Repeated out-of-Africa expansions of Helicobacter pylori driven by replacement of deleterious mutations

Erratum in: Nat Commun. 2023 Mar 20;14(1):1539. doi: 10.1038/s41467-023-37302-5.Helicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori fromEurope and the Middle East trace substantially more ancestry from modern African populations than the humans that carry them. Here, we use a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations, implying selection to remove them during admixture. Simulations show that population fitness can be restored after bottlenecks bymigration and subsequent admixture of small numbers of bacteria from non-bottlenecked populations. We conclude that recent spread of African DNA has been driven by deleterious mutations accumulated during the original out-of-Africa bottleneck.This work was supported by Sequencing Grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (221S0002, 18KK0266, 19H03473, 21H00346 and 22H02871) to Y.Y. F.F.V. is financed by FCT through Assistant Researcher grant CEECIND/03023/2017 and a project grant PTDC/BTM-TEC/3238/ 2020. I.K. studentship was funded by the National Strategic Reference Framework Operational Program “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014-2020, project No. MIS5002486) and sequencing of strains was supported by the InfeNeutra Project (NSRF 2007-2013, project no. MIS450598) of the Ministry of Culture and Edu- cation, Greece. K.T. and the sequencing of KI isolates was supported by Erik Philip-Sörensen Foundation grant G2016-08, and Swedish Society for Medical research (SSMF). All primary bioinformatics and parts of the comparative genomics were performed on resources provided by Swedish National Infrastructure for Computing (SNIC) through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) under projects snic2018-8-24 and uppstore2017270. Work by S.S. was supported by the German Research Foundation (DFG, project number 158 989 968–SFB 900/A1) and by the Bavarian Ministry of Sci- ence and the Arts in the framework of the Bavarian Research Network “New Strategies Against Multi-Resistant Pathogens by Means of Digital Networking—bayresq.net”. D.F. was supported by Shanghai Municipal Science and Technology Major Project No. 2019SHZDZX02.info:eu-repo/semantics/publishedVersio

High Frequency and Diversity of Rearrangements in Polyomavirus BK Noncoding Regulatory Regions Cloned from Urine and Plasma of Israeli Renal Transplant Patients and Evidence for a New Genetic Subtype ▿ †

Polyomavirus BK (BKV) establishes latent infection in various human tissues, including the kidney. Reactivation following renal transplantation (RT) may cause BKV-associated nephropathy, leading to graft loss. BKV reactivation is often associated with extensive rearrangements in the BKV noncoding regulatory region (NCRR). We explored the formation and predominance of the rearrangements versus the diversity of the rearrangements by cloning and characterizing PCR-amplified NCRR sequences from six Israeli RT patients. We found a high frequency and a high degree of diversity of rearrangements: NCRRs that contained major rearrangements (mrNCRRs), including large insertions and deletions, were detected in 0 to 100% of the clones from individual samples (mean, 50% and 67% in plasma and urine, respectively). In addition, we found a high frequency of mrNCRRs that contained single-nucleotide variations (snvNCRRs) among identical mrNCRRs and archetype clones. mrNCRRs were present in plasma and in concomitantly collected urine samples, but for each patient, only a subset of the mrNCRRs and snvNCRRs were present in both compartments at the same time and/or in subsequent samples from the same compartment. Some mrNCRRs were observed over several months, indicating the continuous replication of the viral genomes carrying them. Phylogenetic analysis based on the snvNCRR in the archetype clones grouped isolates from four of the patients into a new subgroup of genotype IV. Genotypes Ib-1 and Ib-2 were also found. Isolates from two patients had NCRRs from two genotypes, one concurrently with a RT and one after a second RT. Our study prompts further investigation of the functional consequences of NCRR rearrangements to assess their biological significance and their putative role in disease progression and prognosis

Helicobacter pylori infection amongst Arab Israeli women with hyperemesis gravidarum—a prospective, controlled study

Objective: Helicobacter pylori has been associated with hyperemesis gravidarum in some geographical regions. The prevalence of H. pylori in Arab Israeli women in the Upper Galilee and its association with hyperemesis gravidarum has not been studied previously. We aimed to examine if hyperemesis gravidarum is associated with H. pylori in this population. Methods: Subjects with hyperemesis gravidarum carrying a singleton fetus were recruited prospectively. Women with an uncomplicated pregnancy served as controls. All patients underwent 13C-urea breath testing to assess for H. pylori infection. Results: A total of 72 subjects, including 24 patients with hyperemesis gravidarum and 48 controls, aged 28.8 ± 5.3 years, were included. H. pylori infection was identified in 75.0% (18/24) of cases and 60.4% (29/48) of controls (p = not significant). H. pylori infection did not correlate with age, fetal sex, or the number of previous pregnancies (p = not significant). Conclusion: H. pylori does not seem to increase the likelihood of hyperemesis gravidarum in Arab Israeli women. However, given the high background prevalence of H. pylori in this population, a larger study is required to corroborate these findings. (MOH20110066

Correlation between Quantitative 13C-Urea Breath Test and Helicobacter pylori Treatment Success in a Population-Based Cohort

Background. There are continual efforts to identify factors which influence the success of first-line therapy for Helicobacter pylori (H. pylori) infection. The 13C-urea breath test result (C13-UBT) utilizes H. pylori urease activity and is a highly accurate diagnostic assay. We aimed to determine whether the magnitude of C13-UBT result is related to treatment success. Methods. Adult patients who underwent a first-time 13C-urea breath test between January 2010 and January 2016 were included. In order to isolate a naïve test-and-treat population who were unlikely to have undergone an initial endoscopy-based H. pylori test, we excluded patients > 45 years and those with a previous C13-UBT. Data were extracted from the Clalit Health Services laboratory database. Results. A total of 94,590 subjects (36.1% male, age 28.5 ± 6.0 years) who underwent a first-time C13-UBT during the study period were included. C13-UBT was positive in 48,509 (51.3%) subjects. A confirmatory posttreatment C13-UBT was performed in 18,375 (37.8%), and eradication was successful in 12,018 (65.4%). The mean C13-UBT recording was 20.6 ± 16.2 DOB in subjects with successful eradication and 19.5 ± 13.1 DOB in subjects with treatment failure (OR, 1.01; 95% CI 1.00-1.01, p<0.01). Among patients in the upper quintile of C13-UBT measurement, eradication was achieved in 67.6%, compared to 62.6% in the lower quintile (OR, 1.22; 95% CI 1.11-1.35, p<0.01). Subjects in the top 1 percentile (C13-UBT ≥ 70 DOB) achieved eradication in 75.0%, compared to 65.3% among subjects with C13-UBT < 70 DOB (OR, 1.59; 95% CI 1.05-2.41, p<0.01). Conclusions. The superiority in H. pylori eradication observed in subjects with a higher C13-UBT DOB is small but significant. Further studies should examine the physiological and microbiological basis for this finding