Urogenit Tract Infect.  2017 Aug;12(2):65-76. 10.14777/uti.2017.12.2.65.

Genetic Variation in Mycoplasma genitalium

• Lee G

• KMID: 2389572
• DOI: http://doi.org/10.14777/uti.2017.12.2.65

Abstract

Mycoplasma genitalium (MG) is the smallest self-replicating bacterium. Although small in size, unique MG genome induces distinctive and often serious characteristics in the infected cells. Due to its small genome and chronic symptomatic characteristics in the infected host, it first appears as a weak, insignificant, and easily controllable microbe. However, it is not a monotonous chrysalis, but rather a multicolored butterfly with various capabilities. Repetitive DNA sequence in MG's immunodominant MgPa operon has been considered as an efficient strategy to evade the host immune surveillance and mediate MG's genetic flexibility. Because of MG's pathogenicity in multiple organs, various antimicrobials are prescribed, further exerting selection pressure on microbes. Consequently, a rapidly increasing drug resistance in macrolide and moxifloxacin has been frequently reported globally, radically decreasing the overall cure rate of infection. Re-infection can be defined as a new MG infection through antigenic variation, while persistent infection refers to recurrent infections caused by the same MG isolate through acquisition of antimicrobial resistance. Therefore, we must differentiate between re-infection and persistent MG infection, and approach them accordingly. The genetic mechanisms of DNA variation in the MgPa operon and antibiotic resistance must be considered for the management of multicolored infection. In this respect, the unique genetic characteristics of MG will be described in detail. We hope that with this manuscript, clinicians can expand their understanding of recurrent MG infections and better choose an appropriate treatment for the infection in clinical setting.

Keyword

Mycoplasma genitalium; Genetics; Recurrence

MeSH Terms

Antigenic Variation
Base Sequence
Butterflies
DNA
Drug Resistance
Drug Resistance, Microbial
Genetic Variation*
Genetics
Genome
Hope
Mycoplasma genitalium*
Mycoplasma*
Operon
Pliability
Recurrence
Virulence
DNA

Figure

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  Fig 1. Phylogenetic tree of 16S rRNA gene sequences reveals that Mycoplasma pneumoniae M129 is closely related with Mycoplasma genitalium (MG). NR074611.1 is MG strain G37 (16S ribosomal RNA), NC000912.1 is M. pneumoniae M129 complete genome (16S ribosomal RNA), NC010503.1 is Ureaplasma parvum serotype 3 str. ATCC27815, complete genome (16S ribosomal RNA), NC011374 is Ureaplasma urealyticum serotype 10 str. ATCC33699, complete genome (16S ribosomal RNA), and AB680681.1 is Mycoplasma hominis gene for 16S ribosomal RNA, strain NBRC14850.

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  Fig. 2. Schematic view of Mycoplasma genitalium (MG). It appears as a flask or pear-shaped cell with a narrow terminal structure (A). This structure is crucial for MG to attach onto the host cell surfaces.

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  Fig. 3. Complete genome sequence in MgPa and MgPar genes of the Mycoplasma genitalium (MG) G37 strain. The expression sites for each of the three genes are present in only one copy; but there are nine repetitive elements in the form of truncated copies of MG191 and MG192 genes dispersed throughout the genome, designated as MgPa repeats or MgPar sequences [31,39,40].

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  Fig. 4. Twenty mgpB DNA sequences from the National Center for Biotechnology Information (NCBI) (https://www.ncbi.nlm.nih.gov/nuccore/) are evaluated for their homology using the Clustal W alignment algorithm (http://www.genome.jp/tools/clustalw/). Locations in the MG191 gene are indicated in the upper area. There are three areas of hot genetic variety in the mgpB gene (520-1,040 bp for B area, 2,340-2,990 bp for EF area, 3,250-3,640 bp for G area). The gray colors represent matching, while the black colors represent mismatching (http://multalin.toulouse.inra.fr/). MG: Mycoplasma genitalium.

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  Fig. 5. Sixty-four partial mgpC DNA sequences (Supplementary Table 2) from the National Center for Biotechnology Information (NCBI) database (https://www.ncbi.nlm.nih.gov/nuccore/) are collected and evaluated for their homology using the Clustal W alignment algorithm (http://www.genome.jp/tools/clustalw/). Locations in the mgpB gene are indicated in the upper area. The gray colors represent matching, while the black colors represent mismatching (http://multalin.toulouse.inra.fr).

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  Fig. 6. Twenty-four partial mgpC DNA sequences (Supplementary Table 3) from patient no. 126 are evaluated from the National Center for Biotechnology Information (NCBI) database (https://www.ncbi.nlm.nih.gov/nuccore/) to investigate the homology using the Clustal W alignment algorithm (http://www.genome.jp/ tools/clustalw/). Ma et al. [50] serially examined the DNA sequence changes in the mgpC gene in serial culturing periods (from the starting point to 4th subculturing period). The DNA sequences of MG192 changed rapidly in vitro within a short period of time. The gray colors represent matching, while the black colors represent mismatching (http://multalin.toulouse.inra.fr/multalin/multalin.html). MG: Mycoplasma genitalium.

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  Fig. 7. Phylogenetic analysis of the MG192 variable sequences from serially cultured in vitro samples from MG infected patients no. 61 and no. 126. Time intervals are described in Table 4. There are greater variations in the MG192 gene during sequential cultures, but the variances are more closely related within an individual patient than between the patients. MG: Mycoplasma genitalium.

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  Fig. 8. Ma et al. [51] intraurethrally inoculated a single cloned Mycoplasma genitalium (MG) strain G37 into one male chimpanzee's urethra. Urethral swabs were obtained at different time points (5 weeks, 9 weeks, and 11 weeks). Phylogenetic analysis in the MG192 gene revealed several MG192 sequences variants during an in vivo study.

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  Fig. 9. JX857899.1(61.0a) is the partial DNA sequences of MG192 gene at the starting point (11/20/2000) obtained from patient no. 61, as presented in Fig. 7. The JX857903.1(61.2e) is the partial DNA sequences of MG192 gene obtained from the same patient post 6 months (05/07/2001). EF117289.1 is the partial DNA sequences of MG strain G37 MgPar 8 region genomic sequence, FJ872575.1 is the partial DNA sequences of MG strain M2321 MgPar 2 region genomic sequence, and FJ872582.1 is the partial DNA sequences of MG strain M2321 MgPar 9 region genomic sequence. JX857903.1(61.2e) may get some AGT repeats in the original MG192 gene (JX857899.1), and newly mutated isolate (JX857903.1) is closely related to the partial DNA sequences of MG strain G37 MgPar 8 region genomic sequence (EF117289.1) (dotted box). MG: Mycoplasma genitalium.

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  Fig. 10. A schematic view of homologous recombination between MG192 and MgPar 8 in the MG type strain G37 during in vitro passage. A presents the alignment of a portion of the MG192 variable region and MgPar 8 in G37-P1, while B demonstrates the alignment of a portion of the recombined MG192 variable region and MgPar 8 in G37-P35, clearly depicting the sequence exchange at the recombination sites. Arrows indicate where sequence exchanges took place, with the reciprocal exchange (gene cross-over) shown by two arrows (area II) and gene conversion shown by one arrow (area I). MG: Mycoplasma genitalium.

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