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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

cell cycle --- nucleoid --- divisome --- cell division --- cell envelope --- cell shape --- chromosome replication --- macromolecular hyperstructures --- Escherichia coli

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Bacterial Physiology was inaugurated as a discipline by the seminal research of Maaløe, Schaechter and Kjeldgaard published in 1958. Their work clarified the relationship between cell composition and growth rate and led to unravel the temporal coupling between chromosome replication and the subsequent cell division by Helmstetter et al. a decade later. Now, after half a century this field has become a major research direction that attracts interest of many scientists from different disciplines. The outstanding question how the most basic cellular processes - mass growth, chromosome replication and cell division - are inter-coordinated in both space and time is still unresolved at the molecular level. Several particularly pertinent questions that are intensively studied follow: (a) what is the primary signal to place the Z-ring precisely between the two replicating and segregating nucleoids? (b) Is this coupling related to the structure and position of the nucleoid itself? (c) How does a bacterium determine and maintain its shape and dimensions? Possible answers include gene expression-based mechanisms, self-organization of protein assemblies and physical principles such as micro-phase separations by excluded volume interactions, diffusion ratchets and membrane stress or curvature. The relationships between biochemical reactions and physical forces are yet to be conceived and discovered. This e-book discusses the above mentioned and related questions. The book also serves as an important depository for state-of-the-art technologies, methods, theoretical simulations and innovative ideas and hypotheses for future testing. Integrating the information gained from various angles will likely help decipher how a relatively simple cell such as a bacterium incorporates its multitude of pathways and processes into a highly efficient self-organized system. The knowledge may be helpful in the ambition to artificially reconstruct a simple living system and to develop new antibacterial drugs.

Chromosome replication --- Bacterial growth --- divisome --- Chromosome Segregation --- Cell Cycle --- Cell Division --- Cell envelope --- size control --- model system Escherichia coli --- nucleoid

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

Science: general issues --- Medical microbiology & virology --- Microbiology (non-medical) --- cell cycle --- nucleoid --- divisome --- cell division --- cell envelope --- cell shape --- chromosome replication --- macromolecular hyperstructures --- Escherichia coli

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Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis and still represents one of the global health threats to mankind. The World Health Organization estimated more than 10 million new cases and reported more than 1.5 million deaths in 2019, thus ranking TB among the main causes of death due to a single pathogen. Standard anti-TB therapy includes four first-line antibiotics that should be administered for at least six months. However, in the case of multi- and extensively drug-resistant TB, second-line medications must be used and these frequently cause severe side effects resulting in poor compliance. Developing new anti-TB drug candidates is therefore of outmost importance. In this Special Issue dedicated to Tuberculosis Drug Discovery and Development, we present the main and latest achievements in the fields of drug and target discovery, host-directed therapy, anti-virulence drugs, and describe the development of two advanced compounds: macozinone and delpazolid. In addition, this Special Issue provides an historical perspective focused on Carlo Forlanini, the inventor of pneumothorax for TB treatment, and includes an overview of the state-of-the-art technologies which are being exploited nowadays in TB drug development. Finally, a summary of TB vaccines that are either approved or undergoing clinical trials concludes the Special Issue.

Research & information: general --- Biology, life sciences --- mycobacteria --- tuberculosis --- multi-drug resistance --- drug discovery --- promiscuous targets --- Mycobacterium tuberculosis --- rifampin --- isoniazid --- mechanisms of resistance --- mutations --- granulomas --- caseum --- cell envelope --- dormancy --- delpazolid --- macozinone --- DprE1 inhibitor --- clinical studies --- discovery --- mode of action --- drug resistance --- toxicity --- target --- energy metabolism --- electron transport chain --- oxidative phosphorylation --- bedaquiline --- Q203 --- MID3 --- pharmacokinetics --- pharmacodynamics --- drug-drug interactions --- in vitro --- in vivo --- drug development --- tuberculosis treatment --- biomarkers --- drug combination --- clinical trial --- BCG --- tuberculosis vaccines --- TBVI --- EDCTP --- IAVI --- CTVD --- host-directed therapy --- anti-virulence compounds --- TB --- post-treatment sequelae --- surgery --- pulmonary rehabilitation --- Carlo Forlanini --- artificial pneumothorax --- n/a --- structure-based drug design --- target-based drug design --- PknB --- PknG --- DNA gyrase --- antibiotic --- mycobacterium --- genomics --- transcriptomics --- proteomics --- metabolomics --- lipidomics --- target identification --- mechanism of action --- antimicrobial drug resistance (AMR) --- target-based screening --- phenotypic screening --- antituberculosis agents --- antimycobacterial --- anti-TB drug pipeline --- privileged targets --- lead generation

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Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis and still represents one of the global health threats to mankind. The World Health Organization estimated more than 10 million new cases and reported more than 1.5 million deaths in 2019, thus ranking TB among the main causes of death due to a single pathogen. Standard anti-TB therapy includes four first-line antibiotics that should be administered for at least six months. However, in the case of multi- and extensively drug-resistant TB, second-line medications must be used and these frequently cause severe side effects resulting in poor compliance. Developing new anti-TB drug candidates is therefore of outmost importance. In this Special Issue dedicated to Tuberculosis Drug Discovery and Development, we present the main and latest achievements in the fields of drug and target discovery, host-directed therapy, anti-virulence drugs, and describe the development of two advanced compounds: macozinone and delpazolid. In addition, this Special Issue provides an historical perspective focused on Carlo Forlanini, the inventor of pneumothorax for TB treatment, and includes an overview of the state-of-the-art technologies which are being exploited nowadays in TB drug development. Finally, a summary of TB vaccines that are either approved or undergoing clinical trials concludes the Special Issue.

Research & information: general --- Biology, life sciences --- mycobacteria --- tuberculosis --- multi-drug resistance --- drug discovery --- promiscuous targets --- Mycobacterium tuberculosis --- rifampin --- isoniazid --- mechanisms of resistance --- mutations --- granulomas --- caseum --- cell envelope --- dormancy --- delpazolid --- macozinone --- DprE1 inhibitor --- clinical studies --- discovery --- mode of action --- drug resistance --- toxicity --- target --- energy metabolism --- electron transport chain --- oxidative phosphorylation --- bedaquiline --- Q203 --- MID3 --- pharmacokinetics --- pharmacodynamics --- drug-drug interactions --- in vitro --- in vivo --- drug development --- tuberculosis treatment --- biomarkers --- drug combination --- clinical trial --- BCG --- tuberculosis vaccines --- TBVI --- EDCTP --- IAVI --- CTVD --- host-directed therapy --- anti-virulence compounds --- TB --- post-treatment sequelae --- surgery --- pulmonary rehabilitation --- Carlo Forlanini --- artificial pneumothorax --- structure-based drug design --- target-based drug design --- PknB --- PknG --- DNA gyrase --- antibiotic --- mycobacterium --- genomics --- transcriptomics --- proteomics --- metabolomics --- lipidomics --- target identification --- mechanism of action --- antimicrobial drug resistance (AMR) --- target-based screening --- phenotypic screening --- antituberculosis agents --- antimycobacterial --- anti-TB drug pipeline --- privileged targets --- lead generation --- mycobacteria --- tuberculosis --- multi-drug resistance --- drug discovery --- promiscuous targets --- Mycobacterium tuberculosis --- rifampin --- isoniazid --- mechanisms of resistance --- mutations --- granulomas --- caseum --- cell envelope --- dormancy --- delpazolid --- macozinone --- DprE1 inhibitor --- clinical studies --- discovery --- mode of action --- drug resistance --- toxicity --- target --- energy metabolism --- electron transport chain --- oxidative phosphorylation --- bedaquiline --- Q203 --- MID3 --- pharmacokinetics --- pharmacodynamics --- drug-drug interactions --- in vitro --- in vivo --- drug development --- tuberculosis treatment --- biomarkers --- drug combination --- clinical trial --- BCG --- tuberculosis vaccines --- TBVI --- EDCTP --- IAVI --- CTVD --- host-directed therapy --- anti-virulence compounds --- TB --- post-treatment sequelae --- surgery --- pulmonary rehabilitation --- Carlo Forlanini --- artificial pneumothorax --- structure-based drug design --- target-based drug design --- PknB --- PknG --- DNA gyrase --- antibiotic --- mycobacterium --- genomics --- transcriptomics --- proteomics --- metabolomics --- lipidomics --- target identification --- mechanism of action --- antimicrobial drug resistance (AMR) --- target-based screening --- phenotypic screening --- antituberculosis agents --- antimycobacterial --- anti-TB drug pipeline --- privileged targets --- lead generation