We are all aware that careless overuse of antibiotics can allow bacteria to develop antimicrobial resistance, but this isn’t the only way that bacteria can become resistant to antibiotic drugs. They can also pick up drug resistance genes from rival bacteria that they kill.
Researchers at the Biozentrum of the University of Basel in Switzerland have now identified a mechanism by which bacteria inject toxic components into competing organisms to cause the rival cells to lyse. The predatory bacteria can then take up the dead cells’ genetic material, including any antibiotic resistance genes, and acquire that antibiotic resistance themselves.
Peter David Ringel, Ph.D., Di Hu, and Marek Basler, Ph.D., report their findings in Cell Reports, in a paper entitled “The Role of Type VI Secretion System Effectors in Target Cell Lysis and Subsequent Horizontal Gene Transfer.”
Antibiotic resistance is a major problem in hospitals, where patients introduce a wide range of pathogenic organisms, and the high use of antibiotics is associated with the development and spread of antimicrobial resistance by and between bacteria. One of these hospital organisms, Acinetobacter baumannii, is known as the “Iraq bug” because multidrug-resistant (MDR) stains of the species caused serious wound infections in U.S. soldiers during the Iraq conflict.
Working with the model organism Acinetobacter baylyi, which is closely related to the Iraq bug, the Biozentrum team has now shown how some bacteria acquire antibiotic resistance directly from rival organisms. The researchers found that the aggressor cells inject their prey with toxic effector proteins using the type IV secretion system (T6SS) as a kind of poison syringe. The studies identified five different effectors. “… each kills the target cells by a distinct mechanism,” the authors write.
“Some of these toxic proteins kill the bacterial competition very effectively, but do not destroy the cells,” explains Basler. “Others severely damage the cell envelope, which leads to lysis of the attacked bacterium and hence the release of its genetic material.” In this case, the killer bacteria can take up the released fragments of DNA, which may carry drug resistance genes that confer that resistance on the acquirer.
Pathogenic bacteria that use this mechanism for horizontal gene transfer can become MDR. “The T6SS, as well as a set of different effectors, can also be found in other pathogens, such as those that cause pneumonia or cholera,” says Basler. In fact, the authors write, “potentially all bacteria that encode an anti-bacterial T6SS and DNA uptake machinery could use their T6SS to acquire new genes. In addition to Vibrio and Acinetobacter, this could be relevant for Campylobacter, Pseudomonas, Agrobacterium, and Ralstonia.”
Not all effectors kill the target organism, as some bacteria have developed or acquired immunity proteins, the researchers found. “We have also been able to identify the corresponding immunity proteins of the five toxic effectors in the predator cells,” Basler says. “For the bacteria, it makes absolute sense to produce not only a single toxin, but a cocktail of various toxins with different effects. This increases the likelihood that the rivals can be successfully eliminated and in some cases also lysed to release their DNA.”
“Importantly, the rate of horizontal gene transfer mediated by T6SSs will vary for each prey-predator pair, because the frequency of DNA acquisition depends on the mode of target cell killing,” the authors conclude. “This suggests that for efficient DNA acquisition from various prey cells, a diverse set of lytic effectors delivered by the predator may be beneficial, as certain prey cells may be immune to some of those effectors.”