Oxamniquine resistance alleles are widespread in Old World Schistosoma mansoni and predate drug deployment

Do mutations required for adaptation occur de novo, or are they segregating within populations as standing genetic variation? This question is key to understanding adaptive change in nature, and has important practical consequences for the evolution of drug resistance. We provide evidence that alleles conferring resistance to oxamniquine (OXA), an antischistosomal drug, are widespread in natural parasite populations under minimal drug pressure and predate OXA deployment. OXA has been used since the 1970s to treat Schistosoma mansoni infections in the New World where S. mansoni established during the slave trade. Recessive loss-of-function mutations within a parasite sulfotransferase (SmSULT-OR) underlie resistance, and several verified resistance mutations, including a deletion (p.E142del), have been identified in the New World. Here we investigate sequence variation in SmSULT-OR in S. mansoni from the Old World, where OXA has seen minimal usage. We sequenced exomes of 204 S. mansoni parasites from West Africa, East Africa and the Middle East, and scored variants in SmSULT-OR and flanking regions. We identified 39 non-synonymous SNPs, 4 deletions, 1 duplication and 1 premature stop codon in the SmSULT-OR coding sequence, including one confirmed resistance deletion (p.E142del). We expressed recombinant proteins and used an in vitro OXA activation assay to functionally validate the OXA-resistance phenotype for four predicted OXA-resistance mutations. Three aspects of the data are of particular interest: (i) segregating OXA-resistance alleles are widespread in Old World populations (4.29–14.91% frequency), despite minimal OXA usage, (ii) two OXA-resistance mutations (p.W120R, p.N171IfsX28) are particularly common (>5%) in East African and Middle-Eastern populations, (iii) the p.E142del allele has identical flanking SNPs in both West Africa and Puerto Rico, suggesting that parasites bearing this allele colonized the New World during the slave trade and therefore predate OXA deployment. We conclude that standing variation for OXA resistance is widespread in S. mansoni

No evidence for schistosome parasite fitness trade-offs in the intermediate and definitive host

Abstract Background The trematode parasite Schistosoma mansoni uses an aquatic snail intermediate and a vertebrate definitive host to complete its life cycle. We previously showed that a key transmission trait—the number of cercariae larvae shed from infected Biomphalaria spp. snails—varies significantly within and between different parasite populations and is genetically controlled by five loci. We investigated the hypothesis that the success of parasite genotypes showing high propagative fitness in the intermediate snail host may be offset by lower reproductive fitness in the definitive vertebrate host. Methods We investigated this trade-off hypothesis by selecting parasite progeny producing high or low number of larvae in the snail and then comparing fitness parameters and virulence in the rodent host. We infected inbred BALB/c mice using two Schistosoma mansoni parasite lines [high shedder (HS) and low shedder (LS) lines] isolated from F2 progeny generated by genetic crosses between SmLE (HS parent) and SmBRE (LS parent) parasites. We used the F3 progeny to infect two populations of inbred Biomphalaria glabrata snails. We then compared life history traits and virulence of these two selected parasite lines in the rodent host to understand pleiotropic effects of genes determining cercarial shedding in parasites infecting the definitive host. Results HS parasites shed high numbers of cercariae, which had a detrimental impact on snail physiology (measured by laccase-like activity and hemoglobin rate), regardless of the snail genetic background. In contrast, selected LS parasites shed fewer cercariae and had a lower impact on snail physiology. Similarly, HS worms have a higher reproductive fitness and produced more viable F3 miracidia larvae than LS parasites. This increase in transmission is correlated with an increase in virulence toward the rodent host, characterized by stronger hepato-splenomegaly and hepatic fibrosis. Conclusions These experiments revealed that schistosome parasite propagative and reproductive fitness was positively correlated in intermediate and definitive host (positive pleiotropy). Therefore, we rejected our trade-off hypothesis. We also showed that our selected schistosome lines exhibited low and high shedding phenotype regardless of the intermediate snail host genetic background. ​ Graphical Abstrac

Prospecting for Zoonotic Pathogens by Using Targeted DNA Enrichment

More than 60 zoonoses are linked to small mammals, including some of the most devastating pathogens in human history. Millions of museum-archived tissues are available to understand natural history of those pathogens. Our goal was to maximize the value of museum collections for pathogen-based research by using targeted sequence capture. We generated a probe panel that includes 39,916 80-bp RNA probes targeting 32 pathogen groups, including bacteria, helminths, fungi, and protozoans. Laboratory-generated, mock-control samples showed that we are capable of enriching targeted loci from pathogen DNA 2,882‒6,746-fold. We identified bacterial species in museum-archived samples, including Bartonella, a known human zoonosis. These results showed that probe-based enrichment of pathogens is a highly customizable and efficient method for identifying pathogens from museum-archived tissues

Disentangling ‘ecosystem services’ and ‘nature’s contributions to people’

People depend on functioning ecosystems, which provide benefits that support human existence and wellbeing. The relationship between people and nature has been experienced and conceptualized in multiple ways. Recently, ecosystem services (ES) concepts have permeated science, government policies, multi-national environmental agreements, and science–policy interfaces. In 2017, the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) introduced a new and closely related concept–Nature’s Contributions to People (NCP). The introduction of NCP has sparked some lively discussion and confusion about the distinguishing characteristics between ES and NCP. In order to clarify their conceptual relation, we identify eleven specific claims about novel elements from the latest NCP literature and analyze how far ES research has already contributed to these corresponding conceptual claims in the existing ES literature. We find a mixed-picture, where on six specific conceptual claims (culture, social sciences and humanities, indigenous and local knowledge, negative contributions of nature, generalizing perspective, non-instrumental values and valuation) NCP does not differ greatly from past ES research, but we also find five conceptual claims (diverse worldviews, context-specific perspective, relational values, fuzzy and fluid reporting categories and groups, inclusive language and framing) where NCP provides novel conceptualizations of people and nature relations

Disentangling ‘ecosystem services’ and ‘nature’s contributions to people’

People depend on functioning ecosystems, which provide benefits that support human existence and wellbeing. The relationship between people and nature has been experienced and conceptualized in multiple ways. Recently, ecosystem services (ES) concepts have permeated science, government policies, multi-national environmental agreements, and science–policy interfaces. In 2017, the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) introduced a new and closely related concept – Nature’s Contributions to People (NCP). The introduction of NCP has sparked some lively discussion and confusion about the distinguishing characteristics between ES and NCP. In order to clarify their conceptual relation, we identify eleven specific claims about novel elements from the latest NCP literature and analyze how far ES research has already contributed to these corresponding conceptual claims in the existing ES literature. We find a mixed-picture, where on six specific conceptual claims (culture, social sciences and humanities, indigenous and local knowledge, negative contributions of nature, generalizing perspective, non-instrumental values and valuation) NCP does not differ greatly from past ES research, but we also find five conceptual claims (diverse worldviews, context-specific perspective, relational values, fuzzy and fluid reporting categories and groups, inclusive language and framing) where NCP provides novel conceptualizations of people and nature relations

Increasing ciprofloxacin resistance of isolates from infected urines of a cross-section of patients in Karachi

<p>Abstract</p> <p>Background</p> <p>The objective of the research was to evaluate the current effectiveness of Ciprofloxacin on the uropathogens prevalent in infected urines of a cross-section of patients in Karachi, Pakistan.</p> <p>Findings</p> <p>An observational study conducted in a private diagnostic laboratory and its branches in key areas of Karachi City from February 2010 to July 2011. A total of 2963 consecutive urine samples were cultured on chocolate agar, CLED medium and selective EMB agar. Growth of possible uropathogens was noted, and compared retrospectively with earlier lab data of suggestive urine cultures (<it>n</it> = 1997) recorded during January 2009 and December 2009. The isolates were identified using routine procedures and the API 20 system and evaluated for their sensitivity to ciprofloxacin by Kirby-Bauer disk diffusion method. Data was subjected to statistical analysis on SPSS version 16. Out of the present-day culture-positive urines, 2409 (80.4%) yielded gram-negative rods, and 554 (18.5%) gram-positive cocci. <it>E.coli</it> (43.1%) was most frequent, followed by <it>Klebsiella pneumoniae</it> (22.4%) and <it>Staphylococcus aureus</it> (15.5%). 57.2% of the Gram-negative bacteria and 48.7% of the Gram-positive isolates were resistant to ciprofloxacin. In the earlier (2009) screening, 39% of Gram-negative rods and 48% of Gram-positive cocci were indifferent to the drug.</p> <p>Conclusions</p> <p>A decrease in bacterial susceptibility of uropathogens to ciprofloxacin, a commonly prescribed drug in our population, is underlined, occurring possibly due to overuse pressure. Empirical initial treatment with ciprofloxacin would be inadequate in more than half of UTI cases, thereby counseling increased C/S testing of urines to provide existing sensitivity data for apt drug prescription.</p

Mapping ecosystem services : from biophysical processes to (Mis)Uses

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