Multi-locus sequence typing of Treponema pallidum subsp. pallidum present in clinical samples from France: Infecting treponemes are genetically diverse and belong to 18 allelic profiles

Abstract

Treponema pallidum subsp. pallidum, the causative agent of sexually transmitted syphilis, detected in clinical samples from France, was subjected to molecular typing using the recently developed Multilocus Sequence Typing system. The samples (n = 133) used in this study were collected from 2010–2016 from patients with diagnosed primary or secondary syphilis attending outpatient centers or hospitals in several locations in France. Altogether, 18 different allelic profiles were found among the fully typed samples (n = 112). There were five allelic variants identified for TP0136, 12 for TP0548, and eight for TP0705. Out of the identified alleles, one, seven, and three novel alleles were identified in TP0136, TP0548, and TP0705, respectively. Partial allelic profiles were obtained from 6 samples. The majority of samples (n = 110) belonged to the SS14-like cluster of TPA isolates while 7 clustered with Nichols-like isolates. Patients infected with Nichols-like samples were more often older (p = 0.041) and more often diagnosed with secondary syphilis (p = 0.033) compared to patients infected with SS14-like samples. In addition, macrolide resistance caused by the A2058G mutation was found to be associated with allelic profile 1.3.1 or with strains belonging to the 1.3.1 lineage (p<0.001). The genetic diversity among TPA strains infecting the European population was surprisingly high, which suggests that additional studies are needed to reveal the full genetic diversity of TPA pathogens infecting humans.

No bejel among Surinamese, Antillean and Dutch syphilis diagnosed patients in Amsterdam between 2006–2018 evidenced by multi-locus sequence typing of Treponema pallidum isolates

“…The most prevalent allelic profile found in this study was the SS14-like strain, 1.3.1 (42%), followed by 1.1.1 (19%) in concordance with similar TPA MLST studies [8,12,15,16]. Until now, these two types have been found in every TPA MLST study [13], while all geographic locations (Czech Republic [16], Switzerland [8], France [12], Cuba [15], and the Netherlands) from which the samples were derived also have less common and unique allelic profiles suggesting the combination of global mixing populations and more local mixing of the hosts (S3 Table). To investigate possible bias in the typable versus not (fully) typable samples these groups were compared based on ethnicity, RPR titer, HIV status and syphilis stage.…”

“…This relatively high ratio of Nichols-like strains versus SS14-like strains was not explained by ethnicity as 2/16 (13%) fully typed samples from Antillean patients, 6/37 (16%) samples from Surinamese patients and 10/50 (20%) samples from Dutch patients, contained Nichols-like strains. Interestingly, all fully typed isolates from secondary stage syphilis patients contained TPA strains belonging to the SS14 clade (S2 Table), whereas an association was found between secondary stage syphilis and Nichols-like strains in a previous study [12].…”

“…Also both 23S rRNA genes were partly sequenced to check for the A2058G and A2059G mutations associated with macrolide resistance. The partial amplification and sequence analysis using Sanger sequencing was performed as described [8,12]. Sequence analyses were performed using Bionumerics version 7.6.3 (Applied Maths, BioMérieux).…”

Peer Review #2 of "A public database for the new MLST scheme for Treponema pallidum subsp. pallidum: surveillance and epidemiology of the causative agent of syphilis (v0.1)"

“…All published whole genome and draft genome sequences of TPA (Pětrošová et al, 2013;Giacani et al, 2010;Pětrošová et al, 2012;Zobaníková et al, 2012;Giacani et al, 2014;Tong et al, 2017;Arora et al, 2016;Sun et al, 2016;Pinto et al, 2016;Strouhal et al, 2018;Grillová et al 2018b), data available at GenBank, as well as sequences obtained by MLST (Grillová et al, 2018a;Pospíšilová et al, 2018) were submitted to the database.…”

“…Recently, we published a new MLST scheme of TPA (Grillová et al, 2018a, Pospíšilová et al 2018. The TPA MLST scheme is somewhat unusual compared to typical MLST schemes reflecting the special characteristics of TPA.…”