Kolokotronis, Sergios-Orestis

Kolokotronis, Sergios-Orestis

Biography

Dr. Sergios-Orestis Kolokotronis is an Assistant Professor in the Department of Epidemiology and Biostatistics in the School of Public Health at SUNY Downstate Medical Center, Brooklyn, NY. Dr. Kolokotronis graduated from Université Paris-Sud XI (BS, Biology; Minor: Mathematical Biology) and Columbia University (MA/MPhil/PhD, Ecology & Evolutionary Biology). As a postdoctoral fellow at the American Museum of Natural History’s Sackler Institute for Comparative Genomics he researched the evolution through time of pathogens and their close relatives (funded by DARPA) and served as the Research Coordinator of the DNA Barcoding Initiative (funded by the Alfred P. Sloan Foundation). He applies evolutionary thinking to questions on the evolution and adaptation of microbial pathogens, their vectors, and reservoir species using genomics and bioinformatics. Organismal systems of interest include RNA viruses, Mycobacterium tuberculosis, MRSA, and eukaryotic parasites, such as malaria and trypanosomes. His latest interests include the microbial ecological context of pathogen transmission and persistence, e.g. microbiomes of ticks and urban birds, and how the urban and industrial environment intensifies natural selection for antibiotic, metal, and pollutant resistance of microbial communities (employing metagenomics). Before joining the SUNY Downstate community he was a faculty member at Fordham University and Barnard College, Columbia University, where he taught a variety of undergraduate and graduate courses and supervised students. Dr. Kolokotronis holds faculty appointments in the College of Medicine (Division of Infectious Diseases, Department of Medicine, and Department of Cell Biology). His lab is based in the Institute for Genomic Health.

Publication Search Results

Now showing 1 - 10 of 51

Open Access
No Observed Effect of Landscape Fragmentation on Pathogen Infection Prevalence in Blacklegged Ticks (Ixodes scapularis) in the Northeastern United States
(Public Library of Science (PLoS), 2015-10-02) Zolnik, Christine P.; Falco, Richard C.; Kolokotronis, Sergios-Orestis; Daniels, Thomas J.
Pathogen prevalence within blacklegged ticks (Ixodes scapularis Say, 1821) tends to vary across sites and geographic regions, but the underlying causes of this variation are not well understood. Efforts to understand the ecology of Lyme disease have led to the proposition that sites with higher host diversity will result in lower disease risk due to an increase in the abundance of inefficient reservoir species relative to the abundance of species that are highly competent reservoirs. Although the Lyme disease transmission cycle is often cited as a model for this "dilution effect hypothesis", little empirical evidence exists to support that claim. Here we tested the dilution effect hypothesis for two pathogens transmitted by the blacklegged tick along an urban-to-rural gradient in the northeastern United States using landscape fragmentation as a proxy for host biodiversity. Percent impervious surface and habitat fragment size around each site were determined to assess the effect of landscape fragmentation on nymphal blacklegged tick infection with Borrelia burgdorferi and Anaplasma phagocytophilum. Our results do not support the dilution effect hypothesis for either pathogen and are in agreement with the few studies to date that have tested this idea using either a landscape proxy or direct measures of host biodiversity.
Open Access
Random Addition Concatenation Analysis: A Novel Approach to the Exploration of Phylogenomic Signal Reveals Strong Agreement between Core and Shell Genomic Partitions in the Cyanobacteria
(Oxford University Press (OUP), 2011-11-16) Narechania, Apurva; Baker, Richard H.; Sit, Ryan; Kolokotronis, Sergios-Orestis; DeSalle, Rob; Planet, Paul J.
Recent whole-genome approaches to microbial phylogeny have emphasized partitioning genes into functional classes, often focusing on differences between a stable core of genes and a variable shell. To rigorously address the effects of partitioning and combining genes in genome-level analyses, we developed a novel technique called Random Addition Concatenation Analysis (RADICAL). RADICAL operates by sequentially concatenating randomly chosen gene partitions starting with a single-gene partition and ending with the entire genomic data set. A phylogenetic tree is built for every successive addition, and the entire process is repeated creating multiple random concatenation paths. The result is a library of trees representing a large variety of differently sized random gene partitions. This library can then be mined to identify unique topologies, assess overall agreement, and measure support for different trees. To evaluate RADICAL, we used 682 orthologous genes across 13 cyanobacterial genomes. Despite previous assertions of substantial differences between a core and a shell set of genes for this data set, RADICAL reveals the two partitions contain congruent phylogenetic signal. Substantial disagreement within the data set is limited to a few nodes and genes involved in metabolism, a functional group that is distributed evenly between the core and the shell partitions. We highlight numerous examples where RADICAL reveals aspects of phylogenetic behavior not evident by examining individual gene trees or a "'total evidence" tree. Our method also demonstrates that most emergent phylogenetic signal appears early in the concatenation process. The software is freely available at http://desalle.amnh.org.
Open Access
Episodic Diversifying Selection Shaped the Genomes of Gibbon Ape Leukemia Virus and Related Gammaretroviruses
(American Society for Microbiology, 2016-02-15) Alfano, Niccolò; Kolokotronis, Sergios-Orestis; Tsangaras, Kyriakos; Roca, Alfred L.; Xu, Wenqin; Eiden, Maribeth V.; Greenwood, Alex D.
Gibbon ape leukemia viruses (GALVs) are part of a larger group of pathogenic gammaretroviruses present across phylogenetically diverse host species of Australasian mammals. Despite the biomedical utility of GALVs as viral vectors and in cancer gene therapy, full genome sequences have not been determined for all of the five identified GALV strains, nor has a comprehensive evolutionary analysis been performed. We therefore generated complete genomic sequences for each GALV strain using hybridization capture and high-throughput sequencing. The four strains of GALV isolated from gibbons formed a monophyletic clade that was closely related to the woolly monkey virus (WMV), which is a GALV strain that likely originated in a gibbon host. The GALV-WMV clade in turn formed a sister group to the koala retroviruses (KoRVs). Genomic signatures of episodic diversifying selection were detected among the gammaretroviruses with concentration in the env gene across the GALV strains that were particularly oncogenic and KoRV strains that were potentially exogenous, likely reflecting their adaptation to the host immune system. In vitro studies involving vectors chimeric between GALV and KoRV-B established that variable regions A and B of the surface unit of the envelope determine which receptor is used by a viral strain to enter host cells. Importance: The gibbon ape leukemia viruses (GALVs) are among the most medically relevant retroviruses due to their use as viral vectors for gene transfer and in cancer gene therapy. Despite their importance, full genome sequences have not been determined for the majority of primate isolates, nor has comprehensive evolutionary analysis been performed, despite evidence that the viruses are facing complex selective pressures associated with cross-species transmission. Using hybridization capture and high-throughput sequencing, we report here the full genome sequences of all the GALV strains and demonstrate that diversifying selection is acting on them, particularly in the envelope gene in functionally important domains, suggesting that host immune pressure is shaping GALV evolution.
Open Access
Testing the Effectiveness of an International Conservation Agreement: Marketplace Forensics and CITES Caviar Trade Regulation
(Public Library of Science (PLoS), 2012-07-25) Doukakis, Phaedra; Pikitch, Ellen K.; Rothschild, Anna; DeSalle, Rob; Amato, George; Kolokotronis, Sergios-Orestis
Background: The international wildlife trade is a key threat to biodiversity. Temporal genetic marketplace monitoring can determine if wildlife trade regulation efforts such as the Convention on International Trade in Endangered Species (CITES) are succeeding. Protected under CITES effective 1997, sturgeons and paddlefishes, the producers of black caviar, are flagship CITES species. Methodology/principal findings: We test whether CITES has limited the amount of fraudulent black caviar reaching the marketplace. Using mitochondrial DNA-based methods, we compare mislabeling in caviar and meat purchased in the New York City area pre and post CITES listing. Our recent sampling of this market reveals a decrease in mislabeled caviar (2006-2008; 10%; n = 90) compared to pre-CITES implementation (1995-1996; 19%; n = 95). Mislabeled caviar was found only in online purchase (n = 49 online/41 retail). Conclusions/significance: Stricter controls on importing and exporting as per CITES policies may be having a positive conservation effect by limiting the amount of fraudulent caviar reaching the marketplace. Sturgeons and paddlefishes remain a conservation priority, however, due to continued overfishing and habitat degradation. Other marine and aquatic species stand to benefit from the international trade regulation that can result from CITES listing.
Open Access
Emergence of the Epidemic Methicillin-Resistant Staphylococcus aureus Strain USA300 Coincides with Horizontal Transfer of the Arginine Catabolic Mobile Element and speG-mediated Adaptations for Survival on Skin
(American Society for Microbiology, 2013-12-31) Planet, Paul J.; LaRussa, Samuel J.; Dana, Ali; Smith, Hannah; Xu, Amy; Ryan, Chanelle; Uhlemann, Anne-Catrin; Boundy, Sam; Goldberg, Julia; Narechania, Apurva; Kulkarni, Ritwij; Ratner, Adam J.; Geoghegan, Joan A.; Kolokotronis, Sergios-Orestis; Prince, Alice
The arginine catabolic mobile element (ACME) is the largest genomic region distinguishing epidemic USA300 strains of methicillin-resistant Staphylococcus aureus (MRSA) from other S. aureus strains. However, the functional relevance of ACME to infection and disease has remained unclear. Using phylogenetic analysis, we have shown that the modular segments of ACME were assembled into a single genetic locus in Staphylococcus epidermidis and then horizontally transferred to the common ancestor of USA300 strains in an extremely recent event. Acquisition of one ACME gene, speG, allowed USA300 strains to withstand levels of polyamines (e.g., spermidine) produced in skin that are toxic to other closely related S. aureus strains. speG-mediated polyamine tolerance also enhanced biofilm formation, adherence to fibrinogen/fibronectin, and resistance to antibiotic and keratinocyte-mediated killing. We suggest that these properties gave USA300 a major selective advantage during skin infection and colonization, contributing to the extraordinary evolutionary success of this clone. Importance: Over the past 15 years, methicillin-resistant Staphylococcus aureus (MRSA) has become a major public health problem. It is likely that adaptations in specific MRSA lineages (e.g., USA300) drove the spread of MRSA across the United States and allowed it to replace other, less-virulent S. aureus strains. We suggest that one major factor in the evolutionary success of MRSA may have been the acquisition of a gene (speG) that allows S. aureus to evade the toxicity of polyamines (e.g., spermidine and spermine) that are produced in human skin. Polyamine tolerance likely gave MRSA multiple fitness advantages, including the formation of more-robust biofilms, increased adherence to host tissues, and resistance to antibiotics and killing by human skin cells.
Open Access
Fine-scale genetic analysis of the exploited Nile monitor (Varanus niloticus) in Sahelian Africa
(Springer Science and Business Media LLC, 2015-03-28) Dowell, Stephanie A; de Buffrénil, Vivian; Kolokotronis, Sergios-Orestis; Hekkala, Evon R
Background: Overexploitation of wildlife populations results in direct consequences, such as extinction and local extirpation, as well as indirect effects including genetic diversity loss and changes in genetic structure. A clear understanding of the underlying genetic patterns of harvested species is necessary for sustainable management. The Nile monitor (Varanus niloticus) is a commercially valuable species in the international leather industry, with the highest levels of exploitation concentrated throughout Sahelian Africa. In this study, we examined the fine-scale genetic patterns of V. niloticus populations in the Sahel, with the expectation that the genetic structure would correspond to riverine drainage basins. The analyses were based on genotypes at 11 microsatellite loci for 318 individuals, spanning three separate watersheds throughout the Sahel. Results: Our analyses identified four genetic clusters throughout the region, one of which (the westernmost population) exhibited very high levels of genetic differentiation (FST = 0.47). Contrary to our expectation, the largest genetic break occurred within a single watershed, the Niger basin, rather than between watersheds. However, other localities displayed evidence of reduced gene flow between watershed boundaries. Across methods, the westernmost population exhibited lower estimates of N e as well as lower levels of genetic diversity compared to the other inferred populations. While we did not detect evidence for recent population bottlenecks, our analyses indicated historic population declines around 1,000-1,800 years ago. Conclusion: We found that the underlying genetic structure of Varanus niloticus across Sahelian Africa reflects historic as well as present-day patterns of riverine drainages. The high degree of differentiation found for the westernmost population indicates the presence of a separate lineage, and should be taken into consideration when setting harvest limits. The historic population decline for two of the populations corresponds to a drastic expansion of an ancient human civilization in the region, suggesting that human exploitation of V. niloticus has a longer history than previously thought.
Open Access
Pre-detection history of extensively drug-resistant tuberculosis in KwaZulu-Natal, South Africa
(Proceedings of the National Academy of Sciences, 2019-10-28) Brown, Tyler S.; Challagundla, Lavanya; Baugh, Evan H.; Omar, Shaheed Vally; Mustaev, Arkady; Auld, Sara C.; Shah, N. Sarita; Kreiswirth, Barry N.; Brust, James C. M.; Nelson, Kristin N.; Narechania, Apurva; Kurepina, Natalia; Mlisana, Koleka; Bonneau, Richard; Eldholm, Vegard; Ismail, Nazir; Kolokotronis, Sergios-Orestis; Robinson, D. Ashley; Gandhi, Neel R.; Mathema, Barun
Antimicrobial-resistant (AMR) infections pose a major threat to global public health. Similar to other AMR pathogens, both historical and ongoing drug-resistant tuberculosis (TB) epidemics are characterized by transmission of a limited number of predominant Mycobacterium tuberculosis (Mtb) strains. Understanding how these predominant strains achieve sustained transmission, particularly during the critical period before they are detected via clinical or public health surveillance, can inform strategies for prevention and containment. In this study, we employ whole-genome sequence (WGS) data from TB clinical isolates collected in KwaZulu-Natal, South Africa to examine the pre-detection history of a successful strain of extensively drug-resistant (XDR) TB known as LAM4/KZN, first identified in a widely reported cluster of cases in 2005. We identify marked expansion of this strain concurrent with the onset of the generalized HIV epidemic 12 y prior to 2005, localize its geographic origin to a location in northeastern KwaZulu-Natal ∼400 km away from the site of the 2005 outbreak, and use protein structural modeling to propose a mechanism for how strain-specific rpoB mutations offset fitness costs associated with rifampin resistance in LAM4/KZN. Our findings highlight the importance of HIV coinfection, high preexisting rates of drug-resistant TB, human migration, and pathoadaptive evolution in the emergence and dispersal of this critical public health threat. We propose that integrating whole-genome sequencing into routine public health surveillance can enable the early detection and local containment of AMR pathogens before they achieve widespread dispersal.
Open Access
Combining genetic and distributional approaches to sourcing introduced species: a case study on the Nile monitor (Varanus niloticus) in Florida
(The Royal Society, 2016-04) Dowell, Stephanie A.; Wood, Jared P.; Campbell, Todd S.; Kolokotronis, Sergios-Orestis; Hekkala, Evon R.
Three separate breeding populations of the Nile monitor (Varanus niloticus) have been identified in Florida, USA, located in Cape Coral, West Palm Beach and Homestead Air Reserve Base. This large, predatory lizard could have negative effects on Florida's native wildlife. Here, we infer the source of the introduced populations using genetic and statistical approaches, as well as estimate the potential non-native distribution of V. niloticus in North America. We collected genetic data from 25 Florida individuals as well as utilized genetic datasets from reference individuals spanning the full native distribution throughout sub-Saharan Africa. Using occurrence data from the inferred source population and the full species range, we built ecological niche models (ENMs) and projected them onto North America to determine regions with suitable climate. Our results indicated that the introduced populations resulted from three separate introduction events, and all originated from the southern coastal region of West Africa. The ENM built from the West African source population predicted only the southernmost portions of North America to be suitable. Conversely, the model derived from the full species' range predicted suitable climates across a large portion of the United States. This information can be used to focus management and eradication efforts.
Open Access
Zoonotic Viruses Associated with Illegally Imported Wildlife Products
(Public Library of Science (PLoS), 2012-01-10) Smith, Kristine M.; Anthony, Simon J.; Switzer, William M.; Epstein, Jonathan H.; Seimon, Tracie; Jia, Hongwei; Sanchez, Maria D.; Huynh, Thanh Thao; Galland, G. Gale; Shapiro, Sheryl E.; Sleeman, Jonathan M.; McAloose, Denise; Stuchin, Margot; Amato, George; Kolokotronis, Sergios-Orestis; Lipkin, W. Ian; Karesh, William B.; Daszak, Peter; Marano, Nina
The global trade in wildlife has historically contributed to the emergence and spread of infectious diseases. The United States is the world's largest importer of wildlife and wildlife products, yet minimal pathogen surveillance has precluded assessment of the health risks posed by this practice. This report details the findings of a pilot project to establish surveillance methodology for zoonotic agents in confiscated wildlife products. Initial findings from samples collected at several international airports identified parts originating from nonhuman primate (NHP) and rodent species, including baboon, chimpanzee, mangabey, guenon, green monkey, cane rat and rat. Pathogen screening identified retroviruses (simian foamy virus) and/or herpesviruses (cytomegalovirus and lymphocryptovirus) in the NHP samples. These results are the first demonstration that illegal bushmeat importation into the United States could act as a conduit for pathogen spread, and suggest that implementation of disease surveillance of the wildlife trade will help facilitate prevention of disease emergence.
Open Access
Mitochondrial genomes reveal an explosive radiation of extinct and extant bears near the Miocene-Pliocene boundary
(Springer Science and Business Media LLC, 2008-07-28) Krause, Johannes; Unger, Tina; Noçon, Aline; Malaspinas, Anna-Sapfo; Kolokotronis, Sergios-Orestis; Stiller, Mathias; Soibelzon, Leopoldo; Spriggs, Helen; Dear, Paul H; Briggs, Adrian W; Bray, Sarah CE; O'Brien, Stephen J; Rabeder, Gernot; Matheus, Paul; Cooper, Alan; Slatkin, Montgomery; Pääbo, Svante; Hofreiter, Michael
Background: Despite being one of the most studied families within the Carnivora, the phylogenetic relationships among the members of the bear family (Ursidae) have long remained unclear. Widely divergent topologies have been suggested based on various data sets and methods. Results: We present a fully resolved phylogeny for ursids based on ten complete mitochondrial genome sequences from all eight living and two recently extinct bear species, the European cave bear (Ursus spelaeus) and the American giant short-faced bear (Arctodus simus). The mitogenomic data yield a well-resolved topology for ursids, with the sloth bear at the basal position within the genus Ursus. The sun bear is the sister taxon to both the American and Asian black bears, and this clade is the sister clade of cave bear, brown bear and polar bear confirming a recent study on bear mitochondrial genomes. Conclusion: Sequences from extinct bears represent the third and fourth Pleistocene species for which complete mitochondrial genomes have been sequenced. Moreover, the cave bear specimen demonstrates that mitogenomic studies can be applied to Pleistocene fossils that have not been preserved in permafrost, and therefore have a broad application within ancient DNA research. Molecular dating of the mtDNA divergence times suggests a rapid radiation of bears in both the Old and New Worlds around 5 million years ago, at the Miocene-Pliocene boundary. This coincides with major global changes, such as the Messinian crisis and the first opening of the Bering Strait, and suggests a global influence of such events on species radiations.