Combining drugs with different penetration profiles can accelerate development of multidrug resistance

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What scares you? As a kid, I hid behind couch cushions while watching Jurassic Park and could never finish a Goosebumps book. Nowadays, I am terrified of the growing epidemic of antimicrobial resistance. And I’m not the only one. Last year, as part of a five-year strategy to combat drug resistance, British Prime Minister David Cameron commissioned a review to examine the economic and health costs of antimicrobial resistance. In their first report published last December, the panel predicted that left unchecked, antimicrobial resistance will lead an extra 100 million deaths by 2050 and cost the world economy up to $100 trillion USD.

Efforts to halt the spread of antimicrobial resistance have focused on removing antibiotics from animal feed and curtailing the overzealous and oftentimes unnecessary use of antibiotics in humans. Another strategy to prevent resistance from developing is combination therapy, when two or more drugs with unique modes of action are taken together to treat an infection. In a paper published this week in the Proceedings of the National Academy of Sciences, a team of mathematicians and biologists led by Dr. Pleuni Pennings at San Francisco State University examined how differences in drug penetrance can impact the effectiveness of combination therapy and subsequent emergence of multidrug resistance.

Combination therapy reduces the risk of drug resistance because in theory, the pathogen needs to acquire multiple mutations at the same time to withstand the assault of multiple drugs. In reality, combination therapies fail to stem the development of resistance for a number of reasons. For example, some patients are started on a single drug first before a second drug is added. This type of treatment regiment facilitates resistance development because bacteria can acquire singular mutations in a stepwise fashion. Another reason is that different drugs have different staying power, which means that even though you may be taking both drugs at the same time, one could pass through your body much faster than the other. This creates periods of “effective monotherapy” where resistance can develop easily to the single long-lived drug. While a lot of attention has been paid to how drugs with different half-lives impact resistance, not a lot is known about how the spatial distribution of drugs influence the evolution of multidrug resistance. That’s where this paper comes in.  Continue reading


Why female house finches prefer redheads over blonds

Walk into any clothing store and you’ll see that the women’s section is more colourful (and bigger!) than the men’s section. Not so in the bird world. In most bird species, males are more colourfully and elaborately dressed than females. This type of sexual dimorphism in which males and females look dramatically different is frequently driven by sexual selection. That is, female preferences for bright colours and ornate decorations have pushed each successive generation of males to evolve more and more flamboyant plumage. But why do female birds prefer brightly coloured males in the first place?

One idea is that ornamental traits like coat colour are indicators that can provide useful information about important survival traits. For example, the theory of parasite-mediated sexual selection proposes that the quality of a male’s ornamental display signals how well he can resist infection by parasites. To test this theory, many researchers are turning to the house finch, a common bird found across North America. Males have variable red-to-yellow colouration on their head, breast and rump whereas female finches are a rather boring greyish brown in colour. The bright red males enjoy more popularity among the females than their more drab yellow rivals. Many factors contribute to male colouration, including nutrition and parasite exposure during feather growth.

Male house finches vary in their colouration from red to yellow. (Image: Diane Pierce, National Geographic)
Male house finches vary in their colouration from red to yellow. (Image: Diane Pierce, National Geographic)

Speaking of parasites, let’s talk about the complex relationship between house finch feather colour and parasite infection. Several studies, including this one in 2004, showed that male house finches infected with the bacteria Mycoplasma gallisepticum develop more yellow and less bright feathers than uninfected males fed the same diet. Yellow males also seem to be at a disadvantage when it comes to surviving an infection. In the mid-to late-1990s, an M. gallisepticum epidemic hit the house finch population in the eastern United States. Surveys conducted before and after the epidemic found that red males survived better than yellow males, which drove the eastern house finch populations to become more homogenously red than populations in the rest of the country. In laboratory experiments, red males from unexposed populations resolved symptoms of M. gallisepticum infection faster than yellow males. So what exactly is going on? How does feather colour affect parasite infection and vice versa? Continue reading