12:27am Tuesday 12 December 2017

Battle of the bugs

Microbiologists have uncovered a sneaky trick the bacterium Pseudomonas aeruginosa uses to oust rival bacteria. Its means of attack helps it survive in the outside environment and may even help it cause infection.

P. aeruginosa is a common bacterium that lives in soil, but it is also an opportunistic pathogen best known for infecting the lungs of cystic fibrosis patients.

The scientists, including Professor Waldemar Vollmer and Dr Nhat Khai Bui of the Institute for Cell and Molecular Biosciences at Newcastle University, discovered that P. aeruginosa injects toxins into rival bacteria with a needle-like puncturing device, called the type VI secretion system (T6SS). The toxins degrade its competitors protective barricades  – their cell walls.

The research report also delineates  the complex defensive mechanisms by which P. aeruginosa protects itself from its own artillery. The findings will be published in the July 21 issue of the journal Nature.

While generally harmless to healthy people, this versatile bacterium takes advantage of those with weakened immune defenses.

P. aeruginosa’s ability to thrive in the thick airway mucous of cystic fibrosis patients and in burned or otherwise severely damaged  skin makes it a major public health concern. All of these environments have one thing in common: other bacteria.  According to lead author Alistair Russell at the University of Washington, “Competition among bacteria is brutal and fierce.”

By killing off competitors, P. aeruginosa widens its territory, thereby leading to its overall success. Moreover, the better able it is to outlast other bacteria in the environment, the better chance it has of coming in contact with and colonizing people. Russell added, “Pseudomonas is never going to encounter an infection site if it can’t survive in the outside world.”

The researchers  have detailed the mechanism of this weapon. “This secretion system,” said Russell, “primarily serves to bypass the protection normally afforded to bacteria by a membrane surrounding their cells.”  Breaching this membrane allows P. aeruginosa to deliver toxic proteins that degrade the bacterial protective shell, the cell wall. After the cell wall is blighted, the cell can no longer withstand the pressure inside. It bursts like an overfilled water balloon.

P. aeruginosa protects itself from its own toxins, and from attack by members of its own species. The study shows that toxins are transported by the T6SS in such a way that they never enter the space where P. aeruginosa’s  cell wall is located, but are injected directly into this space in the cell under attack. To prevent an attack from other members of its species, each P. aeruginosa cell has a set of specific immunity proteins in this cell wall space. There they inactivate any toxins injected by other bacteria. Only bacteria without these immunity proteins – that is, other bacterial species – are susceptible to these toxins.

The study also confirms previous observations of the evolutionary similarity between the T6SS and bacteriophage, viruses that infect bacteria. The puncturing needle-like component of the T6SS and its method of delivery are similar to the mechanisms bacteriophage use to infect bacteria.  Interestingly, in a technique called “phage therapy,” scientists have long sought to exploit the antibacterial properties of these viruses to treat bacterial infections. One limitation is that bacteriophage are relatively unstable and require a host bacterium to increase their numbers. The team are excited by the potential of the antibacterial properties of the T6SS to be used in an analogous way.

Russell explained, “We might be able to take helpful bacteria, give them this system genetically, and increase their ability to clear out professional pathogens: those bacteria who make their living causing disease.”

Knowledge of this complex bacterial antimicrobial mechanism also might help in the design of more sophisticated drugs. “If scientists could inhibit this secretion system in Pseudomonas through a new type of antibiotic, this opportunistic pathogen would not be able to break through the normal, healthy barrier of bacteria in the human body,” Russell said.

The study, published in Nature, was supported by the National Institutes of Health, the European Commission within the DIVINOCELL programme, and a Graduate Research Fellowship from the National Science Foundation.

The study involved Professor Waldemar Vollmer and Dr Nhat Khai Bui of the Center for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Alistair Russell, Joseph Mougous, Michele LeRoux and Rachel D Hood at the University of Washington (UW).

Reference: Type VI secretion delivers bacteriolytic effectors to target cells, Nature. doi:10.1038/nature10244

(Press release adapted from the University of Washington)


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