ABSTRACT
Sequencing of most Treponema pallidum genomes excludes repeat regions in tp0470 and the tp0433 gene, encoding the acidic repeat protein (arp). As a first step to understanding the evolution and function of these genes and the proteins they encode, we developed a protocol to nanopore sequence tp0470 and arp genes from 212 clinical samples collected from ten countries on six continents. Both tp0470 and arp repeat structures recapitulate the whole genome phylogeny, with subclade-specific patterns emerging. The number of tp0470 repeats is on average appears to be higher in Nichols-like clade strains than in SS14-like clade strains. Consistent with previous studies, we found that 14-repeat arp sequences predominate across both major clades, but the combination and order of repeat type varies among subclades, with many arp sequence variants limited to a single subclade. Although strains that were closely related by whole genome sequencing frequently had the same arp repeat length, this was not always the case. Structural modeling of TP0470 suggested that the eight residue repeats form an extended α-helix, predicted to be periplasmic. Modeling of the ARP revealed a C-terminal sporulation-related repeat (SPOR) domain, predicted to bind denuded peptidoglycan, with repeat regions possibly incorporated into a highly charged ß-sheet. Outside of the repeats, all TP0470 and ARP amino acid sequences were identical. Together, our data, along with functional considerations, suggests that both TP0470 and ARP proteins may be involved in T. pallidum cell envelope remodeling and homeostasis, with their highly plastic repeat regions playing as-yet-undetermined roles.
ABSTRACT
Many HIV-positive persons reportedly continue to engage in at-risk behavior. We compared the sexual and drug-using practices of HIV-positive persons before and after the diagnosis of HIV infection to determine whether their behavior had changed. To this end, in 2006, we conducted a cross-sectional study involving clinical centers in five Italian cities. Each center was asked to enroll 100 persons aged 18 years or older who had a diagnosis of HIV infection that dated back at least 2 years. Data were collected with a specifically designed questionnaire, administered during a structured interview. The McNemar chi2 test was used to compare the data before and after the diagnosis. A total of 497 persons participated (65.5% males; median age of 40 years; age range, 34-45 years). The most common exposure categories were: heterosexual contact (43.4%), homosexual contact (27.2%), and injecting drug use (20.6%). Although the percentage of drug users significantly decreased after diagnosis, 32.4% of injectors continued to use drugs, and approximately half of them exchanged syringes. Regarding sexual behavior, after diagnosis there was a significant decrease in the number of sexual partners and in stable relationships and an increase in condom use, both for persons with stable partners and those with occasional partners, although the percentage varied according to the specific sexual practice. These results indicate that though at-risk behavior seems to decrease after the diagnosis of HIV infection, seropositive persons continue to engage in at-risk practices, indicating the need for interventions specifically geared toward HIV-positive persons.
