Simple and intuitive new ideas!

Using a strategy that exploits nature's interactive ecology - they identified eight actinomycetes representing broad phylogenetic diversity from a panel of soil isolates, with a focus on rare actinomycetes, identified by sequencing of 16s rRNA genes , cultured separately, and "bordered" with another actinomycete strain, a total of 28 combinations, after 5 days of culture, an actinomycete strain with abnormal multi-resistance was added to co-culture, and the strains that could inhibit the growth of drug-resistant strains were screen.

Combination, analysis of novel molecules induced by interactions between actinomycetes—molecules that inhibit drug-resistant strains, and finallyA class of antibacterial drugs, dynaplanins, was discover.

Heterologous expression (generated by interactions between actinomycetes) enables the identification of dynaplanin biosynthetic gene clusters, which are ignored by traditional natural product gene cluster detection algorith.

Genome sequencing of partially resistant mutants revealed that the 2-oxoacid dehydrogenase E2 subunit may be a molecular target of dynaplanins, a finding supported by computational modeling of dynaplanin scaffolds within the enzyme's active si.

Therefore, this simple strategy to exploit microbial interactions and natural antibiotic resistance can lead to the discovery of molecules with unique antibacterial activiti.

Furthermore, these results suggest that primary metabolism may be a direct target by chemically perturbing competing microbial interactio.

background

A key realization of the post-genomic era is that many bacterial genomes, including actinomycete genomes, have large clusters of genes encoding biosynthetic natural products, but whose products have not yet been identifi.

Under laboratory conditions, these "silenced" gene clusters are usually poorly expressed in sterile medi.

Therefore, how to design methods that can improve the possibility of capturing new natural products produced by these organisms/gene clusters is an area of ​​great intere.

A variety of new strategies aimed at accelerating natural product discovery have been developed in the last decade, which

Key to this are genome mining tools, which enable targeted studies of gene clusters that could lead to new compoun.

While this approach has proven effective in many examples, it relies onPrioriGene cluster identification may miss atypical gene clusters that encode unique chemical structur.

Silencing gene clusters may require specific ecological cues to stimulate, followed by the production of their respective specialized metabolit.

Some studies willMicroorganisms housed in equipment that can be grown individually in situ(for example, via iChips), infind unique molecules in a chemical symbiotic environment, or useMicrobial co-culture,Utilizing a composite library as an elicitor for the activation of silenced gene clusters (HiTE.

The most common members of the genus Actinomyces isolated from soil

Streptomyces

So-called "rare" actinomycetes, includingMicromonosporamany family members ofThey are relatively understudied due to their significantly lower frequency of occurrence in soil and relatively low growth rat.

A consequence of this competitive landscape is the high frequency of antimicrobial resistance genes in the soil geno.

The strategy is to screen for molecules produced during the interaction of rare actinomycetes,Molecules were specifically screened for inhibiting the growth of "resistant actinomycete" strains (strains of drug-resistant actinomycetes that are resistant to a large number of antibiotic.

This is a

Single, simple discovery pipeline: Focus on understudied microorganisms with high antibiotic-producing potential, cultured in binary microbial interactions to screen for interactions that inhibit resistant strai.

Antibiotics can't handle super bacteria, or can we learn from this idea, in the competitive environment of a variety of other bacteria (no drug pressure), use competitive pressure to interact with other bacteria to create new molecules that can inhibit super bacteria?