Of Mice And Men And Antibiotic Resistance

A recent mBio paper about bacteria and antimicrobial resistance found its way into the popular press, and, as you might expect, it’s not good. The problem aren’t the data in the paper, but the context (or lack thereof) into which the results are placed. Here’s the abstract:

House mice (Mus musculus) thrive in large urban centers worldwide. Nonetheless, little is known about the role that they may play in contributing to environmental contamination with potentially pathogenic bacteria. Here, we describe the fecal microbiome of house mice with emphasis on detection of pathogenic bacteria and antimicrobial resistance genes by molecular methods. Four hundred sixteen mice were collected from predominantly residential buildings in seven sites across New York City over a period of 13 months. 16S rRNA sequencing identified Bacteroidetes as dominant and revealed high levels of Proteobacteria. A targeted PCR screen of 11 bacteria, as indicated by 16S rRNA analyses, found that mice are carriers of several gastrointestinal disease-causing agents, including Shigella, Salmonella, Clostridium difficile, and diarrheagenic Escherichia coli. Furthermore, genes mediating antimicrobial resistance to fluoroquinolones (qnrB) and β-lactam drugs (blaSHV and blaACT/MIR) were widely distributed. Culture and molecular strain typing of C. difficile revealed that mice harbor ribotypes associated with human disease, and screening of kidney samples demonstrated genetic evidence of pathogenic Leptospira species. In concert, these findings support the need for further research into the role of house mice as potential reservoirs for human pathogens and antimicrobial resistance in the built environment.

IMPORTANCE Mice are commensal pests often found in close proximity to humans, especially in urban centers. We surveyed mice from seven sites across New York City and found multiple pathogenic bacteria associated with febrile and gastrointestinal disease as well as an array of antimicrobial resistance genes.

The popular discussion of this paper seems to misunderstand two important things. First, many scary sounding pathogens are also commensals; they live on and in us without causing disease. Second, a fair number of resistance genes are chromosomally encoded, which in English means that if that bacterial species is present, those resistance genes will also be present. In other words, resistance genes indicate the presence or absence of bacterial species (though if they are ‘mobilized’–acquired by a genetic element that can move to other bacteria–that can be a problem).

With that as prelude, let’s move onto the paper. The authors collected poop from 416 mice in seven locations in New York City. Then then screened individual mouse poops with PCR to look for various disease-related and antibiotic resistance genes. They also combined the samples from each of the sites and screened that mixture in the same way.

There are some interesting results. Fourteen percent of the mice are positive for a gene found in Shigella that is part of the machinery which causes shigellic dysentery. It could be that Shigella and enteroinvasive E. coli (Shigella, by the way, is E. coli) exist in mice as a reservoir (though human children can also carry these organisms asymptomatically too).

But things kind of go off the rails when we get to the discussion of resistance genes. Let’s go through some of the resistance genes. First, there’s blaSHV, a family of beta-lactamases (that’s where the b and la in blaSHV come from) that confers resistance to many penicillin derivatives, including third-generation cephalosporins. It’s found in five of the seven DNA pools and 8/146 individual mice. Here’s the thing: many Klebsiella pneumoniae carry blaSHV, and rodents often carry K. pneumoniae (humans do as well). In other words, this just means mice are… rodents (outside of a laboratory breeding colony).

Moving on to blaACT/MIR, a class of beta-lactamases that confers resistance to roughly the same set of antibiotics as blaSHV. blaACT/MIR genes are found in 21 percent of the mice. Zoiks! This sounds bad, except that these are chromosomally-encoded genes that are found in Enterobacter. If that sounds familiar… These genes can be mobilized (and are a problem when they are), but really, all these results are telling us is that rodents carry Enterobacter, which they do (and, again, healthy humans do as well).

Seven percent of mice had a qnrB gene, which confers resistance to ciprofloxacin. This is common in humans, so it shouldn’t be too surprising that mice in contact with humans carry these genes (we would, of course, like qnrB genes to be less frequent). And one percent of mice had mecA which is the gene that confers resistance to methicillin in Staphylococcus aureus (that’s the “M” in MRSA). Again, not shocking for human-associated animals (about one percent of people carry MRSA, and thus, mecA).

It’s not a bad paper, but I think it’s the kind of paper whose results can be overblown. What was found is that human-associated mice have a combination of common commensals*, many of which carry resistance genes, as well as resistance genes that are reasonably common in people. It’s interesting, and worth documenting, but probably not worth the popular media frenzy. A little context would have gone a long way here.

*E. coli, for example, have a beta-lactamase called blaEC; it’s so prevalent you can use it as a positive control. It’s usually not expressed, but when it is expressed has a resistance spectrum similar to blaACT/MIR and blaSHV, depending on the exact form of blaEC.

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