Identification of 16S rRNA mutations in Mycoplasma genitalium potentially associated with tetracycline resistance in vivo but not selected in vitro in M. genitalium and Chlamydia trachomatis

Chloé Le Roy; Arabella Touati; Carla Balcon; Justine Garraud; Jean-Michel Molina; Beatrice Bercot; Bertille de Barbeyrac; Sabine Pereyre; Olivia Peuchant; Cécile Bébéar

doi:10.1093/jac/dkab016

journal article Feb 04, 2021

Identification of 16S rRNA mutations in Mycoplasma genitalium potentially associated with tetracycline resistance in vivo but not selected in vitro in M. genitalium and Chlamydia trachomatis

Chloé Le Roy Arabella Touati Carla Balcon Justine Garraud Jean-Michel Molina Beatrice Bercot

Bertille de Barbeyrac Sabine Pereyre

Olivia Peuchant

Cécile Bébéar

Journal of Antimicrobial Chemotherapy Vol. 76 No. 5 pp. 1150-1154 · Oxford University Press (OUP)

View at Publisher Save 10.1093/jac/dkab016

Abstract

Abstract

Objectives
Tetracyclines are widely used for the treatment of bacterial sexually transmitted infections (STIs) and recently have been used successfully for post-exposure prophylaxis of STIs in MSM. We investigated the in vitro and in vivo development of tetracycline resistance in Chlamydia trachomatis and Mycoplasma genitalium and evaluated 16S rRNA mutations associated with acquired resistance in other bacteria.

Methods
In vitro selection of resistant mutants of reference strains of C. trachomatis and M. genitalium was undertaken by serial passage in medium containing subinhibitory concentrations of tetracycline or doxycycline, respectively. The 16S rRNA gene of the two microorganisms was amplified and sequenced at different passages, as were those of 43 C. trachomatis- and 106 M. genitalium-positive specimens collected in France from 2013 to 2019.

Results
No tetracycline- or doxycycline-resistant strains of C. trachomatis and M. genitalium, respectively, were obtained after 30 serial passages. The tetracycline and doxycycline MICs were unchanged and analysis of the 16S rRNA gene, the molecular target of tetracyclines, of C. trachomatis and M. genitalium revealed no mutation. No mutation in the 16S rRNA gene was detected in C. trachomatis-positive specimens. However, six M. genitalium-positive specimens harboured a mutation potentially associated with tetracycline resistance without known prior tetracycline treatment for patients.

Conclusions
Tetracyclines did not select in vitro-resistant mutants of C. trachomatis or M. genitalium. However, 16S rRNA mutations either responsible for or associated with tetracycline resistance in other bacteria, including mycoplasma species, were identified in several M. genitalium-positive specimens.

Topics

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References

20

[1]

Rowley "Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016" Bull World Health Organ (2019) 10.2471/blt.18.228486

[2]

Kojima "Pre-exposure prophylaxis for HIV infection and new sexually transmitted infections among men who have sex with men" AIDS (2016) 10.1097/qad.0000000000001185

[3]

Berçot "High prevalence and high rate of antibiotic resistance of Mycoplasma genitalium infections in men who have sex with men. A sub-study of the ANRS Ipergay PrEP trial" Clin Infect Dis (2020) 10.1093/cid/ciaa1832

[4]

Prevalence of mutations associated with resistance to macrolides and fluoroquinolones in Mycoplasma genitalium: a systematic review and meta-analysis

Dorothy A Machalek, Yusha Tao, Hannah Shilling et al.

The Lancet Infectious Diseases 2020 10.1016/s1473-3099(20)30154-7

[5]

Post-exposure prophylaxis with doxycycline to prevent sexually transmitted infections in men who have sex with men: an open-label randomised substudy of the ANRS IPERGAY trial

Jean-Michel Molina, Isabelle Charreau, Christian Chidiac et al.

The Lancet Infectious Diseases 2018 10.1016/s1473-3099(17)30725-9

[6]

Somani "Multiple drug-resistant Chlamydia trachomatis associated with clinical treatment failure" J Infect Dis (2000) 10.1086/315372

[7]

Jensen "2016 European guideline on Mycoplasma genitalium infections" J Eur Acad Dermatol Venereol (2016) 10.1111/jdv.13849

[8]

Outcomes of Resistance-guided Sequential Treatment ofMycoplasma genitaliumInfections: A Prospective Evaluation

Tim R H Read, Christopher K Fairley, Gerald L Murray et al.

Clinical Infectious Diseases 2019 10.1093/cid/ciy477

[9]

Durukan "Resistance-guided antimicrobial therapy using doxycycline-moxifloxacin and doxycycline-2.5 g azithromycin for the treatment of Mycoplasma genitalium infection: efficacy and tolerability" Clin Infect Dis (2020) 10.1093/cid/ciz1031

[10]

Dégrange "Reduced susceptibility to tetracyclines is associated in vitro with the presence of 16S rRNA mutations in Mycoplasma hominis and Mycoplasma pneumoniae" J Antimicrob Chemother (2008) 10.1093/jac/dkn118

[11]

Khalil "Monitoring the decrease in susceptibility to ribosomal RNAs targeting antimicrobials and its molecular basis in clinical Mycoplasma bovis isolates over time" Microb Drug Resist (2017) 10.1089/mdr.2016.0268

[12]

Trieber "Mutations in the 16S rRNA genes of Helicobacter pylori mediate resistance to tetracycline" J Bacteriol (2002) 10.1128/jb.184.8.2131-2140.2002

[13]

Suchland "Methodologies and cell lines used for antimicrobial susceptibility testing of Chlamydia spp" Antimicrob Agents Chemother (2003) 10.1128/aac.47.2.636-642.2003

[14]

Waites (2001)

[15]

Pereyre "In vitro selection and characterization of resistance to macrolides and related antibiotics in Mycoplasma pneumoniae" Antimicrob Agents Chemother (2004) 10.1128/aac.48.2.460-465.2004

[16]

Jensen "Detection of Mycoplasma genitalium by PCR amplification of the 16S rRNA gene" J Clin Microbiol (2003) 10.1128/jcm.41.1.261-266.2003

[17]

Sequencing of Gyrase and Topoisomerase IV Quinolone-Resistance-Determining Regions of Chlamydia trachomatis and Characterization of Quinolone-Resistant Mutants Obtained In Vitro

Sophie Dessus-Babus, Cécile M. Bébéar, Alain Charron et al.

Antimicrobial Agents and Chemotherapy 1998 10.1128/aac.42.10.2474

[18]

Zheng "Association of the in vitro susceptibility of clinical isolates of Chlamydia trachomatis with serovar and duration of antibiotic exposure" Sex Transm Dis (2015) 10.1097/olq.0000000000000241

[19]

Bhengraj "Decreased susceptibility to azithromycin and doxycycline in clinical isolates of Chlamydia trachomatis obtained from recurrently infected female patients in India" Chemotherapy (2010) 10.1159/000314998

[20]

O'Neill "Chlamydia trachomatis clinical isolates identified as tetracycline resistant do not exhibit resistance in vitro: whole-genome sequencing reveals a mutation in porB but no evidence for tetracycline resistance genes" Microbiology (2013) 10.1099/mic.0.065391-0

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Metrics

26

Citations

20

References

Details

Published: Feb 04, 2021
Vol/Issue: 76(5)
Pages: 1150-1154
License: View

Authors

C

Chloé Le Roy

Univ. Bordeaux, INRAE, IHMC, EA, 3671, F-33000 Bordeaux, France

A

Arabella Touati

CHU Bordeaux, Department of Bacteriology, National Reference Centre for Bacterial Sexually Transmitted Infections, F-33000 Bordeaux, France

C

Carla Balcon

Univ. Bordeaux, INRAE, IHMC, EA, 3671, F-33000 Bordeaux, France

J

Justine Garraud

Univ. Bordeaux, INRAE, IHMC, EA, 3671, F-33000 Bordeaux, France

J

Jean-Michel Molina

Saint-Louis and Lariboisière Hospitals, APHP, Department of Infectious Diseases, Paris, France

B

Beatrice Bercot

Saint-Louis Hospital, APHP, Bacteriology Unit, National Reference Centre for Bacterial Sexually Transmitted Infections, Paris, France; University of Paris, INSERM, IAME Unit, UMR1137, Paris, France

B

Bertille de Barbeyrac

Univ. Bordeaux, INRAE, IHMC, EA, 3671, F-33000 Bordeaux, France; CHU Bordeaux, Department of Bacteriology, National Reference Centre for Bacterial Sexually Transmitted Infections, F-33000 Bordeaux, France

S

Sabine Pereyre

Univ. Bordeaux, INRAE, IHMC, EA, 3671, F-33000 Bordeaux, France; CHU Bordeaux, Department of Bacteriology, National Reference Centre for Bacterial Sexually Transmitted Infections, F-33000 Bordeaux, France

O

Olivia Peuchant

Univ. Bordeaux, INRAE, IHMC, EA, 3671, F-33000 Bordeaux, France; CHU Bordeaux, Department of Bacteriology, National Reference Centre for Bacterial Sexually Transmitted Infections, F-33000 Bordeaux, France

C

Cécile Bébéar

Univ. Bordeaux, INRAE, IHMC, EA, 3671, F-33000 Bordeaux, France; CHU Bordeaux, Department of Bacteriology, National Reference Centre for Bacterial Sexually Transmitted Infections, F-33000 Bordeaux, France

Funding

internal funding

Cite This Article

Chloé Le Roy, Arabella Touati, Carla Balcon, et al. (2021). Identification of 16S rRNA mutations in Mycoplasma genitalium potentially associated with tetracycline resistance in vivo but not selected in vitro in M. genitalium and Chlamydia trachomatis. Journal of Antimicrobial Chemotherapy, 76(5), 1150-1154. https://doi.org/10.1093/jac/dkab016

Identification of 16S rRNA mutations in Mycoplasma genitalium potentially associated with tetracycline resistance in vivo but not selected in vitro in M. genitalium and Chlamydia trachomatis

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