and promicrobial roles in host-microbe interactions, both in animals and plants. One prominent role of antimicrobial autophagy is to degrade intracellular pathogens or microbial molecules, in a process termed xenophagy. Consequently, microbes evolved mechanisms to hijack or modulate autophagy to escape elimination. Although well-described in animals, the extent to which xenophagy contributes to plant-bacteria interactions remains unknown. Here, we provide evidence that Xanthomonas campestris pv. vesicatoria (Xcv) suppresses host autophagy by utilizing type-III effector XopL. XopL interacts with and degrades the autophagy component SH3P2 via its E3 ligase activity to promote infection. Intriguingly, XopL is targeted for degradation by defense-related selective autophagy mediated by NBR1/Joka2, revealing a complex antagonistic interplay between XopL and the host autophagy machinery. Our results implicate plant antimicrobial autophagy in the depletion of a bacterial virulence factor and unravel an unprecedented pathogen strategy to counteract defense-related autophagy in plant-bacteria interactions.


Asunto(s)
Enfermedades de las Plantas , Factores de Virulencia , Animales , Autofagia , Bacterias/metabolismo , Interacciones Huésped-Patógeno , Enfermedades de las Plantas/microbiología , Factores de Virulencia/genética , Factores de Virulencia/metabolismo
2.
Ecol Food Nutr ; 63(3): 229-250, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38526225

RESUMEN

This study identified determinants of malnutrition among school children in West Bengal, India. A total of 896 children aged between 4 and 13 years in eight districts were evaluated. BMI, weight, and height-for-age z-scores were used to categorize the stages of malnutrition. The study results revealed that the average height of the boys and girls was as per the standards set by the National Council of Health Sciences. Body mass index of the children ranged between 14.4 and 21.42 kg/m2, and stunting was 56.77%. Age and stunting were positively correlated in 5- to 10-year-old children. The most common deficiency was of fluoride.


Asunto(s)
Estatura , Índice de Masa Corporal , Trastornos del Crecimiento , Humanos , India/epidemiología , Niño , Femenino , Masculino , Preescolar , Adolescente , Trastornos del Crecimiento/epidemiología , Desnutrición/epidemiología , Trastornos de la Nutrición del Niño/epidemiología , Peso Corporal , Fluoruros , Estado Nutricional , Estudios Transversales , Instituciones Académicas
3.
J Biol Inorg Chem ; 28(2): 139-152, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36484825

RESUMEN

Several microbial pathogens are capable of forming biofilms. These microbial communities pose a serious challenge to the healthcare sector as they are quite difficult to combat. Given the challenges associated with the antibiotic-based management of biofilms, the research focus has now been shifted towards finding alternate treatment strategies that can replace or complement the antibacterial properties of antibiotics. The field of nanotechnology offers several novel and revolutionary approaches to eradicate biofilm-forming microbes. In this study, we evaluated the antibacterial and antibiofilm efficacy of in-house synthesized, tryptone-stabilized silver nanoparticles (Ts-AgNPs) against the superbug Serratia marcescens. The nanoparticles were of spherical morphology with an average hydrodynamic diameter of 170 nm and considerable colloidal stability with a Zeta potential of - 24 ± 6.15 mV. Ts-AgNPs showed strong antibacterial activities with a minimum inhibitory concentration (MIC50) of 2.5 µg/mL and minimum bactericidal concentration (MBC) of 12.5 µg/mL against S. marcescens. The nanoparticles altered the cell surface hydrophobicity and inhibited biofilm formation. The Ts-AgNPs were also effective in distorting pre-existing biofilms by degrading the extracellular DNA (eDNA) component of the extracellular polymeric substance (EPS) layer. Furthermore, reduction in quorum-sensing (QS)-induced virulence factors produced by S. marcescens indicated that Ts-AgNPs attenuated the QS pathway. Together, these findings suggest that Ts-AgNPs are an important anti-planktonic and antibiofilm agent that can be explored for both the prevention and treatment of infections caused by S. marcescens.


Asunto(s)
Nanopartículas del Metal , Serratia marcescens , Serratia marcescens/genética , Plata/farmacología , Plata/química , Nanopartículas del Metal/química , Matriz Extracelular de Sustancias Poliméricas , Biopelículas , Antibacterianos/farmacología , Antibacterianos/química , Pruebas de Sensibilidad Microbiana
4.
Plant J ; 107(6): 1771-1787, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34250673

RESUMEN

Upon immune activation, chloroplasts switch off photosynthesis, produce antimicrobial compounds and associate with the nucleus through tubular extensions called stromules. Although it is well established that chloroplasts alter their position in response to light, little is known about the dynamics of chloroplast movement in response to pathogen attack. Here, we report that during infection with the Irish potato famine pathogen Phytophthora infestans, chloroplasts accumulate at the pathogen interface, associating with the specialized membrane that engulfs the pathogen haustorium. The chemical inhibition of actin polymerization reduces the accumulation of chloroplasts at pathogen haustoria, suggesting that this process is partially dependent on the actin cytoskeleton. However, chloroplast accumulation at haustoria does not necessarily rely on movement of the nucleus to this interface and is not affected by light conditions. Stromules are typically induced during infection, embracing haustoria and facilitating chloroplast interactions, to form dynamic organelle clusters. We found that infection-triggered stromule formation relies on BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1 (BAK1)-mediated surface immune signaling, whereas chloroplast repositioning towards haustoria does not. Consistent with the defense-related induction of stromules, effector-mediated suppression of BAK1-mediated immune signaling reduced stromule formation during infection. On the other hand, immune recognition of the same effector stimulated stromules, presumably via a different pathway. These findings implicate chloroplasts in a polarized response upon pathogen attack and point to more complex functions of these organelles in plant-pathogen interactions.


Asunto(s)
Cloroplastos/microbiología , Interacciones Huésped-Patógeno/fisiología , Nicotiana/microbiología , Phytophthora infestans/patogenicidad , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/microbiología , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Cloroplastos/efectos de los fármacos , Cloroplastos/inmunología , Dinitrobencenos/farmacología , Luz , Microscopía Confocal , Pinzas Ópticas , Enfermedades de las Plantas/microbiología , Inmunidad de la Planta , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/microbiología , Plantas Modificadas Genéticamente , Especies Reactivas de Oxígeno/metabolismo , Sulfanilamidas/farmacología , Tiazolidinas/farmacología , Nicotiana/efectos de los fármacos , Nicotiana/genética , Nicotiana/inmunología
5.
J Food Sci Technol ; 59(4): 1637-1648, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35250087

RESUMEN

A grain based carbonated beverage premix with adequate nutritional composition and fizzing effect in the form of dry powder has been developed in the current study. Maize and Bengal gram were roasted at temperature 160-180 °C while finger millet at 80-120 °C for 10-30 min. The optimized conditions for the roasting of maize, Bengal gram and finger millet were 180 °C for 10 min, 180 °C for 27 min and 110 °C for 30 min, respectively using face centred composite design and response surface methodology (RSM). The formulation of the beverage premix obtained using linear programming was in the proportion of 30 g, 30 g, 10 g, 20 g and 10 g of roasted maize, Bengal gram, finger millet flours, sugar (powdered) and pea protein isolate, respectively. The effect of carbonation was found to be best with 8% carbonation powder concentration and 1:4 beverage premix to water ratio which showed an overall acceptability of 7.7. The developed carbonated beverage premix was light in color with a positive L* value of 79.01 ± 0.12 and slightly acidic with a pH of 5.56 ± 0.10. The nutritional composition of the final product comprised of 16% protein and several minerals viz. Fe (11.67 mg/100 g), Ca (36.67 mg/100 g) and Mg (86.26 mg/100 g). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05175-5.

6.
BMC Health Serv Res ; 21(1): 1027, 2021 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-34587959

RESUMEN

BACKGROUND: In India, the distribution and retention of biomedical doctors in public sector facilities in rural areas is an obstacle to improving access to health services. The Government of Uttar Pradesh is developing a comprehensive, ten-year Human Resources for Health (HRH) strategy, which includes policies to address rural distribution and retention of government doctors in Uttar Pradesh (UP). We undertook a stakeholder analysis to understand stakeholder positions on particular policies within the strategy, and to examine how stakeholder power and interests would shape the development and implementation of these proposed policies. This paper focuses on the results of the stakeholder analysis pertaining to rural distribution and retention of doctors in the government sector in UP. Our objectives are to 1) analyze stakeholder power in influencing the adoption of policies; 2) compare and analyze stakeholder positions on specific policies, including their perspectives on the conditions for successful policy adoption and implementation; and 3) explore the challenges with developing and implementing a coordinated, 'bundled' approach to strengthening rural distribution and retention of doctors. METHODS: We utilized three forms of data collection for this study - document review, in-depth interviews and focus group discussions. We conducted 17 interviews and three focus group discussions with key stakeholders between September and November 2019. RESULTS: We found that the adoption of a coordinated policy approach for rural retention and distribution of doctors is negatively impacted by governance challenges and fragmentation within and beyond the health sector. Respondents also noted that the opposition to certain policies by health worker associations created challenges for comprehensive policy development. Finally, respondents believed that even in the event of policy adoption, implementation remained severely hampered by several factors, including weak mechanisms of accountability and perceived corruption at local, district and state level. CONCLUSION: Building on the findings of this analysis, we propose several strategies for addressing the challenges in improving access to government doctors in rural areas of UP, including additional policies that address key concerns raised by stakeholders, and improved mechanisms for coordination, accountability and transparency.


Asunto(s)
Médicos , Servicios de Salud Rural , Humanos , India , Políticas , Recursos Humanos
7.
BMC Public Health ; 20(1): 1737, 2020 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-33203407

RESUMEN

BACKGROUND: Ensuring the current public health workforce has appropriate competencies to fulfill essential public health functions is challenging in many low- and middle-income countries. The absence of an agreed set of core competencies to provide a basis for developing and assessing knowledge, skills, abilities, and attitudes contributes to this challenge. This study aims to identify the requisite core competencies for practicing health professionals in mid-level supervisory and program management roles to effectively perform their public health responsibilities in the resource-poor setting of Uttar Pradesh (UP), India. METHODS: We used a multi-step, interactive Delphi technique to develop an agreed set of public health competencies. A narrative review of core competency frameworks and key informant interviews with human resources for health experts in India were conducted to prepare an initial list of 40 competency statements in eight domains. We then organized a day-long workshop with 22 Indian public health experts and government officials, who added to and modified the initial list. A revised list of 54 competency statements was rated on a 5-point Likert scale. Aggregate statement scores were shared with the participants, who discussed the findings. Finally, the revised list was returned to participants for an additional round of ratings. The Wilcoxon matched-pairs signed-rank test was used to identify stability between steps, and consensus was defined using the percent agreement criterion. RESULTS: Stability between the first and second Delphi scoring steps was reached in 46 of the 54 statements. By the end of the second Delphi scoring step, consensus was reached on 48 competency statements across eight domains: public health sciences, assessment and analysis, policy and program management, financial management and budgeting, partnerships and collaboration, social and cultural determinants, communication, and leadership. CONCLUSIONS: This study produced a consensus set of core competencies and domains in public health that can be used to assess competencies of public health professionals and revise or develop new training programs to address desired competencies. Findings can also be used to support workforce development by informing competency-based job descriptions for recruitment and performance management in the Indian context, and potentially can be adapted for use in resource-poor settings globally.


Asunto(s)
Personal de Salud , Salud Pública , Consenso , Técnica Delphi , Humanos , India , Competencia Profesional
9.
J Contemp Dent Pract ; 20(3): 330-334, 2019 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-31204326

RESUMEN

AIM: T-Wire and rotating motion of two-shape (2S), M-wire and rotating motion of ProTaper Gold (PG) are the recent innovations of Nickle Titanium (NiTi) rotary file system by means of thermal treatment. Therefore, a study was planned to assess the shaping ability of 2 Shape and ProTaper Gold using cone beam computed tomography (CBCT) Materials and methods: Thirty freshly extracted mandibular first molars were selected, and Pre-instrumentation CBCT imaging was performed to attain mesial and distal dentin wall measurements followed by chemo-mechanical preparation using the following NiTi files: 2S and ProTaper Gold. Post instrumentation CBCT imaging was performed for evaluation of the volume of removed dentin, apical transportation, and centering ratio. Statistical analysis was confirmed by a suitable analysis test with significance set at 0.05r. RESULTS: In terms of the total volume of removed dentin, apical transportation, and centering ratio there was a significant difference noted between the tow-shape and ProTaper Gold. 2Shape performed better in all aspects compared to ProTaper Gold. CONCLUSION: Two-shape (2S) maintained better original canal anatomy and volume of removed dentin was also less during chemo-mechanical preparation when compared to ProTaper Gold. CLINICAL SIGNIFICANCE: Two-shape (2S) system when used clinically in patients may perform better and produce less canal transportation and canal preparation will be more centered as compared to the ProTaper Gold system.


Asunto(s)
Aleaciones Dentales , Cavidad Pulpar , Tomografía Computarizada de Haz Cónico , Diseño de Equipo , Oro , Humanos , Preparación del Conducto Radicular
10.
J Exp Bot ; 69(6): 1325-1333, 2018 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-29294077

RESUMEN

In plants, the highly conserved catabolic process of autophagy has long been known as a means of maintaining cellular homeostasis and coping with abiotic stress conditions. Accumulating evidence has linked autophagy to immunity against invading pathogens, regulating plant cell death, and antimicrobial defences. In turn, it appears that phytopathogens have evolved ways not only to evade autophagic clearance but also to modulate and co-opt autophagy for their own benefit. In this review, we summarize and discuss the emerging discoveries concerning how pathogens modulate both host and self-autophagy machineries to colonize their host plants, delving into the arms race that determines the fate of interorganismal interaction.


Asunto(s)
Autofagia/fisiología , Interacciones Huésped-Patógeno/inmunología , Inmunidad de la Planta , Plantas/inmunología , Autofagia/inmunología , Plantas/microbiología
11.
Antimicrob Agents Chemother ; 59(10): 6561-7, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26259792

RESUMEN

An effective regimen for treatment of tuberculosis (TB) is comprised of multiple drugs that inhibit a range of essential cellular activities in Mycobacterium tuberculosis. The effectiveness of a regimen is further enhanced if constituent drugs act with synergy. Here, we report that faropenem (a penem) or biapenem, doripenem, or meropenem (carbapenems), which belong to the ß-lactam class of antibiotics, and rifampin, one of the drugs that forms the backbone of TB treatment, act with synergy when combined. One of the reasons (carba)penems are seldom used for treatment of TB is the high dosage levels required, often at the therapeutic limits. The synergistic combination of rifampin and these (carba)penems indicates that (carba)penems can be administered at dosages that are therapeutically relevant. The combination of faropenem and rifampin also limits the frequency of resistant mutants, as we were unable to obtain spontaneous mutants in the presence of these two drugs. The combinations of rifampin and (carba)penems were effective not only against drug-sensitive Mycobacterium tuberculosis but also against drug-resistant clinical isolates that are otherwise resistant to rifampin. A combination of doripenem or biapenem and rifampin also exhibited synergistic activity against Mycobacterium abscessus. Although the MICs of these three drugs alone against M. abscessus are too high to be of clinical relevance, their concentrations in combinations are therapeutically relevant; therefore, they warrant further evaluation for clinical utility to treat Mycobacterium abscessus infection, especially in cystic fibrosis patients.


Asunto(s)
Antituberculosos/farmacología , Carbapenémicos/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium/efectos de los fármacos , Rifampin/farmacología , Doripenem , Sinergismo Farmacológico , Meropenem , Pruebas de Sensibilidad Microbiana , Tienamicinas/farmacología , beta-Lactamas/farmacología
12.
J Immunoassay Immunochem ; 36(6): 639-54, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25837831

RESUMEN

The aim of this article is to express envelope glycoprotein E2 of bovine viral diarrhea virus (BVDV) in yeast Pichia pastoris and its utility as a diagnostic antigen in ELISA. The BVDV E2 gene was cloned into the pPICZαA vector followed by integration into the Pichia pastoris strain X-33 genome for methanol-induced expression. SDS-PAGE and Western blot results showed that the recombinant BVDV E2 protein (72 kDa) was expressed and secreted into the medium at a concentration of 40 mg/L of culture under optimized conditions. An indirect ELISA was then developed by using the yeast-expressed E2 protein. Preliminary testing of 300 field cattle serum samples showed that the E2 ELISA showed a sensitivity of 91.07% and a specificity of 92.02% compared to the reference virus neutralization test. The concordance between the E2 ELISA and VNT was 91.67%. This study demonstrates feasibility of BVDV E2 protein expression in yeast Pichia pastoris for the first time and its efficacy as an antigen in ELISA for detecting BVDV neutralizing antibodies in cattle.


Asunto(s)
Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Diarrea Mucosa Bovina Viral/sangre , Virus de la Diarrea Viral Bovina , Expresión Génica , Pichia , Proteínas del Envoltorio Viral/química , Animales , Diarrea Mucosa Bovina Viral/genética , Diarrea Mucosa Bovina Viral/inmunología , Bovinos , Ensayo de Inmunoadsorción Enzimática/métodos , Pichia/genética , Pichia/metabolismo , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Proteínas del Envoltorio Viral/biosíntesis , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/inmunología
13.
Matern Child Nutr ; 11 Suppl 4: 188-202, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25682798

RESUMEN

Anaemia affects 46% of preschool-aged children in Nepal. A cluster-randomised study was conducted in rural Nepal to test whether providing micronutrient powders (MNP) in addition to enhanced homestead food production (EHFP) programme, consisting of home gardens, poultry and nutrition education, could lead to a higher reduction in anaemia compared with providing only EHFP. This sub-study enrolled 335 children aged 6-9 months into one of three groups: (1) EHFP + MNP; (2) EHFP; or (3) control. The EHFP + MNP group received 60 sachets of MNP for flexible consumption at the start and 6 months later for a total supplementation period of 11 months. The MNP contained 15 micronutrients including iron (10 mg encapsulated ferrous fumarate). Haemoglobin and anthropometry were measured at baseline and post-MNP supplementation. Mean ± SE haemoglobin concentration increased significantly in all groups, with a slightly higher but non-significant increase in the EHFP + MNP and EHFP compared with control (difference-in-differences: 4.1 g L(-1) for EHFP + MNP vs. control; 3.6 g L(-1) for EHFP vs. control; 0.5 g L(-1) for EHFP + MNP vs. EHFP). Anaemia decreased at a slightly higher magnitude in the EHFP + MNP [51.5 percentage points (PP)] than the EHFP (48.6 PP) and control (39.6 PP), with adjusted odds ratios (95% CI) at post-supplementation of 0.52 (0.25-1.12) for EHFP + MNP and 0.69 (0.35-1.36) for EHFP, compared with control. There was no impact on child growth. Combining EHFP and MNP programmes yielded a marginally significant reduction in anaemia among children.


Asunto(s)
Anemia Ferropénica/tratamiento farmacológico , Anemia Ferropénica/epidemiología , Suplementos Dietéticos , Micronutrientes/administración & dosificación , Análisis por Conglomerados , Relación Dosis-Respuesta a Droga , Femenino , Hemoglobinas/metabolismo , Humanos , Lactante , Hierro de la Dieta/administración & dosificación , Hierro de la Dieta/análisis , Modelos Logísticos , Estudios Longitudinales , Masculino , Nepal/epidemiología , Polvos , Prevalencia , Estudios Prospectivos
14.
Matern Child Nutr ; 11(4): 882-96, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23557321

RESUMEN

Global recommendations on strategies to improve infant feeding, care and nutrition are clear; however, there is limited literature that explains methods for tailoring these recommendations to the local context where programmes are implemented. This paper aims to: (1) highlight the individual, cultural and environmental factors revealed by formative research to affect infant and young child feeding and care practices in Baitadi district of Far Western Nepal; and (2) outline how both quantitative and qualitative research methods were used to design a context-specific behaviour change strategy to improve child nutrition. Quantitative data on 750 children aged 12-23 months and their families were collected via surveys administered to mothers. The participants were selected using a multistage cluster sampling technique. The survey asked about knowledge, attitude and behaviours relating to infant and young child feeding. Qualitative data on breastfeeding and complementary feeding beliefs and practices were also collected from a separate sample via focus group discussions with mothers, and key informant interviews with mothers-in-law and husbands. Key findings revealed gaps in knowledge among many informants resulting in suboptimal infant and young child feeding practices - particularly with relation to duration of exclusive breastfeeding and dietary diversity of complementary foods. The findings from this research were then incorporated into a context-specific nutrition behaviour change communication strategy.


Asunto(s)
Conducta Alimentaria , Fenómenos Fisiológicos Nutricionales del Lactante , Desnutrición/dietoterapia , Adulto , Índice de Masa Corporal , Lactancia Materna , Análisis por Conglomerados , Estudios de Evaluación como Asunto , Estudios de Factibilidad , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Lactante , Masculino , Leche Humana , Madres , Nepal , Estudios Retrospectivos , Factores Socioeconómicos , Adulto Joven
15.
J Antimicrob Chemother ; 69(2): 441-4, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24008825

RESUMEN

OBJECTIVES: To perform a multicentre study evaluating the performance of the direct nitrate reductase assay (NRA) for the detection of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis in sputum samples. METHODS: The study was conducted in six laboratories performing tuberculosis diagnosis that were located in six different countries. The NRA was performed directly on sputum samples in parallel with the reference method used at each site. Detection of resistance was performed for rifampicin, isoniazid, ofloxacin and kanamycin. RESULTS: Excellent agreement was obtained for all drugs tested at the majority of sites. The accuracy was 93.7%-100% for rifampicin, 88.2%-100% for isoniazid, 94.6%-100% for ofloxacin and 100% for kanamycin. The majority of NRA results were available at day 21 for sites 1, 2 and 5. Site 3 had a turnaround time of 13.9 days, at site 4 it was 18.4 days and at site 6 it was 16.2 days. The contamination rate ranged between 2.5% and 12%. CONCLUSIONS: Rapid detection of drug resistance by the direct NRA on sputum smear-positive samples was accurate and easy to implement in clinical diagnostic laboratories, making it a good alternative for rapid screening for MDR and XDR tuberculosis.


Asunto(s)
Tuberculosis Extensivamente Resistente a Drogas/diagnóstico , Tuberculosis Extensivamente Resistente a Drogas/enzimología , Pruebas de Sensibilidad Microbiana/normas , Nitrato-Reductasa , Humanos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Tiempo
16.
Cell Biochem Biophys ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702575

RESUMEN

In recent decades, the development of novel antimicrobials has significantly slowed due to the emergence of antimicrobial resistance (AMR), intensifying the global struggle against infectious diseases. Microbial populations worldwide rapidly develop resistance due to the widespread use of antibiotics, primarily targeting drug-resistant germs. A prominent manifestation of this resistance is the formation of biofilms, where bacteria create protective layers using signaling pathways such as quorum sensing. In response to this challenge, the CRISPR-Cas9 method has emerged as a ground-breaking strategy to counter biofilms. Initially identified as the "adaptive immune system" of bacteria, CRISPR-Cas9 has evolved into a state-of-the-art genetic engineering tool. Its exceptional precision in altering specific genes across diverse microorganisms positions it as a promising alternative for addressing antibiotic resistance by selectively modifying genes in diverse microorganisms. This comprehensive review concentrates on the historical background, discovery, developmental stages, and distinct components of CRISPR Cas9 technology. Emphasizing its role as a widely used genome engineering tool, the review explores how CRISPR Cas9 can significantly contribute to the targeted disruption of genes responsible for biofilm formation, highlighting its pivotal role in reshaping strategies to combat antibiotic resistance and mitigate the challenges posed by biofilm-associated infectious diseases.

17.
Biomed Mater ; 19(2)2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38364289

RESUMEN

Respiratory tract infections (RTIs) are a common cause of mortality and morbidity in the human population. The overuse of antibiotics to overcome such infections has led to antibiotic resistance. The emergence of multidrug resistant bacteria is necessitating the development of novel therapeutic techniques in order to avoid a major global clinical threat. Our study aims to investigate the potential of tryptone stabilised silver nanoparticles (Ts-AgNPs) on planktonic and biofilms produced byKlebsiella pneumoniae(K. pneumoniae)and Pseudomonas aeruginosa(P. aeruginosa). The MIC50of Ts-AgNPs was found to be as low as 1.7 µg ml-1and 2.7 µg ml-1forK. pneumoniae and P.aeruginosarespectively. Ts-AgNPs ability to alter redox environment by producing intracellular ROS, time-kill curves showing substantial decrease in the bacterial growth and significantly reduced colony forming units further validate its antimicrobial effect. The biofilm inhibition and eradication ability of Ts-AgNPs was found to be as high as 93% and 97% in both the tested organisms. A significant decrease in the eDNA and EPS quantity in Ts-AgNPs treated cells proved its ability to successfully distort the matrix and matured biofilms. Interestingly Ts-AgNPs also attenuated QS-induced virulence factors production. This study paves way to develop Ts-AgNPs as novel antibiotics against RTIs causing bacterial biofilms.


Asunto(s)
Nanopartículas del Metal , Peptonas , Infecciones del Sistema Respiratorio , Humanos , Plata/farmacología , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Biopelículas , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Pseudomonas aeruginosa
18.
Cureus ; 16(3): e55800, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38586725

RESUMEN

Listeria monocytogenes, a gram-positive bacillus and an intracellular pathogen, is an uncommon cause of illness in the general population. During pregnancy, a perinatal infection can lead to serious complications such as abortion, stillbirth, neonatal sepsis, and meningitis. We present two cases of neonatal meningitis caused by Christie, Atkins, Munch-Peterson (CAMP)-negative Listeria monocytogenes. In the first case, a seven-day-old female term neonate delivered vaginally, presented with high-grade fever and refusal to feed. In view of the suspected late-onset sepsis, a septic workup, including cerebrospinal fluid analysis, was conducted. CSF culture reports obtained showed a growth consistent with Listeria monocytogenes, which was CAMP test negative and susceptible to the penicillin group of drugs, cotrimoxazole, erythromycin, and meropenem. The isolate was identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and confirmed by 16S rRNA sequencing. The blood culture was sterile. At 48 hours of admission, the neonate clinically deteriorated with fluctuation in oxygen saturation below 95% at room air. Thus, she was electively intubated and connected to the mechanical ventilator with appropriate settings. The antibiotics were upgraded to meropenem from the empirical antibiotic therapy. The neonate showed clinical improvement within the next 24 hours of initiating antibiotics according to culture susceptibility and was gradually weaned from the mechanical ventilator to continuous positive airway pressure (CPAP). After 24 hours, she was able to maintain normal saturation at room air. In the second case, an 11-day-old low birth weight neonate, small for gestational age, was presented to the NICU with complaints of loose stools, fever, and refusal to feed for the past two days. In view of the suspected sepsis, relevant investigations were carried out while initiating empirical antibiotics IV piperacillin-tazobactam and IV amikacin for the neonate. Meanwhile, there was a dip in oxygen saturation noted on room air for the neonate and he/she was mechanically ventilated. The CSF culture grew Listeria monocytogenes,which was identified using MALDI-TOF MS and confirmed by 16S rRNA sequencing. The isolate tested negative for the CAMP test and was susceptible to ampicillin, penicillin, cotrimoxazole, erythromycin, and meropenem. The blood culture was sterile. The antibiotics were upgraded to meropenem from the empirical antibiotic therapy, the patient's condition improved, and the baby was eventually discharged.

19.
Chem Biol Interact ; 396: 111027, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38735452

RESUMEN

Antibiotic resistance poses a significant challenge in modern medicine, urging the exploration of innovative approaches to combat bacterial infections. Biofilms, complex bacterial communities encased in a protective matrix, contribute to resistance by impeding antibiotic efficacy and promoting genetic exchange. Understanding biofilm dynamics is crucial for developing effective antimicrobial therapies against antibiotic resistance. This study explores the potential of flavone to combat biofilm-induced antibiotic resistance by employing in-vitro biochemical, cell biology, and Insilico (MD simulation), approaches. Flavone exhibited potent antibacterial effects with a low minimum inhibitory concentration by inducing intracellular reactive oxygen species. Flavones further inhibited the formation of biofilms by 50-60 % and disrupted the pre-formed biofilms by reducing the extracellular polysaccharide substance protective layer formed on the biofilm by 80 %. Quorum sensing (QS) plays a crucial role in bacterial pathogenicity and flavone significantly attenuated the production of QS-induced virulence factors like urease, protease, lipase, hemolysin and prodigiosin pigment in a dose-dependent manner. Further Insilico molecular docking studies along with molecular dynamic simulations run for 100 ns proved the stable binding affinity of flavone with QS-specific proteins which are crucial for biofilm formation. This study demonstrates the therapeutic potential of flavone to target QS-signaling pathway to combat S.marcescens biofilms.


Asunto(s)
Antibacterianos , Biopelículas , Flavonas , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Percepción de Quorum , Biopelículas/efectos de los fármacos , Percepción de Quorum/efectos de los fármacos , Flavonas/farmacología , Flavonas/química , Antibacterianos/farmacología , Antibacterianos/química , Simulación de Dinámica Molecular , Especies Reactivas de Oxígeno/metabolismo , Farmacorresistencia Microbiana/efectos de los fármacos , Factores de Virulencia/metabolismo , Proteínas Bacterianas/metabolismo
20.
Glob Health Sci Pract ; 12(3)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38821871

RESUMEN

The state of Uttar Pradesh (UP), India, has one of the largest single public health systems globally, serving about 235 million people through more than 30,000 public health facilities with approximately 160,000 health personnel. Yet, the UP health system has a shortfall of public health facilities to meet the population's needs, a shortage of clinical and nonclinical health personnel, inequitable distribution of existing health personnel, and low utilization of public health facilities. A robust and effective electronic human resource management system (eHRMS) that provides real-time information about the lifecycle of all health professionals in UP may aid in improving the health workforce, resulting in better health services and improved health outcomes. The Government of UP rolled out Manav Sampada, a comprehensive eHRMS that complied with global norms and requirements. We describe the implementation of Manav Sampada at scale and elaborate on key learnings and adoption strategies. Manav Sampada was based on key principles of integration and data-sharing with other digital systems, included functional components, a minimum dataset, used a lifecycle-based approach, and a workflow-based system, all of which acted to improve human resource data quality. The eHRMS emerged as a valuable tool for key stakeholders in reviewing worker performance, identifying skill-building needs, and allocating resources for training, leading to improved availability and equity in the distribution of a few critical cadres. The eHRMS in UP is well positioned to become an integral part of the Ayushman Bharat Digital Mission, the backbone of India's integrated digital health infrastructure. Linking eHRMS to a planned beneficiary-centric unitized health service delivery system (capturing information at the individual level rather than the aggregate level) will enable the measurement of service delivery and quality, leading to improved workforce management.


Asunto(s)
Fuerza Laboral en Salud , India , Humanos , Personal de Salud/educación
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