I’ve blogged before about how, for children under five, it’s not the ‘sexy’ microbes that kill, but instead, the run of the mill ones: the bacteria that cause diarrhea and pneumonia are the culprits. One of the things I have heard a lot of recently regarding antibiotic development (and related therapies) is that we need to focus on ‘non-paradigm’ and non-model organisms. There’s a problem with that approach:
The non-standard microbes aren’t the ones causing the bulk of bacterial disease.
In roaming around the International Society for Microbial Resistance website, I came across this telling figure:
This chart shows the frequencies of different species of bacteria that are isolated from sick people in hospitals–these include both hospital-acquired infections and infections that require hospitalization (a larger version can be found here). Many of these organisms might not be familiar, although, hopefully, Escherichia coli, Streptococcus, and Staphylococcus aureus (the methicillin resistant strains of Staphylococcus aureus are known as MRSA) are familiar.
What’s important is that most of these bacteria are either ‘model’ organisms or close relatives of model organisms. For example, E. coli, perhaps the ‘ur-model’ organism, and its relatives (the Enterobacteriaceae) comprise 35.3% of the in-patient isolates. Let me make something clear. I’m not arguing that each of these species doesn’t have its own ecology and set of pathologies: different groups of E. coli can differ radically in their ecologies and pathologies. But from a drug development perspective, if you’re trying to identify novel drug targets they are very similar. As a professor of mine said, “Once you throw ’em in the blender, they pretty much look the same.” (He was a wee bit reductionist).
The rest of the organisms, Enterococcus, the staphylococci, and streptococci are very well characterized, and are essentially Gram-positive model organisms. Pseudomonas aeruginosa is the non-enteric Gram-negative model organism. While Acinetobacter baumannii is increasing in frequency, and can have devastating effects [links], it hardly a new organism: the type species of Acinetobacter was identified in 1911 (like most bacterial taxonomy, Acinetobacter taxonomy is a disaster). The only thing that’s even remotely an oddball is Haemophilus influenzae. Considering that H. influenzae was one the first genomes sequenced, it’s hardly a bizarre organism.
When one looks at out-patient infections, the picture is virtually identical, although the rankings change slightly:
(from here; larger image here)
Notice that there are no spirochaetes on the list, and the really funky things like methanotroph anaerobes, well, let’s just say that the medically important are a very restricted depauperate set of the existing microbial diversity. Rather than trying to target ‘novel’ outliers for drug development, we need to focus on new sources of antibiotics.
Note: I’m not saying that we shouldn’t study oddball organisms for their own sake, but as a medical drug development strategy, it doesn’t make much sense to me.