Siderophores and competition for iron govern myxobacterial predation dynamics.

Bacterial predators are decisive organisms that shape microbial ecosystems. In this study, we investigated the role of iron and siderophores during the predatory interaction between two rhizosphere bacteria: Myxococcus xanthus, an epibiotic predator, and Sinorhizobium meliloti, a bacterium that establishes nitrogen-fixing symbiosis with legumes. The results show that iron enhances the motility of the predator and facilitates its predatory capability, and that intoxication by iron is not used by the predator to prey, although oxidative stress increases in both bacteria during predation. However, competition for iron plays an important role in the outcome of predatory interactions. Using combinations of predator and prey mutants (non-producers and overproducers of siderophores), we have investigated the importance of competition for iron in predation. The results demonstrate that the competitor that, via the production of siderophores, obtains sufficient iron for growth and depletes metal availability for the opponent will prevail in the interaction. Consequently, iron fluctuations in soils may modify the composition of microbial communities by altering the activity of myxobacterial predators. In addition, siderophore overproduction during predation can alter soil properties, affecting the productivity and sustainability of agricultural operations.

Myxococcus xanthus predation: an updated overview.

Bacterial predators are widely distributed across a variety of natural environments. Understanding predatory interactions is of great importance since they play a defining role in shaping microbial communities in habitats such as soils. Myxococcus xanthus is a soil-dwelling bacterial predator that can prey on Gram-positive and Gram-negative bacteria and even on eukaryotic microorganisms. This model organism has been studied for many decades for its unusual lifecycle, characterized by the formation of multicellular fruiting bodies filled with myxospores. However, less is known about its predatory behavior despite being an integral part of its lifecycle. Predation in M. xanthus is a multifactorial process that involves several mechanisms working synergistically, including motility systems to efficiently track and hunt prey, and a combination of short-range and contact-dependent mechanisms to achieve prey death and feed on them. In the short-range attack, M. xanthus is best known for the collective production of secondary metabolites and hydrolytic enzymes to kill prey and degrade cellular components. On the other hand, contact-dependent killing is a cell-to-cell process that relies on Tad-like and type III secretion systems. Furthermore, recent research has revealed that metals also play an important role during predation, either by inducing oxidative stress in the prey, or by competing for essential metals. In this paper, we review the current knowledge about M. xanthus predation, focusing on the different mechanisms used to hunt, kill, and feed on its prey, considering the most recent discoveries and the transcriptomic data available.

Transcriptomic response of Sinorhizobium meliloti to the predatory attack of Myxococcus xanthus.

Bacterial predation impacts microbial community structures, which can have both positive and negative effects on plant and animal health and on environmental sustainability. Myxococcus xanthus is an epibiotic soil predator with a broad range of prey, including Sinorhizobium meliloti, which establishes nitrogen-fixing symbiosis with legumes. During the M. xanthus-S. meliloti interaction, the predator must adapt its transcriptome to kill and lyse the target (predatosome), and the prey must orchestrate a transcriptional response (defensome) to protect itself against the biotic stress caused by the predatory attack. Here, we describe the transcriptional changes taking place in S. meliloti in response to myxobacterial predation. The results indicate that the predator induces massive changes in the prey transcriptome with up-regulation of protein synthesis and secretion, energy generation, and fatty acid (FA) synthesis, while down-regulating genes required for FA degradation and carbohydrate transport and metabolism. The reconstruction of up-regulated pathways suggests that S. meliloti modifies the cell envelop by increasing the production of different surface polysaccharides (SPSs) and membrane lipids. Besides the barrier role of SPSs, additional mechanisms involving the activity of efflux pumps and the peptide uptake transporter BacA, together with the production of H2O2 and formaldehyde have been unveiled. Also, the induction of the iron-uptake machinery in both predator and prey reflects a strong competition for this metal. With this research we complete the characterization of the complex transcriptional changes that occur during the M. xanthus-S. meliloti interaction, which can impact the establishment of beneficial symbiosis with legumes.

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Development versus predation: Transcriptomic changes during the lifecycle of Myxococcus xanthus.

Myxococcus xanthus is a multicellular bacterium with a complex lifecycle. It is a soil-dwelling predator that preys on a wide variety of microorganisms by using a group and collaborative epibiotic strategy. In the absence of nutrients this myxobacterium enters in a unique developmental program by using sophisticated and complex regulatory systems where more than 1,400 genes are transcriptional regulated to guide the community to aggregate into macroscopic fruiting bodies filled of environmentally resistant myxospores. Herein, we analyze the predatosome of M. xanthus, that is, the transcriptomic changes that the predator undergoes when encounters a prey. This study has been carried out using as a prey Sinorhizobium meliloti, a nitrogen fixing bacteria very important for the fertility of soils. The transcriptional changes include upregulation of genes that help the cells to detect, kill, lyse, and consume the prey, but also downregulation of genes not required for the predatory process. Our results have shown that, as expected, many genes encoding hydrolytic enzymes and enzymes involved in biosynthesis of secondary metabolites increase their expression levels. Moreover, it has been found that the predator modifies its lipid composition and overproduces siderophores to take up iron. Comparison with developmental transcriptome reveals that M. xanthus downregulates the expression of a significant number of genes coding for regulatory elements, many of which have been demonstrated to be key elements during development. This study shows for the first time a global view of the M. xanthus lifecycle from a transcriptome perspective.

Exercise Capacity and Physical Activity in Non-Cystic Fibrosis Bronchiectasis after a Pulmonary Rehabilitation Home-Based Programme: A Randomised Controlled Trial.

BACKGROUND: Patients with chronic respiratory disease have low exercise capacity and limited physical activity (PA), which is associated with worsening dyspnoea, exacerbations, and quality of life. The literature regarding patients with non-cystic fibrosis bronchiectasis (non-CF BQ) is scarce, especially regarding the use of cardiopulmonary exercise tests (CPET) to assess the effects of home-based pulmonary rehabilitation programmes (HPRP). The aim was to evaluate the effect of an HPRP on the exercise capacity of non-CF BQ patients using CPET and PA using an accelerometer. METHODS: Our study describes a non-pharmacological clinical trial in non-CF BQ patients at the Virgen Macarena University Hospital (Seville, Spain). The patients were randomised into two groups: a control group (CG), which received general advice on PA and educational measures, and the intervention group (IG), which received a specific 8-week HPRP with two hospital sessions. The variables included were those collected in the CPET, the accelerometer, and others such as a 6 min walking test (6MWT) and dyspnoea. The data were collected at baseline and at an 8-week follow-up. RESULTS: After the intervention, there was a significant increase in peak VO2 in the IG, which was not evidenced in the GC (IG 66.8 ± 15.5 mL/min p = 0.001 vs. CG 62.2 ± 14.14 mL/min, p = 0.30). As well, dyspnoea according to the mMRC (modified Medical Research Council), improved significantly in IG (2.19 ± 0.57 to 1.72 ± 0.05, p = 0.047) vs. CG (2.07 ± 0.7 to 2.13 ± 0.64, p = 0.36). In addition, differences between the groups in walked distance (IG 451.19 ± 67.99 m, p = 0.001 vs. CG 433.13 ± 75.88 m, p = 0.981) and in physical activity (IG 6591 ± 3482 steps, p = 0.007 vs. CG 4824 ± 3113 steps, p = 0.943) were found. CONCLUSION: Participation in a specific HPRP improves exercise capacity, dyspnoea, walked distance, and PA in non-CF BQ patients.

Inspiratory Muscle Training in Patients with Chronic Obstructive Pulmonary Disease (COPD) as Part of a Respiratory Rehabilitation Program Implementation of Mechanical Devices: A Systematic Review.

Chronic Obstructive Pulmonary Disease (COPD) is a complex and heterogeneous disease, with pulmonary and extrapulmonary manifestations, which leads to the need to personalize the assessment and treatment of these patients. The latest updates of national and international guidelines for the management of COPD reveal the importance of respiratory rehabilitation (RR) and its role in improving symptoms, quality of life, and psychosocial sphere of patients. Within RR, the inspiratory muscle training (IMT) has received special interest, showing benefits in maximum inspiratory pressure, perception of well-being, and health status in patients with chronic heart disease, respiratory diseases, and dyspnea during exercise. The aim of this review is to assess the efficacy of IMT in COPD patients through the use of inspiratory muscle training devices, compared with respiratory rehabilitation programs without inspiratory muscle training. In the last years, many mechanical devices focused on inspiratory muscle training have been developed, some of them, such as the AirOFit PRO™, PowerBreath®, or FeelBreathe®, have shown clear benefits. The active search for candidate patients to undergo the RR program with inspiratory muscle training using this type of device in COPD patients represents an advance in the treatment of this disease, with direct benefits on the quality of life of the patients. In this article, we review the available evidence on IMT in these patients and describe the different devices used for it.

Mechanisms of Action of Non-Canonical ECF Sigma Factors.

Extracytoplasmic function (ECF) sigma factors are subunits of the RNA polymerase specialized in activating the transcription of a subset of genes responding to a specific environmental condition. The signal-transduction pathways where they participate can be activated by diverse mechanisms. The most common mechanism involves the action of a membrane-bound anti-sigma factor, which sequesters the ECF sigma factor, and releases it after the stimulus is sensed. However, despite most of these systems following this canonical regulation, there are many ECF sigma factors exhibiting a non-canonical regulatory mechanism. In this review, we aim to provide an updated and comprehensive view of the different activation mechanisms known for non-canonical ECF sigma factors, detailing their inclusion to the different phylogenetic groups and describing the mechanisms of regulation of some of their representative members such as EcfG from Rhodobacter sphaeroides, showing a partner-switch mechanism; EcfP from Vibrio parahaemolyticus, with a phosphorylation-dependent mechanism; or CorE from Myxococcus xanthus, regulated by a metal-sensing C-terminal extension.

Antimicrobial Activity of Metals and Metalloids.

Competition shapes evolution. Toxic metals and metalloids have exerted selective pressure on life since the rise of the first organisms on the Earth, which has led to the evolution and acquisition of resistance mechanisms against them, as well as mechanisms to weaponize them. Microorganisms exploit antimicrobial metals and metalloids to gain competitive advantage over other members of microbial communities. This exerts a strong selective pressure that drives evolution of resistance. This review describes, with a focus on arsenic and copper, how microorganisms exploit metals and metalloids for predation and how metal- and metalloid-dependent predation may have been a driving force for evolution of microbial resistance against metals and metalloids.

Chronic Effects of a Training Program Using a Nasal Inspiratory Restriction Device on Elite Cyclists.

This study compared the response of a 9-week cycling training on ventilatory efficiency under two conditions: (i) Combined with respiratory muscle training (RMT) using a new nasal restriction device (FeelBreathe) (FB group) and (ii) without RMT (Control group). Eighteen healthy elite cyclists were randomly separated into the FB group (n = 10) or Control group (n = 8). Gas exchange was measured breath by breath to measure ventilatory efficiency during an incremental test on a cycloergometer before (Pre) and after (Post) the nine weeks of training. The FB group showed higher peak power (Δ (95%HDI) (0.82 W/kg (0.49, 1.17)), VO2max (5.27 mL/kg/min (0.69, 10.83)) and VT1 (29.3 W (1.8, 56.7)) compared to Control at PostFINAL. The FB group showed lower values from Pre to PostPRE in minute ventilation (VE) (-21.0 L/min (-29.7, -11.5)), Breathing frequency (BF) (-5.1 breaths/min (-9.4, -0.9)), carbon dioxide output (VCO2) (-0.5 L/min (-0.7, -0.2)), respiratory equivalents for oxygen (EqO2) (-0.8 L/min (-2.4, 0.8)), heart rate (HR) (-5.9 beats/min (-9.2, -2.5)),, respiratory exchange ratio (RER) (-0.1 (-0.1, -0.0) and a higher value in inspiratory time (Tin) (0.05 s (0.00, 0.10)), expiratory time (Tex) (0.11 s (0.05, 0.17)) and end-tidal partial pressure of CO2 (PETCO2) (0.3 mmHg (0.1, 0.6)). In conclusion, RMT using FB seems to be a new and easy alternative ergogenic tool which can be used at the same time as day-to-day training for performance enhancement.

The antibiotic crisis: How bacterial predators can help.

Discovery of antimicrobials in the past century represented one of the most important advances in public health. Unfortunately, the massive use of these compounds in medicine and other human activities has promoted the selection of pathogens that are resistant to one or several antibiotics. The current antibiotic crisis is creating an urgent need for research into new biological weapons with the ability to kill these superbugs. Although a proper solution requires this problem to be addressed in a variety of ways, the use of bacterial predators is emerging as an excellent strategy, especially when used as whole cell therapeutic agents, as a source of new antimicrobial agents by awakening silent metabolic pathways in axenic cultures, or as biocontrol agents. Moreover, studies on their prey are uncovering mechanisms of resistance that can be shared by pathogens, representing new targets for novel antimicrobial agents. In this review we discuss potential of the studies on predator-prey interaction to provide alternative solutions to the problem of antibiotic resistance.

Copper and Melanin Play a Role in Myxococcus xanthus Predation on Sinorhizobium meliloti.

Myxococcus xanthus is a soil myxobacterium that exhibits a complex lifecycle with two multicellular stages: cooperative predation and development. During predation, myxobacterial cells produce a wide variety of secondary metabolites and hydrolytic enzymes to kill and consume the prey. It is known that eukaryotic predators, such as ameba and macrophages, introduce copper and other metals into the phagosomes to kill their prey by oxidative stress. However, the role of metals in bacterial predation has not yet been established. In this work, we have addressed the role of copper during predation of M. xanthus on Sinorhizobium meliloti. The use of biosensors, variable pressure scanning electron microscopy, high-resolution scanning transmission electron microscopy, and energy dispersive X ray analysis has revealed that copper accumulates in the region where predator and prey collide. This accumulation of metal up-regulates the expression of several mechanisms involved in copper detoxification in the predator (the P1 B-ATPase CopA, the multicopper oxidase CuoA and the tripartite pump Cus2), and the production by the prey of copper-inducible melanin, which is a polymer with the ability to protect cells from oxidative stress. We have identified two genes in S. meliloti (encoding a tyrosinase and a multicopper oxidase) that participate in the biosynthesis of melanin. Analysis of prey survivability in the co-culture of M. xanthus and a mutant of S. meliloti in which the two genes involved in melanin biosynthesis have been deleted has revealed that this mutant is more sensitive to predation than the wild-type strain. These results indicate that copper plays a role in bacterial predation and that melanin is used by the prey to defend itself from the predator. Taking into consideration that S. meliloti is a nitrogen-fixing bacterium in symbiosis with legumes that coexists in soils with M. xanthus and that copper is a common metal found in this habitat as a consequence of several human activities, these results provide clear evidence that the accumulation of this metal in the soil may influence the microbial ecosystems by affecting bacterial predatory activities.

Transcriptome dynamics of the Myxococcus xanthus multicellular developmental program.

The bacterium Myxococcus xanthus exhibits a complex multicellular life cycle. In the presence of nutrients, cells prey cooperatively. Upon starvation, they enter a developmental cycle wherein cells aggregate to produce macroscopic fruiting bodies filled with resistant myxospores. We used RNA-Seq technology to examine the transcriptome of the 96 hr developmental program. These data revealed that 1415 genes were sequentially expressed in 10 discrete modules, with expression peaking during aggregation, in the transition from aggregation to sporulation, or during sporulation. Analysis of genes expressed at each specific time point provided insights as to how starving cells obtain energy and precursors necessary for assembly of fruiting bodies and into developmental production of secondary metabolites. This study offers the first global view of developmental transcriptional profiles and provides important tools and resources for future studies.

Fumadora con múltiples recaídas / Smokers with multiple relapses

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Metal-responsive RNA polymerase extracytoplasmic function (ECF) sigma factors.

In order to survive, bacteria must adapt to multiple fluctuations in their environment, including coping with changes in metal concentrations. Many metals are essential for viability, since they act as cofactors of indispensable enzymes. But on the other hand, they are potentially toxic because they generate reactive oxygen species or displace other metals from proteins, turning them inactive. This dual effect of metals forces cells to maintain homeostasis using a variety of systems to import and export them. These systems are usually inducible, and their expression is regulated by metal sensors and signal-transduction mechanisms, one of which is mediated by extracytoplasmic function (ECF) sigma factors. In this review, we have focused on the metal-responsive ECF sigma factors, several of which are activated by iron depletion (FecI, FpvI and PvdS), while others are activated by excess of metals such as nickel and cobalt (CnrH), copper (CarQ and CorE) or cadmium and zinc (CorE2). We focus particularly on their physiological roles, mechanisms of action and signal transduction pathways.

Definición y epidemiología de la enfermedad tromboembólica venosa / No disponible

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The complex global response to copper in the multicellular bacterium Myxococcus xanthus.

The complex copper response of the multicellular proteobacterium M. xanthus includes structural genes similar to those described in other bacteria, such as P1B-type ATPases, multicopper oxidases, and heavy metal efflux systems. However, the two time-dependent expression profiles of the different copper systems are unique. There are a number of genes responsible for an immediate response, whose expression increases after the addition of copper, but rapidly decreases thereafter to basal levels. The regulatory element that controls this early response is CorE, a novel extracytoplasmic function σ factor that is activated by Cu2+ and inactivated by Cu+. Other genes are part of a maintenance response. These genes show a profile that slows up after the copper addition and reaches a plateau at 24-48 h incubation. Most of the genes involved in this response are encoded by the operon curA, which is regulated by the two-component system CorSR. Moreover, other genes involved in the maintenance response are regulated by different regulatory elements that remain unknown. Additionally, copper activates the transcription of the structural genes for carotenoid synthesis through a mechanism that requires the activation of the σ factor CarQ. Bearing in mind that M. xanthus is not very resistant to copper, it is speculated that the complexity of its copper response might be related to its complex life cycle.

El porqué de la GesEPOC en nuestro entorno / The Rationale for GesEPOC in Our Environmen

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