Lin X, Litvintseva AP, Nielsen K, Patel S, Floyd A, et al. (2007) αADα Hybrids of Cryptococcus neoformans: Evidence of Same-Sex Mating in Nature and Hybrid Fitness. PLoS Genet 3(10): e186 doi:10.1371/journal.pgen.0030186

I always suspected fungi to have the richest sexual life of all living beings. Now, with same-sex mating, they are a step ahead. There is an interesting case for genetics problems unisexual hybridization.

Cryptococcus neoformans is a ubiquitous human fungal pathogen that causes meningoencephalitis in predominantly immunocompromised hosts. The fungus is typically haploid, and sexual reproduction involves two individuals with opposite mating types/sexes, α and a. However, the overwhelming predominance of mating type (MAT) α over a in C. neoformans populations limits α–a mating in nature. Recently it was discovered that C. neoformans can undergo same-sex mating under laboratory conditions, especially between α isolates. Whether same-sex mating occurs in nature and contributes to the current population structure was unknown. In this study, natural αADα hybrids that arose by fusion between two α cells of different serotypes (A and D) were identified and characterized, providing definitive evidence that same-sex mating occurs naturally. A novel truncated allele of the mating-type-specific cell identity determinant SXI1α was also identified as a genetic factor likely involved in this process. In addition, laboratory-constructed αADα strains exhibited hybrid vigor both in vitro and in vivo, providing a plausible explanation for their relative abundance in nature despite the fact that AD hybrids are inefficient in meiosis/sporulation and are trapped in the diploid state. These findings provide insights on the origins, genetic mechanisms, and fitness impact of unisexual hybridization in the Cryptococcus population.

I just had lunch the other day with ‘Rose’, one of my AIDS patients.  It was the greatest thing, to see her – just like a ‘normal’ person. 

Who would believe that just last year, Rose nearly died from a terrible opportunistic infection called ‘Cryptococcus’. 

When Rose came into the hospital, she was thin, wasted and very weak.  She had been having fevers for sometime.  AIDS had been ravaging her immune system and without those defenses, she was extremely susceptible to infection.  Certain types of infections tend to occur in advanced AIDS, and she was now fighting a battle with Cryptococcus neoformans, a nasty fungus.  By the time she came in, this fungus was ‘everywhere’ – it was growing out of her blood. 

We put her on the most powerful medicine we could – amphotericin, or ‘ampho-terrible’.  It was a difficult medicine to take, especially for someone so sick.  Her blood levels dropped to less than half of what they should have been, her electrolytes were profoundly deranged , she felt weak and feverish.  There weren’t any options though – we had no choice but to try and treat her, or face certain death.  She managed to make it though those difficult days, eventually regaining enough strength to walk the halls of the hospital.  Each day I saw a slight improvement – I knew she was a strong person.  Rose had a 15 year old son to live for. 

Her husband had died from AIDS some time ago – her son was all she had – they needed each other.  Slowly we brought Rose back – she improved enough to be discharged home after several weeks.I had lost many patients from AIDS before, but this time I was determined not to give up.  I knew that close follow-up would be essential to restoring her immune system and finally beating the fungus. 

I placed Rose on highly active anti-retroviral therapy or HAART.  She needed help in remembering to take the meds, since the virus also affected her memory.  I went to her house and realized that it was too much for her to handle.  Rose wasn’t taking all the meds the right way.  I brought her a pill box, with the days of the week in a row, and little compartments for morning and nightly medications. We filled up the compartments together– each day she just had to flip the lid and take whatever was in the box. 

I continued to follow her closely – checking up on her every week.  For some doctors, that can be a lot to ask, given our busy schedules.  I knew if Rose was going to be saved though, this was the only way.  She really needed help. I watched as the weeks and months went by – her blood counts improved.  Rose started gaining weight.  She was becoming strong again.  Now she could see for herself that this disease of AIDS was treatable! I felt confident Rose would ‘make it’.  I was so happy yesterday to see her doing so well – what a miracle!
RW