The first time I met the genus Pseudomonas, I was a brand-new graduate student doing a rotation in David Figurski’s lab at Columbia University. Dave works on “promiscuous” plasmids that can move to many different species of bacteria. These plasmids pay their rent by providing multiple antibiotic resistance genes and other goodies to the bugs that host them. In that lab, we commonly cultured new strains with three or four different antibiotics in order to select for particular plasmids. Novice that I was, it seemed to me that such cultures would be pretty foolproof in terms of contamination – I mean, how many “wild” bacteria could live in such a drug-laden soup?
Pseudomonas aeruginosa, for one. It wasn’t long before I managed to contaminate a plate with something that grew bright green colonies and had a weird grape-like odor. A senior grad student in the lab diagnosed it immediately. “But how can it survive on there?” I asked. “It’s Pseudomonas,” he laughed.
While many bacteria pick up drug resistance genes here and there through mobile genetic elements such as plasmids and transposons, P. aeruginosa has resistances baked right into its genome. It carries multiple drug-specific resistance genes as well as general-purpose pumps that throw antibiotics out of the cell before they can even act.
One Pseudomonas cousin, now known as Burkholderia cepacia, takes this tough-guy act a step further; it can actually use penicillin as a food source. Imagine hornets passing around a can of Raid so they can take long pulls from it while commenting on its pleasant flavor, and you’ve got the general idea. These are some seriously bad-assed bugs.
Given all that, perhaps it shouldn’t come as a surprise that P. aeruginosa is also covered in venomous spines. That was the conclusion of a paper published last summer by researchers at the University of Washington, and discussed in an accompanying News & Views article in Nature.
The authors start off the paper with an excellent description of the microbial world:
Competition for niches among bacteria is widespread, fierce and deliberate. These organisms produce factors ranging in complexity from small diffusible molecules to multicomponent machines, in order to inhibit the proliferation of rival cells.
It’s a jungle down there at the micrometer scale, and P. aeruginosa is the honey badger.
This is a heavily armed conflict on all sides. While we often think of antibiotics as brilliant products of medical research, microbes invented them. Penicillin is just a fungus’s way to get ahead of its bacterial competitors; penicillin resistance is the bacterial side’s countermeasure. We’re naive newcomers to a battle that’s been raging for billions of years.
One of the more sophisticated siege machines in play is called the Type VI secretion system, a set of proteins found in many Gram-negative bacteria. The Type VI system injects proteins from one cell directly into another when they touch, in a manner similar to the way some bacteriophages transfer their genetic material into their hosts. That similarity could be a case of convergent evolution, in which form followed function, or the bacteria might have ripped off the mechanism directly from an ancient phage infection that went awry. I favor the latter explanation, largely because it fits so well with the general Pseudomonas attitude. Scrapping an infecting pathogen to build a weapon just sounds like something it would do.
In P. aeruginosa, the Type VI system exports at least three proteins, called Tse1, Tse2, and Tse3. All three, the new paper explains, are poisonous to other Gram-negative bacteria. Tse1 and Tse3 attack the peptidoglycan structure that lies in the periplasmic space between the outer and inner membranes of Gram-negative cells, causing the cell to fall apart or lyse. Earlier work had shown that Tse2 is toxic when it enters the cytoplasm, but it’s not clear exactly how it kills. When P. aeruginosa contacts another Gram-negative bacterium, it can use its Type VI secretion system to inject these toxins into the periplasmic space, killing off its competition so it can colonize a new food source.
That’s all well and good, but there’s a problem: the Tse proteins can also kill P. aeruginosa. To solve that, the bacteria carry antidotes, called Tsi1, Tsi2, and Tsi3. Each poison/antidote pair is expressed from a bicistronic operon (two genes transcribed from a single promoter), so whenever a cell manufactures the poison, it simultaneously produces the antidote for itself.
If Pseudomonas is producing both poison and antidote, though, why not just secrete the poison into the environment, antibiotic-style, rather than inject it through direct contact? It could be that these particular toxins don’t work well when diluted in the surrounding fluid, or that the whole toxin-plus-injection system evolved as a complete setup. Evolution doesn’t analyze a problem and calculate the most efficient way of doing things, it just tries out solutions until something works, and this works. It’s also possible that Pseudomonas is playing a more sophisticated game that we still haven’t fully uncovered. Transfering a toxin through direct contact could allow the bacterium to perform some kind of recognition step so that it won’t inject its brethren. Bayonets are less likely to cause collateral damage than bombs.
Whatever Pseudomonas is up to, it’s certainly a good system to keep studying. Besides being a pathogen in its own right, especially in patients with cystic fibrosis or immune deficiencies, this genus provides a nice sampling of the kinds of adaptations bacteria have evolved to survive in ferociously competitive environments. If it shows up as a contaminant in your lab, though, just throw those plates into the autoclave. That’s one thing even Pseudomonas can’t survive – yet.
1. Alistair B. Russell, Rachel D. Hood, Nhat Khai Bui, Michele LeRoux, Waldemar Vollmer & Joseph D. Mougous (2011). Type VI secretion delivers bacteriolytic
effectors to target cells, Nature, DOI: 10.1038/nature10244