Mycoplasma Pneumoniae: An overview

 

BY DR TIM SANDLE | PHARMACEUTICAL MICROBIOLOGY AND CONTAMINATION CONTROL EXPERT

25th October

 

Mycoplasmas are very simple bacteria. They have a minimalist genome and no protective cell wall (due to the absence of peptidoglycan). In fact, mycoplasmas possess the smallest genomes of any organism able to replicate itself.  Mycoplasma genitalium is said to be the world's smallest free-living bacterium with only 525 genes, as opposed to the 4,288 of the bacterium Escherichia coli.1

 

Nevertheless, mycoplasmas are common and successful pathogens that can cause infections in the lungs, joints, breasts and udders of animals (including atypical pneumonia).

 

The parasitic bacteria possess an ability to glide, which aids their relative infectivity. Adenosine triphosphate (ATP) is important for this process and is the substance generated in the mitochondria that provides energy that the mycoplasma molecular motors use for gliding2. They are parasitic because they need to hijack other cells to reproduce due to their limited metabolic activity.

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As well as some species being infectious agents, mycoplasma contamination of cell lines can drastically change cell metabolism and therefore negatively impact research data.

 

Of the mycoplasma, M. pneumoniae causes respiratory tract infections, damaging the lining of the respiratory tract (including the throat, windpipe and lungs). This article considers this organism in further detail.

 

Escaping the immune response

 

Certain species of mycoplasmas, including M. pneumoniae, can cause persistent and difficult-to-treat infections in humans and animals. Part of the occurrence of infection relates to how mycoplasmas escape the immune response.

 

Research has shown how mycoplasmas 'mask' themselves3. An important component of this mechanism is due to enzymes called recombinase4 and ribonucleotide reductase5. Consequently, as revealed by cryo-electron tomography, mycoplasmas regularly change their surface proteins to confuse the immune system.

Antibiotic resistance

 

As antibiotics commonly target the cell wall, mycoplasmas often have a general resistance to them. In addition, globally, M. pneumoniae organisms are showing resistance to the macrolide antibiotics (and some tetracycline antibiotics), such as erythromycin and azithromycin (commonly used to treat patients with respiratory infections). This resistance can complicate treatment6. 

 

To redress this, it has been observed that the interactions between ribosomes and other complexes in the cell change in response to the drug. This suggests that an antibiotic can have an effect that reaches far beyond the specific complex it binds to. This can help design combinations of antibiotics to increase their efficiency7.

 

 

Cell cultures

 

Mycoplasma contamination of continuous cell cultures ranges from 15-35%, with primary cell cultures exhibiting a minimum 1% contamination rate8. This affects the production of many biologicals, including advanced cellular medicinal products (ATMPs)9. M. pneumoniae is a potential contaminant because it can be easily spread by personnel working with cells, via droplets or touch. Therefore, the maintenance of asepsis is important. Another source of contamination is the media holding the cells or their components.

 

Mycoplasma contamination of cells is difficult to spot because they cannot be detected visually by turbidity of fluid or under the inverted microscope. The use of contaminated cells affects cell physiology, leading to erroneous results or the loss of unique cell lines - in some cases, cell pathogenicity occurs. 

 

In terms of bioprocessing, the absence of a cell wall, coupled with their small size and relative plasticity, allows mycoplasma to pass through sterilising filters that would otherwise prevent contamination.

 

Therefore, there needs to be an emphasis upon testing and control. With testing, there are many methods to test for mycoplasma contamination such as histochemical staining, using acridine orange, or DAPI, ELISA and PCR methods.

 

If mycoplasma contamination is detected in a cell culture, the culture may be discarded (by autoclaving), or an attempt can be made to eliminate the contamination using anti- mycoplasma drugs designed to block or inhibit protein synthesis and DNA replication10. The use of such drugs is of variable success. Another method is UV radiation, although care is required not to damage the actual cell culture. Hence, prevention is invariably the best strategy.

 

References

 

1.    Jonathan R. Karr, Jayodita C. Sanghvi, Derek N. Macklin, Miriam V. Gutschow, Jared M. Jacobs, Benjamin Bolival, Nacyra Assad-Garcia, John I. Glass, Markus W. Covert. A Whole-Cell Computational Model Predicts Phenotype from Genotype. Cell, 2012; 150 (2): 389 DOI: 10.1016/j.cell.2012.05.044


2.    Takuma Toyonaga, Takayuki Kato, Akihiro Kawamoto, Noriyuki Kodera, Tasuku Hamaguchi, Yuhei O. Tahara, Toshio Ando, Keiichi Namba, and Makoto Miyata. Chained Structure of Dimeric F1-like ATPase in Mycoplasma mobile Gliding Machinery. mBio, 2021 DOI: 10.1128/mBio.01414-21


3.    Czurda et al. Xer1-Mediated Site-Specific DNA Inversions and Excisions in Mycoplasma agalactiae. Journal of Bacteriology, 2010; 192 (17): 4462 DOI: 10.1128/JB.01537-09


4.    Rohini Chopra-Dewasthaly, Joachim Spergser, Martina Zimmermann, Christine Citti, Wolfgang Jechlinger, Renate Rosengarten. Vpma phase variation is important for survival and persistence of Mycoplasma agalactiae in the immunocompetent host. PLOS Pathogens, 2017; 13 (9): e1006656  


5.    Vivek Srinivas, Hugo Lebrette, Daniel Lundin, Yuri Kutin, Margareta Sahlin, Michael Lerche, Jürgen Eirich, Rui M. M. Branca, Nicholas Cox, Britt-Marie Sjöberg, Martin Högbom. Metal-free ribonucleotide reduction powered by a DOPA radical in Mycoplasma pathogens. Nature, 2018; DOI: 10.1038/s41586-018-0653-6


6.    University of Alabama at Birmingham. "On the watch for antibiotic-resistant mycoplasma pneumoniae." See: http://www.uab.edu/news/innovation/item/8816-on-the-watch-for-antibiotic-resistant-mycoplasma-pneumoniae  


7.    Liang Xue, Swantje Lenz, Maria Zimmermann-Kogadeeva, Dimitry Tegunov, Patrick Cramer, Peer Bork, Juri Rappsilber, Julia Mahamid. Visualizing translation dynamics at atomic detail inside a bacterial cell. Nature, 2022; DOI: 10.1038/s41586-022-05255-2


8.    Uphoff CC, Drexler HG. Comparative antibiotic eradication of mycoplasma infections from continuous cell lines. In Vitro Cell Dev Biol Anim. 2002;38(2):86–89


9.    Hay RJ, Macy ML, Chen TR. Mycoplasma infection of cultured cells. Nature. 1989;339(6224):487–488. doi: 10.1038/339487a0


10.    Uphoff CC, Denkmann SA, & Drexler HG (2012). Treatment of Mycoplasma contamination in cell cultures with Plasmocin. BioMed Research International, 2012

 

 

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