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1.
Adapting to survive: How Candida overcomes host-imposed constraints during human colonization.
Alves, R, Barata-Antunes, C, Casal, M, Brown, AJP, Van Dijck, P, Paiva, S
PLoS pathogens. 2020;(5):e1008478
Abstract
Successful human colonizers such as Candida pathogens have evolved distinct strategies to survive and proliferate within the human host. These include sophisticated mechanisms to evade immune surveillance and adapt to constantly changing host microenvironments where nutrient limitation, pH fluctuations, oxygen deprivation, changes in temperature, or exposure to oxidative, nitrosative, and cationic stresses may occur. Here, we review the current knowledge and recent findings highlighting the remarkable ability of medically important Candida species to overcome a broad range of host-imposed constraints and how this directly affects their physiology and pathogenicity. We also consider the impact of these adaptation mechanisms on immune recognition, biofilm formation, and antifungal drug resistance, as these pathogens often exploit specific host constraints to establish a successful infection. Recent studies of adaptive responses to physiological niches have improved our understanding of the mechanisms established by fungal pathogens to evade the immune system and colonize the host, which may facilitate the design of innovative diagnostic tests and therapeutic approaches for Candida infections.
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2.
Protein kinase-mediated signalling in priming: Immune signal initiation, propagation, and establishment of long-term pathogen resistance in plants.
Hake, K, Romeis, T
Plant, cell & environment. 2019;(3):904-917
Abstract
"Priming" in plant phytopathology describes a phenomenon where the "experience" of primary infection by microbial pathogens leads to enhanced and beneficial protection of the plant against secondary infection. The plant is able to establish an immune memory, a state of systemic acquired resistance (SAR), in which the information of "having been attacked" is integrated with the action of "being prepared to defend when it happens again." Accordingly, primed plants are often characterized by faster and stronger activation of immune reactions that ultimately result in a reduction of pathogen spread and growth. Prerequisites for SAR are (a) the initiation of immune signalling subsequent to pathogen recognition, (b) a rapid defence signal propagation from a primary infected local site to uninfected distal parts of the plant, and (c) a switch into an immune signal-dependent establishment and subsequent long-lasting maintenance of phytohormone salicylic acid-based systemic immunity. Here, we provide a summary on protein kinases that contribute to these three conceptual aspects of "priming" in plant phytopathology, complemented by data addressing the role of protein kinases crucial for immune signal initiation also for signal propagation and SAR.
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3.
Complex interplay between neutral and adaptive evolution shaped differential genomic background and disease susceptibility along the Italian peninsula.
Sazzini, M, Gnecchi Ruscone, GA, Giuliani, C, Sarno, S, Quagliariello, A, De Fanti, S, Boattini, A, Gentilini, D, Fiorito, G, Catanoso, M, et al
Scientific reports. 2016;:32513
Abstract
The Italian peninsula has long represented a natural hub for human migrations across the Mediterranean area, being involved in several prehistoric and historical population movements. Coupled with a patchy environmental landscape entailing different ecological/cultural selective pressures, this might have produced peculiar patterns of population structure and local adaptations responsible for heterogeneous genomic background of present-day Italians. To disentangle this complex scenario, genome-wide data from 780 Italian individuals were generated and set into the context of European/Mediterranean genomic diversity by comparison with genotypes from 50 populations. To maximize possibility of pinpointing functional genomic regions that have played adaptive roles during Italian natural history, our survey included also ~250,000 exomic markers and ~20,000 coding/regulatory variants with well-established clinical relevance. This enabled fine-grained dissection of Italian population structure through the identification of clusters of genetically homogeneous provinces and of genomic regions underlying their local adaptations. Description of such patterns disclosed crucial implications for understanding differential susceptibility to some inflammatory/autoimmune disorders, coronary artery disease and type 2 diabetes of diverse Italian subpopulations, suggesting the evolutionary causes that made some of them particularly exposed to the metabolic and immune challenges imposed by dietary and lifestyle shifts that involved western societies in the last centuries.
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4.
Carbohydrate availability and exercise training adaptation: too much of a good thing?
Bartlett, JD, Hawley, JA, Morton, JP
European journal of sport science. 2015;(1):3-12
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Abstract
Traditional nutritional approaches to endurance training have typically promoted high carbohydrate (CHO) availability before, during and after training sessions to ensure adequate muscle substrate to meet the demands of high daily training intensities and volumes. However, during the past decade, data from our laboratories and others have demonstrated that deliberately training in conditions of reduced CHO availability can promote training-induced adaptations of human skeletal muscle (i.e. increased maximal mitochondrial enzyme activities and/or mitochondrial content, increased rates of lipid oxidation and, in some instances, improved exercise capacity). Such data have led to the concept of 'training low, but competing high' whereby selected training sessions are completed in conditions of reduced CHO availability (so as to promote training adaptation), but CHO reserves are restored immediately prior to an important competition. The augmented training response observed with training-low strategies is likely regulated by enhanced activation of key cell signalling kinases (e.g. AMPK, p38MAPK), transcription factors (e.g. p53, PPARδ) and transcriptional co-activators (e.g. PGC-1α), such that a co-ordinated up-regulation of both the nuclear and mitochondrial genomes occurs. Although the optimal practical strategies to train low are not currently known, consuming additional caffeine, protein, and practising CHO mouth-rinsing before and/or during training may help to rescue the reduced training intensities that typically occur when 'training low', in addition to preventing protein breakdown and maintaining optimal immune function. Finally, athletes should practise 'train-low' workouts in conjunction with sessions undertaken with normal or high CHO availability so that their capacity to oxidise CHO is not blunted on race day.
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5.
Genotypic and functional impact of HIV-1 adaptation to its host population during the North American epidemic.
Cotton, LA, Kuang, XT, Le, AQ, Carlson, JM, Chan, B, Chopera, DR, Brumme, CJ, Markle, TJ, Martin, E, Shahid, A, et al
PLoS genetics. 2014;(4):e1004295
Abstract
HLA-restricted immune escape mutations that persist following HIV transmission could gradually spread through the viral population, thereby compromising host antiviral immunity as the epidemic progresses. To assess the extent and phenotypic impact of this phenomenon in an immunogenetically diverse population, we genotypically and functionally compared linked HLA and HIV (Gag/Nef) sequences from 358 historic (1979-1989) and 382 modern (2000-2011) specimens from four key cities in the North American epidemic (New York, Boston, San Francisco, Vancouver). Inferred HIV phylogenies were star-like, with approximately two-fold greater mean pairwise distances in modern versus historic sequences. The reconstructed epidemic ancestral (founder) HIV sequence was essentially identical to the North American subtype B consensus. Consistent with gradual diversification of a "consensus-like" founder virus, the median "background" frequencies of individual HLA-associated polymorphisms in HIV (in individuals lacking the restricting HLA[s]) were ∼ 2-fold higher in modern versus historic HIV sequences, though these remained notably low overall (e.g. in Gag, medians were 3.7% in the 2000s versus 2.0% in the 1980s). HIV polymorphisms exhibiting the greatest relative spread were those restricted by protective HLAs. Despite these increases, when HIV sequences were analyzed as a whole, their total average burden of polymorphisms that were "pre-adapted" to the average host HLA profile was only ∼ 2% greater in modern versus historic eras. Furthermore, HLA-associated polymorphisms identified in historic HIV sequences were consistent with those detectable today, with none identified that could explain the few HIV codons where the inferred epidemic ancestor differed from the modern consensus. Results are therefore consistent with slow HIV adaptation to HLA, but at a rate unlikely to yield imminent negative implications for cellular immunity, at least in North America. Intriguingly, temporal changes in protein activity of patient-derived Nef (though not Gag) sequences were observed, suggesting functional implications of population-level HIV evolution on certain viral proteins.
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6.
The role of variable DNA tandem repeats in bacterial adaptation.
Zhou, K, Aertsen, A, Michiels, CW
FEMS microbiology reviews. 2014;(1):119-41
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Abstract
DNA tandem repeats (TRs), also designated as satellite DNA, are inter- or intragenic nucleotide sequences that are repeated two or more times in a head-to-tail manner. Because TR tracts are prone to strand-slippage replication and recombination events that cause the TR copy number to increase or decrease, loci containing TRs are hypermutable. An increasing number of examples illustrate that bacteria can exploit this instability of TRs to reversibly shut down or modulate the function of specific genes, allowing them to adapt to changing environments on short evolutionary time scales without an increased overall mutation rate. In this review, we discuss the prevalence and distribution of inter- and intragenic TRs in bacteria and the mechanisms of their instability. In addition, we review evidence demonstrating a role of TR variations in bacterial adaptation strategies, ranging from immune evasion and tissue tropism to the modulation of environmental stress tolerance. Nevertheless, while bioinformatic analysis reveals that most bacterial genomes contain a few up to several dozens of intra- and intergenic TRs, only a small fraction of these have been functionally studied to date.
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Modeling phenotypic metabolic adaptations of Mycobacterium tuberculosis H37Rv under hypoxia.
Fang, X, Wallqvist, A, Reifman, J
PLoS computational biology. 2012;(9):e1002688
Abstract
The ability to adapt to different conditions is key for Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), to successfully infect human hosts. Adaptations allow the organism to evade the host immune responses during acute infections and persist for an extended period of time during the latent infectious stage. In latently infected individuals, estimated to include one-third of the human population, the organism exists in a variety of metabolic states, which impedes the development of a simple strategy for controlling or eradicating this disease. Direct knowledge of the metabolic states of M. tuberculosis in patients would aid in the management of the disease as well as in forming the basis for developing new drugs and designing more efficacious drug cocktails. Here, we propose an in silico approach to create state-specific models based on readily available gene expression data. The coupling of differential gene expression data with a metabolic network model allowed us to characterize the metabolic adaptations of M. tuberculosis H37Rv to hypoxia. Given the microarray data for the alterations in gene expression, our model predicted reduced oxygen uptake, ATP production changes, and a global change from an oxidative to a reductive tricarboxylic acid (TCA) program. Alterations in the biomass composition indicated an increase in the cell wall metabolites required for cell-wall growth, as well as heightened accumulation of triacylglycerol in preparation for a low-nutrient, low metabolic activity life style. In contrast, the gene expression program in the deletion mutant of dosR, which encodes the immediate hypoxic response regulator, failed to adapt to low-oxygen stress. Our predictions were compatible with recent experimental observations of M. tuberculosis activity under hypoxic and anaerobic conditions. Importantly, alterations in the flow and accumulation of a particular metabolite were not necessarily directly linked to differential gene expression of the enzymes catalyzing the related metabolic reactions.
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8.
Immune adaptations that maintain homeostasis with the intestinal microbiota.
Hooper, LV, Macpherson, AJ
Nature reviews. Immunology. 2010;(3):159-69
Abstract
Humans harbour nearly 100 trillion intestinal bacteria that are essential for health. Millions of years of co-evolution have moulded this human-microorganism interaction into a symbiotic relationship in which gut bacteria make essential contributions to human nutrient metabolism and in return occupy a nutrient-rich environment. Although intestinal microorganisms carry out essential functions for their hosts, they pose a constant threat of invasion owing to their sheer numbers and the large intestinal surface area. In this Review, we discuss the unique adaptations of the intestinal immune system that maintain homeostatic interactions with a diverse resident microbiota.
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Pro-inflammatory variants of DRB1 and RAGE genes are associated with susceptibility to pediatric type 1 diabetes: a new hypothesis on the adaptive role of autoimmunity.
Damiani, G, Campo, I, Zorzetto, M, Bozzi, V, Disabella, E, Caroli, A, Ferrarotti, I, D'Annunzio, G, Pasi, A, Martinetti, M, et al
Rivista di biologia. 2007;(2):285-304
Abstract
Functional polymorphisms of two MHC genes (DRB1 and RAGE) were analysed in Italian pediatric patients with Type 1 diabetes and in a control group. The diabetic condition is related positively to the positive electric charge of the pocket 4 of pro-inflammatory DRB1 alleles (R = 0.5072, P = 0.0001) and negatively to at least one anti-inflammatory RAGE allele (R = -0.2200, P = 0.0106). The association DRB1-disease decreases from high risk positively charged alleles to low risk negatively ones. A multiple regression model including the effect of electric charges at positions 70 and 74 of the DRB1 explains more than 31% of the variability of our data. The addition of the RAGE dependent variables does not increase the significance of the model. Our results confirm that the interaction between a negatively charged amino acid of insulin autoantigenic peptides and a positively charged DRB1 is the key event triggering the autoimmune process. The linkage disequilibrium between RAGE and DRB1 is the main cause of the association between the variants of RAGE and the initial outcome of the disease. However, since RAGE ligands increase during the disease progression, the observed association suggests that the proinflammatory RAGE and DRB1 polymorphisms synergize to activate the immune response which leads to the complications of diabetes. These evidences support a new hypothesis that considers the largely unexplored role of the MHC genes in genetic adaptation to a variable environment and in the maintenance of the metabolic biodiversity. A mechanism based on the maternal immunization against the negatively charged autoantigens, such as the insulin peptide B9-23, and on the fetal-maternal interaction might transform the physiological adaptation into adaptive changes of the genetic population structure. According to the "thrifty-genotype" hypothesis, "thrifty DRB alleles" with a positive charge are responsible for the susceptibility to diabetes and for an efficient storage of caloric intake in arctic climates with scarce food availability while "non-thrifty DRB alleles" with a negative or neutral charge are advantaged in tropical climates with constant food supply.
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10.
Physiological changes associated with the pre-event taper in athletes.
Mujika, I, Padilla, S, Pyne, D, Busso, T
Sports medicine (Auckland, N.Z.). 2004;(13):891-927
Abstract
Some of the physiological changes associated with the taper and their relationship with athletic performance are now known. Since the 1980s a number of studies have examined various physiological responses associated with the cardiorespiratory, metabolic, hormonal, neuromuscular and immunological systems during the pre-event taper across a number of sports. Changes in the cardiorespiratory system may include an increase in maximal oxygen uptake, but this is not a necessary prerequisite for taper-induced gains in performance. Oxygen uptake at a given submaximal exercise intensity can decrease during the taper, but this response is more likely to occur in less-skilled athletes. Resting, maximal and submaximal heart rates do not change, unless athletes show clear signs of overreaching before the taper. Blood pressure, cardiac dimensions and ventilatory function are generally stable, but submaximal ventilation may decrease. Possible haematological changes include increased blood and red cell volume, haemoglobin, haematocrit, reticulocytes and haptoglobin, and decreased red cell distribution width. These changes in the taper suggest a positive balance between haemolysis and erythropoiesis, likely to contribute to performance gains. Metabolic changes during the taper include: a reduced daily energy expenditure; slightly reduced or stable respiratory exchange ratio; increased peak blood lactate concentration; and decreased or unchanged blood lactate at submaximal intensities. Blood ammonia concentrations show inconsistent trends, muscle glycogen concentration increases progressively and calcium retention mechanisms seem to be triggered during the taper. Reduced blood creatine kinase concentrations suggest recovery from training stress and muscle damage, but other biochemical markers of training stress and performance capacity are largely unaffected by the taper. Hormonal markers such as testosterone, cortisol, testosterone : cortisol ratio, 24-hour urinary cortisol : cortisone ratio, plasma and urinary catecholamines, growth hormone and insulin-like growth factor-1 are sometimes affected and changes can correlate with changes in an athlete's performance capacity. From a neuromuscular perspective, the taper usually results in markedly increased muscular strength and power, often associated with performance gains at the muscular and whole body level. Oxidative enzyme activities can increase, along with positive changes in single muscle fibre size, metabolic properties and contractile properties. Limited research on the influence of the taper on athletes' immune status indicates that small changes in immune cells, immunoglobulins and cytokines are unlikely to compromise overall immunological protection. The pre-event taper may also be characterised by psychological changes in the athlete, including a reduction in total mood disturbance and somatic complaints, improved somatic relaxation and self-assessed physical conditioning scores, reduced perception of effort and improved quality of sleep. These changes are often associated with improved post-taper performances. Mathematical models indicate that the physiological changes associated with the taper are the result of a restoration of previously impaired physiological capacities (fatigue and adaptation model), and the capacity to tolerate training and respond effectively to training undertaken during the taper (variable dose-response model). Finally, it is important to note that some or all of the described physiological and psychological changes associated with the taper occur simultaneously, which underpins the integrative nature of relationships between these changes and performance enhancement.