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Dysregulation of bacterial proteolytic machinery by a new class of antibiotics
TLDR
A new class of antibiotics is shown to have antibacterial activity against Gram-positive bacteria in vitro and in several rodent models of bacterial infection, implying a new target, which is identified as ClpP, the core unit of a major bacterial protease complex.
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Structures of ClpP in complex with acyldepsipeptide antibiotics reveal its activation mechanism
TLDR
The direction of the conformational movement and the hydrophobic clustering that stabilizes the closed structure are markedly different from those of other ATP-dependent proteases, providing unprecedented insights into the activation of ClpP.
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The antibiotic ADEP reprogrammes ClpP, switching it from a regulated to an uncontrolled protease
TLDR
The molecular mechanism of ADEP action is analysed and it is demonstrated that ADEPs abrogate ClpP interaction with cooperating Hsp100 adenosine triphosphatases (ATPases) and cause a complete functional reprogramming of the Clp–protease complex.
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Human commensals producing a novel antibiotic impair pathogen colonization
TLDR
It is shown that nasal Staphylococcus lugdunensis strains produce lugdunin, a novel thiazolidine-containing cyclic peptide antibiotic that prohibits colonization by S. aureus, and a rare example of a non-ribosomally synthesized bioactive compound from human-associated bacteria.
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New Class of Bacterial Phenylalanyl-tRNA Synthetase Inhibitors with High Potency and Broad-Spectrum Activity
TLDR
Treatment with the phenyl-thiazolylurea-sulfonamides reduced the bacterial titer in various organs by up to 3 log units, supporting the potential value of Phe-RS as a target in antibacterial therapy.
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Small cationic antimicrobial peptides delocalize peripheral membrane proteins
TLDR
It is shown that peptide integration into the membrane causes delocalization of essential peripheral membrane proteins essential for respiration and cell-wall biosynthesis, limiting cellular energy and undermining cell- wall integrity.
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Inducing secondary metabolite production by the endophytic fungus Fusarium tricinctum through coculture with Bacillus subtilis.
Coculturing the fungal endophyte Fusarium tricinctum with the bacterium Bacillus subtilis 168 trpC2 on solid rice medium resulted in an up to 78-fold increase in the accumulation in constitutively…
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Antibiotic acyldepsipeptides activate ClpP peptidase to degrade the cell division protein FtsZ
TLDR
It is reported that ADEP prevents cell division in Gram-positive bacteria and induces strong filamentation of rod-shaped Bacillus subtilis and swelling of coccoid S. aureus and Streptococcus pneumoniae.
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Specific and Potent Inhibition of NAD+-dependent DNA Ligase by Pyridochromanones*
TLDR
The pyridochromanones demonstrate that diverse eubacterial DNA ligases can be addressed by a single inhibitor without affecting eukaryotic ligases or other DNA-binding enzymes, which proves the value of DNA ligase as a novel target in antibacterial therapy.
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Postgenomic strategies in antibacterial drug discovery.
TLDR
The lessons learned from the genomics era are summarized and discovery strategies resulting from that knowledge are described including anti-virulence strategies and immunotherapeutic approaches.
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