Rabinovich, A. | bioRxiv Science

bioRxiv2026

Lineage-specific tprK diversification and Treponema pallidum transmission dynamics in Buenos Aires, Argentina

BackgroundSyphilis rates are rising globally, with increases in congenital syphilis in South America particularly concerning. The characterization of contemporary South American Treponema pallidum (Tp) strains is crucial to syphilis vaccine development, yet few genomic epidemiology studies have focused on this region. Here, we performed whole genome sequencing (WGS) of Tp from Buenos Aires, Argentina, as well as deep sequencing of the hypervariable tprK locus, which is critical to Tp immune evasion. MethodsPeople with primary, secondary, or congenital syphilis were enrolled at two clinics in Buenos Aires between October 2018 and January 2023, including individuals associated with intra-household transmission. Hybrid capture WGS was performed and a core genome phylogeny generated. K-mer-based methods using full-length tprK PacBio long reads were used to uncover differences in diversity and detect Tp transmission. FindingsTp genomes were recovered from 70 individuals in Buenos Aires and primarily belonged to globally dominant SS14 sublineage-1 and Nichols sublineage-8, as did Tp from Brazil (n=8). Peruvian samples (n=3) all belonged to sublineage-1. Two individuals from Argentina had co-infections with Nichols- and SS14-lineage strains. Macrolide resistance via A2058G occurred in 27/70 (38.6%) samples. Across 56 samples, tprK allelic diversity was significantly increased in secondary syphilis, oral lesions, and SS14-lineage strains compared to primary syphilis, anogenital lesions, and Nichols-lineage strains, respectively. Increased diversity in SS14-lineage strains is driven by an enhanced repertoire of V7-specific donor sequences. tprK sequences from intra-household transmissions were more similar than unrelated samples with identical core genomes. InterpretationTp circulating in South America is closely related to dominant global sublineages. Increased tprK diversity in the SS14 lineage may influence Tps ability to escape host immunity. tprK profiling is a promising tool to elucidate syphilis transmission networks. This study underscores the utility of genomics to yield insights into Tp pathogenesis. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSAlthough whole genome sequencing (WGS) and genomic epidemiology have contributed to an understanding of the global diversity of Treponema pallidum (Tp), very few strains from South America have been sequenced to date. On January 6th, 2026, we performed a PubMed search including terms "syphilis genomic epidemiology", "South America", "Treponema pallidum", and "Argentina". We excluded studies of ancient Tp samples found in South American archeological sites. A single Tp sample from Argentina was originally sequenced in 2016 and included in subsequent analyses of global diversity. Nine Peruvian samples were previously sequenced in a study of global diversity on six continents. Thirty-three samples from Cali, Colombia were predominantly SS14-lineage and genotypic macrolide resistance was found in half of strains. Additionally, studies of Tp in Buenos Aires using a multi-locus sequence typing approach have shown circulation of strains belonging to both Nichols and SS14 lineages, with an increasing rate of macrolide resistance over time. Five previous studies have examined tprK in clinical specimens and consistently shown increased tprK diversity in specimens associated with secondary syphilis compared to primary syphilis lesions. One study has shown that loss of tprK donor cassettes is associated with reduced tprK diversity, consistent with results from in vitro experiments. A single study has shown that tprK sequence content is more similar in samples with a suspected epidemiologic link, though no prior studies have looked at tprK diversity in the context of known syphilis transmission events. Added value of this studyThis study is the first to use WGS to comprehensively examine Tp transmission in a large South American city, yielding 96 samples from 70 individuals. We also add the first contemporary Tp genomes from Brazil. In contrast to findings from England, Australia, and other high-income countries, no Tp sublineages are associated with demographic groups or sexual networks in Buenos Aires. Two of seventy patients were co-infected with both Nichols- and SS14-lineage strains, showing the previously unappreciated frequency of conditions that permit inter-strain recombination-driven diversification of Tp. This study also reveals novel aspects of Tp pathogenesis, including lineage-specific differences in tprK diversity. We also develop methods for the analysis of tprK relatedness between samples and demonstrate that tprK sequences are more similar in samples from individuals within intra-household syphilis transmission chains compared to those from epidemiologically unrelated individuals. Implications of all the available evidenceTp strains circulating in Buenos Aires are genetically similar to those circulating worldwide and in Brazil and Peru but are noteworthy for the low (but rising) rate of macrolide resistance. Lineage-specific patterns of tprK antigenic variation could result in differences between Nichols- and SS14-lineage strains interactions with the host immune system. Finally, we show that tprK profiling holds promise to identify samples from within a syphilis transmission chain and could play an important role in public health.

microbiology↗

bioRxiv2024

Sensory perception of fluctuating light in Arabidopsis

When exposed to shade from neighbours, competitive plants modify their growth patterns to improve access to light. In dense plant stands, ranging from forests to humid grasslands and crops, shade is interrupted by sunflecks penetrating the canopy. Relatively infrequent, minute-scale interruptions can significantly contribute to the daily light input. However, given the short duration and the time gap between these low frequency sunflecks (LFS), whether plants can sense them was unknown. Here we show that phytochrome B (phyB), cryptochrome 1 (cry1), cry2, and UV RESISTANCE LOCUS 8 (UVR8) cooperatively perceive LFS to reduce hypocotyl growth in Arabidopsis thaliana. LFS also enhanced the expression of photosynthetic and photo-protective genes and initiated pre-emptive acclimation to water restriction. Repeated LFS increased the nuclear abundance of cry1 and UVR8. This positive feedback enhanced the sensitivity to subsequent LFS and even to the shade between LFS. LFS reduced the nuclear abundance of the growth regulator PHYTOCHROME INTERACTING FACTOR 4 (PIF4), which only slowly recovered upon return to shade, further amplifying the signal. The dynamics of the photo-sensory system under fluctuating light helps adjust plants to the prevailing conditions.

plant biology↗

bioRxiv2021

Coordinate regulation of liver ferroportin degradation and de novo synthesis determines serum iron levels in mice

The iron hormone hepcidin is transcriptionally activated by iron or inflammation via distinct, partially overlapping pathways. We addressed how iron affects inflammatory hepcidin levels and the ensuing hypoferremic response. Dietary iron overload did not mitigate hepcidin induction in LPS-treated wt mice but prevented effective inflammatory hypoferremia. Likewise, LPS modestly decreased serum iron in hepcidin-deficient Hjv-/-mice, model of hemochromatosis. Synthetic hepcidin triggered hypoferremia in control but not iron-loaded wt animals. Furthermore, it dramatically decreased hepatic and splenic ferroportin in Hjv-/-mice on standard or iron-deficient diet, but only triggered hypoferremia in the latter. Mechanistically, iron antagonized hepcidin responsiveness by inactivating IRPs in the liver and spleen, to stimulate ferroportin mRNA translation. Prolonged LPS treatment eliminating ferroportin mRNA permitted hepcidin-mediated hypoferremia in iron-loaded mice. Thus, de novo ferroportin synthesis is critical determinant of serum iron and finetunes hepcidin-dependent functional outcomes. Our data uncover a crosstalk between hepcidin and IRE/IRP systems that controls tissue ferroportin expression and determines serum iron levels. Moreover, they suggest that hepcidin supplementation therapy is more efficient combined with iron depletion.

immunology↗

bioRxiv2020

ASpli2: Integrative analysis of splicing landscapesthrough RNA-Seq assays

Genome-wide analysis of alternative splicing has been a very active field of research since the early days of NGS (Next generation sequencing) technologies. Since then, ever-growing data availability and the development of increasingly sophisticated analysis methods have uncovered the complexity of the general splicing repertoire. However, independently of the considered quantification methodology, very often changes in variant concentration profiles can be hard to disentangle. In order to tackle this problem we present ASpli2, a computational suite implemented in R, that allows the identification of changes in both, annotated and novel alternative splicing events, and can deal with complex experimental designs. Our analysis workflow relies on the analysis of differential usage of subgenic features in combination with a junction-based description of local splicing changes. Analyzing simulated and real data we found that the consolidation of these signals resulted in a robust proxy of the occurrence of splicing alterations. While junction-based signals allowed us to uncover annotated as well and non-annotated events, bin-associated signals notably increased recall capabilities at a very competitive performance in terms of precision.

bioinformatics↗