The skin is a complex and dynamic ecosystem that is inhabited by bacteria, archaea, fungi and viruses. These microbes—collectively referred to as the skin microbiota—are fundamental to skin physiology and immunity. Interactions between skin microbes and the host can fall anywhere along the continuum between mutualism and pathogenicity. In this Review, we highlight how host–microbe interactions depend heavily on context, including the state of immune activation, host genetic predisposition, barrier status, microbe localization, and microbe–microbe interactions. We focus on how context shapes the complex dialogue between skin microbes and the host, and the consequences of this dialogue for health and disease.

Skin microbiota–host interactions

Tuberculosis (TB) is the leading infectious cause of mortality worldwide, due in part to a limited understanding of its clinical pathogenic spectrum of infection and disease. Historically, scientific research, diagnostic testing, and drug treatment have focused on addressing one of two disease states: latent TB infection or active TB disease. Recent research has clearly demonstrated that human TB infection, from latent infection to active disease, exists within a continuous spectrum of metabolic bacterial activity and antagonistic immunological responses. This revised understanding leads us to propose two additional clinical states: incipient and subclinical TB. The recognition of incipient and subclinical TB, which helps divide latent and active TB along the clinical disease spectrum, provides opportunities for the development of diagnostic and therapeutic interventions to prevent progression to active TB disease and transmission of TB bacilli. In this report, we review the current understanding of the pathogenesis, immunology, clinical epidemiology, diagnosis, treatment, and prevention of both incipient and subclinical TB, two emerging clinical states of an ancient bacterium.

Incipient and Subclinical Tuberculosis: a Clinical Review of Early Stages and Progression of Infection.

The discovery of the genetic code and tRNAs as decoders of the code transformed life science. However, after establishing the role of tRNAs in protein synthesis, the field moved to other parts of the RNA world. Now, tRNA research is blooming again, with demonstration of the involvement of tRNAs in various other pathways beyond translation and in adapting translation to environmental cues. These roles are linked to the presence of tRNA sequence variants known as isoacceptors and isodecoders, various tRNA base modifications, the versatility of protein binding partners and tRNA fragmentation events, all of which collectively create an incalculable complexity. This complexity provides a vast repertoire of tRNA species that can serve various functions in cellular homeostasis and in adaptation of cellular functions to changing environments, and it likely arose from the fundamental role of RNAs in early evolution.

The emerging complexity of the tRNA world: mammalian tRNAs beyond protein synthesis

Tuberculosis (TB) lesions are extremely complex and dynamic. Here, we review the multiple types and fates of pulmonary lesions that form following infection by Mycobacterium tuberculosis and the impact of this spatial and temporal heterogeneity on the bacteria they harbor. The diverse immunopathology of granulomas and cavities generates a plethora of microenvironments to which M. tuberculosis bacilli must adapt. This in turn affects the replication, metabolism, and relative density of bacterial subpopulations, and consequently their respective susceptibility to chemotherapy. We outline recent developments that support a paradigm shift in our understanding of lesion progression. The simple model according to which lesions within a single individual react similarly to the systemic immune response no longer prevails. Host-pathogen interactions within lesions are a dynamic process, driven by subtle and local differences in signaling pathways, resulting in diverging trajectories of lesions within a single host. The spectrum of TB lesions is a continuum with a large overlap in the lesion types found in latently infected and active TB patients. We hope this overview will guide TB researchers in the design, choice of read-outs, and interpretation of future studies in the search for predictive biomarkers and novel therapies.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/imr.12252

Heterogeneity in tuberculosis pathology, microenvironments and therapeutic responses.

Compared with traditional model bacteria, the processes of growth and division are unusual in mycobacteria In this Review, Rubin and Kieser discuss polar growth, asymmetric division and cell wall remodelling in mycobacteria and consider how these processes might contribute to the population heterogeneity and pathogenesis of Mycobacterium tuberculosis

/pdf/how-sisters-grow-apart-mycobacterial-growth-and-division-37fscdauxb.pdf

How sisters grow apart: mycobacterial growth and division.

We have taken the first steps towards a complete reconstruction of the Mycobacterium tuberculosis regulatory network based on ChIP-Seq and combined this reconstruction with system-wide profiling of messenger RNAs, proteins, metabolites and lipids during hypoxia and re-aeration. Adaptations to hypoxia are thought to have a prominent role in M. tuberculosis pathogenesis. Using ChIP-Seq combined with expression data from the induction of the same factors, we have reconstructed a draft regulatory network based on 50 transcription factors. This network model revealed a direct interconnection between the hypoxic response, lipid catabolism, lipid anabolism and the production of cell wall lipids. As a validation of this model, in response to oxygen availability we observe substantial alterations in lipid content and changes in gene expression and metabolites in corresponding metabolic pathways. The regulatory network reveals transcription factors underlying these changes, allows us to computationally predict expression changes, and indicates that Rv0081 is a regulatory hub.

/pdf/the-mycobacterium-tuberculosis-regulatory-network-and-3urp6p3foc.pdf

The Mycobacterium tuberculosis regulatory network and hypoxia.

Approaches to ensuring ecological efficiency of feed methionine production

The article presents studies of the influence of the recipe composition, in particular, the mass fraction of herbal additives on the organoleptic, functional and technological properties of food systems of a combined composition using raw materials of animal (beef, lamb, poultry) and vegetable (soy okara, carrots) origin. The results of the study of soybean-minced okara for food safety indicators are also presented. The functional and technological indicators of meat chopped semi-finished products were also determined: moisture-binding capacity = 89.1%, water-holding capacity = 77.4%, fat-holding capacity = 83.2%. The output of meat chopped semi-finished products with PCC is 91%. The obtained values for the quality characteristics indicate the prospects of using this type of soybean-minced okara: directly for food, as well as for the production of minced meat semi-finished products, such as cutlets, minced meat, steaks; to design and optimize recipes for semi-finished products. 

Research of the soy okara impact on the quality indicators of meat chopped semi-finished products

«green agenda» of economic development and alternative sources of food protein

Soy minced okara was used for the targeted enrichment of minced meat semi-finished 
products with dietary fibers (DF). Additionally, it is a source of high-grade protein in amino acid 
composition, as well as potassium, calcium, magnesium, phosphorus, iron. Okara was used as a 
component of a protein-carbohydrate composition (PCC). Chickpea flour and whey protein 
concentrate were used to balance the amino acid composition of beech and correct the functional 
and technological properties of food systems

Irina Glotova

Papers

The Mycobacterium tuberculosis regulatory network and hypoxia.

Approaches to ensuring ecological efficiency of feed methionine production

Research of the soy okara impact on the quality indicators of meat chopped semi-finished products

«green agenda» of economic development and alternative sources of food protein

Method for producing dietary cutlets with dietary fibers