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1.
Essays Biochem ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39290148

RESUMO

Phage lysins, bacteriophage-encoded enzymes tasked with degrading their host's cell wall, are increasingly investigated and engineered as novel antibacterials across diverse applications. Their rapid action, tuneable specificity, and low likelihood of resistance development make them particularly interesting. Despite numerous application-focused lysin studies, the art of their recombinant production remains relatively undiscussed. Here, we provide an overview of the available expression systems for phage lysin production and discuss key considerations guiding the choice of a suitable recombinant host. We systematically surveyed recent literature to evaluate the hosts used in the lysin field and cover various recombinant systems, including the well-known bacterial host Escherichia coli or yeast Saccharomyces cerevisiae, as well as plant, mammalian, and cell-free systems. Careful analysis of the limited studies expressing lysins in various hosts suggests a host-dependent effect on activity. Nonetheless, the multitude of available expression systems should be further leveraged to accommodate the growing interest in phage lysins and their expanding range of applications.

2.
PeerJ ; 12: e17724, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39175749

RESUMO

Discovering new deep hydrothermal vent systems is one of the biggest challenges in ocean exploration. They are a unique window to elucidate the physical, geochemical, and biological processes that occur on the seafloor and are involved in the evolution of life on Earth. In this study, we present a molecular analysis of the microbial composition within the newly discovered hydrothermal vent field, JaichMaa 'ja 'ag, situated in the Southern Pescadero Basin within the Gulf of California. During the cruise expedition FK181031 in 2018, 33 sediment cores were collected from various sites within the Pescadero vent fields and processed for 16S rRNA amplicon sequence variants (ASVs) and geochemical analysis. Correlative analysis of the chemical composition of hydrothermal pore fluids and microbial abundances identified several sediment-associated phyla, including Thermotogota, that appear to be enriched in sediment horizons impacted by hydrothermal fluid flow. Comparative analysis of Thermotogota with the previously explored Auka hydrothermal vent field situated 2 km away displayed broad similarity between the two locations, although at finer scales (e.g., ASV level), there were notable differences that point to core-to-core and site-level factors revealing distinct patterns of distribution and abundance within these two sediment-hosted hydrothermal vent fields. These patterns are intricately linked to the specific physical and geochemical conditions defining each vent, illuminating the complexity of this unique deep ocean chemosynthetic ecosystem.


Assuntos
Sedimentos Geológicos , Fontes Hidrotermais , Fontes Hidrotermais/microbiologia , Sedimentos Geológicos/microbiologia , Sedimentos Geológicos/química , RNA Ribossômico 16S/genética , Biodiversidade , Água do Mar/microbiologia , Água do Mar/química , California , Bactérias/genética , Bactérias/classificação
3.
Microb Biotechnol ; 17(7): e14513, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38962879

RESUMO

The phage lysin field has done nothing but grow in the last decades. As a result, many different research groups around the world are contributing to the field, often with certain methodological differences that pose a challenge to the interpretation and comparison of results. In this work, we present the case study of three Acinetobacter baumannii-targeting phage lysins (wild-type endolysin LysMK34 plus engineered lysins eLysMK34 and 1D10) plus one lysin with broad activity against Gram-positive bacteria (PlySs2) to provide exemplary evidence on the risks of generalization when using one of the most common lysin evaluation assays: the killing assay with resting cells. To that end, we performed killing assays with the aforementioned lysins using hypo-, iso- and hypertonic buffers plus human serum either as the reaction or the dilution medium in a systematic manner. Our findings stress the perils of creating hypotonic conditions or a hypotonic shock during a killing assay, suggesting that hypotonic buffers should be avoided as a test environment or as diluents before plating to avoid overestimation of the killing effect in the assayed conditions. As a conclusion, we suggest that the nature of both the incubation and the dilution buffers should be always clearly identified when reporting killing activity data, and that for experimental consistency the same incubation buffer should be used as a diluent for posterior serial dilution and plating unless explicitly required by the experimental design. In addition, the most appropriate buffer mimicking the final application must be chosen to obtain relevant results.


Assuntos
Acinetobacter baumannii , Bacteriófagos , Bacteriófagos/química , Bacteriófagos/fisiologia , Bacteriófagos/genética , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/virologia , Concentração Osmolar , Viabilidade Microbiana/efeitos dos fármacos , Soluções Tampão , Humanos , Proteínas Virais/genética , Proteínas Virais/metabolismo , Proteínas Virais/química , Endopeptidases/metabolismo , Endopeptidases/química
4.
Artigo em Inglês | MEDLINE | ID: mdl-39080103

RESUMO

Endolysins, proteins encoded by phages to lyse their hosts and release their progeny, have evolved to adapt to the structural features of each host. The endolysins from Staphylococcus-infecting phages typically feature complex architectures with two enzymatically active domains (EADs) and one cell wall-binding domain (CBD) belonging to the bacterial SH3 (SH3b) superfamily. This study focuses on three SH3b-like CBDs from representative staphylococcal phage endolysins (LysRODI, LysC1C and LysIPLA5) that were structurally and functionally characterized. While RODI_CBD and C1C_CBD were assigned to the well-known SH3_5 family, a new family, SH3b_T (PF24246), was identified using the CBD from LysIPLA5 as a model. GFP-fused CBDs were created to assess their differential binding to a collection of staphylococcal strains. IPLA5_CBD showed enhanced binding to Staphylococcus epidermidis, while RODI_CBD and C1C_CBD exhibited distinct binding profiles, with RODI_CBD targeting Staphylococcus aureus specifically and C1C_CBD displaying broad binding. Sequence comparisons suggested that a few differences in key amino acids could be responsible for the latter binding difference. The CBDs modulated the activity spectrum of synthetic EAD-CBD combinations in accordance with the previous binding profiles, but in a manner that was also dependent on the EAD present in the fusion protein. These results serve as a context for the diversity and versatility of SH3b domains in staphylococcal endolysins, providing insights on how (i) the CBDs from this superfamily have diverged to adapt to diverse bacterial ligands in spite of sharing a common fold; and (ii) the evolution of specificity relies on the EAD-CBD combination rather than solely the CBD.

5.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-39025362

RESUMO

INTRODUCTION: Greater Trochanteric Pain Syndrome (GTPS) is a multifactorial clinical condition affecting the lateral area of the hip. Although conservative treatment shows good results, some patients may still require surgical bursectomy, which can be performed either openly or endoscopically. One of the main technical difficulties of the endoscopic procedure is intraoperative bleeding, which can hinder the medical team's vision and increase the operation time for endoscopic treatment of GTPS. HYPOTHESIS: An instillation of vasoconstrictors and local anesthetics before endoscopy will cause less intraoperative bleeding, which will translate into shorter surgical time. MATERIALS AND METHODS: A prospective cohort was retrospectively divided based on the use or absence of a preoperative instillation of physiological saline solution with epinephrine and lidocaine. Surgical time was measured in each procedure and compared between the two groups. RESULTS: 139 hips from 139 patients were included in the analysis. 102 patients were included in the instillation group versus 37 in the control group. The surgical time was significantly shorter in the instillation group than in the control group, with an average (standard deviation) of 52.01 (14.71) and 72.30 (11.70) minutes, respectively (p < 0.001). CONCLUSION: The instillation of a physiological saline solution with epinephrine and lidocaine prior to the surgical treatment of GTPS is effective in reducing surgical times, likely due to a reduction in intraoperative bleeding. Future research should focus on more direct outcomes such as intraoperative blood loss and between different instillation protocols.

6.
Environ Technol ; : 1-13, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940278

RESUMO

Covered anaerobic lagoons (CALs) are Latin America's main livestock waste treatment systems. Mexico has 680 CALs that present low biogas yields (0.05 m3 m-3 digester d-1) and low COD removal rates (< 60%). This work focused on diagnosing CAL´s low performance in dairy farms by determining and analyzing operational parameters. Seven CALs located in the main dairy basin of Mexico were analyzed. The sampling areas for each CAL were the supernatant, the active zone, settled sludge, and digester inlet and outlet. The variation of the process parameter values corroborated that CALs appeared stratified and not working as expected. The sludge zone, comprising 50-58% of total solids content and 1-15% of total CALs volume, showed an elemental compounds content suitable for organic fertilizer (340, 48, and 5 kg t-1 of C, N, and S, respectively). However, this zone contained, at least, 85% of the slowly hydrolysable material; the methanogenic potential was less than 87 mL CH4 g VS-1, and the C/N ratio ranged from 4.9 to 17, outside of the optimal range. The biogas produced did not exceed 60% of methane content and more than 3000 ppm of H2S. The sludge zone significantly influences the lagoon's dynamics since it is a nutrient sink. Furthermore, the lack of agitation is the leading cause for the low energy yield and the low removal of organic matter rate. This work provides valuable information to address the operational problems within the CALs improving our understanding that shall allow proposing reactivation alternatives.

7.
Arch Cardiol Mex ; 94(3): 300-308, 2024 02 01.
Artigo em Espanhol | MEDLINE | ID: mdl-38301069

RESUMO

Background: Congenital heart disease is the most common birth defect and the leading cause of childhood mortality in high-income countries. In these countries, the prognosis for a child born with congenital heart disease is excellent, with over 90% achieving adulthood. However, in the low and lower-middle-income countries, as ours, the outlook is starkly different. In Chiapas, because of the progress of the hemodynamics program, more and more types of congenital heart diseases are susceptible to being treated by cardiac catheterization. Objective: To show the global experience of the interventionism in congenital heart diseases in Chiapas from its inception to recent days. Method: Through a retrospective study from April 2016 to June 2023, we reviewed the electronic files of the total of patients who underwent cardiac catheterism during the same period of time. Results: A total of 1000 procedures were performed, 581 in female patients, with a median age of 4 years (1 day to 77 years). Of the total procedures, 115 (11.5%) were diagnostic catheterizations and 885 (88.5%) were interventional. Conclusions: Cardiac catheterization in pediatrics in Chiapas has displaced cardiac surgery in a large percentage, and the results that have been obtained are undoubtedly encouraging, which already represents a decentralization in the care of congenital heart diseases in our country.


Antecedentes: Las cardiopatías congénitas son el defecto congénito más común y la primera causa de mortalidad infantil en los países de alto ingreso económico. En estos países, el pronóstico de los pacientes nacidos con estos defectos es excelente, llegando el 90% de ellos hasta la edad adulta. Sin embargo, en los países de mediano o bajo ingreso económico, como el nuestro, el pronóstico es completamente distinto. En el Estado de Chiapas, como resultado del avance del programa de hemodinamia, cada vez más tipos de cardiopatías congénitas son susceptibles de ser tratadas por cateterismo cardiaco. Objetivo: Mostrar la experiencia global actual de la hemodinamia en cardiopatías congénitas en Chiapas después de haber alcanzado los primeros 1000 casos realizados desde el inicio de nuestro programa. Método: A través de un estudio retrospectivo que abarcó de abril de 2016 a junio de 2023 revisamos los expedientes electrónicos del total de pacientes que fueron llevados a cateterismo cardiaco durante ese periodo. Resultados: Se realizaron un total de 1000 procedimientos, 581 en pacientes del sexo femenino, con una mediana de edad de 4 años (1 día a 77 años). Del total de los procedimientos, 115 (11.5%) fueron cateterismos diagnósticos y 885 (88.5%) intervencionistas. Conclusiones: El cateterismo cardiaco en cardiopatías congénitas en el Estado de Chiapas ha desplazado a la cirugía cardiaca en un amplio porcentaje, y los resultados obtenidos son sin duda alentadores, lo cual representa ya una descentralización en la atención de las cardiopatías congénitas en nuestro país.


Assuntos
Cateterismo Cardíaco , Cardiopatias Congênitas , Humanos , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/terapia , Cardiopatias Congênitas/epidemiologia , Estudos Retrospectivos , Feminino , Cateterismo Cardíaco/estatística & dados numéricos , Lactente , Masculino , México/epidemiologia , Criança , Pré-Escolar , Adolescente , Recém-Nascido , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Procedimentos Cirúrgicos Cardíacos/métodos
8.
Viruses ; 16(2)2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-38400074

RESUMO

The second symposium of the Belgian Society for Viruses of Microbes (BSVoM) took place on 8 September 2023 at the University of Liège with 141 participants from 10 countries. The meeting program covered three thematic sessions opened by international keynote speakers: two sessions were devoted to "Fundamental research in phage ecology and biology" and the third one to the "Present and future applications of phages". During this one day symposium, four invited keynote lectures, nine selected talks and eight student pitches were given along with thirty presented posters. The president of the Belgian Society for Viruses of Microbes, Prof. Yves Briers, took advantage of this symposium to launch the Phage Valley concept that will put the spotlight on the exceptionally high density of researchers investigating viruses of microbes as well as the successful triple helix approach between academia, industry and government in Belgium.


Assuntos
Bacteriófagos , Humanos , Bélgica , Meio Ambiente , Ecologia , Estudantes
9.
Microbiol Spectr ; 11(6): e0181323, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37971248

RESUMO

IMPORTANCE: Engineered lysins are considered as highly promising alternatives for antibiotics. Our previous screening study using VersaTile technology identified 1D10 as a possible lead compound with activity against Acinetobacter baumannii strains under elevated human serum concentrations. In this manuscript, we reveal an unexpected mode of action and exceptional thermoresistance for lysin 1D10. Our findings shed new light on the development of engineered lysins, providing valuable insights for future research in this field.


Assuntos
Bacteriófagos , Humanos , Bacteriófagos/genética , Antibacterianos/farmacologia , Bactérias Gram-Negativas
10.
Cells ; 12(15)2023 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-37566095

RESUMO

In the last few years, the volume of research produced on phage lysins has grown spectacularly due to the interest in using them as alternative antimicrobials. As a result, a plethora of naming customs has sprouted among the different research groups devoted to them. While the naming diversity accounts for the vitality of the topic, on too many occasions it also creates some confusion and lack of comparability between different works. This article aims at clarifying the ambiguities found among names referring to phage lysins. We do so by tackling the naming customs historically, framing their original adoption, and employing a semantic classification to facilitate their discussion. We propose a periodization of phage lysin research that begins at the discovery era, in the early 20th century, enriches with a strong molecular biology period, and grows into a current time of markedly applied research. During these different periods, names referring to the general concepts surrounding lysins have been created and adopted, as well as other more specific terms related to their structure and function or, finally, names that have been coined for the antimicrobial application and engineering of phage lysins. Thus, this article means to serve as an invitation to the global lysin community to take action and discuss a widely supported, standardized nomenclature.


Assuntos
Bacteriófagos , N-Acetil-Muramil-L-Alanina Amidase
11.
Front Bioeng Biotechnol ; 11: 1220336, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37449090

RESUMO

Polymeric nanoparticles (NPs) present some ideal properties as biomedical nanocarriers for targeted drug delivery such as enhanced translocation through body barriers. Biopolymers, such as polyhydroxyalkanoates (PHAs) are gaining attention as nanocarrier biomaterials due to their inherent biocompatibility, biodegradability, and ability to be vehiculized through hydrophobic media, such as the lung surfactant (LS). Upon colonization of the lung alveoli, below the LS layer, Streptococcus pneumoniae, causes community-acquired pneumonia, a severe respiratory condition. In this work, we convert PHA NPs into an antimicrobial material by the immobilization of an enzybiotic, an antimicrobial enzyme, via a minimal PHA affinity tag. We first produced the fusion protein M711, comprising the minimized PHA affinity tag, MinP, and the enzybiotic Cpl-711, which specifically targets S. pneumoniae. Then, a PHA nanoparticulate suspension with adequate physicochemical properties for pulmonary delivery was formulated, and NPs were decorated with M711. Finally, we assessed the antipneumococcal activity of the nanosystem against planktonic and biofilm forms of S. pneumoniae. The resulting system displayed sustained antimicrobial activity against both, free and sessile cells, confirming that tag-mediated immobilization of enzybiotics on PHAs is a promising platform for bioactive antimicrobial functionalization.

12.
Front Physiol ; 14: 1200115, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37250131

RESUMO

Type 2 Diabetes Mellitus (T2DM) is a rapidly rising disease with cardiovascular complications constituting the most common cause of death among diabetic patients. Chronic hyperglycemia can induce vascular dysfunction through damage of the components of the vascular wall, such as vascular smooth muscle cells (VSMCs), which regulate vascular tone and contribute to vascular repair and remodeling. These functions are dependent on intracellular Ca2+ changes. The mechanisms by which T2DM affects Ca2+ handling in VSMCs still remain poorly understood. Therefore, the objective of this study was to determine whether and how T2DM affects Ca2+ homeostasis in VSMCs. We evaluated intracellular Ca2+ signaling in VSMCs from Zucker Diabetic Fatty rats using Ca2+ imaging with Fura-2/AM. Our results indicate that T2DM decreases Ca2+ release from the sarcoplasmic reticulum (SR) and increases the activity of store-operated channels (SOCs). Moreover, we were able to identify an enhancement of the activity of the main Ca2+ extrusion mechanisms (SERCA, PMCA and NCX) during the early stage of the decay of the ATP-induced Ca2+ transient. In addition, we found an increase in Ca2+ entry through the reverse mode of NCX and a decrease in SERCA and PMCA activity during the late stage of the signal decay. These effects were appreciated as a shortening of ATP-induced Ca2+ transient during the early stage of the decay, as well as an increase in the amplitude of the following plateau. Enhanced cytosolic Ca2+ activity in VSMCs could contribute to vascular dysfunction associated with T2DM.

14.
Biomacromolecules ; 24(2): 613-627, 2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-36594453

RESUMO

This work provides the first description of the synthesis and characterization of water-soluble chitosan (Cs) derivatives based on the conjugation of both diethylaminoethyl (DEAE) and catechol groups onto the Cs backbone (Cs-DC) in order to obtain a Cs derivative with antioxidant and antimicrobial properties. The degree of substitution [DS (%)] was 35.46% for DEAE and 2.53% for catechol, determined by spectroscopy. Changes in the molecular packing due to the incorporation of both pendant groups were described by X-ray diffraction and thermogravimetric analysis. For Cs, the crystallinity index was 59.46% and the maximum decomposition rate appeared at 309.3 °C, while for Cs-DC, the values corresponded to 16.98% and 236.4 °C, respectively. The incorporation of DEAE and catechol groups also increases the solubility of the polymer at pH > 7 without harming the antimicrobial activity displayed by the unmodified polymer. The catecholic derivatives increase the radical scavenging activity in terms of the half-maximum effective concentration (EC50). An EC50 of 1.20 µg/mL was found for neat hydrocaffeic acid (HCA) solution, while for chitosan-catechol (Cs-Ca) and Cs-DC solutions, concentrations equivalent to free HCA of 0.33 and 0.41 µg/mL were required, respectively. Cell culture results show that all Cs derivatives have low cytotoxicity, and Cs-DC showed the ability to reduce the activity of reactive oxygen species by 40% at concentrations as low as 4 µg/mL. Polymeric nanoparticles of Cs derivatives with a hydrodynamic diameter (Dh) of around 200 nm, unimodal size distributions, and a negative ζ-potential were obtained by ionotropic gelation and coated with hyaluronic acid in aqueous suspension, providing the multifunctional nanoparticles with higher stability and a narrower size distribution.


Assuntos
Anti-Infecciosos , Quitosana , Nanopartículas , Quitosana/farmacologia , Quitosana/química , Polímeros/farmacologia , Catecóis/farmacologia , Catecóis/química , Nanopartículas/química , Anti-Infecciosos/farmacologia
15.
Antibiotics (Basel) ; 11(10)2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36290106

RESUMO

Phage lysins are a promising alternative to common antibiotic chemotherapy. However, they have been regarded as less effective against Gram-negative pathogens unless engineered, e.g., by fusing them to antimicrobial peptides (AMPs). AMPs themselves pose an alternative to antibiotics. In this work, AMP P87, previously derived from a phage lysin (Pae87) with a presumed nonenzymatic mode-of-action, was investigated to improve its antibacterial activity. Five modifications were designed to maximize the hydrophobic moment and net charge, producing the modified peptide P88, which was evaluated in terms of bactericidal activity, cytotoxicity, MICs or synergy with antibiotics. P88 had a better bactericidal performance than P87 (an average of 6.0 vs. 1.5 log-killing activity on Pseudomonas aeruginosa strains treated with 10 µM). This did not correlate with a dramatic increase in cytotoxicity as assayed on A549 cell cultures. P88 was active against a range of P. aeruginosa isolates, with no intrinsic resistance factors identified. Synergy with some antibiotics was observed in vitro, in complex media, and in a respiratory infection mouse model. Therefore, P88 can be a new addition to the therapeutic toolbox of alternative antimicrobials against Gram-negative pathogens as a sole therapeutic, a complement to antibiotics, or a part to engineer proteinaceous antimicrobials.

16.
Front Sports Act Living ; 4: 949021, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35873210

RESUMO

This umbrella review aimed to analyze the different variables of resistance training and their effect on hypertrophy, and to provide practical recommendations for the prescription of resistance training programs to maximize hypertrophy responses. A systematic research was conducted through of PubMed/MEDLINE, SPORTDiscus and Web of Science following the preferred reporting items for systematic reviews and meta-analyses statement guidelines. A total of 52 meta-analyses were found, of which 14 met the inclusion criteria. These studies were published between 2009 and 2020 and comprised 178 primary studies corresponding to 4,784 participants. Following a methodological quality analysis, nine meta-analyses were categorized as high quality, presenting values of 81-88%. The remaining meta-analyses were rated as moderate quality, with values between 63-75%. Based on this umbrella review, we can state that at least 10 sets per week per muscle group is optimal, that eccentric contractions seem important, very slow repetitions (≥10 s) should be avoided, and that blood flow restriction might be beneficial for some individuals. In addition, other variables as, exercise order, time of the day and type of periodization appear not to directly influence the magnitude of muscle mass gains. These findings provide valuable information for the design and configuration of the resistance training program with the aim of optimizing muscle hypertrophy.

17.
Cardiol Young ; : 1-3, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35510298

RESUMO

Complications related to pulmonary artery stenting are potentially life-threatening. We reported a novel technique of how to achieve the introduction of a partial dilated stent into a long sheath using a snare in the event of a iatrogenic perforation of a balloon catheter.There are no publications of similar techniques describing successful resolution of this type of complication.

18.
Microorganisms ; 10(4)2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35456768

RESUMO

Antibiotic resistance is one of the major challenges that humankind shall face in the short term. (Bacterio)phage therapy is a valuable therapeutic alternative to antibiotics and, although the concept is almost as old as the discovery of phages, its wide application was hindered in the West by the discovery and development of antibiotics in the mid-twentieth century. However, research on phage therapy is currently experiencing a renaissance due to the antimicrobial resistance problem. Some countries are already adopting new ad hoc regulations to favor the short-term implantation of phage therapy in clinical practice. In this regard, the Phage Therapy Work Group from FAGOMA (Spanish Network of Bacteriophages and Transducing Elements) recently contacted the Spanish Drugs and Medical Devices Agency (AEMPS) to promote the regulation of phage therapy in Spain. As a result, FAGOMA was asked to provide a general view on key issues regarding phage therapy legislation. This review comes as the culmination of the FAGOMA initiative and aims at appropriately informing the regulatory debate on phage therapy.

19.
Acta Crystallogr D Struct Biol ; 78(Pt 4): 435-454, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35362467

RESUMO

Phage lysins are a source of novel antimicrobials to tackle the bacterial antibiotic-resistance crisis. The engineering of phage lysins is being explored as a game-changing technological strategy to introduce a more precise approach in the way in which antimicrobial therapy is applied. Such engineering efforts will benefit from a better understanding of lysin structure and function. In this work, the antimicrobial activity of the endolysin from Pseudomonas aeruginosa phage JG004, termed Pae87, has been characterized. This lysin had previously been identified as an antimicrobial agent candidate that is able to interact with the Gram-negative surface and disrupt it. Further evidence is provided here based on a structural and biochemical study. A high-resolution crystal structure of Pae87 complexed with a peptidoglycan fragment showed a separate substrate-binding region within the catalytic domain, 18 Šaway from the catalytic site and located on the opposite side of the lysin molecule. This substrate-binding region was conserved among phylogenetically related lysins lacking an additional cell-wall-binding domain, but not among those containing such a module. Two glutamic acids were identified to be relevant for the peptidoglycan-degradation activity, although the antimicrobial activity of Pae87 was seemingly unrelated. In contrast, an antimicrobial peptide-like region within the Pae87 C-terminus, named P87, was found to be able to actively disturb the outer membrane and display antibacterial activity by itself. Therefore, an antimicrobial mechanism for Pae87 is proposed in which the P87 peptide plays the role of binding to the outer membrane and disrupting the cell-wall function, either with or without the participation of the catalytic activity of Pae87.


Assuntos
Bacteriófagos , Fagos de Pseudomonas , Peptídeos Antimicrobianos , Bacteriófagos/metabolismo , Muramidase/metabolismo , Pseudomonas aeruginosa
20.
Arch Cardiol Mex ; 92(2): 157-164, 2022 04 04.
Artigo em Espanhol | MEDLINE | ID: mdl-34010273

RESUMO

Introduction: As a result of technological advances, more and more types of congenital heart diseases are susceptible to being treated in the hemodynamic laboratory. The sum of more advanced imaging techniques as well as the development of a diversity of devices specially manufactured for use in children has allowed a better selection of patients and therefore that many of them can be corrected through cardiac catheterization or some patients with more complex congenital heart diseases require fewer surgical procedures or, if they do require them, that these may be of less complexity and risk. Objective: We decided to show the global experience of the interventionism in congenital heart diseases in Chiapas from its inception to recent days. Methods: Through a retrospective study from April 2016 to August 2020, we reviewed the electronic files of the total of patients who underwent cardiac catheterism during the same period of time. Results: A total of 510 procedures were performed, 300 in female patients, with a median age of 4 years (8 days - 77 years). Of the total procedures, 67 (13.1%) were diagnostic catheterizations and 443 (86.9%) were interventional. Conclusions: Cardiac catheterization in congenital heart disease in Chiapas has become a very valuable option with encouraging results which represents a possible decentralization in the care of congenital heart diseases in our country.


Introducción: Como resultado de avances tecnológicos, cada vez más tipos de cardiopatías congénitas son susceptibles a ser tratadas en el laboratorio de hemodinamia. La suma de técnicas de imagen más avanzadas, así como el desarrollo de una diversidad de dispositivos especialmente fabricados para su uso en niños ha permitido una mejor selección de pacientes y, por ende, que muchos de ellos pueden ser corregidos en su totalidad por medio de cateterismo cardiaco o bien que algunos pacientes con enfermedades cardiacas más complejas requieran menos procedimientos quirúrgicos o si los requieren, que estos sean de menor complejidad y riesgo. Objetivo: Decidimos mostrar la experiencia global de la hemodinamia en cardiopatías congénitas en Chiapas desde sus inicios hasta últimas fechas. Método: Mediante un estudio retrospectivo que abarcó de abril de 2016 a agosto de 2020 revisamos los expedientes electrónicos del total de pacientes que fueron llevados a cateterismo cardiaco durante ese periodo de tiempo. Resultados: Un total de 510 procedimientos fueron llevados a cabo, 300 en pacientes del sexo femenino, con una mediana de edad de 4 años (8 días - 77 años). Del total de procedimientos, 67 (13.1%) fueron cateterismos diagnósticos y 443 (86.9%) intervencionistas. Conclusión: El cateterismo cardiaco en cardiopatías congénitas en el Estado de Chiapas se ha convertido en una opción muy valiosa con resultados bastante alentadores, lo cual representa ya una posible descentralización en la atención de las cardiopatías congénitas en nuestro país.


Assuntos
Cardiologia , Cardiopatias Congênitas , Adolescente , Adulto , Idoso , Cateterismo Cardíaco/métodos , Criança , Pré-Escolar , Feminino , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/cirurgia , Hemodinâmica , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
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