By turning off the lights, setting up an oatmeal-based bed and slipping some extra vitamins into their food, researchers have persuaded the supposedly asexual mold that makes penicillin to have sex. The fungi's ability to switch it up sexually could help industrial scientists breed more efficient antibiotic-producing strains or even lead to the discovery of new, useful compounds.

Penicillium chrysogenum is the original and still-used source of penicillin. It creates a nitrogen and carbon ring structure called beta-lactam, which prevents bacteria from building cell walls. This antibiotic helps the microscopic fungi kill any bacteria that might try to live where the fungi grows; it is also what doctors have used to combat bacterial illness since the 1940s.

Despite decades of study, researchers still believed that the fungi only reproduced asexually. That misunderstanding limited how scientists could genetically manipulate the fungi for industrial antibiotic production. The idea that P. chrysogenum was asexual persisted because fungal sex is complicated. Fungi—a group that includes large mushrooms growing on the forest floor and microscopic molds colonizing stale bread—have many different strategies for reproducing: Some clone themselves asexually. Others navigate a mating scene populated not by one member of a different sex but thousands of sexes. Some yeast can switch gender completely. The number of sexes in the fungal world depends on the species.

Paul Dyer, a fungal biologist at the University of Nottingham in England, suspected that P. chrysogenum would reproduce sexually if given the right encouragement. A complete sequencing of the fungi's genome revealed that P. chyrosogenum still carried the genes needed for mating. "That told us that there was perhaps sexual compatibility there," he says. So Dyer and researchers at several other European institutions tried to find the ideal conditions that would encourage P.chrysogenum to have sex.

First, Dyer and his colleagues paired strains with compatible mating genes (P. chyrosogenum has two different sexes) and grew them with different food and light conditions. The winning combination was an oatmeal-base supplemented with a vitamin called biotin. After five weeks in the dark, the fungi produced special structures called cleistothecia and ascospores, which only occur after sexual reproduction. Genetic analysis confirmed that genes had been sexually recombined. "We've now revealed its secret sexual side," Dyer says.

Furthermore, the researchers discovered that the genes that regulate the fungi's sexual ability also control the amount of penicillin it produces; the fungi that are having sex make more penicillin. The team published their findings online in January in Proceedings of the National Academy of Sciences. "I've believed for a long time that these guys were having sex but they were just doing it in secret," says Joan W. Bennett, a professor of plant biology and pathology at Rutgers University, who was not involved in the work.

P. chrysogenum isn't the only previously asexual fungi recently reclassified as a reluctant sexual reproducer. Dyer's lab group has also discovered that Aspergillus fumigatus, a mold commonly found in compost heaps and leaf litter, can also reproduce sexually.

The fact that sex in fungi is more widespread than many scientists had thought is one reason to get excited about the findings, says Bennett, but there are also practical reasons.

Just as humans have bred cows to produce more milk than their wild cousins; sexually reproducing P. chrysogenum could be bred to produce more penicillin. Industrial strains with high antibiotic concentrations are already in use, says study co-author and Ulrich Kück, a professor of molecular botany at Ruhr University Bochum in Germany. Those strains, however, are "very genetically unstable," he explains, and penicillin production tends to decrease as the fungal culture ages. "In industry you have to improve your strains every month or every week," he says. "Crossing a high-producing strain with a healthy partner strain would be very valuable."

6 Comments

1. 1. And Then What? 01:29 PM 2/8/13

   Something has always puzzled me about medicines like Penicillin which are taken orally. How it is that medicine that has to go through what is essentially an “acid bath” in our stomachs is still intact in the lower gut? I am assuming that this must be the case since they are most likely absorbed through the intestinal walls o reach the blood stream.

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2. 2. Profitsup 02:32 PM 2/8/13

   See the Collage Kids have said: that SEX CAN SAVE YOUR LIFE WERE RIGHT!

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3. 3. dadster 12:11 AM 2/10/13

   If there was a better way of producing penicillin nature would have done it in the billions of years it had at it's disposal. What man produces in the industrial factory by genetic tweaking will be of inferior quality and stability. It's effects also would not last long warranting recurring application of penicillin adding to the cost of treatment for the patient and the profit of the researchers and to the pharmaceuticals . Of course , ultimately the pharma win through high powered advertisements and media barrage and, the people pay for all that .

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4. 4. nodyl03 in reply to And Then What? 05:09 AM 2/14/13

   Many medicines rely on the acid in the stomach to become soluble. The pH in the stomach is so low that the molecules are able to be ionised and hence become soluble in an aqueous medium and would be able to enter the blood stream.
   
   On the other hand, some tablets have a special coating to limit their dissolution in the stomach (in an acidic environment) but would dissolve in the intestine (where the pH is not acidic, such as pH6.8). In other word they remain as an intact tablet in the stomach but would start to dissolve in the intestines. Such tablets are referred to as delayed release tablets. According to wikipedia:""Delayed release" is also commonly used in a different sense in the pharmacological industry, to refer to oral medicines that do not immediately disintegrate and release the active ingredient(s) into the body. An example is enteric coated oral medications, which dissolve in the intestines rather than the stomach".
   
   Hope this helps ;)

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5. 5. And Then What? in reply to nodyl03 06:53 AM 2/14/13

   Thank you for taking the time to supply me with some info. I was aware of the tablet type such as those with enteric coating, but I was specifically thinking of the liquid medicines containing penicillin that my children took when they were younger. Your description of this type medicine being activated, so to speak, by the acid in the stomach in preparation for its absorption in the Intestine makes perfect sense.

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6. 6. Ramil 10:49 AM 2/14/13

   The idea that evolution is a process directed toward improving something to help a different species (that needs penicillin to cure its diseases, for example) is really a serious misunderstanding of how evolution works. If making more penicillin was of any benefit to the mold itself, those strains that made more penicillin would gradually our-reproduce those that made less, not because they were "trying" to improve their lot by making more penicillin, just as giraffes did not gradually grow longer necks from trying to reach higher leaves to eat from tall trees. So cross-breeding penicillin-producing molds to produce a greater yield of penicillin would not have occurred in nature, because penicillin molds that produce more penicillin have no evolutionary advantage over the "regular" ones. It is the same as antibiotic-resistant bacteria only thriving in the presence of antibiotics, because it is only the presence of antibiotics that allows them to out-reproduce their Petri-dish mates, and gradually replace them, not because they strove to become antibiotic-resistant so their children could have a more secure life.

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