Mike the Mad Biologist

Salmonella, Shigella, and Lactose, Oh My!

It’s never made much sense to me why the pathogenic bacteria Salmonella and Shigella (which is really E. coli) have lost the ability to use lactose (milk sugar). In Shigella, we know that when we restore some lost functions through genetic manipulation (e.g., cadaverine production), they actually prevent these altered Shigella from causing disease. But lactose seems to be a good sugar to be able to grow on–they’re exposed to it from time to time (in infants).

The genus Salmonella contains two species: S. enteriditis, which causes disease* and can’t use lactose as a carbon source, and S. bongorii, which can grow on lactose and does not cause disease.

A recent study genetically engineered a S. enteritidis strain that contained the E. coli lactose utilization genes–it could grow on lactose. The authors observed that the LacI repressor, a molecule that shuts off the genes that allow growth on lactose, also inhibited the ability of S. enteritidis to cause disease, including its ability to survive in macrophages (these are immune system cells that usually gobble up and destroy bacteria and viruses, but, in the case of S. enteritidis, the bacteria usually survive in the cells and then can be released back into the body).

Interestingly, when the authors hunted through the genome of S. bongorii, they found relatives of two of the four genes involved in lactose utilization…including the LacI repressor.

Mind you, it’s not clear what exactly the LacI repressor does to prevent disease or why this would evolve (although shutting off genes activated under stressful conditions, like getting EATED!, when there’s lots of yummy sugar around strikes me as a good thing to do). Still, it will be interesting to see how many more gene losses by pathogens are, in fact, adaptations to a pathogenic life history.

*Salmonella taxonomy is a nightmare. ‘Nuff said.

Cited article: Eswarappa SM, Karnam G, Nagarajan AG, Chakraborty S, Chakravortty D. 2009. lac Repressor Is an Antivirulence Factor of Salmonella enterica: Its Role in the Evolution of Virulence in Salmonella. PLoS ONE 4(6): e5789. doi:10.1371/journal.pone.0005789

Comments

  1. #1 Dan
    June 12, 2009

    Uh, Mike, the species is S. enterica. Enteriditis is one of the serovars of that species. You’ve proven your own point- the taxonomy is a pain.

  2. #2 JohnV
    June 12, 2009

    Something similar is seen in Burkholderia pseudomallei and B. thailandensis. B. pseudomallei is virulent and cannot utilize arabinose while B. thailandensis can grow on arabinose and is avirulent. B. pseudomallei has a few left over genes from the ara operon present in B. thailandensis. When the operon was restored in B. pseudomallei, its LD50 increased 10-fold (with arabinose) or 100-fold (without arabinose). Looks like type 3 secretion was repressed.

    http://iai.asm.org/cgi/content/full/72/7/4172

  3. #3 becca
    June 12, 2009

    So let me see if I get it. The LacI repressor gets turned off in acidic conditions (providing a way to stop nomming lactose when lactic acid gets too high? it’s been too long since I had bacteriology!). So it’s also turned on in the acidic environment of a macrophage, and it happens to inhibit some SPI-2 regulated genes which are critical for survival in macrophages and therefore virulence.
    Is that right?

  4. #4 VJ BinCT
    June 12, 2009

    Salmonella, Shigella, Rickettsia, and Yersinia, Attorneys at Law.

    I have told my dentist (whose name is Hacker!) to form a practice called Hacker, Pullman and Yankovich, PC

  5. #5 drdrA
    June 12, 2009

    In the genus Salmonellae, there are two species: Salmonella enterica, and Salmonella bongori. The species Salmonella enterica is further subdivided into 6 subspecies- just to make it ultra confusing- the first of these is ssp. I Enterica. So now we’ve got Salmonella enterica subspecies Enterica – within this subspecies there are over 1400 different serotypes, of which serotype Enteritidis is just one. This particular serotype is one of the two top gastrointestinal disease causing serotypes of Salmonellae in the world- either #1 or #2 depending on the country and the year.

    Does your head hurt yet?

    The other subspecies belonging to S.enterica subsp. Enterica colonize reptiles asymptomatically (usually), but can cause disease in people – this is sporadic- and no one really understands why these subspecies don’t circulate in mammalian and avian populations. Salmonella bongori is also primarily associated with cold blooded vertebrates… but it can cause disease in people as well! It’s just freaking rare.(http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=130773)

  6. #6 microfool
    June 12, 2009

    As for why Salmonellae don’t have lactose operons, I think double-doc hit the nail on the head: these are reptile and bird associated spp. and probably don’t find milk sugar that often.

    As for lacI being a black hole mutation towards virulence, I have a feeling that this work is going nowhere. I imagine over-expressing any DNA binding protein might have an effect on virulence.

    Finally, the authors state: “This result unequivocally demonstrates that LacI suppresses the virulence in S. enterica.” How does any PI let the word “unequivocally” slip into a publication? My PhD mentor would have throttled me.

  7. #7 Dan
    June 14, 2009

    I think that its worth keeping in mind that the lac operon isn’t only involved in degrading lactose. Both lacZ and lacY are active on glycerol-galactoside, a sugar that is found in plants (http://dx.doi.org/10.1016/0022-5193(79)90260-1). Species that aren’t primarily found in the guts of infant mammals, like Citrobacter or Serratia, can have lac operons. Even some Salmonella enterica strains posses a lac operon (http://mbe.oxfordjournals.org/cgi/content/full/22/3/683)- or at least lacZ and lacY. microfool might be right, but I think the reason that most Salmonella don’t have lac is likely to be more complicated.

    That said, I agree in the worry that the results in this paper might be driven by over-expression of lacI. It would have been really nice (and not that hard!) to see the effect of a chromosomal copy.

  8. #8 ligtv
    June 18, 2009

    thanks.