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2. Seroprevalence and risk factors for brucellosis amongst livestock and humans in a multi-herd ranch system in Kagera, Tanzania.

Author

Lyimo, Beatus, Hugho, Ephrasia, Mathew, Coletha, Mayenga, Charles, Lukambagire, Abdul Hamid, Lyimo, Samson, Munuo, Lidia, Byukusenge, Maurice, Withall, Jodie, Ashford, Roland T., Mmbaga, Blandina T., Makondo, Zachariah, McGiven, John, Radzio-Basu, Jessica, Ganda, Erika, Middlebrook, Earl A., Bartlow, Andrew W., Fair, Jeanne M., Shirima, Gabriel, and Sriranganathan, Nammalwar

Published
2024
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4. Retrospective Single Nucleotide Polymorphism Analysis of Host Resistance and Susceptibility to Ovine Johne's Disease Using Restored FFPE DNA.

Author

Kravitz, Amanda, Liao, Mingsi, Morota, Gota, Tyler, Ron, Cockrum, Rebecca, Manohar, B. Murali, Ronald, B. Samuel Masilamoni, Collins, Michael T., and Sriranganathan, Nammalwar

Subjects
PARATUBERCULOSIS, SINGLE nucleotide polymorphisms, DISEASE resistance of plants, MYCOBACTERIUM avium paratuberculosis, GENOME-wide association studies
Abstract

Johne's disease (JD), also known as paratuberculosis, is a chronic, untreatable gastroenteritis of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP) infection. Evidence for host genetic resistance to disease progression exists, although it is limited due to the extended incubation period (years) and diagnostic challenges. To overcome this, previously restored formalin-fixed paraffin embedded tissue (FFPE) DNA from archived FFPE tissue cassettes was utilized for a novel retrospective case-control genome-wide association study (GWAS) on ovine JD. Samples from known MAP-infected flocks with ante- and postmortem diagnostic data were used. Cases (N = 9) had evidence of tissue infection, compared to controls (N = 25) without evidence of tissue infection despite positive antemortem diagnostics. A genome-wide efficient mixed model analysis (GEMMA) to conduct a GWAS using restored FFPE DNA SNP results from the Illumina Ovine SNP50 Bead Chip, identified 10 SNPs reaching genome-wide significance of p < 1 × 10−6 on chromosomes 1, 3, 4, 24, and 26. Pathway analysis using PANTHER and the Kyoto Encyclopedia of Genes and Genomes (KEGG) was completed on 45 genes found within 1 Mb of significant SNPs. Our work provides a framework for the novel use of archived FFPE tissues for animal genetic studies in complex diseases and further evidence for a genetic association in JD. [ABSTRACT FROM AUTHOR]

Published
2024
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11. The Probiotic Bacillus subtilis MB40 Improves Immunity in a Porcine Model of Listeriosis

Author

Garvey, Sean M., Emami, Nima K., Guice, Justin L., Sriranganathan, Nammalwar, Penet, Christopher, Rhoads, Robert P., Spears, Jessica L., Dalloul, Rami A., El-Kadi, Samer W., Garvey, Sean M., Emami, Nima K., Guice, Justin L., Sriranganathan, Nammalwar, Penet, Christopher, Rhoads, Robert P., Spears, Jessica L., Dalloul, Rami A., and El-Kadi, Samer W.

Abstract

Probiotics for humans and direct-fed microbials for livestock are increasingly popular dietary ingredients for supporting immunity. The aim of this study was to determine the effects of dietary supplementation of Bacillus subtilis MB40 (MB40) on immunity in piglets challenged with the foodborne pathogen Listeria monocytogenes (LM). Three-week-old piglets (n = 32) were randomly assigned to four groups: (1) basal diet, (2) basal diet with LM challenge, (3) MB40-supplemented diet, and (4) MB40-supplemented diet with LM challenge. Experimental diets were provided throughout a 14-day (d) period. On d8, piglets in groups 2 and 4 were intraperitoneally inoculated with LM at 108 CFU/mL per piglet. Blood samples were collected at d1, d8, and d15 for biochemical and immune response profiling. Animals were euthanized and necropsied at d15 for liver and spleen bacterial counts and intestinal morphological analysis. At d15, LM challenge was associated with increased spleen weight (p = 0.017), greater circulating populations of neutrophils (p = 0.001) and monocytes (p = 0.008), and reduced ileal villus height to crypt depth ratio (p = 0.009), compared to non-challenged controls. MB40 supplementation reduced LM bacterial counts in the liver and spleen by 67% (p < 0.001) and 49% (p < 0.001), respectively, following the LM challenge, compared to the basal diet. MB40 supplementation was also associated with decreased circulating concentrations of monocytes (p = 0.007). Altogether, these data suggest that MB40 supplementation is a safe and well-tolerated approach to enhance immunity during systemic Listeria infection.

Published
2023

13. Brucella

Author

Sriranganathan, Nammalwar, Seleem, Mohamed N., Olsen, Steven C., Samartino, Luis E., Whatmore, Adrian M., Bricker, Betsy, O'Callaghan, David, Halling, Shirley M., Crasta, Oswald R., Wattam, Alice R., Purkayastha, Anjan, Sobral, Bruno W., Snyder, Eric E., Williams, Kelley P., Yu, Gong-Xi, Ficht, Thomas A., Roop, R. Martin, II, de Figueiredo, Paul, Boyle, Stephen M., He, Yongqun, Tsolis, Renée M., Nene, Vishvanath, editor, and Kole, Chittaranjan, editor

Published
2009
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17. Roles of bacterial membrane vesicles

Author

Avila-Calderón, Eric Daniel, Araiza-Villanueva, Minerva Georgina, Cancino-Diaz, Juan Carlos, López-Villegas, Edgar Oliver, Sriranganathan, Nammalwar, Boyle, Stephen M., and Contreras-Rodríguez, Araceli

Published
2015
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22. List of contributors

Author

Banach, Marcin, primary, Bindhani, Birendra K., additional, Catala, Alexis, additional, Chen, Daqin, additional, Chen, Jiafu, additional, Chitkara, Mansi, additional, Dahman, Yaser, additional, Das, Subash, additional, Dhiman, Sonia, additional, Ding, Mingye, additional, Elango, Ganesh, additional, Garg, Babita, additional, Glickman, Randolph D., additional, Gorbyk, Petro Petrovych, additional, Hassounah, Ibrahim A., additional, Hudson, Amanda G., additional, Hughes, Bethany R., additional, Ioelovich, Michael, additional, Jain, Atul, additional, Javaheri, Hoda, additional, Jena, Padan K., additional, Ji, Zhenguo, additional, Jindal, Manish, additional, Joseph, Eugene G., additional, Joshi, Anjali, additional, Katare, Om Prakash, additional, Kaur, Ranjot, additional, Kimsawatde, Gade C., additional, Kumar, Rajendra, additional, Lerman, Leonid Borysovych, additional, Liang, Xiaojuan, additional, Maguire, Greg, additional, Mahajan, Roop L., additional, Maswadi, Saher, additional, Nash, Kelly L., additional, Parida, Umesh K., additional, Petranovska, Alla Leonidivna, additional, Pulit-Prociak, Jolanta, additional, Pylypchuk, Ievgen Volodymyrovych, additional, Roopan, Selvaraj Mohana, additional, Rout, Niranjan, additional, Sandhu, Inderjeet Singh, additional, Shehata, Nader A., additional, Singh, Bhupinder, additional, Singh, Narinder, additional, Singh, Thakur Gurjeet, additional, Sriranganathan, Nammalwar, additional, Sulaiman, Basel Al-Chikh, additional, Turanska, Svitlana Petrivna, additional, Varga, Melinda, additional, Verma, Gaurav, additional, Wan, Zhongyi, additional, Xiang, Weidong, additional, Yasmin, Zannatul, additional, Zhong, Jiasong, additional, and Zhou, Yang, additional

Published
2016
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30. Essential Gene(s) Targeted by Peptide Nucleic Acids Kills Mycobacterium smegmatis in Culture and in Infected Macrophages

Author

Islam, Md. Ariful, Khatun, Mst. Minara, Sriranganathan, Nammalwar, and Boyle, Stephen M.

Subjects
Middlebrook 7H9 Broth Culture, Peptide Nucleic Acid, J774A.1 Murine Macrophage Cell Line, Antisense Therapy, Cell Penetrating Peptide, humanities, Mycobacterium
Abstract

Background: Antisense peptide nucleic acids (PNAs) exhibit growth inhibitory effects on bacteria by inhibiting the expression of essential genes and could be promising therapeutic agents for treating bacterial infections. A study was carried out to determine the efficacy of several antisense PNAs in inhibiting extracellular and intracellular growth of Mycobacterium smegmatis. Methods : Six PNAs obtained from a commercial supplier were tested to evaluate the inhibitory effect on bacterial growth by inhibiting the expression of the following essential genes: inhA (a fatty acid elongase), rpsL (ribosomal S12 protein), gyrA (DNA gyrase), pncA (pyrazinamidase), polA (DNA polymerase I) and rpoC (RNA polymerase β subunit) of M. smegmatis . Each PNA was tested at 20 μM, 10 μM, 5 μM and 2.5 μM concentrations to determine whether they caused a dose dependent killing of M. smegmatis cultured in Middlebrook 7H9 broth or in a J774A.1 murine macrophage cell line. Results : In Middlebrook broth, the strong growth inhibitory effect against M. smegmatis was observed by PNAs targeting the inhA and rpsL genes at all four concentrations. The PNAs targeting the pncA, polA and rpoC genes were found to exhibit strong growth inhibition against M. smegmatis but only at 20 μM concentration. No growth inhibition of M. smegmatis was seen in pure culture when treated with PNAs targeting gyrA and a mismatch PNA targeting dnaG (DNA primase). All six PNAs showed killing of M. smegmatis in J774A.1 macrophage cell line that were statistically significant (p < 0.05). Conclusion: It may be concluded from this study that PNAs could be potential therapeutics for mycobacterial infections. This research was funded through grants from NIH to SMB (5R03AI083735-02) and from The Islamic Development Bank to MAI. Published version

Published
2021

34. The Paratuberculosis Paradigm Examined: A Review of Host Genetic Resistance and Innate Immune Fitness in Mycobacterium avium subsp. Paratuberculosis Infection

Author

Kravitz, Amanda, Pelzer, Kevin, Sriranganathan, Nammalwar, Kravitz, Amanda, Pelzer, Kevin, and Sriranganathan, Nammalwar

Abstract

Paratuberculosis, or Johne’s Disease (JD) is a debilitating chronic enteritis mainly affecting ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). This organism causes worldwide economic losses to the livestock industry, and is of public health importance due to the potential zoonotic risk between MAP and Crohn’s disease (CD) in humans. Without economical treatments, or a vaccine capable of preventing infection without causing cross-reactions with bovine tuberculosis, test-and-cullmethods for disease control are imperative. Unfortunately, difficulties in diagnostics and long subclinical stage hinder adequate control and is further complicated by variation in MAP exposure outcome. Interestingly, the majority of infections result in asymptomatic presentation and never progress to clinical disease. One contributing factor is host genetics, where polymorphisms in innate immune genes have been found to influence resistance and susceptibility to disease. Candidate genes identified across studies overlap with those found in CD and tuberculosis including; Solute carrier family 11 member 1 gene (SLC11A1), Nucleotide-binding-oligomerization domain containing gene 2 (NOD2), Major histocompatibility complex type II (MHC-II), and Toll-like receptor (TLR) genes. This review will highlight evidence supporting the vital role of these genes in MAP infection outcome, associated challenges, and implications for the future of JD research.

Published
2021

38. Contaminated Heparin associated with adverse clinical events and activation of the contact system

Author

Kishimoto, Takashi Kei, Viswanathan, Karthik, Ganguly, Tanmoy, Elankumaran, Subbiah, Smith, Sean, Pelzer, Kevin, Lansing, Jonathan C., Sriranganathan, Nammalwar, Zhao, Ganlin, Galcheva-Gargova, Zoya, Al-Hakim, Ali, Bailey, Gregory Scott, Fraser, Blair, Roy, Sucharita, Rogers-Cotrone, Thomas, Buhse, Lucinda, Whary, Mark, Fox, James, Nasr, Moheb, Dal Pan, Gerald J., Shriver, Zachary, Langer, Robert S., Venkataraman, Ganesh, Austen, Frank, Woodcock, Janet, and Sasisekharan, Ram

Subjects
Chondroitin -- Health aspects, Heparin -- Composition, Heparin -- Health aspects
Abstract

A study was conducted to determine whether contaminated heparin containing oversulphated chondroitin sulphate (OSCS) was responsible for adverse clinical events in patients administered this during dialysis. Results indicated that there was a connection between the two and suggested further and quick research.

Published
2008

45. Establishment of a gene expression system in Ochrobactrum anthropi

Author

Seleem, Mohamed N., Ali, Mohammed, Boyle, Stephen M., Mukhopadhyay, Biswarup, Witonsky, Sharon G., Schurig, Gerhardt G., and Sriranganathan, Nammalwar

Subjects
Bacterial genetics -- Research, Bioremediation -- Research, Bacterial proteins -- Research, Bacterial proteins -- Structure, Biological sciences
Abstract

An enhanced gene expression system in Ochrobactrum anthropi was established to allow rapid and easy one-step purification of recombinant protein directly from Ochrobactrum anthropi. It was suggested that the newly described vectors will enhance genetic manipulation and characterization and will facilitate the use of Ochrobactrum as a potential bioremediation tool and a biopesticide agent.

Published
2006

48. Carboxyl-terminal protease regulates Brucella suis morphology in culture and persistence in macrophages and mice

Author

Bandara, Aloka B., Sriranganathan, Nammalwar, Schurig, Gerhardt G., and Boyle, Stephen M.

Subjects
Macrophages -- Analysis, Biological sciences
Abstract

The putative carboxyl-terminal processing protease (CtpA) of Brucella suis 1330 is a member of a novel family of endoproteases involved in the maturation of proteins destined for the cell envelope. The B. suis CtpA protein shared up to 77% homology with CtpA proteins of other bacteria. A CtpA-deficient Brucella strain (1330[delta]ctpA), generated by allelic exchange, produced smaller colonies on enriched agar plates and exhibited a 50% decrease in growth rate in enriched liquid medium and no growth in salt-free enriched medium compared to the wild-type strain 1330 or the ctpA-complemented strain 1330[delta]ctpA[pBBctpA]. Electron microscopy revealed that in contrast to the native coccobacillus shape of wild-type strain 1330, strain 1330[delta]ctpA possessed a spherical shape, an increased cell diameter, and cell membranes partially dissociated from the cell envelope. In the J774 mouse macrophage cell line, 24 h after infection, the CFU of the strain 1330[delta]ctpA declined by approximately 3 [log.sub.10] CFU relative to wild-type strain 1330. Nine weeks after intraperitoneal inoculation of BALB/c mice, strain 1330[delta]ctpA had cleared from spleens but strain 1330 was still present. These observations suggest that the CtpA activity is necessary for the intracellular survival of B. suis. Relative to the saline-injected mice, strain 1330[delta]ctpA-vaccinated mice exhibited 4 to 5 l[og.sub.10] CFU of protection against challenge with virulent B. abortus strain 2308 or B. suis strain 1330 but no protection against B. melitensis strain 16 M. This is the first report correlating a CtpA deficiency with cell morphology and attenuation of B. suis.

Published
2005

49. Proteomic Analysis of Membrane Blebs of Brucella abortus 2308 and RB51 and Their Evaluation as an Acellular Vaccine

Author

Araiza-Villanueva, Minerva, Avila-Calderon, Eric Daniel, Flores-Romo, Leopoldo, Calderon-Amador, Juana, Sriranganathan, Nammalwar, Al Qublan, Hamzeh, Witonsky, Sharon G., Aguilera-Arreola, Ma. Guadalupe, Ruiz-Palma, Maria del Socorro, Ruiz, Enrico A., Suarez-Gueemes, Francisco, Gomez-Lunar, Zulema, and Contreras-Rodriguez, Araceli

Subjects
Gram-negative bacteria, brucellosis, membrane blebs, Brucella abortus, vaccines, complex mixtures, eye diseases
Abstract

Membrane blebs are released from Gram-negative bacteria, however, little is known about Brucella blebs. This work pursued two objectives, the first was to determine and identify the proteins in the membrane blebs by proteomics and in silico analysis. The second aim was to evaluate the use of membrane blebs of Brucella abortus 2308 and B. abortus RB51 as an acellular vaccine in vivo and in vitro. To achieve these aims, membrane blebs from B. abortus 2308 and RB51 were obtained and then analyzed by liquid chromatography coupled to mass spectrometry. Brucella membrane blebs were used as a "vaccine" to induce an immune response in BALB/c mice, using the strain B. abortus RB51 as a positive vaccine control. After subsequent challenge with B. abortus 2308, CFUs in spleens were determined; and immunoglobulins IgG1 and IgG2a were measured in murine serum by ELISA. Also, activation and costimulatory molecules induced by membrane blebs were analyzed in splenocytes by flow cytometry. Two hundred and twenty eight proteins were identified in 2308 membrane blebs and 171 in RB51 blebs, some of them are well-known Brucella immunogens such as SodC, Omp2b, Omp2a, Omp10, Omp16, and Omp19. Mice immunized with membrane blebs from rough or smooth B. abortus induced similar protective immune responses as well as the vaccine B. abortus RB51 after the challenge with virulent strain B. abortus 2308 (P < 0.05). The levels of IgG2a in mice vaccinated with 2308 membrane blebs were higher than those vaccinated with RB51 membrane blebs or B. abortus RB51 post-boosting. Moreover, mice immunized with 2308 blebs increased the percentage of activated B cells (CD19(+)CD69(+)) in vitro. Therefore, membrane blebs are potential candidates for the development of an acellular vaccine against brucellosis, especially those derived from the rough strains so that serological diagnostic is not affected. CONACYTConsejo Nacional de Ciencia y Tecnologia (CONACyT) [CB-2011-01, 169259]; SIP-IPN [20182152, 20195737]; SAGARPA-CONACYTConsejo Nacional de Ciencia y Tecnologia (CONACyT) [2017-02-291311]; ICYT-DF/IPN; PIFI-IPN scholarship; COFAA-IPN; SNI-CONACYTConsejo Nacional de Ciencia y Tecnologia (CONACyT); SIP-EDI This work was funded by CONACYT CB-2011-01 No. 169259, SIP-IPN 20182152, SIP-IPN 20195737, SAGARPA-CONACYT 2017-02-291311, and ICYT-DF/IPN. MA-V and EA-C were supported by CONACYT and PIFI-IPN scholarships. MA-A, ER, and AC-R were supported by fellowships from COFAA-IPN, SIP-EDI, and SNI-CONACYT.

Published
2019

50. Overexpression of wbkF gene in Brucella abortus RB51WboA leads to increased O-polysaccharide expression and enhanced vaccine efficacy against B. abortus 2308, B. melitensis 16M, and B. suis 1330 in a murine brucellosis model

Author

Dabral, Neha, Burcham, Grant N., Jain-Gupta, Neeta, Sriranganathan, Nammalwar, Vemulapalli, Ramesh, Dabral, Neha, Burcham, Grant N., Jain-Gupta, Neeta, Sriranganathan, Nammalwar, and Vemulapalli, Ramesh

Abstract

Brucella abortus RB51 is an attenuated, stable, spontaneous rough mutant derived in the laboratory from the virulent strain B. abortus 2308. Previous studies discovered that the wboA gene, which encodes a glycosyltransferase required for synthesis of the O-polysaccharide, is disrupted in strain RB51 by an IS711 element. However, complementation of strain RB51 with a functional wboA gene (strain RB51WboA) does not confer it a smooth phenotype but results in low levels of cytoplasmic O-polysaccharide synthesis. In this study, we asked if increasing the potential availability of bactoprenol priming precursors in strain RB51WboA would increase the levels of O-polysaccharide synthesis and enhance the protective efficacy against virulent Brucella challenge. To achieve this, we overexpressed the wbkF gene, which encodes a putative undecaprenyl-glycosyltransferase involved in bactoprenol priming for O-polysaccharide polymerization, in strain RB51WboA to generate strain RB51WboAKF. In comparison to strain RB51WboA, strain RB51WboAKF expressed higher levels of O-polysaccharide, but was still attenuated and remained phenotypically rough. Mice immunized with strain RB51WboAKF developed increased levels of smooth LPS-specific serum antibodies, primarily of IgG2a and IgG3 isotype. Splenocytes from mice vaccinated with strain RB51WboAKF secreted higher levels of antigen-specific IFN-gamma and TNF-alpha and contained more numbers of antigen-specific IFN-gamma secreting CD4(+) and CD8(+) T lymphocytes when compared to those of the RB51 or RB51WboA vaccinated groups. Immunization with strain RB51WboAKF conferred enhanced protection against virulent B. abortus 2308, B. melitensis 16M and B. suis 1330 challenge when compared to the currently used vaccine strains. Our results suggest that strain RB51WboAKF has the potential to be a more efficacious vaccine than its parent strain in natural hosts.

Published
2019
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