Tolerance to Ceftriaxone in Neisseria gonorrhoeae: Rapid Induction in WHO P Reference Strain and Detection in Clinical Isolates
Abstract
:1. Introduction
2. Results
2.1. Ceftriaxone Tolerance Emerges Rapidly
2.2. Some Circulating Strains of N. gonorrhoeae Are Tolerant to Ceftriaxone
2.3. No Decreased Susceptibility to Ceftriaxone during Induction of Tolerance
2.4. Tolerance Not Associated with Accelerated Induction of Ceftriaxone Resistance
3. Discussion
4. Materials and Methods
4.1. Bacterial Strains
4.2. Induction of Tolerance to Ceftriaxone
4.3. Tolerance Disc (TD) Test
4.4. Susceptibility Testing
4.5. Induction of Ceftriaxone Resistance
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
- Piszczek, J.; Jean, R.S.; Khaliq, Y. Gonorrhea: Treatment update for an increasingly resistant organism. Can. Pharm. J. 2015, 148, 82–89. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Unemo, M.; Seifert, H.S.; Hook, E.W., 3rd; Hawkes, S.; Ndowa, F.; Dillon, J.-A.R. Gonorrhoea. Nat. Rev. Dis. Prim. 2019, 5, 79. [Google Scholar] [CrossRef] [PubMed]
- Springer, C.; Salen, P. Gonorrhea. In StatPearls [Internet]; StatPearls Publishing: Treasure Island, FL, USA, 2022. Available online: https://www.ncbi.nlm.nih.gov/books/NBK558903/ (accessed on 26 April 2022).
- Hill, S.A.; Masters, T.L.; Wachter, J. Gonorrhea—An evolving disease of the new millennium. Microb. Cell 2016, 3, 371–389. [Google Scholar] [CrossRef] [PubMed]
- Bignell, C.; Unemo, M.; The European STI Guidelines Editorial Board. 2012 European guideline on the diagnosis and treatment of gonorrhoea in adults. Int. J. STD AIDS 2013, 24, 85–92. [Google Scholar] [CrossRef] [PubMed]
- Tedijanto, C.; Olesen, S.W.; Grad, Y.H.; Lipsitch, M. Estimating the proportion of bystander selection for antibiotic resistance among potentially pathogenic bacterial flora. Proc. Natl. Acad. Sci. USA 2018, 115, E11988–E11995. [Google Scholar] [CrossRef] [Green Version]
- Kenyon, C.; Buyze, J.; Spiteri, G.; Cole, M.J.; Unemo, M. Population-Level Antimicrobial Consumption Is Associated with Decreased Antimicrobial Susceptibility in Neisseria gonorrhoeae in 24 European Countries: An Ecological Analysis. J. Infect Dis. 2020, 221, 1107–1116. [Google Scholar] [CrossRef] [Green Version]
- Levin-Reisman, I.; Ronin, I.; Gefen, O.; Braniss, I.; Shoresh, N.; Balaban, N.Q. Antibiotic tolerance facilitates the evolution of resistance. Science 2017, 355, 826–830. [Google Scholar] [CrossRef]
- Sulaiman, J.E.; Lam, H. Evolution of Bacterial Tolerance Under Antibiotic Treatment and Its Implications on the Development of Resistance. Front. Microbiol. 2021, 12, 617412. [Google Scholar] [CrossRef]
- Kotková, H.; Cabrnochová, M.; Lichá, I.; Tkadlec, J.; Fila, L.; Bartošová, J.; Melter, O. Evaluation of TD test for analysis of persistence or tolerance in clinical isolates of Staphylococcus aureus. J. Microbiol. Methods 2019, 167, 105705. [Google Scholar] [CrossRef]
- Brauner, A.; Fridman, O.; Gefen, O.; Balaban, N.Q. Distinguishing between resistance, tolerance and persistence to antibiotic treatment. Nat. Rev. Microbiol. 2016, 14, 320–330. [Google Scholar] [CrossRef]
- Brauner, A.; Shoresh, N.; Fridman, O.; Balaban, N.Q. An Experimental Framework for Quantifying Bacterial Tolerance. Biophys. J. 2017, 112, 2664–2671. [Google Scholar] [CrossRef] [Green Version]
- Kussell, E.; Kishony, R.; Balaban, N.; Leibler, S. Bacterial Persistence: A model of survival in changing environments. Genetics 2005, 169, 1807–1814. [Google Scholar] [CrossRef] [Green Version]
- Fridman, O.; Goldberg, A.; Ronin, I.; Shoresh, N.; Balaban, N. Optimization of lag time underlies antibiotic tolerance in evolved bacterial populations. Nature 2014, 513, 418–421. [Google Scholar] [CrossRef]
- Levin-Reisman, I.; Brauner, A.; Ronin, I.; Balaban, N.Q. Epistasis between antibiotic tolerance, persistence, and resistance mutations. Proc. Natl. Acad. Sci. USA 2019, 116, 14734–14739. [Google Scholar] [CrossRef] [Green Version]
- Santi, I.; Manfredi, P.; Maffei, E.; Egli, A.; Jenal, U. Evolution of Antibiotic Tolerance Shapes Resistance Development in Chronic Pseudomonas aeruginosa Infections. mBio 2021, 12, e03482-20. [Google Scholar] [CrossRef]
- Walter, N.D.; Born, S.E.M.; Robertson, G.T.; Reichlen, M.; Dide-Agossou, C.; Ektnitphong, V.A.; Rossmassler, K.; Ramey, M.E.; Bauman, A.A.; Ozols, V.; et al. Mycobacterium tuberculosis precursor rRNA as a measure of treatment-shortening activity of drugs and regimens. Nat. Commun. 2021, 12, 2899. [Google Scholar] [CrossRef]
- Voskuil, M. Bacterial Replication and Bioenergetics in Antibiotic Lethality and Treatment-Shortening Activity; ECCMID: Lisbon, Portugal, 2022. [Google Scholar]
- Jenal, U. Mechanisms of Antimicrobial Tolerance; ECCMID: Lisbon, Portugal, 2022. [Google Scholar]
- Cohen, N.R.; Lobritz, M.A.; Collins, J.J. Microbial Persistence and the Road to Drug Resistance. Cell Host Microbe 2013, 13, 632–642. [Google Scholar] [CrossRef] [Green Version]
- Blondeau, J.; Hansen, G.; Metzler, K.; Hedlin, P. The Role of PK/PD Parameters to Avoid Selection and Increase of Resistance: Mutant Prevention Concentration. J. Chemother. 2004, 16 (Suppl. S3), 1–19. [Google Scholar] [CrossRef]
- Wiuff, C.; Andersson, D.I. Antibiotic treatment in vitro of phenotypically tolerant bacterial populations. J. Antimicrob. Chemother. 2007, 59, 254–263. [Google Scholar] [CrossRef]
- Hamad, M.A.; Austin, C.R.; Stewart, A.L.; Higgins, M.; Vázquez-Torres, A.; Voskuil, M.I. Adaptation and Antibiotic Tolerance of Anaerobic Burkholderia pseudomallei. Antimicrob. Agents Chemother. 2011, 55, 3313–3323. [Google Scholar] [CrossRef]
- Lazarovits, G.; Gefen, O.; Cahanian, N.; Adler, K.; Fluss, R.; Levin-Reisman, I.; Ronin, I.; Motro, Y.; Moran-Gilad, J.; Balaban, N.Q.; et al. Prevalence of Antibiotic Tolerance and Risk for Reinfection Among E. coli Bloodstream Isolates: A Prospective Cohort Study. Clin. Infect. Dis. 2022; online ahead of print. [Google Scholar] [CrossRef] [PubMed]
- Gefen, O.; Chekol, B.; Strahilevitz, J.; Balaban, N.Q. TDtest: Easy detection of bacterial tolerance and persistence in clinical isolates by a modified disk-diffusion assay. Sci. Rep. 2017, 7, 41284. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bauer, A.W.; Perry, D.M.; Kirby, W.M.M. Single-Disk Antibiotic-Sensitivity Testing of Staphylococci: An analysis of technique and results. AMA Arch. Intern. Med. 1959, 104, 208–216. [Google Scholar] [CrossRef] [PubMed]
- Mechler, L.; Herbig, A.; Paprotka, K.; Fraunholz, M.; Nieselt, K.; Bertram, R. A Novel Point Mutation Promotes Growth Phase-Dependent Daptomycin Tolerance in Staphylococcus aureus. Antimicrob. Agents Chemother. 2015, 59, 5366–5376. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Van Den Bergh, B.; Michiels, J.E.; Wenseleers, T.; Windels, E.M.; Vanden Boer, P.; Kestemont, D.; De Meester, L.; Verstrepen, K.J.; Verstraeten, N.; Fauvart, M.; et al. Frequency of antibiotic application drives rapid evolutionary adaptation of Escherichia coli persistence. Nat. Microbiol. 2016, 1, 16020. [Google Scholar] [CrossRef] [Green Version]
- Russell, M. Neisseria gonorrhoeae selectively suppresses the development of Th1 and Th2 cells, and enhances Th17 cell responses, through TGF-β-dependent mechanisms. Mucosal Immunol. 2012, 5, 320–331. [Google Scholar] [CrossRef] [Green Version]
- Kenyon, C.R.; Schwartz, I.S. Effects of Sexual Network Connectivity and Antimicrobial Drug Use on Antimicrobial Resistance in Neisseria gonorrhoeae. Emerg. Infect. Dis. 2018, 24, 1195–1203. [Google Scholar] [CrossRef] [Green Version]
- Kenyon, C.; De Baetselier, I.; Wouters, K. Screening for STIs in PrEP cohorts results in high levels of antimicrobial consumption. Int. J. STD AIDS 2020, 31, 1215–1218. [Google Scholar] [CrossRef]
- Kenyon, C. Dual Azithromycin/Ceftriaxone Therapy for Gonorrhea in PrEP Cohorts Results in Levels of Macrolide Consumption That Exceed Resistance Thresholds by Up to 7-Fold. J. Infect. Dis. 2021, 224, 1623–1624. [Google Scholar] [CrossRef]
- Van Dijck, C.; Laumen, J.; Zlotorzynska, M.; Basil, S.S.; Kenyon, C. Association between STI screening intensity in men who have sex with men and gonococcal susceptibility in 21 States in the USA: An ecological study. Sex. Transm. Infect. 2020, 96, 537–540. [Google Scholar] [CrossRef]
- Chow, E.P.F.; Camilleri, S.; Ward, C.; Huffam, S.; Chen, M.Y.; Bradshaw, C.S.; Fairley, C.K. Duration of gonorrhoea and chlamydia infection at the pharynx and rectum among men who have sex with men: A systematic review. Sex. Health 2016, 13, 199–204. [Google Scholar] [CrossRef] [Green Version]
- Dekaboruah, E.; Suryavanshi, M.V.; Chettri, D.; Verma, A.K. Human microbiome: An academic update on human body site specific surveillance and its possible role. Arch. Microbiol. 2020, 202, 2147–2167. [Google Scholar] [CrossRef]
- Yu, L.C.-H.; Wang, J.-T.; Wei, S.-C.; Ni, Y.-H. Host-microbial interactions and regulation of intestinal epithelial barrier function: From physiology to pathology. World J. Gastrointest. Pathophysiol. 2012, 3, 27–43. [Google Scholar] [CrossRef]
- Round, J.L.; Mazmanian, S.K. The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 2009, 9, 313–323, Erratum in Nat. Rev. Immunol. 2009, 9, 600. [Google Scholar] [CrossRef]
- Morse, S.A.; Lysko, P.G.; McFarland, L.; Knapp, J.S.; Sandstrom, E.; Critchlow, C.; Holmes, K.K. Gonococcal strains from homosexual men have outer membranes with reduced permeability to hydrophobic molecules. Infect. Immun. 1982, 37, 432–438. [Google Scholar] [CrossRef] [Green Version]
- Ma, K.C.; Mortimer, T.D.; Hicks, A.L.; Wheeler, N.E.; Sánchez-Busó, L.; Golparian, D.; Taiaroa, G.; Rubin, D.H.F.; Wang, Y.; Williamson, D.A.; et al. Adaptation to the cervical environment is associated with increased antibiotic susceptibility in Neisseria gonorrhoeae. Nat. Commun. 2020, 11, 4126. [Google Scholar] [CrossRef]
- Raisman, J.C.; Fiore, M.A.; Tomin, L.; Adjei, J.K.O.; Aswad, V.X.; Chu, J.; Domondon, C.J.; Donahue, B.A.; Masciotti, C.A.; McGrath, C.G.; et al. Evolutionary paths to macrolide resistance in a Neisseria commensal converge on ribosomal genes through short sequence duplications. PLoS ONE 2022, 17, e0262370. [Google Scholar] [CrossRef]
- Kueakulpattana, N.; Wannigama, D.L.; Luk-In, S.; Hongsing, P.; Hurst, C.; Badavath, V.N.; Jenjaroenpun, P.; Wongsurawat, T.; Teeratakulpisan, N.; Kerr, S.J.; et al. Multidrug-resistant Neisseria gonorrhoeae infection in heterosexual men with reduced susceptibility to ceftriaxone, first report in Thailand. Sci. Rep. 2021, 11, 21659. [Google Scholar] [CrossRef]
- Vincent, L.R.; Kerr, S.R.; Tan, Y.; Tomberg, J.; Raterman, E.L.; Hotopp, J.C.D.; Unemo, M.; Nicholas, R.A.; Jerse, A.E. In Vivo-Selected Compensatory Mutations Restore the Fitness Cost of Mosaic penA Alleles That Confer Ceftriaxone Resistance in Neisseria gonorrhoeae. mBio 2018, 9, e01905-17. [Google Scholar] [CrossRef] [Green Version]
- Laumen, J.G.E.; Manoharan-Basil, S.S.; Verhoeven, E.; Abdellati, S.; De Baetselier, I.; Crucitti, T.; Xavier, B.B.; Chapelle, S.; Lammens, C.; Van Dijck, C.; et al. Molecular pathways to high-level azithromycin resistance in Neisseria gonorrhoeae. J. Antimicrob. Chemother. 2021, 76, 1752–1758. [Google Scholar] [CrossRef]
- Gong, Z.; Lai, W.; Liu, M.; Hua, Z.; Sun, Y.; Xu, Q.; Xia, Y.; Zhao, Y.; Xie, X. Novel Genes Related to Ceftriaxone Resistance Found among Ceftriaxone-Resistant Neisseria gonorrhoeae Strains Selected In Vitro. Antimicrob. Agents Chemother. 2016, 60, 2043–2051. [Google Scholar] [CrossRef] [Green Version]
- Lee, D.Y.J.; Ashcroft, M.M.; Chow, E.P.F.; Sait, M.; De Petra, V.; Tschaepe, M.; Lange, S.; Taiaroa, G.; Bradshaw, C.S.; Whiley, D.M.; et al. Reflex Detection of Ciprofloxacin Resistance in Neisseria gonorrhoeae by Use of the SpeeDx ResistancePlus GC Assay. J. Clin. Microbiol. 2021, 59, e00089-21. [Google Scholar] [CrossRef]
- Unemo, M.; Golparian, D.; Sánchez-Busó, L.; Grad, Y.; Jacobsson, S.; Ohnishi, M.; Lahra, M.M.; Limnios, A.; Sikora, A.E.; Wi, T.; et al. The novel 2016 WHO Neisseria gonorrhoeae reference strains for global quality assurance of laboratory investigations: Phenotypic, genetic and reference genome characterization. J. Antimicrob. Chemother. 2016, 71, 3096–3108. [Google Scholar] [CrossRef]
- BioMerieux, Inc. Etest®: Trusted Leader in MIC Gradient Strip Technology USA. 2022. Available online: https://www.biomerieuxusa.com/sites/subsidiary_us/files/prn_056750_rev_03.a_etest_brochure_final_art_0.pdf (accessed on 6 May 2022).
Tolerance | |||
---|---|---|---|
YES | NO | Proportion | |
Anorectal | 7 | 2 | 78% |
Urogenital | 3 | 6 | 33% |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Balduck, M.; Laumen, J.G.E.; Abdellati, S.; De Baetselier, I.; de Block, T.; Manoharan-Basil, S.S.; Kenyon, C. Tolerance to Ceftriaxone in Neisseria gonorrhoeae: Rapid Induction in WHO P Reference Strain and Detection in Clinical Isolates. Antibiotics 2022, 11, 1480. https://doi.org/10.3390/antibiotics11111480
Balduck M, Laumen JGE, Abdellati S, De Baetselier I, de Block T, Manoharan-Basil SS, Kenyon C. Tolerance to Ceftriaxone in Neisseria gonorrhoeae: Rapid Induction in WHO P Reference Strain and Detection in Clinical Isolates. Antibiotics. 2022; 11(11):1480. https://doi.org/10.3390/antibiotics11111480
Chicago/Turabian StyleBalduck, Margaux, Jolein Gyonne Elise Laumen, Saïd Abdellati, Irith De Baetselier, Tessa de Block, Sheeba Santhini Manoharan-Basil, and Chris Kenyon. 2022. "Tolerance to Ceftriaxone in Neisseria gonorrhoeae: Rapid Induction in WHO P Reference Strain and Detection in Clinical Isolates" Antibiotics 11, no. 11: 1480. https://doi.org/10.3390/antibiotics11111480