ArticleAntimicrobial agents and chemotherapy2012
Myxobacterium-produced antibiotic TA (myxovirescin) inhibits type II signal peptidase.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 94 citations in OpenAlex.
- Antibiotic-producing microorganisms: taxonomic diversity, screening strategies, and emerging and underexploited antibacterial targets.Archives of microbiology · 2026Review
- Predatory myxobacteria lay at the cross-roads of metallo-β-lactamase evolution.Communications biology · 2026Article
- Article
- Targeting of the Gram-Negative Outer Membrane for Antibiotic Discovery and Potentiation.ACS infectious diseases · 2026Review
- ARTS-DB 2.0: an expanded database for target-directed genome mining across bacteria and fungi.Database : the journal of biological databases and curation · 2026Article
- Breaking the outer membrane barrier: structure, targets, and antimicrobial strategies for Gram-negative bacteria.Frontiers in microbiology · 2026Review
- Milestones in the development ofJournal of bacteriology · 2025Review
- Coevolutionary history of predation constrains the evolvability of antibiotic resistance in prey bacteria.npj antimicrobials and resistance · 2025Article
- Computational Design of Cyclic Peptide Inhibitors of a Bacterial Membrane Lipoprotein Peptidase.ACS chemical biology · 2024Article
- Review
- Tackling the outer membrane: facilitating compound entry into Gram-negative bacterial pathogens.npj antimicrobials and resistance · 2023Review
- The evolution of short- and long-range weapons for bacterial competition.Nature ecology & evolution · 2023Article
- Two reasons to kill: predation and kin discrimination in myxobacteria.Microbiology (Reading, England) · 2023Review
- Identification and heterologous expression of the globomycin biosynthetic gene cluster.Synthetic and systems biotechnology · 2023Article
- Combining Signal Peptidase and Lipoprotein Processing Inhibitors Overcomes Ayr Resistance in Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2023Article
- Chromosomal organization of biosynthetic gene clusters suggests plasticity of myxobacterial specialized metabolism including descriptions for nine novel species:bioRxiv : the preprint server for biology · 2023Article
- Making a chink in their armor: Current and next-generation antimicrobial strategies against the bacterial cell envelope.Advances in microbial physiology · 2023Article
- Thiocillin contributes to the ecological fitness ofFrontiers in microbiology · 2023Article
- Chromosomal organization of biosynthetic gene clusters, including those of nine novel species, suggests plasticity of myxobacterial specialized metabolism.Frontiers in microbiology · 2023Article
- Genetic components ofFrontiers in microbiology · 2023Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Antibiotic TA is a macrocyclic secondary metabolite produced by myxobacteria that has broad-spectrum bactericidal activity. The structure of TA is unique, and its molecular target is unknown. Here, we sought to elucidate TA's mode of action (MOA) through two parallel genetic approaches. First, chromosomal Escherichia coli TA-resistant mutants were isolated. One mutant that showed specific resistance toward TA was mapped and resulted from an IS4 insertion in the lpp gene, which encodes an abundant outer membrane (Braun's) lipoprotein. In a second approach, the comprehensive E. coli ASKA plasmid library was screened for overexpressing clones that conferred TA(r). This effort resulted in the isolation of the lspA gene, which encodes the type II signal peptidase that cleaves signal sequences from prolipoproteins. In whole cells, TA was shown to inhibit Lpp prolipoprotein processing, similar to the known LspA inhibitor globomycin. Based on genetic evidence and prior globomycin studies, a block in Lpp expression or prevention of Lpp covalent cell wall attachment confers TA(r) by alleviating a toxic buildup of mislocalized pro-Lpp. Taken together, these data argue that LspA is the molecular target of TA. Strikingly, the giant ta biosynthetic gene cluster encodes two lspA paralogs that we hypothesize play a role in producer strain resistance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.