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Research products from students and faculty in the Center.  Student co-authors are indicated with (§) for undergraduates and (‡) for graduates; postdocs are indicated by (*).

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Monteiro, E.F., C. Fernandez-Becerra, M.S. Araujo, M.R. Messias, L.S. Ozaki, A.M. Ribeiro de Castro Duarte, M.G. Bueno, J.L. Catao-Dias, C.R. Fernandes Chagas, B.S. Mathias, M. Gomes dos Santos, S.V. Santos, M.M. Holcman, J.C. Souza Jr., and K. Kirchgatter (2020) Naturally acquired humoral immunity against malaria parasites in non-human primates from the Brazilian Amazon, Cerrado and Atlantic Forest. Pathogens 9:525.
https://doi.org/10.3390/pathogens9070525

Non-human primates (NHPs) have been shown to be infected by parasites of the genus Plasmodium, the etiological agent of malaria in humans, creating potential risks of zoonotic transmission. Plasmodium brasilianum, a parasite species similar to P. malariae of humans, have been described in NHPs from Central and South America, including Brazil. The merozoite surface protein 1 (MSP1), besides being a malaria vaccine candidate, is highly immunogenic. Due to such properties, we tested this protein for the diagnosis of parasite infection. We used recombinant proteins of P. malariae MSP1, as well as of P. falciparum and P. vivax, for the detection of antibodies anti-MSP1 of these parasite species, in the sera of NHPs collected in different regions of Brazil. About 40% of the NHP sera were confirmed as reactive to the proteins of one or more parasite species. A relatively higher number of reactive sera was found in animals from the Atlantic Forest than those from the Amazon region, possibly reflecting the former more intense parasite circulation among NHPs due to their proximity to humans at a higher populational density. The presence of Plasmodium positive NHPs in the surveyed areas, being therefore potential parasite reservoirs, needs to be considered in any malaria surveillance program.

Rosenberg, M.S. (2020) A fresh look at the biodiversity lexicon for fiddler crabs (Decapoda: Brachyura: Ocypodidae). Part 2: Biogeography. Journal of Crustacean Biology 40:364-383.
https://doi.org/10.1093/jcbiol/ruaa029

Fiddler crabs (Ocypodidae Rafinesque, 1815) occupy most tropical and semitropical coastlines worldwide where they are keystone species and ecosystem engineers. I present updated ranges for all 105 species and explore both global and local patterns to establish a baseline distribution as species ranges begin to shift with climate change. Globally, the average number of species per occupied coastline is five, with only limited allopatry observed within the group. Cohesive species assemblages were used to define four zoogeographic fiddler realms containing 24 provinces and transitional zones. These regions can serve as units of study when trying to explore which factors influence the distribution of coastal species.

Garg, A., D. Leipe, and P. Uetz (2019) The disconnect between DNA and species names: Lessons from reptile species in the NCBI taxonomy database. Zootaxa 4706:401-407.
https://doi.org/10.11646/zootaxa.4706.3.1

We compared the species names in the Reptile Database, a dedicated taxonomy database, with those in the NCBI taxonomy database, which provides the taxonomic backbone for the GenBank sequence database. About 67% of the known ~11,000 reptile species are represented with at least one DNA sequence and a binary species name in GenBank. However, a common problem arises through the submission of preliminary species names (such as “Pelomedusa sp. A CK-2014”) to GenBank and thus the NCBI taxonomy. These names cannot be assigned to any accepted species names and thus create a disconnect between DNA sequences and species. While these names of unknown taxonomic meaning sometimes get updated, often they remain in GenBank which now contains sequences from ~1,300 such “putative” reptile species tagged by informal names (~15% of its reptile names). We estimate that NCBI/GenBank probably contain tens of thousands of such “disconnected” entries. We encourage sequence submitters to update informal species names after they have been published, otherwise the disconnect will cause increasing confusion and possibly misleading taxonomic conclusions.

Uetz, P., S. Cherikh, G. Shea, I. Ineich, P.D. Campbell, I.V. Doronin, J. Rosado, A. Wynn, K.A. Tighe, R. McDiarmid, J.L. Lee, G. Köhler, R. Ellis, P. Doughty, C.J. Raxworthy, L. Scheinberg, A. Resetar, M. Sabaj, G. Schneider, M. Franzen, F. Glaw, W. Böhme, S. Schweiger, R. Gemel, P. Couper, A. Amey, E. Dondorp, G. Ofer, S. Meiri, and V. Wallach (2019) A global catalog of primary reptile type specimens. Zootaxa 4695:438-450.
https://doi.org/10.11646/zootaxa.4695.5.2

We present information on primary type specimens for 13,282 species and subspecies of reptiles compiled in the Reptile Database, that is, holotypes, neotypes, lectotypes, and syntypes. These represent 99.4% of all 13,361 currently recognized taxa (11,050 species and 2311 subspecies). Type specimens of 653 taxa (4.9%) are either lost or not located, were never designated, or we did not find any information about them. 51 species are based on iconotypes. To map all types to physical Global type catalog of reptiles collections we have consolidated all synonymous and ambiguous collection acronyms into an unambiguous list of 364 collections holding these primary types. The 10 largest collections possess more than 50% of all (primary) reptile types, the 36 largest collections possess more than 10,000 types and the largest 73 collections possess over 90% of all types. Of the 364 collections, 107 hold type specimens of only 1 species or subspecies. Dozens of types are still in private collections. In order to increase their utility, we recommend that the description of type specimens be supplemented with data from high-resolution images and CT-scans, and clear links to tissue samples and DNA sequence data (when available). We request members of the herpetological community provide us with any missing type information to complete the list.

Rosenberg, M.S. (2019) A fresh look at the biodiversity lexicon for fiddler crabs (Decapoda: Brachyura: Ocypodidae). Part 1: Taxonomy. Journal of Crustacean Biology 39:729-738.
https://doi.org/10.1093/jcbiol/ruz057

Fiddler crabs (Ocypodidae) have gone through a gradual series of taxonomic revisions and refinements over the last 40 years, culminating most recently with an expansion from a single genus into eleven different genera. I examine the opportunities presented by these revisions with respect to establishing formal names for previously established clades at a variety of taxonomic levels that were otherwise previously impossible to name due to historical compression of these crabs into a single genus, including the establishment or reestablishment of three tribes (Ucini, Gelasimini, and Minucini) and ten subgenera: Uca (Uca), Uca (Acanthoplax), Gelasimus (Gelasimus), Gelasimus (Mesuca), Austruca (Austruca), Austruca (Cuneatuca), Austruca (Sinduca), Tubuca (Tubuca), Tubuca (Australuca), and Tubuca (Angustuca). A previously overlooked synonymy between Gelasimus excisa (Nobili, 1906) and G. neocultrimana (Bott, 1973) is discussed, and the former name is adopted as valid.

Zhu, B., L.C. Macleod, E. Newsome, J. Liu, and P. Xu (2019) Aggregatibacter actinomycetemcomitans mediates protection of Porphyromonas gingivalis from Streptococcus sanguinis hydrogen peroxide production in multi-species biofilms. Scientific Reports 9:4944.
https://doi.org/10.1038/s41598-019-41467-9

Mixed species biofilms are shaped and influenced by interactions between species. In the oral cavity, dysbiosis of the microbiome leads to diseases such as periodontitis. Porphyromonas gingivalis is a keystone pathogen of periodontitis. In this study, we showed that polymicrobial biofilm formation promoted the tolerance of Porphyromonas gingivalisto oxidative stress under micro-aerobic conditions. The presence of Streptococcus sanguinis, an oral commensal bacterium, inhibited the survival of P. gingivalis in dual-species biofilms via the secretion of hydrogen peroxide (H2O2). Interestingly, this repression could be attenuated by the presence of Aggregatibacter actinomycetemcomitansin tri-species biofilms. It was also shown that the katA gene, encoding a cytoplasmic catalase in A. actinomycetemcomitans, was responsible for the reduction of H2O2 produced by S. sanguinis, which consequently increased the biomass of P. gingivalis in tri-species biofilms. Collectively, these findings reveal that polymicrobial interactions play important roles in shaping bacterial community in biofilm. The existence of catalase producers may support the colonization of pathogens vulnerable to H2O2, in the oral cavity. The catalase may be a potential drug target to aid in the prevention of periodontitis.

Kent, B.§, T. Raymond, P.D. Mosier, A.A. Johnson, and 2016–2017 VCU Phage Hunters (2018) Complete Genome Sequences of Bacillus Phages Janet and OTooleKemple52. Genome Announcements :e00083-18.
https://doi.org/10.1128/genomeA.00083-18

We report here the genome sequences of two novel Bacillus cereus group-infecting bacteriophages, Janet and OTooleKemple52. These bacteriophages are double-stranded DNA-containing Myoviridae isolated from soil samples. While their genomes share a high degree of sequence identity with one another, their host preferences are unique.

Gao, X., E.F. Petricoin III, K.R. Ward, S.R. Goldberg, T.M. Duane, D. Bonchev, T. Arodz, and R.F. Diegelmann (2018) Network proteomics of human dermal wound healing. Physiological Measurement 39:124002.
https://doi.org/10.1088/1361-6579/aaee19

Objective: The healing of wounds is critical in protecting the human body against environmental factors. The mechanisms involving protein expression during this complex physiological process have not been fully elucidated.

Approach: Here, we use reverse-phase protein microarrays (RPPA) involving 94 phosphoproteins to study tissue samples from tubes implanted in healing dermal wounds in seven human subjects tracked over two weeks. We compare the proteomic profiles to proteomes of controls obtained from skin biopsies from the same subjects.

Main results: Compared to previous proteomic studies of wound healing, our approach focuses on wound tissue instead of wound fluid, and has the sensitivity to go beyond measuring only highly abundant proteins. To study the temporal dynamics of networks involved in wound healing, we applied two network analysis methods that integrate the experimental results with prior knowledge about protein–protein physical and regulatory interactions, as well as higher-level biological processes and associated pathways.

Significance: We uncovered densely connected networks of proteins that are up- or down-regulated during human wound healing, as well as their relationships to microRNAs and to proteins outside of our set of targets that we measured with proteomic microarrays.

Wang, H., G.E. Kellogg, P. Xu, and Y. Zhang (2018) Exploring the binding mechanisms of diaminopimelic acid analogs to meso-diaminopimelate dehydrogenase by molecular modeling. Journal of Molecular Graphics & Modelling 83:100-111.
https://doi.org/10.1016/j.jmgm.2018.05.011

Meso-Diaminopimelic acid (meso-2,6-diamino-heptanedioic acid, DAP) is an important component of the cell wall of many bacteria. Meso-diaminopimelate dehydrogenase (m-Ddh) is a critical enzyme in the process of converting tetrahydrodipicolinate to DAP. Here, we are proposing that DAP analogs targeting m-Ddh may be considered as potential antibiotics. Four DAP analogs without significant structural change from DAP have been obtained and their inhibitory potencies against m-Ddh from the P. gingivalis strain W83 show significant differences from that of DAP. However, their inhibitory mechanisms as for how simple structural change influences the inhibitory potency remain unknown. Therefore, we employed molecular modeling methods to obtain insight into the inhibitory mechanisms of DAP and analogs with m-Ddh. The predicted binding mode of DAP was highly consistent with the experimental structural data and disclosed the important roles played by the binding pocket residues. According to our predictions, the isoxazoline ring of compounds 1 and 2 and the double bonds in compounds 3 and 4 had distinct influences on these compounds’ binding to m-Ddh. This enriched understanding of the inhibitory mechanisms of DAP and these four analogs to m-Ddh has provided new and relevant information for future rational development of potent inhibitors targeting m-Ddh.

Zhu, B.*, L.C. Macleod, T. Kitten, and P. Xu (2018) Streptococcus sanguinis biofilm formation & interaction with oral pathogens. Future Microbiology 13:915-932.
https://doi.org/10.2217/fmb-2018-0043

Caries and periodontitis are the two most common human dental diseases and are caused by dysbiosis of oral flora. Although commensal microorganisms have been demonstrated to protect against pathogens and promote oral health, most previous studies have addressed pathogenesis rather than commensalism. Streptococcus sanguinis is a commensal bacterium that is abundant in the oral biofilm and whose presence is correlated with health. Here, we focus on the mechanism of biofilm formation in S. sanguinis and the interaction of S. sanguinis with caries- and periodontitis-associated pathogens. In addition, since S. sanguinis is well known as a cause of infective endocarditis, we discuss the relationship between S. sanguinis biofilm formation and its pathogenicity in endocarditis.

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