Red ribbons for AIDS and Sexual Health Awareness [Image: Sexual Health Buckinghamshire, NHS, United Kingdom]

International news outlets covered the following study carried out at University College London recently, much to my excitement.  We at USOM and within the international mycoplasmology community are thrilled to see attention paid to these underdiagnosed but critically important pathogens.  The study discussed the prevalence of a sexually transmitted pathogen, Mycoplasma genitalium (“Mge”).  Mge has historically been extremely difficult to diagnose, with a small number of experts* serving as reference laboratories for its identification.  There is no equivalent of the rapid Strep screen  that can yield a quick and accurate diagnosis.  This is a very serious concern for three important reasons:

1.) Mycoplasmas, and especially Mge,  require specialized antibiotic treatment in order to completely cure a patient.  Since many of the symptoms are the same as chlamydia or gonorrhea, it can be difficult for doctors, PAs, and ARNPs to know which infection a patient currently has.  This is quite important, since Mge like all mycoplasmas only responds to certain drugs, and the medication needs to be takenfor a longer course to eliminate the infection.  Failure to eliminate the infections leads to antibiotic resistant strains.  Eliminating the infection is critically important when considers point 2, and especially point 3, and caregivers cannot decide on the best course of treatment without a reliable way to diagnose the infection.

2) Mge infection is significantly associated with pelvic inflammatory disease, impaired fertility and adverse pregnancy outcomes.  Because of this untreated Mge infection is likely to have long-term consequences on one’s future ability to conceive children, and increases the likelihood of miscarriage or preterm birth should an infected woman become pregnant.

3.) Mge infection has been associated with increased rates of HIV infection.  While on the surface this may seem incidental- exposure to one sexually transmitted pathogen indicates that you may have been exposed to multiple- additional research indicated that the relationship between the two organisms was a bit more sophisticated.  One study showed that Mge-infected patients showed increased shedding of HIV viral particles.  In other words, patients infected with both Mge and HIV were more likely to infect their partners.  The bad news didn’t end there, though.  Mge-infected individuals were also more likely to become infected with HIV, because the Mge bacteria are very, very good at recruiting HIV’s favorite target cells to the genital tract.  Taken together, Mge infection would seem to both make HIV-negative patients more susceptible to infection and HIV-positive patients into “super-spreaders”. 

The “new STD” is not new, nor is it necessarily more prevalent, but it is getting more attention through improved specialized tests.  Finding a rapid, sensitive, and specific way to diagnose this infection should be a priority, and I am hopeful these articles are important step in that direction.   
 

A "valentine" made from M. genitalium cells, courtesy of our friends at the Balish Laboratory

NOTE: This article originally appeared at www.infectiousnews.com  

*Laboratories featuring worldwide experts in the diagnosis of Mge can be found at the University of Alabama Birmingham, Washington University, Louisiana State University, The Johns Hopkins University, and Statens Serum Institut

Mycoplasmas are exceptional subjects for imaging. The specialized manner in which Mycoplasma pneumoniae, as an example, interacts with host cells requires the attachment (or terminal) organelle, a polar extension of the cell. This important virulence-associated feature couldn’t have been predicted de novo from any technique; microscopy was essential. Knowing about that structure and similar ones in other mycoplasma species has led to advances in understanding interactions with the host, cell movement, and cell division, and has even contributed to nanotechnology.

SEM of Mycoplasma genitalium G37. We can see the outside, but not the inside! Courtesy of J.M. Hatchel and the Miami University Center for Advanced Microscopy and Imaging.

What’s the best way to approach imaging of mycoplasmas? The answer depends heavily upon what the question being asked is. Continuing with the example of the attachment organelle, Biberfeld and Biberfeld (Journal of Bacteriology, 1970, 102:855-861) established its presence using both scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and both those techniques provided different kinds of information. TEM images of thin sections of M. pneumoniae cells clearly showed the highly differentiated, electron-dense, cytoskeletal core of the attachment organelle, and although we now use techniques for processing of cells for SEM that result in greater reproducibility than back in 1970, their SEM images of whole cells strongly indicated the differentiated nature of this organelle.

Compared to SEM, TEM is much better suited to the task of identifying internal structures. However, when these structures occupy very small volumes, they may be missed unless a lot of thin sections are examined. Moreover, one can’t reliably extrapolate the shape of a cell from thin sections. An early description of Mycoplasma iowae (Jordan  et al., 1982, International Journal of Systematic Bacteriology, 32:108-115) showed TEM images that suggested a coccobacillary shape, which has been refuted numerous times by SEM (e.g., Gallagher and Rhoades, 1983, Avian Diseases, 27:211-217). And SEM images of attachment organelle cores prepared by detergent extraction (Hatchel and Balish, 2008, Microbiology, 154:286-295), though subject to less consistent extraction of peripheral components, lead to greater reproducibility in measuring dimensions of internal structures than TEM, since sectioning is unlikely to be strictly parallel to the object being measured.

The bottom line: use the technique that answers your question with the greatest reproducibility, but don’t reinvent the wheel; excellent protocols for imaging of mycoplasmas by TEM and SEM, as well as newer and fancier techniques, have been published. And don’t rely on the wrong kind of data to interpret your results.

The United States Organization for Mycoplasmology is a newly founded organization based on a long-standing discipline. Founding members have been working in this field for decades, and noticed an undeniable trend:  mycoplasmas are often at the center of studies producing fundamental findings in biological sciences.  Because of their minimalist lifestyle, mycoplasmas make outstanding conceptual models, and have been featured in some truly groundbreaking moments in biological research. From one of the earliest complete genome sequences, to the minimal genome concept, to mechanistic understanding of antigenic variation, to infectious causes of asthma, to modeling emerging infectious diseases, to the first synthetic cell, mycoplasmas are often at the forefront of advances in biological science. That is the basis of our logo: we are always ahead of the curve!