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2016
Sundararaman, SA, Plenderleith LJ, Liu W, Loy DE, Learn GH, Li Y, Shaw KS, Ayouba A, Peeters M, Speede S, Shaw GM, Bushman FD, Brisson D, Rayner JC, Sharp PM, Hahn BH.  2016.  Genomes of cryptic chimpanzee Plasmodium species reveal key evolutionary events leading to human malaria. Nature Communications. 7:11078. Abstractsundararaman2016.pdf

African apes harbor at least six Plasmodium species of the subgenus Laverania, one of which gave rise to human Plasmodium falciparum. Here we use a selective amplification strategy to sequence the genome of chimpanzee parasites classified as Plasmodium reichenowi and Plasmodium gaboni based on subgenomic fragments. Genome-wide analyses show that these parasites indeed represent distinct species, with no evidence of cross-species mating. Both P. reichenowi and P. gaboni are 10-fold more diverse than P. falciparum, indicating a very recent origin of the human parasite. We also find a remarkable Laverania-specific expansion of a multi-gene family involved in erythrocyte remodeling, and show that a short region on chromosome 4, which encodes two essential invasion genes, was horizontally transferred into a recent P. falciparum ancestor. Our results validate the selective amplification strategy for characterising cryptic pathogen species, and reveal evolutionary events that likely predisposed the precursor of P. falciparum to colonise humans

Adalsteinsson, SA, D’Amico V, Shriver GW, Brisson D, Buler JJ.  2016.  Scale-dependent effects of nonnative plant invasion on host-seeking tick abundance. Ecosphere. 7(3):e01317.adalsteinsson2016-ecosphere.pdf
2015
Yue, M, Han X, Masi LD, Zhu C, Ma X, Zhang J, Wu R, Schmieder R, Kaushik RS, Fraser GP, Zhao S, McDermott PF, Weill F-X, Mainil JG, Arze C, Fricke FW, Edwards RA, Brisson D, Zhang NR, Rankin SC, Schifferli DM.  2015.  Allelic variation contributes to bacterial host specificity. Nature Communications. 6:8754. Abstractyue2015a.pdf

Understanding the molecular parameters that regulate cross-species transmission and host adaptation of potential pathogens is crucial to control emerging infectious disease. Although microbial pathotype diversity is conventionally associated with gene gain or loss, the role of pathoadaptive nonsynonymous single-nucleotide polymorphisms (nsSNPs) has not been systematically evaluated. Here, our genome-wide analysis of core genes within Salmonella enterica serovar Typhimurium genomes reveals a high degree of allelic variation in surface-exposed molecules, including adhesins that promote host colonization. Subsequent multinomial logistic regression, MultiPhen and Random Forest analyses of known/suspected adhesins from 580 independent Typhimurium isolates identifies distinct host-specific nsSNP signatures. Moreover, population and functional analyses of host-associated nsSNPs for FimH, the type 1 fimbrial adhesin, highlights the role of key allelic residues in host-specific adherence in vitro. Together, our data provide the first concrete evidence that functional differences between allelic variants of bacterial proteins likely contribute to pathoadaption to diverse hosts.

Seifert, SN, Khatchikian CE, Zhou W, Brisson D.  2015.  Evolution and population genomics of the Lyme borreliosis pathogen, Borrelia burgdorferi. Trends in Genetics. 31(4):201-207. Abstractseifert2015a.pdfcover.tif_.jpg

Population genomic studies have the potential to ad- dress many unresolved questions about microbial pathogens by facilitating the identification of genes underlying ecologically important traits, such as novel virulence factors and adaptations to humans or other host species. Additionally, this framework improves estimations of population demography and evolutionary history to accurately reconstruct recent epidemics and identify the molecular and environmental factors that resulted in the outbreak. The Lyme disease bacterium, Borrelia burgdorferi, exemplifies the power and promise of the application of population genomics to microbial pathogens. We discuss here the future of evolutionary studies in B. burgdorferi, focusing on the primary evolutionary forces of horizontal gene transfer, natural selection, and migration, as investigations transition from analyses of single genes to genomes.

Devevey, G, Nguyen T, Graves CJ, Murray S, Brisson D.  2015.  First to arrive takes all: Inhibitory priority effects dominate competition between co-infecting Borrelia burgdorferi strains. BMC Infectious Diseases. 15:61. Abstractdevevey2015a.pdf

Background: The diversity of pathogen strains is often overlooked, even though it is fundamental in medical, epidemiological or evolutionary perspectives. In the bacteria Borrelia burgdorferi s.s., responsible for Lyme disease, it is assumed that diversity of Outer surface protein C (OspC) gene is the product of selection to evade the immune system, explaining why wild hosts and tick vectors are often coinfected. We tested this hypothesis by conducting controlled mouse sequential coinfection by two of three selected OspC strains (type A, K and N) in nine groups (AA, AK, AN, KA, KK, KN, NA, NK, NN). We assessed competition between strains as the frequency of organ infection by the primary and the secondary strains, and the transmission of bacteria to naïve ticks through four xenodiagnoses. We measured generalist and strain-specific immunoglobulin G, characteristic of the acquired immune response.

Results: We found that regardless of the identity of the strains, the secondary strains were virtually not transmitted to ticks, whereas primary strains were well transmitted. The mechanism was the absence of dispersion into organs by the secondary strain. The immune response developed against the primary strain was inefficient at clearing the bacteria; however, regardless of the identity of the strains, the immune response against the secondary strain for both the specific and generalist antibodies was inexistent.

Conclusions: The strong inhibitory priority effect that we observed suggests that the diversity of strains would disappear quickly if not all conditions are met in nature. The acquired immune response does not seem to be the physiological mechanism responsible for this exclusion. We suggest that rather than to immune response from hosts, some specific ecological conditions such as host diversity and tick phenology are the mechanisms that maintain the diversity of OspC strains in wild population of Borrelia burgdorferi.

Khatchikian, CE, Foley EA, Barbu CM, Ancca-Juarez J, Borrini-Mayori K, Quispe-Machaca V, Naquira C, Brisson D, Levy MZ.  2015.  Population structure of the Chagas disease vector Triatoma infestans in an urban environment. PLoS Neglected Tropical Diseases. 9(2):e0003425. Abstractkhatchikian2015a.pdfWebsite

Chagas disease is a vector-borne disease endemic in Latin America. Triatoma infestans, a common vector of this disease, has recently expanded its range into rapidly developing cities of Latin America. We aim to identify the environmental features that affect the coloniza- tion and dispersal of T. infestans in an urban environment. We amplified 13 commonly used microsatellites from 180 T. infestans samples collected from a sampled transect in the city of Arequipa, Peru, in 2007 and 2011. We assessed the clustering of subpopulations and the effect of distance, sampling year, and city block location on genetic distance among pairs of insects. Despite evidence of genetic similarity, the majority of city blocks are characterized by one dominant insect genotype, suggesting the existence of barriers to dispersal. Our analyses show that streets represent an important barrier to the colonization and dispersion of T. infestans in Arequipa. The genetic data describe a T. infestans infestation history characterized by persistent local dispersal and occasional long-distance migration events that partially parallels the history of urban development.

Khatchikian, CE, Nadelman RB, Nowakowski J, Schwartz I, Levy MZ, Brisson D, Wormser GP.  2015.  Public Health Impact of Strain Specific Immunity to Borrelia burgdorferi. BMC Microbiology. 15:472. Abstractkhatchikian2015c.pdf

Background
Lyme disease, caused by Borrelia burgdorferi, is the most common tick-borne infection in the United States. Although humans can be infected by at least 16 different strains of B. burgdorferi, the overwhelming majority of infections are due to only four strains. It was recently demonstrated that patients who are treated for early Lyme disease develop immunity to the specific strain of B. burgdorferi that caused their infection. The aim of this study is to estimate the reduction in cases of Lyme disease in the United States that may occur as a result of type specific immunity.

Methods
The analysis was performed based on three analytical models that assessed the effects of type specific immunity. Observational data on the frequency with which different B. burgdorferi strains cause human infection in culture-confirmed patients with an initial episode of erythema migrans diagnosed between 1991 and 2005 in the Northeastern United States were used in the analyses.

Results
Assuming a reinfection rate of 3 % and a total incidence of Lyme disease per year of 300,000, the estimated number of averted cases of Lyme disease per year ranges from 319 to 2378 depending on the duration of type specific immunity and the model used.

Conclusion
Given the assumptions of the analyses, this analysis suggests that type specific immunity is likely to have public health significance in the United States.

Khatchikian, CE, Prusinski M, Stone M, Backenson BP, Wang I-N, Foley E, Seifert SN, Levy MZ, Brisson D.  2015.  Recent and rapid population growth and range expansion of the Lyme disease tick vector, Ixodes scapularis, in North America. Evolution. 69(7):1678-1689. Abstractkhatchikian2015b.pdf

Migration is a primary force of biological evolution that alters allele frequencies and introduces novel genetic variants into populations. Recent migration has been proposed as the cause of the emergence of many infectious diseases, including those carried by blacklegged ticks in North America. Populations of blacklegged ticks have established and flourished in areas of North America previously thought to be devoid of this species. The recent discovery of these populations of blacklegged ticks may have resulted from either in situ growth of long-established populations that were maintained at very low densities or by migration and colonization from established populations. These alternative evolutionary hypotheses were investigated using Bayesian phylogeographic approaches in order to infer the origin and migratory history of recently detected blacklegged tick populations in the Northeastern United States. The data and results indicate that newly detected tick populations are not the product of in situ population growth from a previously established population but from recent colonization resulting in a geographic range expansion. This expansion in the geographic range proceeded primarily through progressive and local migration events from southern populations to proximate northern locations although long-distance migration events were also detected.

2014
Khatchikian, CE, Nadelman RB, Nowakowski J, Schwartz I, Wormser GP, Brisson D.  2014.  Evidence for strain-specific immunity in patients treated for early Lyme disease. Infection and Immunity. 82(4):1408-1413. Abstractkhatchikian2014a.pdf

Lyme disease, caused by Borrelia burgdorferi, is the most commonly reported vector-borne disease in the United States. Many patients treated for early Lyme disease incur another infection in subsequent years, suggesting that previous exposure to B. burgdorferi may not elicit a protective immune response. However, identical strains are almost never detected from patients who have been infected multiple times, suggesting that B. burgdorferi exposure may elicit strain-specific immunity. Probabilistic and simulation models assuming biologically realistic data derived from patients in the northeastern United States suggest that patients treated for early Lyme disease develop protective immunity that is strain specific and lasts for at least 6 years.

Selected as article of significant interest.

Vuong, HB, Canham CD, Fonseca DM, Brisson D, Morin PJ, Smouse PE, Ostfeld RS.  2014.  Occurrence and transmission efficiencies of Borrelia burgdorferi ospC types in avian and mammalian wildlife. Infection, Genetics, and Evolution. 27:594–600. Abstractvuong2014a.pdf

Borrelia burgdorferi s.s., the bacterium that causes Lyme disease in North America, circulates among a suite of vertebrate hosts and their tick vector. The bacterium can be differentiated at the outer surface protein C (ospC) locus into 25 genotypes. Wildlife hosts can be infected with a suite of ospC types but knowledge on the transmission efficiencies of these naturally infected hosts to ticks is still lacking. To evaluate the occupancy and detection of ospC types in wildlife hosts, we adapted a likelihood-based species patch occupancy model to test for the occurrence probabilities (ψ - "occupancy") and transmission efficiencies (ε - "detection") of each ospC type. We detected differences in ospC occurrence and transmission efficiencies from the null models with HIS (human invasive strains) types A and K having the highest occurrence estimates, but both HIS and non-HIS types having high transmission efficiencies. We also examined ospC frequency patterns with respect to strains known to be invasive in humans across the host species and phylogenetic groups. We found that shrews and to a lesser extent, birds, were important host groups supporting relatively greater frequencies of HIS to non-HIS types. This novel method of simultaneously assessing occurrence and transmission of ospC types provides a powerful tool in assessing disease risk at the genotypic level in naturally infected wildlife hosts and offers the opportunity to examine disease risk at the community level.

Zhou, W, Brisson D.  2014.  Potentially conflicting selective forces that shape the vls antigenic variation system in Borrelia burgdorferi. Infection, Genetics and Evolution. 27:559–565. Abstractzhou2014a.pdf

Changing environmental conditions present an evolutionary challenge for all organisms. The environment of microbial pathogens, including the adaptive immune responses of the infected host, changes rapidly and is lethal to the pathogen lineages that cannot quickly adapt. The dynamic immune environment creates strong selective pressures favoring microbial pathogen lineages with antigenic variation systems that maximize the antigenic divergence among expressed antigenic variants. However, divergence among expressed antigens may be constrained by other molecular features such as the efficient expression of functional proteins. We computationally examined potential conflicting selection pressures on antigenic variation systems using the vls antigenic variation system in Borrelia burgdorferi as a model system. The vls system alters the sequence of the expressed antigen by recombining gene fragments from unexpressed but divergent 'cassettes' into the expression site, vlsE. The in silico analysis of natural and altered cassettes from seven lineages in the B. burgdorferi sensu lato species complex revealed that sites that are polymorphic among unexpressed cassettes, as well as the insertion/deletion mutations, are organized to maximize divergence among the expressed antigens within the constraints of translational ability and high translational efficiency. This study provides empirical evidence that conflicting selection pressures on antigenic variation systems can limit the potential antigenic divergence in order to maintain proper molecular function.

Richer, LM, Brisson D, Melo R, Ostfeld RS, Zeidner N, Gomes-Solecki M.  2014.  Reservoir Targeted Vaccine Against Borrelia burgdorferi: A New Strategy to Prevent Lyme Disease Transmission. Journal of Infectious Diseases. 18(11):1809-1816. Abstractricher2014.pdf

A high prevalence of infection with Borrelia burgdorferi in ixodid ticks is correlated with a high incidence of Lyme disease. The transmission of B. burgdorferi to humans can be disrupted by targeting 2 key elements in its enzootic cycle: the reservoir host and the tick vector. In a prospective 5-year field trial, we show that oral vaccination of wild white-footed mice resulted in outer surface protein A-specific seropositivity that led to reductions of 23% and 76% in the nymphal infection prevalence in a cumulative, time-dependent manner (2 and 5 years, respectively), whereas the proportion of infected ticks recovered from control plots varied randomly over time. Significant decreases in tick infection prevalence were observed within 3 years of vaccine deployment. Implementation of such a long-term public health measure could substantially reduce the risk of human exposure to Lyme disease.

Leichty, AR, Brisson D.  2014.  Selective Whole Genome Amplification for Re-Sequencing Target Microbial Species from Complex Natural Samples. Genetics. 198(2):473-481. Abstractleichty2014a.pdfdigest_all.txtfile_s2.txt

Population genomic analyses have demonstrated power to address major questions in evolutionary and molecular microbiology. Collecting populations of genomes is hindered in many microbial species by the absence of a cost effective and practical method to collect ample quantities of sufficiently pure genomic DNA for next-generation sequencing. Here we present a simple method to amplify genomes of a target microbial species present in a complex, natural sample. The selective whole genome amplification (SWGA) technique amplifies target genomes using nucleotide sequence motifs that are common in the target microbe genome, but rare in the background genomes, to prime the highly processive phi29 polymerase. SWGA thus selectively amplifies the target genome from samples in which it originally represented a minor fraction of the total DNA. The post-SWGA samples are enriched in target genomic DNA, which are ideal for population resequencing. We demonstrate the efficacy of SWGA using both laboratoryprepared mixtures of cultured microbes as well as a natural host–microbe association. Targeted amplification of Borrelia burgdorferi mixed with Escherichia coli at genome ratios of 1:2000 resulted in. >105-fold amplification of the target genomes with, <6.7-fold amplification of the background. SWGA-treated genomic extracts from Wolbachia pipientis-infected Drosophila melanogaster resulted in up to 70% of high-throughput resequencing reads mapping to the W. pipientis genome. By contrast, 2–9% of sequencing reads were derived from W. pipientis without prior amplification. The SWGA technique results in high sequencing coverage at a fraction of the sequencing effort, thus allowing population genomic studies at affordable costs.

Onder, O, Shao W, Lam H, Brisson D.  2014.  Tracking sources of blood meals using unidentified tandem mass spectral libraries. Nature Protocols. 9(4):842-850. Abstractonder2014a.pdf

Identifying the species on which hematophagous arthropods feed is crucial for studying the factors that affect pathogen distributions and that can aid public health. Here we describe a protocol to identify the species a parasitic arthropod has previously fed upon by identifying the source of the remnants of a previous blood meal via shotgun proteomics and spectral matching. The protocol is a nontargeted approach that uses the entire detected blood proteome for source identification; it does not require a priori knowledge of genome or protein sequences. Instead, reference spectral libraries are compiled from the blood of multiple host species by using SpectraST, which takes ∼4 d; the identification of the species from which a previous blood meal of a hematophagous arthropod was taken is achieved with spectral matching against the reference spectral libraries, which takes approximately another 4 d. This method is robust against random degradation of the blood meal and can identify unknown blood remnants months after the feeding event.

2013
Voordouw, MJ, Tupper H, Onder O, Devevey G, Graves CJ, Kemps BD, Brisson D.  2013.  Reductions in human Lyme disease risk due to the effects of oral vaccination on tick-to-mouse and mouse-to-tick transmission, Apr. Vector Borne Zoonotic Dis. 13(4):203-14., Number 4 AbstractPDFWebsite

Vaccinating wildlife is becoming an increasingly popular method to reduce human disease risks from pathogens such as Borrelia burgdorferi, the causative agent of Lyme disease. To successfully limit human disease risk, vaccines targeting the wildlife reservoirs of B. burgdorferi must be easily distributable and must effectively reduce pathogen transmission from infected animals, given that many animals in nature will be infected prior to vaccination. We assessed the efficacy of an easily distributable oral bait vaccine based on the immunogenic outer surface protein A (OspA) to protect uninfected mice from infection and to reduce transmission from previously infected white-footed mice, an important reservoir host of B. burgdorferi. Oral vaccination of white-footed mice effectively reduces transmission of B. burgdorferi at both critical stages of the Lyme disease transmission cycle. First, oral vaccination of uninfected white-footed mice elicits an immune response that protects mice from B. burgdorferi infection. Second, oral vaccination of previously infected mice significantly reduces the transmission of B. burgdorferi to feeding ticks despite a statistically nonsignificant immune response. We used the estimates of pathogen transmission to and from vaccinated and unvaccinated mice to model the efficacy of an oral vaccination campaign targeting wild white-footed mice. Projection models suggest that the effects of the vaccine on both critical stages of the transmission cycle of B. burgdorferi act synergistically in a positive feedback loop to reduce the nymphal infection prevalence, and thus human Lyme disease risk, well below what would be expected from either effect alone. This study suggests that oral immunization of wildlife with an OspA-based vaccine can be a promising long-term strategy to reduce human Lyme disease risk.

Lerner, MB, Dailey J, Goldsmith BR, Brisson D, Johnson ATC.  2013.  Detecting Lyme disease using antibody-functionalized single-walled carbon nanotube transistors. Biosensors and Bioelectronics. 45:163-167. Abstractlerner2013a.pdf

We developed a novel detection method for osteopontin (OPN), a new biomarker for prostate cancer, by attaching a genetically engineered single-chain variable fragment (scFv) protein with high binding a!nity for OPN to a carbon nanotube "eld-e#ect transistor (NT-FET). Chemical functionalization using diazonium salts is used to covalently attach scFv to NT-FETs, as con"rmed by atomic force microscopy, while preserving the activity of the biological binding site for OPN. Electron transport measurements indicate that functionalized NT-FET may be used to detect the binding of OPN to the complementary scFv protein. A concentration-dependent increase in the source!drain current is observed in the regime of clinical signi"cance, with a detection limit of approximately 30 fM. The scFv-NT hybrid devices exhibit selectivity for OPN over other control proteins. These devices respond to the presence of OPN in a background of concentrated bovine serum albumin, without loss of signal. On the basis of these observations, the detection mechanism is attributed to changes in scattering at scFv protein-occupied defect sites on the carbon nanotube sidewall. The functionalization procedure described here is expected to be generalizable to any antibody containing an accessible amine group and to result in biosensors appropriate for detection of corresponding complementary proteins at fM concentrations.

Brisson, D, Zhou W, Jutras B, Casjens S, Stevenson B.  2013.  Distribution of Lyme disease spirochete cp32 prophages and natural diversity among their lipoprotein-encoding erp loci. Applied and Environmental Microbiology. 79:4115-4128. Abstractbrisson2013a.pdf

Lyme disease spirochetes possess complex genomes, consisting of a main chromosome and 20 or more smaller replicons. Among those small DNAs are the cp32 elements, a family of prophages that replicate as circular episomes. All complete cp32s contain an erp locus, which encodes surface-exposed proteins. Sequences were compared for all 193 erp alleles carried by 22 different strains of Lyme disease-causing spirochete to investigate their natural diversity and evolutionary histories. These included multiple iso- lates from a focus where Lyme disease is endemic in the northeastern United States and isolates from across North America and Europe. Bacteria were derived from diseased humans and from vector ticks and included members of 5 different Borrelia geno- species. All erp operon 5=-noncoding regions were found to be highly conserved, as were the initial 70 to 80 bp of all erp open reading frames, traits indicative of a common evolutionary origin. However, the majority of the protein-coding regions are highly diverse, due to numerous intra- and intergenic recombination events. Most erp alleles are chimeras derived from se- quences of closely related and distantly related erp sequences and from unknown origins. Since known functions of Erp surface proteins involve interactions with various host tissue components, this diversity may reflect both their multiple functions and the abilities of Lyme disease-causing spirochetes to successfully infect a wide variety of vertebrate host species.

Onder, O, Shao W, Kemps B, Lam H, Brisson D.  2013.  Identifying sources of tick blood meals using unidentified tandem mass spectral libraries. Nature Communications. 4:1746. AbstractPDF

Rapid and reliable identification of the vertebrate species on which a disease vector previously parasitized is imperative to study ecological factors that affect pathogen distribution and can aid the development of public health programs. Here we describe a proteome profiling technique designed to identify the source of blood meals of haematophagous arthropods. This method employs direct spectral matching and thus does not require a priori knowledge of any genetic or protein sequence information. Using this technology, we detect remnants of blood in blacklegged ticks (Ixodes scapularis) and correctly determine the vertebrate species from which the blood was derived, even 6 months after the tick had fed. This biological fingerprinting methodology is sensitive, fast, cost-effective and can potentially be adapted for other biological and medical applications when existing genome-based methods are impractical or ineffective.

Graves, C, Ros VID, Stevenson B, Sniegowski P, Brisson D.  2013.  Natural selection promotes antigenic evolvability. PLoS Pathogens. 9(11):e1003766. Abstractgraves2013a.pdfWebsite

The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed ‘cassettes’ that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios) and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish chronic infections.

Foley, EA, Khatchikian CE, Hwang J, Ancca-Juárez J, Borrini-Mayori K, Quıspe-Machaca VR, Levy MZ, Brisson D.  2013.  Population structure of the Chagas disease vector, Triatoma infestans, in an urban environment. Molecular Ecology. 22:5162–5171. Abstractfoley2013a.pdf

The increasing rate of biological invasions resulting from human transport or human- mediated changes to the environment has had devastating ecological and public health consequences. The kissing bug, Triatoma infestans, has dispersed through the Peruvi- an city of Arequipa. The biological invasion of this insect has resulted in a public health crisis, putting thousands of residents of this city at risk of infection by Trypano- soma cruzi and subsequent development of Chagas disease. Here, we show that popu- lations of Tria. infestans in geographically distinct districts within and around this urban centre share a common recent evolutionary history although current gene flow is restricted even between proximal sites. The population structure among the Tria. infe- stans in different districts is not correlated with the geographical distance between dis- tricts. These data suggest that migration among the districts is mediated by factors beyond the short-range migratory capabilities of Tria. infestans and that human move- ment has played a significant role in the structuring of the Tria. infestans population in the region. Rapid urbanization across southern South America will continue to cre- ate suitable environments for Tria. infestans, and knowledge of its urban dispersal pat- terns may play a fundamental role in mitigating human disease risk.

2012
Tripepi, M, You J, Temel S, Onder O, Brisson D, Pohlschroder M.  2012.  N-glycosylation of Haloferax volcanii flagellins requires known Agl proteins and is essential for biosynthesis of stable flagella, Sep. J Bacteriol. 194:4876-87., Number 18 AbstractPDFWebsite

N-glycosylation, a posttranslational modification required for the accurate folding and stability of many proteins, has been observed in organisms of all domains of life. Although the haloarchaeal S-layer glycoprotein was the first prokaryotic glycoprotein identified, little is known about the glycosylation of other haloarchaeal proteins. We demonstrate here that the glycosylation of Haloferax volcanii flagellins requires archaeal glycosylation (Agl) components involved in S-layer glycosylation and that the deletion of any Hfx. volcanii agl gene impairs its swimming motility to various extents. A comparison of proteins in CsCl density gradient centrifugation fractions from supernatants of wild-type Hfx. volcanii and deletion mutants lacking the oligosaccharyltransferase AglB suggests that when the Agl glycosylation pathway is disrupted, cells lack stable flagella, which purification studies indicate consist of a major flagellin, FlgA1, and a minor flagellin, FlgA2. Mass spectrometric analyses of FlgA1 confirm that its three predicted N-glycosylation sites are modified with covalently linked pentasaccharides having the same mass as that modifying its S-layer glycoprotein. Finally, the replacement of any of three predicted N-glycosylated asparagines of FlgA1 renders cells nonmotile, providing direct evidence for the first time that the N-glycosylation of archaeal flagellins is critical for motility. These results provide insight into the role that glycosylation plays in the assembly and function of Hfx. volcanii flagella and demonstrate that Hfx. volcanii flagellins are excellent reporter proteins for the study of haloarchaeal glycosylation processes.

Schwanz, LE, Previtali MA, Gomes-Solecki M, Brisson D, Ostfeld RS.  2012.  Immunochallenge reduces risk sensitivity during foraging in white-footed mice, Jan. Animal Behaviour. 83:155-161., Number 1 AbstractPDFWebsite

Foraging behaviour has the potential to impact interactions among species in a community and is influenced, in part, by individual condition and fear of predation. These relationships are exemplified by white-footed mice, Peromyscus leucopus, in mixed hardwood forest communities of the northeastern U.S.A., whose foraging behaviour can influence the population ecology of several prey items and the disease ecology of human Lyme disease and its tick vector. We examined whether dosage of an immunogen influenced foraging behaviour in wild white-footed mice at foraging arenas. Low-dose mice preferentially favoured safe (covered) food patches over risky food patches, whereas high-dose mice showed no preference based on patch safety. Immunochallenge did not alter foraging time in patches of equal risk. The results reveal fitness costs of an immune response, namely that immunochallenged mice favour increased energy consumption over safety from predation, presumably leading to greater mortality. Acceptance of risky patches for foraging by immunochallenged mice suggests that mice mounting this immune response will forage in a greater proportion of their home ranges and encounter a greater number of patchily distributed prey items and ticks carrying pathogens. (C) 2011 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

Khatchikian, CE, Prusinski M, Stone M, Backenson PB, I.N. Wang, M.Z. Levy, Brisson D.  2012.  Contemporary population expansion of blacklegged Ticks (Ixodes scapularis). Ecosphere. 3:10. AbstractPDFWebsite

The population densities of many organisms have changed dramatically in recent history. Increases in the population density of medically relevant organisms are of particular importance to public health as they are often correlated with the emergence of infectious diseases in human populations. Our aim is to delineate increases in density of a common disease vector in North America, the blacklegged tick, and to identify the environmental factors correlated with these population dynamics. Empirical data that capture the growth of a population are often necessary to identify environmental factors associated with these dynamics. We analyzed temporally- and spatially-structured field collected data in a geographical information systems framework to describe the population growth of blacklegged ticks (Ixodes scapularis) and to identify environmental and climatic factors correlated with these dynamics. The density of the ticks increased throughout the study’s temporal and spatial ranges. Tick density increases were positively correlated with mild temperatures, low precipitation, low forest cover, and high urbanization. Importantly, models that accounted for these environmental factors accurately forecast future tick densities across the region. Tick density increased annually along the south-to-north gradient. These trends parallel the increases in human incidences of diseases commonly vectored by I. scapularis. For example, I. scapularis densities are correlated with human Lyme disease incidence, albeit in a non-linear manner that disappears at low tick densities, potentially indicating that a threshold tick density is needed to support epidemiologically-relevant levels of the Lyme disease bacterium. Our results demonstrate a connection between the biogeography of this species and public health.

Nadelman, RB, Hanincova K, Mukherjee P, Liveris D, Nowakowski J, McKenna D, Brisson D, Cooper D, Bittker S, Madison G, Holmgren D, Schwartz I, Wormser GP.  2012.  Differentiation of Reinfection from Relapse in Lyme Disease Patients with Recurrent Erythema Migrans Using Molecular Microbiologic Tools. New England Journal of Medicine. 367:1883-1890. Abstract

Background
Erythema migrans is the most common manifestation of Lyme disease. Recurrences are not uncommon, and although they are usually attributed to reinfection rather than relapse of the original infection, this remains somewhat controversial. We used molecular typing of Borrelia burgdorferi isolates obtained from patients with culture-confirmed episodes of erythema migrans to distinguish between relapse and reinfection.
Methods
We determined the genotype of the gene encoding outer-surface protein C (ospC) of B. burgdorferi strains detected in cultures of skin or blood specimens obtained from patients with consecutive episodes of erythema migrans. After polymerase-chain- reaction amplification, ospC genotyping was performed by means of reverse line- blot analysis or DNA sequencing of the nearly full-length gene. Most strains were further analyzed by determining the genotype according to the 16S–23S ribosomal RNA intergenic spacer type, multilocus sequence typing, or both. Patients received standard courses of antibiotics for erythema migrans.
Results
B. burgdorferi isolates obtained from 17 patients who received a diagnosis of ery- thema migrans between 1991 and 2011 and who had 22 paired episodes of this lesion (initial and second episodes) were available for testing. The ospC genotype was found to be different at each initial and second episode. Apparently identical genotypes were identified on more than one occasion in only one patient, at the first and third episodes, 5 years apart, but different genotypes were identified at the second and fourth episodes.
Conclusions
None of the 22 paired consecutive episodes of erythema migrans were associated with the same strain of B. burgdorferi on culture. Our data show that repeat episodes of erythema migrans in appropriately treated patients were due to reinfection and not relapse. (Funded by the National Institutes of Health and the William and Sylvia Silberstein Foundation.)