Impact of 16S rRNA Single Nucleotide Polymorphisms on Mycoplasma genitalium Organism Load with Doxycycline Treatment

Antimicrob Agents Chemother. 2022 May 17;66(5):e0024322. doi: 10.1128/aac.00243-22. Epub 2022 Apr 14.


Doxycycline targets the 16S rRNA and is widely used for the treatment of sexually transmitted infections. While it is not highly effective at eradicating Mycoplasma genitalium infections, it can reduce organism load. The aim of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in the 16S rRNA gene of M. genitalium and change in organism load. M. genitalium samples were collected from 56 men prior to commencing doxycycline and at a median of 13 of 14 doses. These were sequenced for the 16S rRNA, and the association between 16S rRNA SNPs and change in organism load was determined. 16S rRNA sequences were available for 52/56 (92.9%) M. genitalium-infected men, of which 20 (38.5%) had an undetectable load, 26 (50.0%) had a decrease in M. genitalium load (median change of 105-fold), and 6 (11.5%) had an increase in load (median change of 5-fold). The most common SNPs identified were A742G (10/52 [19.2%]), GG960-961TT/C (7/52 [13.5%]), and C1435T (28/52 [53.8%]) (M. genitalium numbering). None were associated with a change in organism load (P = 0.76, 0.16, and 0.98, respectively). Using pooled published data from 28 isolates, no clear relationship between the SNPs and doxycycline MIC was identified. In conclusion, the low efficacy of doxycycline against M. genitalium does not appear to be due to variation in the 16S rRNA gene.

Keywords: 16S rRNA gene; Mycoplasma genitalium; antibiotic resistance; doxycycline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Doxycycline* / pharmacology
  • Drug Resistance, Bacterial
  • Humans
  • Male
  • Mycoplasma Infections* / drug therapy
  • Mycoplasma Infections* / microbiology
  • Mycoplasma genitalium* / drug effects
  • Mycoplasma genitalium* / growth & development
  • Polymorphism, Single Nucleotide
  • Prevalence
  • RNA, Ribosomal, 16S* / genetics


  • Anti-Bacterial Agents
  • RNA, Ribosomal, 16S
  • Doxycycline