The world has finally woken up to the grave fact that we face the imminent collapse of our first-line medical protection against pathogenic microorganisms – antibiotics. The pharmaceutical industry churns out over 100,000 tons of antibiotics every year, and much of that tonnage is inexpertly over- or mis-prescribed and has led to a plethora of multiply antibiotic-resistant superbugs. But where do these pathogens acquire the genes for antibiotic resistance? There seem to be three answers: overuse of antibiotics either selects for pre-existent resistance mutations lying in bacterial genomes, or fortuitous de novo mutations that occur in the face of the intense selection pressure of antibiotic treatment. And there is a third way. For over 30 years, microbiologists have suspected that pathogenic bacteria obtain their resistance genes from the very organisms that supply our antibiotics in the first place – actinobacteria, otherwise known as actinomycetes, which look like fine filamentous fungal hyphae and inhabit soils.

One single genus of actinobacteria, Streptomyces, has made a gigantic contribution, from the days of Alexander Fleming to the present, to the production of our antibiotic arsenal. Over 80% of our antibiotics have been sourced from them. From streptomycin, in the 1940s, to the cephalosporins, chloramphenicol, neomycin and the tetracyclines and on to erythromycin, vancomycin and gentomycin in more recent years – and many others.

Actinobacteria produce all these toxic antibacterials in order to attack and destroy competing species in the soil around them, and, to make sure that they do not succumb to their own poison, they contain a suite of protective antibiotic resistance genes. On top of that, actinobacteria collect resistance genes from each other so that they are an equally rich source of antibiotics, and antibiotic resistance, at the same time. In an open-access paper published June 7th in Nature Communications, titled “Dissemination of antibiotic resistance genes from antibiotic producers to pathogens”, Xinglin Jiang et al have painstakingly proved the microbiologists suspicion that pathogens purloin resistance genes from actinobacteria by tracking a route they call “carry-back” – horizontal gene transfer in both directions – by which the resistance genes get transferred.

Their suspicions were alerted by the discovery that many of the resistance genes in important gram-negative pathogens like E. coli and Pseudomonas aeruginosa bore remarkable sequence similarity to antibiotic resistance genes from actinobacteria. So, if pathogens import their resistance from the actinobacteria resistance factories, how do they do it? The team provide evidence that pathogens encounter actinobacteria in places like farmyard soil or clinical waste, and conjugate with them – a form of bacterial “sex” that transfers pathogen DNA into the actinobacteria. Once there, the pathogen DNA recombines with actinobacterial DNA to form a sandwich of actinobacterial DNA – rich in resistance genes – flanked by pathogen DNA. When the actinobacterial cell dies this DNA sandwich lives on, quite viable, in the soil where it can eventually be picked up by transport through the cell membranes of other pathogens, a process called natural transformation, and reincorporated into their genomes – a loaded gun ready to cause medical havoc.