Immunization with PfGBP130 generates antibodies that inhibit RBC invasion by P. falciparum parasites

BackgroundDespite decades of effort, Plasmodium falciparum malaria remains a leading killer of children. The absence of a highly effective vaccine and the emergence of parasites resistant to both diagnosis as well as treatment hamper effective public health interventions.Methods and resultsTo discover new vaccine candidates, we used our whole proteome differential screening method and identified PfGBP130 as a parasite protein uniquely recognized by antibodies from children who had developed resistance to P. falciparum infection but not from those who remained susceptible. We formulated PfGBP130 as lipid encapsulated mRNA, DNA plasmid, and recombinant protein-based immunogens and evaluated the efficacy of murine polyclonal anti-PfGBP130 antisera to inhibit parasite growth in vitro. Immunization of mice with PfGBP130-A (aa 111–374), the region identified in our differential screen, formulated as a DNA plasmid or lipid encapsulated mRNA, but not as a recombinant protein, induced antibodies that inhibited RBC invasion in vitro. mRNA encoding the full ectodomain of PfGBP130 (aa 89–824) also generated parasite growth-inhibitory antibodies.ConclusionWe are currently advancing PfGBP130-A formulated as a lipid-encapsulated mRNA for efficacy evaluation in non-human primates

Genomic plasticity and antibody response of <i>Bordetella bronchiseptica</i> strain HT200, a natural variant from a thermal spring

ABSTRACT Classical Bordetella species are primarily isolated from animals and humans causing asymptomatic infection to lethal pneumonia. However, isolation of these bacteria from any extra-host environmental niche has not been reported so far. Here, we have characterized the genomic plasticity and antibody response of Bordetella bronchiseptica strain HT200, isolated from a thermal spring. Genomic ANI value and SNPs-based phylogenetic tree suggest a divergent evolution of strain HT200 from a human-adapted lineage of B. bronchiseptica. Growth and survivability assay showed strain HT200 retained viability for more than 5 weeks in the filter-sterilized spring water. In addition, genes or loci encoding the Bordetella virulence factors such as DNT, ACT and LPS O-antigen were absent in strain HT200, while genes encoding other virulence factors were highly divergent. Phenotypically, strain HT200 was non-hemolytic and showed weak hemagglutination activity, but was able to colonize in the respiratory organs of mice. Further, both infection and vaccination with strain HT200 induced protective antibody response in mouse against challenge infection with virulent B. bronchiseptica strain RB50. In addition, genome of strain HT200 (DSM 26023) showed presence of accessory genes and operons encoding predicted metabolic functions pertinent to the ecological conditions of the thermal spring.</jats:p

Characterization of three novel SXT/R391 integrating conjugative elements ICEMfuInd1a and ICEMfuInd1b, and ICEMprChn1 identified in the genomes of Marinomonas fungiae JCM 18476T and Marinomonas profundimaris strain D104.

The genus Marinomonas comprises Gram negative bacteria which are widespread in the marine environment and there is no report on the genomic analysis of SXT/R391 ICEs derived from this group of bacteria. This study describes the genomic features of three new SXT/R391 integrating conjugating elements (ICEs) identified in the genome of Marinomonas fungiae JCM 18476T (ICEMfuInd1a and ICEMfuInd1b) and in Marinomonas profundimaris strain D104 (ICEMprChn1). Structural organizations of the three ICEs were similar to the typical SXT/R391 family of ICEs and showed high degree of conservation in the core genes. Sequence analysis revealed ICEMfuInd1b and ICEMprChn1 were inserted into the genome at 5’-end of the typical host prfC gene, while ICEMfuInd1a was inserted at 5’-end of the atypical hipA-like gene. Despite their coexisting, the ICEMfuInd1a and ICEMfuInd1b were not present in a tandem fashion in the genome of M. fungiae. Phylogenetic analyses revealed the three ICEs either evolved independently or high degrees of recombination events had masked their common evolution from SXT-like ancestors. Further, we found that the typical entry exclusion mechanism mediated by the TraG/EeX protein pair was likely defective in preventing the conjugative transfer of a second copy of the same S (SXT) group ICE in M. fungiae due to mutations. Our analysis showed the presence of 16, 25 and 27 variable genes in the hotspots of ICEMfuInd1a, ICEMfuInd1b and ICEMprChn1 respectively, many of which were not reported earlier for SXT/R391 ICEs. Sequence analysis predicted these hotspot regions were shaped by acquisition of genes through homologous recombination between the SXT and R391 related ICEs or mobile genetic elements present in disparate marine bacteria. Multidrug resistance genes which are hallmark feature of SXT/R391 ICEs were not present in either of the two ICEs from M. fungiae but were present within a transposon cassette in the HS-1 of the ICEMprChn1 from M. profundimaris. Finally, our data provided information on the genetic diversity and predicted functions encoded by variable genes present in the hotspot regions of these new ICEs

Draft Genome Sequences of Vibrio alginolyticus Strain S6-61 and Vibrio diabolicus Strain S7-71, Isolated from Corals in the Andaman Sea

We report the draft genome sequences of Vibrio alginolyticus strain S6-61 and Vibrio diabolicus strain S7-71, isolated from the corals Pocillopora verrucosa and Fungia danai , respectively. The genomes of strains S6-61 and S7-71 contain 4,880 and 4,641 protein coding genes, respectively, and harbor genes associated with the ectoine biosynthesis pathway. </jats:p

Draft Genome Sequence of Rhizobium pusense Strain NRCPB10 ^T (LMG 25623 ^T ) Isolated from Rhizosphere Soil of Chickpeas ( <i>Cicer arietinum</i> L.) Grown in India

ABSTRACT Rhizobium pusense strain NRCPB10 T was isolated from rhizosphere soil of chickpeas ( Cicer arietinum L.). Based upon the draft genome sequence, the genome is 5.28 Mb and encodes 5,064 proteins. </jats:p

Draft Genome Sequences of Two Vibrio fortis Strains Isolated from Coral ( <i>Fungia</i> sp.) from the Andaman Sea

We report the draft genome sequences of Vibrio fortis strains AN-60 and S7-72, which were isolated from coral ( Fungia sp.) from the Andaman Sea. The genome sizes for strains AN-60 and S7-72 are 5.43 and 5.53 Mb, respectively. Both strains harbor genes associated with protocatechuate and azathioprine degradation and the sulfate reduction pathway. </jats:p

Draft Genome Sequence of <i>Marinomonas fungiae</i> Strain AN44 ^T (JCM 18476 ^T ), Isolated from the Coral <i>Fungia echinata</i> from the Andaman Sea

ABSTRACT Marinomonas fungiae strain AN44 T was isolated from mucus of the coral Fungia echinata . Optimum growth occurs at 3 to 5% NaCl. The draft genome is 4.2 Mb, with 3,776 protein-coding genes. It harbors genes for the degradation of aromatic compounds, such as quinate, ferulate, p -coumarate, protocatechuate, and p -hydroxyphenylacetate. </jats:p

Draft Genome Sequence of <i>Gulbenkiania indica</i> Strain HT27 ^T (DSM 17901 ^T ) Isolated from a Sulfur Spring in India

ABSTRACT Gulbenkiania indica strain HT27 T was isolated from a sulfur spring. Here, we report the first representative draft genome sequence of a type strain of the genus Gulbenkiania . The estimated genome is 2.8 Mb, with 2,713 protein-coding sequences. </jats:p