Stress Physiology of Lactic Acid Bacteria Papadimitriou, Konstantinos; Alegría, Ángel; Bron, Peter A ...
Microbiology and molecular biology reviews,
09/2016, Volume:
80, Issue:
3
Journal Article
Peer reviewed
Open access
Lactic acid bacteria (LAB) are important starter, commensal, or pathogenic microorganisms. The stress physiology of LAB has been studied in depth for over 2 decades, fueled mostly by the ...technological implications of LAB robustness in the food industry. Survival of probiotic LAB in the host and the potential relatedness of LAB virulence to their stress resilience have intensified interest in the field. Thus, a wealth of information concerning stress responses exists today for strains as diverse as starter (e.g., Lactococcus lactis), probiotic (e.g., several Lactobacillus spp.), and pathogenic (e.g., Enterococcus and Streptococcus spp.) LAB. Here we present the state of the art for LAB stress behavior. We describe the multitude of stresses that LAB are confronted with, and we present the experimental context used to study the stress responses of LAB, focusing on adaptation, habituation, and cross-protection as well as on self-induced multistress resistance in stationary phase, biofilms, and dormancy. We also consider stress responses at the population and single-cell levels. Subsequently, we concentrate on the stress defense mechanisms that have been reported to date, grouping them according to their direct participation in preserving cell energy, defending macromolecules, and protecting the cell envelope. Stress-induced responses of probiotic LAB and commensal/pathogenic LAB are highlighted separately due to the complexity of the peculiar multistress conditions to which these bacteria are subjected in their hosts. Induction of prophages under environmental stresses is then discussed. Finally, we present systems-based strategies to characterize the "stressome" of LAB and to engineer new food-related and probiotic LAB with improved stress tolerance.
Breast cancer is the most frequent cancer among women worldwide. Therapeutic strategies to prevent or treat metastatic disease are still inadequate although great progress has been made in treating ...early-stage breast cancer. Cancer stem-like cells (CSCs) that are endowed with high plasticity and self-renewal properties have been shown to play a key role in breast cancer development, progression, and metastasis. A subpopulation of CSCs that combines tumor-initiating capacity and a dormant/quiescent/slow cycling status is present throughout the clinical history of breast cancer patients. Dormant/quiescent/slow cycling CSCs are a key component of tumor heterogeneity and they are responsible for chemoresistance, tumor migration, and metastatic dormancy, defined as the ability of CSCs to survive in target organs and generate metastasis up to two decades after diagnosis. Understanding the strategies that are used by CSCs to resist conventional and targeted therapies, to interact with their niche, to escape immune surveillance, and finally to awaken from dormancy is of key importance to prevent and treat metastatic cancer. This review summarizes the current understanding of mechanisms involved in CSCs chemoresistance, dissemination, and metastasis in breast cancer, with a particular focus on dormant cells. Finally, we discuss how advancements in the detection, molecular understanding, and targeting of dormant CSCs will likely open new therapeutic avenues for breast cancer treatment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Understanding how antibody responses to SARS-CoV-2 evolve during infection may provide important insight into therapeutic approaches and vaccination for COVID-19. Here we profile the antibody ...responses of 162 COVID-19 symptomatic patients in the COVID-BioB cohort followed longitudinally for up to eight months from symptom onset to find SARS-CoV-2 neutralization, as well as antibodies either recognizing SARS-CoV-2 spike antigens and nucleoprotein, or specific for S2 antigen of seasonal beta-coronaviruses and hemagglutinin of the H1N1 flu virus. The presence of neutralizing antibodies within the first weeks from symptoms onset correlates with time to a negative swab result (p = 0.002), while the lack of neutralizing capacity correlates with an increased risk of a fatal outcome (p = 0.008). Neutralizing antibody titers progressively drop after 5-8 weeks but are still detectable up to 8 months in the majority of recovered patients regardless of age or co-morbidities, with IgG to spike antigens providing the best correlate of neutralization. Antibody responses to seasonal coronaviruses are temporarily boosted, and parallel those to SARS-CoV-2 without dampening the specific response or worsening disease progression. Our results thus suggest compromised immune responses to the SARS-CoV-2 spike to be a major trait of COVID-19 patients with critical conditions, and thereby inform on the planning of COVID-19 patient care and therapy prioritization.
Defective cell migration causes delayed wound healing (WH) and chronic skin lesions. Autologous micrograft (AMG) therapies have recently emerged as a new effective and affordable treatment able to ...improve wound healing capacity. However, the precise molecular mechanism through which AMG exhibits its beneficial effects remains unrevealed. Herein we show that AMG improves skin re-epithelialization by accelerating the migration of fibroblasts and keratinocytes. More specifically, AMG-treated wounds showed improvement of indispensable events associated with successful wound healing such as granulation tissue formation, organized collagen content, and newly formed blood vessels. We demonstrate that AMG is enriched with a pool of WH-associated growth factors that may provide the starting signal for a faster endogenous wound healing response. This work links the increased cell migration rate to the activation of the extracellular signal-regulated kinase (ERK) signaling pathway, which is followed by an increase in matrix metalloproteinase expression and their extracellular enzymatic activity. Overall we reveal the AMG-mediated wound healing transcriptional signature and shed light on the AMG molecular mechanism supporting its potential to trigger a highly improved wound healing process. In this way, we present a framework for future improvements in AMG therapy for skin tissue regeneration applications.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The quality of some leavened, sourdough baked goods is not always consistent, unless a well propagated sourdough starter culture is used for the dough fermentation. Among the different types of ...sourdough used, the traditional sourdough has attracted the interest of researchers, mainly because of its large microbial diversity, especially with respect to lactic acid bacteria. Variation in this diversity and the factors that cause it will impact on quality and is the subject of this review.
Sourdough microbial diversity is mainly caused by the following factors: (i) sourdough is obtained through spontaneous, multi-step fermentation; (ii) it is propagated using flour, whose nutrient content may vary according to the batch and to the crop, and which is naturally contaminated by microorganisms; and (iii) it is propagated under peculiar technological parameters, which vary depending on the historical and cultural background and type of baked good. In the population dynamics leading from flour to mature sourdough, lactic acid bacteria (several species of Lactobacillus sp., Leuconostoc sp., and Weissella sp.) and yeasts (mainly Saccharomyces cerevisiae and Candida sp.) outcompete other microbial groups contaminating flour, and interact with each other at different levels. Ecological parameters qualitatively and quantitatively affecting the dominant sourdough microbiota may be classified into specific technological parameters (e.g., percentage of sourdough used as inoculum, time and temperature of fermentation) and parameters that are not fully controlled by those who manage the propagation of sourdough (e.g., chemical, enzyme and microbial composition of flour).
Although some sourdoughs have been reported to harbour a persistent dominant microbiota, the stability of sourdough ecosystem during time is debated. Indeed, several factors may interfere with the persistence of species and strains associations that are typical of a given sourdough: metabolic adaptability to the stressing conditions of sourdough, nutritional and antagonistic interactions among microorganisms, intrinsic robustness of microorganisms, and existence of a stable house microbiota.
Further studies have to be performed in order to highlight hidden mechanisms underlying the microbial structure and stability of sourdough. The comprehension of such mechanisms would be helpful to assess the most appropriate conditions that allow keeping a given traditional sourdough as a stable microbial ecosystem, thus preserving, during time, the typical traits of the resulting product.
•Lactic acid bacteria and yeasts dominate traditional sourdoughs.•Different specific technological parameters lead to sourdough microbial diversity.•Microbial stability is not ensured by application of constant technology parameters.•Flour and house microbiota affect microbial stability of traditional sourdough.•Succession of microorganisms causes variations of sourdough performances over time.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Facilitated transport membranes are particularly promising in different separations, as they are potentially able to overcome the trade-off behavior usually encountered in solution-diffusion ...membranes. The reaction activated transport is a process in which several mechanisms take place simultaneously, and requires a rigorous theoretical analysis, which unfortunately is often neglected in current studies more focused on material development. In this work, we selected and reviewed the main mathematical models introduced to describe mobile and fixed facilitated transport systems in steady state conditions, in order to provide the reader with an overview of the existing mathematical tools. An analytical solution to the mass transport problem cannot be achieved, even when considering simple reaction schemes such as that between oxygen (solute) and hemoglobin (carrier) (A+C⇄AC), that was thoroughly studied by the first works dealing with this type of biological facilitated transport. Therefore, modeling studies provided approximate analytical solutions and comparison against experimental observations and exact numerical calculations. The derivation, the main assumptions, and approximations of such modeling approaches is briefly presented to assess their applicability, precision, and flexibility in describing and understanding mobile and fixed site carriers facilitated transport membranes. The goal is to establish which mathematical tools are more suitable to support and guide the development and design of new facilitated transport systems and materials. Among the models presented, in particular, those from Teramoto and from Morales-Cabrera et al. seem the more flexible and general ones for the mobile carrier case, while the formalization made by Noble and coauthors appears the most complete in the case of fixed site carrier membranes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The drivers for the establishment and composition of the sourdough microbiota, with particular emphasis on lactic acid bacteria, are reviewed and discussed. More than 60 different species of ...lactobacilli were identified from sourdoughs, showing the main overlapping between sourdough and human intestine ecosystems. The microbial kinetics during sourdough preparation was described by several studies using various methodological approaches, including culture-dependent and -independent (e.g., high throughput sequencing), and metabolite and meta-transcriptome analyses. Although the abundant microbial diversity harbored by flours, a succession of dominating and sub-dominating populations of lactic acid bacteria suddenly occurred during sourdough propagation, leading to the progressive assembly of the bacterial community. The contribution of all the potential sources (house microbiota, flour, types of flours and additional ingredients) for contaminating lactic acid bacteria was compared with the aim to find overlapping or specific routes that affect the sourdough microbiota. Once established and mature, pros and cons regarding the stability of the sourdough lactic acid bacteria biota were also reviewed, showing contradictory results, which were mainly dependent on the species/strains.
Probably, the future research efforts should be dedicated to decrease the sources/drivers of noticeable variation rather than to full standardization of the process for sourdough preparation and use.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
This study aimed at assessing the dynamics of lactic acid bacteria and other Firmicutes associated with durum wheat organs and processed products. 16S rRNA gene-based high-throughput sequencing ...showed that Lactobacillus, Streptococcus, Enterococcus, and Lactococcus were the main epiphytic and endophytic genera among lactic acid bacteria. Bacillus, Exiguobacterium, Paenibacillus, and Staphylococcus completed the picture of the core genus microbiome. The relative abundance of each lactic acid bacterium genus was affected by cultivars, phenological stages, other Firmicutes genera, environmental temperature, and water activity (aw) of plant organs. Lactobacilli, showing the highest sensitivity to aw, markedly decreased during milk development (Odisseo) and physiological maturity (Saragolla). At these stages, Lactobacillus was mainly replaced by Streptococcus, Lactococcus, and Enterococcus. However, a key sourdough species, Lactobacillus plantarum, was associated with plant organs during the life cycle of Odisseo and Saragolla wheat. The composition of the sourdough microbiota and the overall quality of leavened baked goods are also determined throughout the phenological stages of wheat cultivation, with variations depending on environmental and agronomic factors.
Cheeses are inherently microbiologically and biochemically dynamic. Numerous biotic and abiotic drivers govern the establishment and assembly of a core microbiota in cheese, which, for ...internally-ripened cheeses, having an intermediate to long period of ripening, consists of starter and non-starter lactic acid bacteria (SLAB and NSLAB). The management of this dynamic ecosystem has to consider this core as a super-organism, which results from the sums of microbial metabolisms and interactions among individual microbes.
This review focuses on all presumptive drivers, raw and pasteurized milk, farming system and house microbiota, and intrinsic and extrinsic factors during cheese manufacture and ripening, which qualitatively and mainly depending on the farm management system and cheese variety may influence the populations of SLAB and NSLAB. The interactions between these two microbial groups are described also.
The cheese ecosystem shows a variable flux of its core microbiota from milking through manufacture to ripening. Many and diverse drivers establish and assembly the lactic acid bacteria biota. If such drivers are efficient to guarantee microbial and cheese diversities, on the other hand, their control is the fundamental pre-requisite to synchronize and balance microbiological events. The methodological approaches (e.g., omics techniques and integrated system biology) have markedly improved to concretize this ambitious goal. Facing and improving the knowledge on the main drivers, the current step should focus on a unique puzzle of coexisting species/biotypes likely a super-organism, whose guide has to consider all casehardened microbial elements.
•Cheeses are microbiologically and biochemically dynamic.•Biotic and abiotic drivers govern the establishment/assembly of a core microbiota.•The core microbiota consists of starter and non-starter lactic acid bacteria.•The sums of microbial metabolisms and interactions result in a super-organism to be driven.•All presumptive drivers that influence the core microbiota are described.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The metabolism of hydroxycinnamic acids by strictly heterofermentative lactic acid bacteria (19 strains) was investigated as a potential alternative energy route. Lactobacillus curvatus PE5 was the ...most tolerant to hydroxycinnamic acids, followed by strains of Weissella spp., Lactobacillus brevis, Lactobacillus fermentum, and Leuconostoc mesenteroides, for which the MIC values were the same. The highest sensitivity was found for Lactobacillus rossiae strains. During growth in MRS broth, lactic acid bacteria reduced caffeic, p-coumaric, and ferulic acids into dihydrocaffeic, phloretic, and dihydroferulic acids, respectively, or decarboxylated hydroxycinnamic acids into the corresponding vinyl derivatives and then reduced the latter compounds to ethyl compounds. Reductase activities mainly emerged, and the activities of selected strains were further investigated in chemically defined basal medium (CDM) under anaerobic conditions. The end products of carbon metabolism were quantified, as were the levels of intracellular ATP and the NAD(+)/NADH ratio. Electron and carbon balances and theoretical ATP/glucose yields were also estimated. When CDM was supplemented with hydroxycinnamic acids, the synthesis of ethanol decreased and the concentration of acetic acid increased. The levels of these metabolites reflected on the alcohol dehydrogenase and acetate kinase activities. Overall, some biochemical traits distinguished the common metabolism of strictly heterofermentative strains: main reductase activity toward hydroxycinnamic acids, a shift from alcohol dehydrogenase to acetate kinase activities, an increase in the NAD(+)/NADH ratio, and the accumulation of supplementary intracellular ATP. Taken together, the above-described metabolic responses suggest that strictly heterofermentative lactic acid bacteria mainly use hydroxycinnamic acids as external acceptors of electrons.