Bejel (endemic syphilis) is a neglected non-venereal disease caused by Treponema pallidum subsp. endemicum (TEN). Although it is mostly present in hot, dry climates, a few cases have been found outside of these areas. The aim of this work was the sequencing and analysis of TEN isolates obtained from "syphilis patients" in Cuba, which is not considered an endemic area for bejel. Genomes were obtained by pool segment genome sequencing or direct sequencing methods, and the bioinformatics analysis was performed according to an established pipeline. We obtained four genomes with 100%, 81.7%, 52.6%, and 21.1% breadth of coverage, respectively. The sequenced genomes revealed a non-clonal character, with nucleotide variability ranging between 0.2-10.3 nucleotide substitutions per 100 kbp among the TEN isolates. Nucleotide changes affected 27 genes, and the analysis of the completely sequenced genome also showed a recombination event between tprC and tprI, in TP0488 as well as in the intergenic region between TP0127-TP0129. Despite limitations in the quality of samples affecting breadth of sequencing coverage, the determined non-clonal character of the isolates suggests a persistent infection in the Cuban population rather than a single outbreak caused by imported case.
- MeSH
- bakteriální vakcíny genetika MeSH
- lidé MeSH
- rekombinace genetická MeSH
- syfilis * diagnóza epidemiologie prevence a kontrola MeSH
- Treponema pallidum * genetika MeSH
- vývoj vakcíny MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- úvodníky MeSH
OBJECTIVES: This study aimed to determine the allelic profiles of Treponema pallidum in patients confirmed with syphilis in Cuba (2018-2019) and to explore mutations leading to macrolide and tetracycline resistance. METHODS: Multilocus sequence typing and polymerase chain reaction of rrn loci (23S and 16S rDNA), followed by Sanger sequencing, were used to define the allelic profile of TPA and resistance mutations, respectively. RESULTS: Allelic profile 1.3.1 and the recombinant profile were identified, with 15.7.3 having an increased frequency. We did not detect the presence of the T. pallidum subspecies endemicum among syphilis patients, as in previous reports. A high frequency of macrolide-resistant strains and the absence of mutations potentially causing tetracycline resistance were found. CONCLUSIONS: Understanding the current status of treponemal infection in Cuban patients provides insights into the syphilis epidemiology.
- MeSH
- genotyp MeSH
- lidé MeSH
- makrolidy farmakologie MeSH
- syfilis * epidemiologie MeSH
- Treponema pallidum * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Kuba MeSH
- MeSH
- dospělí MeSH
- lidé MeSH
- polymerázová řetězová reakce metody MeSH
- senzitivita a specificita MeSH
- sérologická diagnostika syfilis metody MeSH
- syfilis diagnóza farmakoterapie MeSH
- Treponema pallidum genetika izolace a purifikace MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Kuba MeSH
Syphilis, caused by Treponema pallidum subsp. pallidum (TPA), remains an important public health problem with an increasing worldwide prevalence. Despite recent advances in in vitro cultivation, genetic variability of this pathogen during infection is poorly understood. Here, we present contemporary and geographically diverse complete treponemal genome sequences isolated directly from patients using a methyl-directed enrichment prior to sequencing. This approach reveals that approximately 50% of the genetic diversity found in TPA is driven by inter- and/or intra-strain recombination events, particularly in strains belonging to one of the defined genetic groups of syphilis treponemes: Nichols-like strains. Recombinant loci were found to encode putative outer-membrane proteins and the recombination variability was almost exclusively found in regions predicted to be at the host-pathogen interface. Genetic recombination has been considered to be a rare event in treponemes, yet our study unexpectedly showed that it occurs at a significant level and may have important impacts in the biology of this pathogen, especially as these events occur primarily in the outer membrane proteins. This study reveals the existence of strains with different repertoires of surface-exposed antigens circulating in the current human population, which should be taken into account during syphilis vaccine development.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The increased prevalence of syphilis in Cuba prompted us to map the circulating Treponema pallidum subsp. pallidum allelic profiles in this geographic region. METHODS: Samples were collected from 2012 to 2017, from 83 male patients with ulcers or skin lesions, and were examined using multilocus sequence typing. Additionally, we analyzed the 23S rDNA and 16S rDNA regions for the presence of possible mutations leading to macrolide and tetracycline resistance. RESULTS: Among 94% of fully typed strains, we found 7 different allelic profiles, of which 4 had not been previously described. More than 87% of patients were infected with the T. pallidum SS14-like group and only 8.2% with T. pallidum Nichols-like group. As in other countries, the 1.3.1 allelic profile (ie, SS14-like) was the most common. In addition, 1 of the newly described allelic profiles represents T. pallidum strains that arose by recombination events between members of different T. pallidum subgroups. More than 90% of patients were infected with treponemes harboring the A2058G mutation. However, we found no potential tetracycline-resistant T. pallidum mutations. CONCLUSIONS: Our results suggest that, in Cuba, tetracycline antibiotics could be used to treat syphilis in penicillin-allergic patients instead of macrolides.
- MeSH
- alely MeSH
- antibakteriální látky MeSH
- bakteriální léková rezistence genetika MeSH
- dospělí MeSH
- lidé MeSH
- makrolidy terapeutické užití MeSH
- multilokusová sekvenční typizace MeSH
- mutace MeSH
- syfilis farmakoterapie mikrobiologie MeSH
- techniky typizace bakterií MeSH
- tetracyklin terapeutické užití MeSH
- Treponema pallidum klasifikace genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Kuba MeSH
