Variations in gene organization and DNA uptake signal sequence in the folP region between commensal and pathogenic Neisseria species

BACKGROUND: Horizontal gene transfer is an important source of genetic variation among Neisseria species and has contributed to the spread of resistance to penicillin and sulfonamide drugs in the pathogen Neisseria meningitidis. Sulfonamide resistance in Neisseria meningitidis is mediated by altered chromosomal folP genes. At least some folP alleles conferring resistance have been horizontally acquired from other species, presumably from commensal Neisseriae. In this work, the DNA sequence surrounding folP in commensal Neisseria species was determined and compared to corresponding regions in pathogenic Neisseriae, in order to elucidate the potential for inter-species DNA transfer within this region. RESULTS: The upstream region of folP displayed differences in gene order between species, including an insertion of a complete Correia element in Neisseria lactamica and an inversion of a larger genomic segment in Neisseria sicca, Neisseria subflava and Neisseria mucosa. The latter species also had DNA uptake signal sequences (DUS) in this region that were one base different from the DUS in pathogenic Neisseriae. Another interesting finding was evidence of a horizontal transfer event from Neisseria lactamica or Neisseria cinerea that introduced a novel folP allele to the meningococcal population. CONCLUSION: Genetic recombination events immediately upstream of folP and horizontal transfer have resulted in sequence differences in the folP region between the Neisseria species. This variability could be a consequence of the selective pressure on this region exerted by the use of sulfonamide drugs

High prevalence and extended deletions in Plasmodium falciparum hrp2/3 genomic loci in Ethiopia.

Deletions in Plasmodium falciparum histidine rich protein 2(pfhrp2) gene threaten the usefulness of the most widely used HRP2-based malaria rapid diagnostic tests (mRDTs) that cross react with its structural homologue, PfHRP3. Parasites with deleted pfhrp2/3 genes remain undetected and untreated due to 'false-negative' RDT results. As Ethiopia recently launched malaria elimination by 2030 in certain selected areas, the availability of RDTs and the scale of their use have rapidly increased in recent years. Thus, it is important to explore the presence and prevalence of deletion in the target genes, pfhrp2 and pfhrp3. From a total of 189 febrile patients visited Adama Malaria Diagnostic centre, sixty-four microscopically-and polymerase chain reaction (PCR)-confirmed P. falciparum clinical isolates were used to determine the frequency of pfhrp2/3 gene deletions. Established PCR assays were applied to DNA extracted from blood spotted onto filter papers to amplify across pfhrp2/3 exons and flanking regions. However, analysis of deletions in pfhrp2, pfhrp3 and flanking genomic regions was successful for 50 of the samples. The pfhrp2 gene deletion was fixed in the population with all 50(100%) isolates presenting a deletion variant. This deletion extended downstream towards the Pf3D7 0831900 (MAL7PI.230) gene in 11/50 (22%) cases. In contrast, only 2/50 (4%) of samples had deletions for the Pf3D7 0831700 (MALPI.228) gene, upstream of pfhrp2. Similarly, the pfhrp3 gene was deleted in all isolates (100%), while 40% of the isolates had an extension of the deletion to the downstream flanking region that codes for Pf3D7 13272400 (MAL13PI.485).The pfhrp3 deletion also extended upstream to Pf3D7 081372100 (MAL13PI.475) region in 49/50 (95%) of the isolates, exhibiting complete absence of the locus. Although all samples showed deletions of pfhrp2 exon regions, amplification of an intron region was successful in five cases. Two different repeat motifs in the intron regions were observed in the samples tested. Pfhrp2/3 gene deletions are fixed in Ethiopia and this will likely reduce the effectiveness of PfHRP2-based mRDTs. It will be important to determine the sensitivity PfHRP 2/3-based RDTs in these populations and conduct a countrywide survey to determine the extent of these deletions and its effect on routine RDT-based malaria diagnosis

Variations in gene organization and DNA uptake signal sequence in the region between commensal and pathogenic species-2

<p><b>Copyright information:</b></p><p>Taken from "Variations in gene organization and DNA uptake signal sequence in the region between commensal and pathogenic species"</p><p>BMC Microbiology 2006;6():11-11.</p><p>Published online 17 Feb 2006</p><p>PMCID:PMC1431543.</p><p>Copyright © 2006 Qvarnstrom and Swedberg; licensee BioMed Central Ltd.</p>) ; c) Z2491; d) MC58; e) 8013; f) ; g) ; h) . Numbers flanked by dotted arrows specify distances in base pairs between adjacent start- and stop codons. Triangles illustrate various DNA uptake signal sequences: ▷: GCCGTCTGAA; ▶: GCGTCTGAA; : GCCGTTGAA; : GCCGTCGAA; : GCCGTTGAA; : CCGTCTGAA; : CGTCTGAA. Triangles pointing towards each other illustrate inverted repeats. For the complete nucleotide sequences, see Additional file

Variations in gene organization and DNA uptake signal sequence in the region between commensal and pathogenic species-0

<p><b>Copyright information:</b></p><p>Taken from "Variations in gene organization and DNA uptake signal sequence in the region between commensal and pathogenic species"</p><p>BMC Microbiology 2006;6():11-11.</p><p>Published online 17 Feb 2006</p><p>PMCID:PMC1431543.</p><p>Copyright © 2006 Qvarnstrom and Swedberg; licensee BioMed Central Ltd.</p>other species. Open reading frames are visualized as colored block arrows (the tip of each arrow symbolizing the stop codon) and labeled with their designations according to the text. Non-coding regions are visualized as solid lines. The gene and the Correia element in were only partially sequenced. The symbol // means that 13 kb sequence separating from has been omitted in the figure. The intergenic regions are defined by dotted vertical lines and designated TC (-), DM (-), MF (-) and FU (-upstream), respectively

Hyperparasitaemia during clinical malaria episodes in infants aged 0–24 months and its association with in utero exposure to Plasmodium falciparum

Abstract Objective Existing information has shown that infants who are prenatally exposed to P. falciparum are susceptible to subsequent malaria infections. However, the effect of prenatal exposure to P. falciparum on parasite density during clinical malaria episodes has not been fully elucidated. This study is a component of a prospective cohort study for which initial results have been published. This component was designed to determine the effect of prenatal exposure to P. falciparum on parasite density during clinical malaria episodes in the first 24 months of life. A total of 215 infants were involved and monitored for clinical malaria episodes defined by fever (≥ 37 °C) and parasitaemia. The geometric mean parasite counts between exposed and unexposed infants were compared using independent samples t test. The effect of in utero exposure to P. falciparum on parasite density was assessed using binary logistic regression. Results The geometric mean parasite count per µl of blood during clinical malaria episodes in exposed infants was 24,889 (95% CI 18,286–31,490) while in unexposed infants it was 14,035 (95% CI 12,111–15,960), P  0.05)