Potency of Solithromycin Against Fast- and Slow-Growing Chlamydial Organisms

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 2018 Jun 13

PMID 29891601

Citations 2

Authors

Leiqiong Gao

Yao Wang

Ziyu Hua

Enmei Liu

Li Shen

Affiliations

Soon will be listed here.

Abstract

Evidence is provided that solithromycin is a bactericidal against not only fast-growing chlamydial organisms but also those slowed by gamma interferon (IFN-γ) At sublethal concentrations, Sol impedes homotypic fusion of -containing vacuoles and reduces secretion of the type III secretion (T3S) effector IncA. Sol may therefore represent a potential new clinical treatment for infections. Selective perturbation of the T3S system suggests a novel mode of antibacterial action for Sol that warrants further investigation.

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References

Beatty W, Belanger T, Desai A, Morrison R, Byrne G . Tryptophan depletion as a mechanism of gamma interferon-mediated chlamydial persistence. Infect Immun. 1994; 62(9):3705-11. PMC: 303021. DOI: 10.1128/iai.62.9.3705-3711.1994. View

Hatch T . Disulfide cross-linked envelope proteins: the functional equivalent of peptidoglycan in chlamydiae?. J Bacteriol. 1996; 178(1):1-5. PMC: 177613. DOI: 10.1128/jb.178.1.1-5.1996. View

Hua Z, Frohlich K, Zhang Y, Feng X, Zhang J, Shen L . Andrographolide inhibits intracellular Chlamydia trachomatis multiplication and reduces secretion of proinflammatory mediators produced by human epithelial cells. Pathog Dis. 2015; 73(1):1-11. PMC: 4542904. DOI: 10.1093/femspd/ftu022. View

Hawser S, Morrissey I, Lemos B, Keedy K, Fernandes P . Surveillance of the activity of solithromycin (CEM-101) against bacteria from respiratory tract infections. Int J Antimicrob Agents. 2017; 50(1):17-22. DOI: 10.1016/j.ijantimicag.2017.01.035. View

Zhang Y, Xian Y, Gao L, Elaasar H, Wang Y, Tauhid L . Novel Detection Strategy To Rapidly Evaluate the Efficacy of Antichlamydial Agents. Antimicrob Agents Chemother. 2016; 61(2). PMC: 5278686. DOI: 10.1128/AAC.02202-16. View

Nans A, Kudryashev M, Saibil H, Hayward R . Structure of a bacterial type III secretion system in contact with a host membrane in situ. Nat Commun. 2015; 6:10114. PMC: 4682100. DOI: 10.1038/ncomms10114. View

Rao X, Deighan P, Hua Z, Hu X, Wang J, Luo M . A regulator from Chlamydia trachomatis modulates the activity of RNA polymerase through direct interaction with the beta subunit and the primary sigma subunit. Genes Dev. 2009; 23(15):1818-29. PMC: 2720258. DOI: 10.1101/gad.1784009. View

File Jr T, Eckburg P, Talbot G, Llorens L, Friedland H . Macrolide therapy for community-acquired pneumonia due to atypical pathogens: outcome assessment at an early time point. Int J Antimicrob Agents. 2017; 50(2):247-251. DOI: 10.1016/j.ijantimicag.2017.01.043. View

Hackstadt T, SHAW E, Fischer E . The Chlamydia trachomatis IncA protein is required for homotypic vesicle fusion. Cell Microbiol. 2001; 1(2):119-30. DOI: 10.1046/j.1462-5822.1999.00012.x. View

10.

Rekart M, Gilbert M, Meza R, Kim P, Chang M, Money D . Chlamydia public health programs and the epidemiology of pelvic inflammatory disease and ectopic pregnancy. J Infect Dis. 2012; 207(1):30-8. DOI: 10.1093/infdis/jis644. View

11.

Suchland R, Dimond Z, Putman T, Rockey D . Demonstration of Persistent Infections and Genome Stability by Whole-Genome Sequencing of Repeat-Positive, Same-Serovar Chlamydia trachomatis Collected From the Female Genital Tract. J Infect Dis. 2017; 215(11):1657-1665. PMC: 6543881. DOI: 10.1093/infdis/jix155. View

12.

Mancuso A, Gandhi M, Slish J . Solithromycin (CEM-101): A New Fluoroketolide Antibiotic and Its Role in the Treatment of Gonorrhea. J Pharm Pract. 2017; 31(2):195-201. DOI: 10.1177/0897190017708073. View

13.

Fifer H, Natarajan U, Jones L, Alexander S, Hughes G, Golparian D . Failure of Dual Antimicrobial Therapy in Treatment of Gonorrhea. N Engl J Med. 2016; 374(25):2504-6. DOI: 10.1056/NEJMc1512757. View

14.

Wang J, Frohlich K, Buckner L, Quayle A, Luo M, Feng X . Altered protein secretion of Chlamydia trachomatis in persistently infected human endocervical epithelial cells. Microbiology (Reading). 2011; 157(Pt 10):2759-2771. PMC: 3353392. DOI: 10.1099/mic.0.044917-0. View

15.

Belland R, Nelson D, Virok D, Crane D, Hogan D, Sturdevant D . Transcriptome analysis of chlamydial growth during IFN-gamma-mediated persistence and reactivation. Proc Natl Acad Sci U S A. 2003; 100(26):15971-6. PMC: 307677. DOI: 10.1073/pnas.2535394100. View

16.

Suchland R, Geisler W, Stamm W . Methodologies and cell lines used for antimicrobial susceptibility testing of Chlamydia spp. Antimicrob Agents Chemother. 2003; 47(2):636-42. PMC: 151736. DOI: 10.1128/AAC.47.2.636-642.2003. View

17.

Darville T, Hiltke T . Pathogenesis of genital tract disease due to Chlamydia trachomatis. J Infect Dis. 2010; 201 Suppl 2:S114-25. PMC: 3150527. DOI: 10.1086/652397. View

18.

Shen L, Macnaughtan M, Frohlich K, Cong Y, Goodwin O, Chou C . Multipart Chaperone-Effector Recognition in the Type III Secretion System of Chlamydia trachomatis. J Biol Chem. 2015; 290(47):28141-28155. PMC: 4653673. DOI: 10.1074/jbc.M115.670232. View

19.

Cong Y, Gao L, Zhang Y, Xian Y, Hua Z, Elaasar H . Quantifying promoter activity during the developmental cycle of Chlamydia trachomatis. Sci Rep. 2016; 6:27244. PMC: 4893696. DOI: 10.1038/srep27244. View

20.

Buege M, Brown J, Aitken S . Solithromycin: A novel ketolide antibiotic. Am J Health Syst Pharm. 2017; 74(12):875-887. DOI: 10.2146/ajhp160934. View