Foul brood

[Follow up to Lariocidin last Weds: launched on "5th March" in error earlier, so you may have read it already]

Was I talking about spending a life-time culturing Paenibacillus spp.? I was. It is common enough in science. You pick a final year undergraduate project at random or because you have crush on one of the post-grads and you spend the next 40 years working out minuter details of what your supervisor was interested in . . . who got there because their supervisor was. But really Paenibacillus? never 'eard of it. I used to teach microbiology at The Institute but that doesn't mean I knew anything about it!

So I looked it up. Paeni- means almost and bacillus means little stick. They are distantly related to old Blob pals like Bacillus and Lactobacillus. Perhaps the most common example with in the genus is Paenibacillus larvae the causative agent of American foul-brood a fatal infestation of honeycomb. But there is also Paenibacillus vortex which grows in such striking patterns [L] on a Petri dish. Other Paenibacillus strains are valued for the anti-microbial properties and also for making industrially useful enzymes. 

But back to foul-brood, which can pop up pretty much anywhere in the world to the despair of bee-keepers. But no surprises when it turns out that there is a lot of diversity within the species Paenibacillus larvae some more damaging than others. One of the key diagnostic signatures are variations among their ERIC sequences. Whoa! that's a rabbit hole because ERICs were discovered by my then boss Paul Sharp just about the time I started working for him in the early 90s. It's also a bit odd to continue using ERIC for species which are not even in the same Kingdom as Enterobacteria.

Bacterial genomes, in contrast to ours, have only small stretches of non-coding DNA between the genes which get translated into protein. The phrase "DNA makes [RNA and RNA makes] protein and protein make everything else" has a lot of explanatory power. All enzymes, transporters, channels,  essential for everyday life are all proteins. Enterobacterial repetitive intergenic consensus (ERIC) is a ~127bp sequence which is found between genes in multiple copies in a lot of 'enterics' include E. coli and Salmonella - here's fragment of the ERIC consensus sequence clipped from the 1991 paper:

note the funny arrows on top of the sequence - they indicate the palindromes where CTTAC - pairs anti-parallel with - GTAAG to form a stable double helix structure. There are too many ERICs around, and the palindromes are too long for this to be a noisy coincidence; and molecular biologists have spent the last 25 years trying to figure out their function. It took Paul a couple of sessions in the pub to come up with ERIC as a memorable, expressive and mildly amusing acronym.

Around about then for Paul's birthday for a jape, I commissioned The Brother of the Beloved BTB, a graphic designer, to make The Boss a pack of business cards. This was before the WWW but after e-mails, so we included name, addr, eddr, phone and fax - and round the edge the 127 As Ts Cs and Gs of the newly discovered ERIC sequence. I thought that was a clever in-joke that might jump-start a geeky conversation about mutual progress at the frontier of sequence analysis. He thought it / I was weird.

Lasso them microdogies

My correspondent G continues to scour through the interwebs looking for Blobocopy. I tell 'er she should start 'er own effin' blog but she's too busy scouring the interwebs. She did though submit The Blob's one-and-only guest blog [cw: asthma] in 2019. The latest alert concerned the discovery of a novel source of potent antibiotics in a Canadian soil sample. This happens occasionally as in the discovery of Eleftheria terrae ten years ago or more to the point discovery of Teixobactin - a chemical from that novel microbe that kills pathogens like MRSA. Back in my 2015 report, I bet that Teixobactin would give its discoverers a Nobel gong within ten years. But they haven't even got a production schedule sorted [there are technical hurdles] let alone FDA approval. Science is Hard.

Gerry Wright [L,L] has been on this line of research for at least ten years but Manoj Jangra [L.R] only came to the lab as a post-doc a tuthree years ago. He is holding [yea! 3-D printers!] a model of their novel antibiotic. If you squint, the molecule looks like a lasso = lariat hence "lariocidin". Their discovery is important because lariocidin nobbles other bacteria in a novel way - by interfering with the bacterial ribosome and preventing protein synthesis. 

When bacteria become resistant to antibiotics, researchers tend to modify [add a bell, drop a whistle] the antibiotic chemically, so that the bacteria no longer recognise the cause of their own demise. But that tends to buy only a few years until the bacteria develop their own modification in the arms-race. It is hoped that, by presenting a completely new method of attack, the effective life of lariocidin (and its inevitable derivatives) will be longer. And lariocidin's structure is radically different from existing antibiotics, so that will pose an extra challenge for the target pathogens. On the safety-side, bacterial ribosomes are functionally equivalent [make proteins] but structurally different from mammalian ribosomes; so there is not going to be cross-toxicity to both pathogen and patient.

Seems that the soil sample from which the lariocidin-producing Paenibacillus was isolated came from the garden of one of the lab techs in Wright's lab at McMasters U. But that's the easy bit, it only needs a trowel. I assured G that her garden was full of bacteria killing each other but even the a silver plated trowel isn't going to get her a Nobel. Wright sensibly enlisted the help of a team from University of Illinois Chicago UIC, who provided complementary expertise.

Wright seems to have a thing about Paenibacillus: in 2016 he was scrabbling about in the bowels of the New Mexico earth to find an ecosystem uncontaminated by humans. There they uncovered Paenibacillus sp LC321whose genome held a number of potential target antibiotics. One of the nice threads in that tale is that Wright heard about these New Mexico caves by going to a lecture by Hazel Barton, an Akron U spelunking microbiologist.  Note to self: always go to lunchtime seminars! Like me at Aled Edwards' giving side-eye to same-old same-old research funding.

Microdogies? It's a Rawhide reference. Dogie: an orphan calf.