Treponema pallidum macrolide resistance and molecular epidemiology in southern Africa, 2008-2018

2021 ◽  
Author(s):  
Johanna M.E. Venter ◽  
Etienne E Müller ◽  
Mahlape P Mahlangu ◽  
Ranmini S Kularatne
Keyword(s):  
South Africa ◽  
Molecular Epidemiology ◽  
Southern Africa ◽  
Treponema Pallidum ◽  
Point Mutations ◽  
Macrolide Resistance ◽  
Penicillin G ◽  
23S Rrna ◽  
Molecular Heterogeneity ◽  
Strain Type

Treponema pallidum macrolide resistance and clinical treatment failure have emerged rapidly within communities where macrolides have been used as convenient, oral therapeutic alternatives to benzathine penicillin G for syphilis, or for other clinical indications. Macrolides are not included in the South African syndromic management guidelines for genital ulcer disease; however, in 2015, a 1 gram dose of azithromycin was incorporated into treatment algorithms for genital discharge. We determined the prevalence of 23S rRNA macrolide resistance-associated point mutations in 135 T. pallidum -positive surveillance specimens from Botswana, Zimbabwe and South Africa between 2008 and 2018. Additionally, we investigated the association between macrolide resistance, T. pallidum strain type and HIV co-infection. A significant increase in the prevalence of the A2058G macrolide resistance-associated point mutation was observed in specimens collected after 2015. There was a high level of molecular heterogeneity among T. pallidum strains circulating in the study communities, with strain type 14d/f being the most predominant in South Africa. Fourteen novel strain types, derived from three new tpr -gene restriction fragment length polymorphism patterns and seven new tp0548 -gene sequence types, were identified. There was an association between A2058G-associated macrolide resistance and T. pallidum strain types 14d/f and 14d/g, but no association between T. pallidum macrolide resistance and HIV co-infection. The majority of T. pallidum strains, as well as strains containing the A2058G mutation, belonged to the SS14-like clade. This is the first study to extensively detail the molecular epidemiology and emergence of macrolide resistance in T. pallidum in southern Africa.

scholarly journals Molecular Typing and Macrolide Resistance Analyses ofTreponema pallidumin Heterosexuals and Men Who Have Sex with Men in Japan, 2017

2018 ◽  
Vol 57 (1) ◽  
Author(s):  
Mizue Kanai ◽  
Yuzo Arima ◽  
Shingo Nishiki ◽  
Ken Shimuta ◽  
Ichiro Itoda ◽  
...  
Keyword(s):  
Molecular Typing ◽  
Treponema Pallidum ◽  
Macrolide Resistance ◽  
23S Rrna ◽  
Rrna Gene ◽  
Content Type ◽  
Heterosexual Women ◽  
23S Rrna Gene ◽  
Strain Type ◽  
Sex With Men

ABSTRACTIn recent years, syphilis notifications have increased dramatically in Japan. We carried out molecular typing and macrolide resistance analyses ofTreponema pallidumsubsp.pallidumsamples collected from patients at four clinics and a hospital in Tokyo and Osaka prefectures in 2017. The macrolide resistant strain type 14d/f (SS14-like clade) was found in significantly more cases of syphilis among heterosexuals than in those among men who have sex with men (MSM); i.e., 79% (31/39) of the strains from heterosexuals were 14d/f compared to 37% (7/19) of those from MSM (odds ratio [OR], 6.6; 95% confidence interval [CI], 1.7 to 26.7;P = 0.002). In addition, 83% (50/60) of the strains were identified as macrolide resistant with an A2058G mutation in the 23S rRNA gene; 90% (35/39) of the strains from heterosexuals were macrolide resistant compared to 58% (11/19) of those from MSM. The odds of having the resistant mutation were considerably higher in the former (OR, 6.4; 95% CI, 1.3 to 33.5;P = 0.02). Heterosexual women and heterosexual men showed similar distributions, and the association remained the same when restricted to men. The strain type distribution and the prevalence of macrolide resistance differed substantially between syphilis strains from heterosexual cases and from MSM cases, suggesting distinct epidemiologic profiles for the two communities and providing important insight into the dynamics of syphilis in Japan.

scholarly journals Molecular typing and macrolide resistance analyses ofTreponema pallidumin heterosexuals and men who have sex with men communities in Japan, 2017

2018 ◽  
Author(s):  
Mizue Kanai ◽  
Yuzo Arima ◽  
Shingo Nishiki ◽  
Ken Shimuta ◽  
Ichiro Itoda ◽  
...  
Keyword(s):  
Molecular Typing ◽  
Treponema Pallidum ◽  
Macrolide Resistance ◽  
23S Rrna ◽  
Rrna Gene ◽  
23S Rrna Gene ◽  
Strain Type ◽  
Sex With Men ◽  
Insight Into ◽  
Resistant Mutation

AbstractIn recent years, syphilis notifications have increased dramatically in Japan. We performed molecular typing and analyzed macrolide resistance ofTreponema pallidumsamples collected from four clinics and a hospital in Tokyo and Osaka prefectures in 2017.Macrolide resistant strain type 14d/f was found significantly more in heterosexual syphilis cases compared with those strains identified in men who have sex with men (MSM) syphilis cases. The proportion of 14d/f among heterosexuals was 79% (31/39) compared to 37% (7/19) among MSM [OR, 6.6 (95% CI, 1.7 to 26.7); P=0.002]. 83% (50/60) of the strains were identified as macrolide resistant with an A2058G mutation at the 23S rRNA gene. 90% (35/39) of the heterosexual strains were macrolide resistant, relative to 58% (11/19) of MSM strains; the odds of having the resistant mutation was considerably higher in heterosexuals compared with MSM [OR, 6.4 (95% CI, 1.3 to 33.5); P=0.02]. Heterosexual females and males showed similar distributions, and the results remained the same when restricted to men.The strain type distribution and frequency of macrolide resistance differed substantially between heterosexual and MSM syphilis samples, suggesting distinct epidemiologic profiles for the two communities and insight into syphilis transmission dynamics in Japan.

scholarly journals Macrolide resistance in Helicobacter pylori: rapid detection of point mutations and assays of macrolide binding to ribosomes.

1997 ◽  
Vol 41 (12) ◽  
pp. 2724-2728 ◽  
Author(s):  
A Occhialini ◽  
M Urdaci ◽  
F Doucet-Populaire ◽  
C M Bébéar ◽  
H Lamouliatte ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Point Mutations ◽  
Restriction Enzymes ◽  
The United States ◽  
Drug Binding ◽  
Macrolide Resistance ◽  
Rrna Genes ◽  
23S Rrna ◽  
Dependent Manner ◽  
H Pylori

Resistance of Helicobacter pylori to macrolides is a major cause of failure of eradication therapies. Single base substitutions in the H. pylori 23S rRNA genes have been associated with macrolide resistance in the United States. Our goal was to extend this work to European strains, to determine the consequence of this mutation on erythromycin binding to H. pylori ribosomes, and to find a quick method to detect the mutation. Seven pairs of H. pylori strains were used, the parent strain being naturally susceptible to macrolides and the second strain having acquired an in vivo resistance during a treatment regimen that included clarithromycin. The identity of the strains was confirmed by random amplified polymorphic DNA testing with two different primers, indicating that resistance was the result of the selection of variants of the infecting strain. All resistant strains were found to have point mutations at position 2143 (three cases) or 2144 (four cases) but never on the opposite DNA fragment of domain V of the 23S rRNA gene. The mutation was A-->G in all cases except one (A-->C) at position 2143. Using BsaI and BbsI restriction enzymes on the amplified products, we confirmed the mutations of A-->G at positions 2144 and 2143, respectively. Macrolide binding was tested on purified ribosomes isolated from four pairs of strains with [14C]erythromycin. Erythromycin binding increased in a dose-dependent manner for the susceptible strain but not for the resistant one. In conclusion we suggest that the limited disruption of the peptidyltransferase loop conformation, caused by a point mutation, reduces drug binding and consequently confers resistance to macrolides. Finally, the macrolide resistance could be detected without sequencing by performing restriction fragment length polymorphism with appropriate restriction enzymes.

scholarly journals Molecular Mechanisms of Macrolide Resistance in Clinical Isolates of Mycoplasma pneumoniae from China

2009 ◽  
Vol 53 (5) ◽  
pp. 2158-2159 ◽  
Author(s):  
Deli Xin ◽  
Zuhuang Mi ◽  
Xu Han ◽  
Ling Qin ◽  
Jing Li ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Molecular Mechanism ◽  
Mycoplasma Pneumoniae ◽  
Respiratory Tract Infections ◽  
Molecular Mechanisms ◽  
Point Mutations ◽  
Macrolide Resistance ◽  
The Other ◽  
23S Rrna ◽  
Tract Infections

ABSTRACT Fifty clinical Mycoplasma pneumoniae strains were isolated from 370 children with respiratory tract infections. Four strains were susceptible to macrolides, while the other 46 (92%) were macrolide resistant. The molecular mechanism of resistance was shown to be associated with point mutations in 23S rRNA at positions 2063 and 2064.

scholarly journals Antistreptococcal Activity of Telithromycin Compared with Seven Other Drugs in Relation to Macrolide Resistance Mechanisms in Russia

2002 ◽  
Vol 46 (9) ◽  
pp. 2963-2968 ◽  
Author(s):  
Roman S. Kozlov ◽  
Tatiana M. Bogdanovitch ◽  
Peter C. Appelbaum ◽  
Lois Ednie ◽  
Leonid S. Stratchounski ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Ribosomal Protein ◽  
Streptococcus Pyogenes ◽  
Prevalence Rate ◽  
Resistance Mechanism ◽  
Resistance Mechanisms ◽  
Macrolide Resistance ◽  
Penicillin G ◽  
23S Rrna

ABSTRACT The susceptibilities of 468 recent Russian clinical Streptococcus pneumoniae isolates and 600 Streptococcus pyogenes isolates, from 14 centers in Russia, to telithromycin, erythromycin, azithromycin, clarithromycin, clindamycin, levofloxacin, quinupristin-dalfopristin, and penicillin G were tested. Penicillin-nonsusceptible S. pneumoniae strains were rare except in Siberia, where their prevalence rate was 13.5%: most were penicillin intermediate, but for three strains (two from Smolensk and one from Novosibirsk) the MICs of penicillin G were 4 or 8 μg/ml. Overall, 2.5% of S. pneumoniae isolates were resistant to erythromycin. Efflux was the prevalent resistance mechanism (five strains; 41.7%), followed by ribosomal methylation encoded by constitutive erm(B), which was found in four isolates. Ribosomal mutation was the mechanism of macrolide resistance in three isolates; one erythromycin-resistant S. pneumoniae isolate had an A2059G mutation in 23S rRNA, and two isolates had substitution of GTG by TPS at positions 69 to 71 in ribosomal protein L4. All S. pyogenes isolates were susceptible to penicillin, and 11% were erythromycin resistant. Ribosomal methylation was the most common resistance mechanism for S. pyogenes (89.4%). These methylases were encoded by erm(A) [subclass erm(TR)] genes, and their expression was inducible in 96.6% of isolates. The rest of the erythromycin-resistant Russian S. pyogenes isolates (7.6%) had an efflux resistance mechanism. Telithromycin was active against 100% of pneumococci and 99.2% of S. pyogenes, and levofloxacin and quinupristin-dalfopristin were active against all isolates of both species.

scholarly journals Rapid Detection, by PCR and Reverse Hybridization, of Mutations in the Helicobacter pylori 23S rRNA Gene, Associated with Macrolide Resistance

1999 ◽  
Vol 43 (7) ◽  
pp. 1779-1782 ◽  
Author(s):  
Leen-Jan van Doorn ◽  
Yvette J. Debets-Ossenkopp ◽  
Armelle Marais ◽  
Ricardo Sanna ◽  
Francis Mégraud ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Fragment Length Polymorphism ◽  
Simultaneous Detection ◽  
Point Mutations ◽  
Macrolide Resistance ◽  
23S Rrna ◽  
Rrna Gene ◽  
Reverse Hybridization ◽  
23S Rrna Gene ◽  
H Pylori

ABSTRACT A PCR-based reverse hybridization system (research prototype kit INNO-LiPA for H. pylori resistance) was developed and evaluated for simultaneous detection of 23S ribosomal DNA point mutations, associated with macrolide resistance in Helicobacter pylori. Fifty-seven H. pylori strains (51 natural, 6 laboratory-derived artificial, 52 resistant, and 5 susceptible strains) were tested by PCR-LiPA (detecting mutations A2115→G, G2141→A, A2142→G, A2142→C, A2143→G, A2143→C, and A2143→T), DNA sequencing, restriction fragment length polymorphism, and/or hybridization to oligonucleotide probes. Results were highly concordant, but PCR-LiPA appears to be more sensitive for the simultaneous detection of multiple mutants.

scholarly journals Treponema pallidum Strain Types and Association with Macrolide Resistance in Sydney, Australia: New TP0548 Gene Types Identified

2016 ◽  
Vol 54 (8) ◽  
pp. 2172-2174 ◽  
Author(s):  
Phillip Read ◽  
Kaitlin A. Tagg ◽  
Neisha Jeoffreys ◽  
Rebecca J. Guy ◽  
Gwendolyn L. Gilbert ◽  
...  
Keyword(s):  
Classification Scheme ◽  
Treponema Pallidum ◽  
Macrolide Resistance ◽  
Strain Typing ◽  
Content Type ◽  
Strain Type ◽  
Sydney Australia

Strain typing ofTreponema pallidum, using the three-target enhanced classification scheme, was performed with 191 samples obtained between 2004 and 2011 in Sydney, Australia. The most common strain type was 14d/g (92/191 samples [48%]). Two new TP0548 gene types were detected (m and n). Strain type was associated with macrolide resistance and possible acquisition outside Australia.

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