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1.
Nat Commun ; 11(1): 1299, 2020 03 10.
Article in English | MEDLINE | ID: mdl-32157077

ABSTRACT

The responses of cells to their surroundings are mediated by the binding of cell surface proteins (CSPs) to extracellular signals. Such processes are regulated via dynamic changes in the structure, composition, and expression levels of CSPs. In this study, we demonstrate the possibility of decorating bacteria with artificial, self-assembled receptors that imitate the dynamic features of CSPs. We show that the local concentration of these receptors on the bacterial membrane and their structure can be reversibly controlled using suitable chemical signals, in a way that resembles changes that occur with CSP expression levels or posttranslational modifications (PTMs), respectively. We also show that these modifications can endow the bacteria with programmable properties, akin to the way CSP responses can induce cellular functions. By programming the bacteria to glow, adhere to surfaces, or interact with proteins or mammalian cells, we demonstrate the potential to tailor such biomimetic systems for specific applications.


Subject(s)
Escherichia coli/metabolism , Receptors, Artificial/metabolism , Bacterial Adhesion , Bacterial Proteins/metabolism , Cell Line, Tumor , Cell Membrane/metabolism , Fluorescence , Humans
2.
Nat Commun ; 9(1): 3886, 2018 09 24.
Article in English | MEDLINE | ID: mdl-30250274

ABSTRACT

Tuberculosis (TB) is a devastating and rapidly spreading disease caused by Mycobacterium tuberculosis (Mtb). Therapy requires prolonged treatment with a combination of multiple agents and interruptions in the treatment regimen result in emergence and spread of multi-drug resistant (MDR) Mtb strains. MDR Mtb poses a significant global health problem, calling for urgent development of novel drugs to combat TB. Here, we report the 3.3 Å resolution structure of the ~2 MDa type-I fatty acid synthase (FAS-I) from Mtb, determined by single particle cryo-EM. Mtb FAS-I is an essential enzymatic complex that contributes to the virulence of Mtb, and thus a prime target for anti-TB drugs. The structural information for Mtb FAS-I we have obtained enables computer-based drug discovery approaches, and the resolution achieved by cryo-EM is sufficient for elucidating inhibition mechanisms by putative small molecular weight inhibitors.


Subject(s)
Bacterial Proteins/chemistry , Drug Discovery/methods , Fatty Acid Synthases/chemistry , Mycobacterium tuberculosis/chemistry , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Bacterial Proteins/antagonists & inhibitors , Bacterial Proteins/isolation & purification , Catalytic Domain , Cryoelectron Microscopy , Fatty Acid Synthases/antagonists & inhibitors , Fatty Acid Synthases/isolation & purification , Models, Molecular , Mycobacterium tuberculosis/pathogenicity , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purification , Tuberculosis/drug therapy , Tuberculosis/microbiology , Virulence
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