[Interventionism in congenital heart disease in Chiapas. The history after thousand cases performed]. / El intervencionismo en cardiopatías congénitas en Chiapas. La historia luego de mil casos realizados.

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.

Meeting Report of the Second Symposium of the Belgian Society for Viruses of Microbes and Launch of the Phage Valley.

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.

Distinct mode of action of a highly stable, engineered phage lysin killing Gram-negative bacteria.

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.

What's in a Name? An Overview of the Proliferating Nomenclature in the Field of Phage Lysins.

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.

Enzybiotic-mediated antimicrobial functionalization of polyhydroxyalkanoates.

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.

Alterations of the Ca2+ clearing mechanisms by type 2 diabetes in aortic smooth muscle cells of Zucker diabetic fatty rat.

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.

DEAE/Catechol-Chitosan Conjugates as Bioactive Polymers: Synthesis, Characterization, and Potential Applications.

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.

Improvement of the Antibacterial Activity of Phage Lysin-Derived Peptide P87 through Maximization of Physicochemical Properties and Assessment of Its Therapeutic Potential.

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.

Resistance Training Variables for Optimization of Muscle Hypertrophy: An Umbrella Review.

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.

Partially open stent after balloon catheter iatrogenic perforation. How to solve this complication using a novel technique? The Mij-Her technique.

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.

Monomodular Pseudomonas aeruginosa phage JG004 lysozyme (Pae87) contains a bacterial surface-active antimicrobial peptide-like region and a possible substrate-binding subdomain.

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.

Essential Topics for the Regulatory Consideration of Phages as Clinically Valuable Therapeutic Agents: A Perspective from Spain.

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.

Current outlook after 4 years since the beginning of interventional cardiology in congenital heart disease in Chiapas State / Panorama actual a 4 años del inicio de la cardiología intervencionista en cardiopatías congénitas en el Estado de Chiapas.

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.

Nanomedicina para enfrentar la pandemia de COVID-19: un análisis bibliométrico de las publicaciones de Web of Science con la herramienta Bibliometrix de R / Nanomedicine in the struggle against COVID-19: a bibliometric analysis of Web of Science publications with the R-tool Bibliometrix

La enfermedad de COVID-19, a poco más de un año de su aparición, ha provocado más de 2 000 000 de muertes y más de 100 000 000 de contagios a nivel mundial. Ante esta situación, científicos de varias disciplinas han trabajado arduamente para luchar contra ella. Una de las disciplinas involucradas en la investigación sobre COVID-19 es la nanomedicina, que se define como la aplicación de la nanotecnología en medicina. El objetivo de este trabajo es explorar, mediante un análisis bibliométrico, la producción científica sobre nanomedicina aplicada a la COVID-19. Se realizó una búsqueda de publicaciones en Web of Science para el período 2019 - 2021, la cual abarcó cinco áreas de la nanomedicina: administración de fármacos, fármacos y terapia, imagenología in vivo, biosensores y biomateriales. Los datos obtenidos de Web of Science se procesaron en Bibliometrix, una herramienta de código abierto, programada en lenguaje R, que sirve para hacer análisis bibliométricos. Se encontraron 155 publicaciones, las cuales en su mayoría son artículos y revisiones de literatura. Más del 70 por ciento de estas se concentraron en las áreas de administración de fármacos y biosensores. Las revistas científicas donde se han publicado más artículos son ACS Nano, Biosensors & Bioelectronics y Nanomaterials. Los países con mayor producción científica son Estados Unidos, India y China. Las contribuciones más relevantes de la nanomedicina en la lucha contra la COVID-19 son el desarrollo de nanovacunas y el diseño de biosensores nanoestructurados para el diagnóstico(AU)

In the period barely exceeding one year elapsed after its emergence, COVID-19 has caused more than 100 000 000 contagions and more than 2 000 000 deaths worldwide. Faced with this situation, scientists from various disciplines have arduously struggled against the disease. One of the disciplines involved in research about COVID-19 is nanomedicine, which is defined as the medical application of nanotechnology. The purpose of the study was to describe the current status of research about COVID-19 oriented nanomedicine through a bibliometric analysis. A search was conducted for Web of Science publications from the period 2019-2021, covering five nanomedicine areas: 1) drug administration, 2) drugs and therapy, 3) in vivo imaging, 4) biosensors and 5) biomaterials. The data obtained from Web of Science were processed with Bibliometrix, an open code tool programmed in R-language useful for bibliometric analysis. A total 155 publications were found, most of which were articles and literature reviews. More than 70percent of the publications dealt with drug administration and biosensors. The scientific journals publishing the largest number of articles were ACS Nano, Biosensors & Bioelectronics and Nanomaterials. The countries with the largest scientific production were the United States, India and China. The most relevant contributions of nanomedicine to the struggle against COVID-19 are the development of nano vaccines and the design of nanostructured biosensors for diagnosis.

Prognostic factors in cancer patients infected with SARS-CoV-2: a Latin American country results.

PURPOSE: The aim of this study was to evaluate the demographic characteristics, clinical and pathological factors, and the outcome of cancer and COVID-19 patients in Mexico. PATIENTS AND METHODS: A prospective, multicentric study was performed through a digital platform to have a national registry of patients with cancer and positive SARS-CoV-2 test results through reverse transcription quantitative polymerase chain reaction (RT-qPCR). We performed the analysis through a multivariate logistic regression model and Cox proportional hazard model. RESULTS: From May to December 2020, 599 patients were registered with an average age of 56 years with 59.3% female; 27.2% had hypertension. The most frequent diagnoses were breast cancer (30.4%), lymphoma (14.7%), and colorectal cancer (14.0%); 72.1% of patients had active cancer and 23.5% of patients (141/599) were deceased, the majority of which were men (51.7%). This study found that the prognostic factors that reduced the odds of death were gender (OR = 0.42, p = 0.031) and oxygen saturation (OR = 0.90, p = 0.0001); meanwhile, poor ECOG (OR = 5.4, p = 0.0001), active disease (OR = 3.9, p = 0.041), dyspnea (OR = 2.5, p = 0.027), and nausea (OR = 4.0, p = 0.028) increased the odds of death. In the meantime, the factors that reduce survival time were age (HR = 1.36, p = 0.035), COPD (HR = 8.30, p = 0.004), having palliative treatment (HR = 10.70, p = 0.002), and active cancer without treatment (HR = 8.68, p = 0.008). CONCLUSION: Mortality in cancer patients with COVID-19 is determined by prognostic factors whose identification is necessary. In our cancer population, we have observed that being female, younger, non-COPD, with non-active cancer, good performance status, and high oxygen levels reduce the probability of death.

DEAE-chitosan nanoparticles as a pneumococcus-biomimetic material for the development of antipneumococcal therapeutics.

Advanced biomaterials provide an interesting and versatile platform to implement new and more effective strategies to fight bacterial infections. Chitosan is one of these biopolymers and possesses relevant features for biomedical applications. Here we synthesized nanoparticles of chitosan derivatized with diethylaminoethyl groups (ChiDENPs) to emulate the choline residues in the pneumococcal cell wall and act as ligands for choline-binding proteins (CBPs). Firstly, we assessed the ability of diethylaminoethyl (DEAE) to sequester the CBPs present in the bacterial surface, thus promoting chain formation. Secondly, the CBP-binding ability of ChiDENPs was purposed to encapsulate a bio-active molecule, the antimicrobial enzyme Cpl-711 (ChiDENPs-711), with improved stability over non-derivatized chitosan. The enzyme-loaded system released more than 90% of the active enzybiotic in ≈ 2 h, above the usual in vivo half-life of this kind of enzymes. Therefore, ChiDENPs provide a promising platform for the controlled release of CBP-enzybiotics in biological contexts.

Mining of Gram-Negative Surface-Active Enzybiotic Candidates by Sequence-Based Calculation of Physicochemical Properties.

Phage (endo)lysins are nowadays one of the most promising ways out of the current antibiotic resistance crisis. Either as sole therapeutics or as a complement to common antibiotic chemotherapy, lysins are already entering late clinical phases to get regulatory agencies' authorization. Even the old paradigm of the inability of lysins to attack Gram-negative bacteria from without has already been overcome in a variety of ways: either by engineering approaches or investigating the natural mechanisms by which some wild-type lysins are able to interact with the bacterial surface. Such inherent ability of some lysins has been linked to antimicrobial peptide (AMP)-like regions, which are, on their own, a significant source for novel antimicrobials. Currently, though, many of the efforts for searching novel lysin-based antimicrobial candidates rely on experimental screenings. In this work, we have bioinformatically analyzed the C-terminal end of a collection of lysins from phages infecting the Gram-negative genus Pseudomonas. Through the computation of physicochemical properties, the probability of such regions to be an AMP was estimated by means of a predictive k-nearest neighbors (kNN) model. This way, a subset of putatively membrane-interacting lysins was obtained from the original database. Two of such candidates (named Pae87 and Ppl65) were prospectively tested in terms of muralytic, bacteriolytic, and bactericidal activity. Both of them were found to possess an activity against Pseudomonas aeruginosa and other Gram-negative bacterial pathogens, implying that the prediction of AMP-like regions could be a useful approach toward the mining of phage lysins to design and develop antimicrobials or antimicrobial parts for further engineering.

Sequence-Function Relationships in Phage-Encoded Bacterial Cell Wall Lytic Enzymes and Their Implications for Phage-Derived Product Design.

Phage (endo)lysins are thought to be a viable alternative to usual antibiotic chemotherapy to fight resistant bacterial infections. However, a comprehensive view of lysins' structure and properties regarding their function, with an applied focus, is somewhat lacking. Current literature suggests that specific features typical of lysins from phages infecting Gram-negative bacteria (G-) (higher net charge and amphipathic helices) are responsible for improved interaction with the G- envelope. Such antimicrobial peptide (AMP)-like elements are also of interest for antimicrobial molecule design. Thus, this study aims to provide an updated view on the primary structural landscape of phage lysins to clarify the evolutionary importance of several sequence-predicted properties, particularly for the interaction with the G- surface. A database of 2,182 lysin sequences was compiled, containing relevant information such as domain architectures, data on the phages' host bacteria, and sequence-predicted physicochemical properties. Based on such classifiers, an investigation of the differential appearance of certain features was conducted. This analysis revealed different lysin architectural variants that are preferably found in phages infecting certain bacterial hosts. In particular, some physicochemical properties (higher net charge, hydrophobicity, hydrophobic moment, and aliphatic index) were associated with G- phage lysins, appearing specifically at their C-terminal end. Information on the remarkable genetic specialization of lysins regarding the features of the bacterial hosts is provided, specifically supporting the nowadays-common hypothesis that lysins from G- usually contain AMP-like regions. IMPORTANCE Phage-encoded lytic enzymes, also called lysins, are one of the most promising alternatives to common antibiotics. The potential of lysins as novel antimicrobials to tackle antibiotic-resistant bacteria not only arises from features such as a lower chance to provoke resistance but also from their versatility as synthetic biology parts. Functional modules derived from lysins are currently being used for the design of novel antimicrobials with desired properties. This study provides a view of the lysin diversity landscape by examining a set of phage lysin genes. We have uncovered the fundamental differences between the lysins from phages that infect bacteria with different superficial architectures and, thus, the reach of their specialization regarding cell wall structures. These results provide clarity and evidence to sustain some of the common hypotheses in current literature, as well as making available an updated and characterized database of lysins sequences for further developments.

Utilization of Agave durangensis leaves by Bacillus cereus 4N for polyhydroxybutyrate (PHB) biosynthesis.

Lignocellulosic wastes may provide a means to economize polyhydroxybutyrate (PHB) production. This study has proposed the use of Agave durangensis leaves obtained from the artisanal mezcal industry as a novel substrate for this aim. Results revealed an increase in PHB biosynthesis (0.32 g/L) and improvement in %PHB (16.79-19.51%) by Bacillus cereus 4N when A. durangensis leaves used as carbon source were physically pre-treated by ultrasound for 30 min (ADL + US30') and thermally pre-treated (ADL + Q). Chemical analyses and SEM studies revealed compositional and morphological changes when A. durangensis leaves were physically pre-treated. Also, elemental analysis of growth media showed that carbon/nitrogen ratios of 14-21, and low nitrogen, hydrogen, and protein content were well-suited for PHB biosynthesis. Confocal microscopy revealed morphological changes in the bacterial cell and carbonosome structure under the influence of different substrates. Finally, Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) analyses showed that homopolymeric PHB with a high thermal-resistance (271.94-272.89 °C) was produced. Therefore, the present study demonstrates the potential use of physically pre-treated A. durangensis leaves to produce PHB. These results promote the development of a circular economy in Mexico, where lignocellulosic wastes can be employed to produce value-added biotechnological products.