REPRODUCTION REVIEW Ectopic pregnancy in animals and humans

Abstract Ectopic pregnancy denotes a pregnancy occurring elsewhere than in the cavity of the uterus. This pathology has been recognised for years and it causes numerous maternal deaths during the first trimester of pregnancy. While this condition is wellknown in humans, it is rarely diagnosed in animals. However, the causes and mechanisms leading to an ectopic implantation of the ovum are not always clearly defined in humans or animals. Two types of ectopic pregnancy are mainly recognized: (1) tubal pregnancy occurs when an oocyte is fertilized and then remains in the oviduct and (2) abdominal pregnancy occurs when the gestation develops in the peritoneal cavity. The latter may be subdivided into two subtypes: the primary form, when a fertilized oocyte enters the peritoneal cavity and becomes attached to the mesentery or abdominal viscera, and the secondary form, which follows the rupture of an oviduct or the uterus after the fetus has been implanted, and the fetus is expelled into the peritoneal cavity. Cornual, ovarian and cervical ectopic locations are less frequent. Several differences exist in ectopic pregnancies between human beings and animal species. While abdominal pregnancy has been described in both human and animal species, tubal ectopic pregnancies would appear to be restricted to primates. Other than anecdotal cases, this pathological condition does not occur in laboratory, domestic or farm animals. Several factors are described as being the cause of these differences

Staphylococcus aureus nasal carriage could be a risk for development of clinical infections in rabbits

[EN] Although nasal carriage has been described as a risk factor for Staphylococcus aureus infections in humans, there is a scarcity of studies about S. aureus nasal carriers in animals. In rabbits, S. aureus is one of the most important pathogens responsible for a number of different types of infections. This study was designed to determine the extent of staphylococcal nasal carriage and to establish whether a relationship exists between nasal carriage and development of lesions. One hundred and sixteen rabbits with and without chronic signs of staphylococcosis from 6 industrial rabbitries were monitored. Nasal swabs for microbiological assessments were obtained from all animals. Microbiological results showed that 56% of the animals carried S. aureus in their nasal cavities with significantly higher incidence in animals with staphylococcal-related lesions (84.2%) compared to apparently healthy animals (28.8%). Additionally, the S. aureus strains isolated from the nasal cavity and lesions were clonally related in 91.7% of animals. This suggests that nasal carriage of S. aureus in rabbits could be a risk for development of clinical infections.This study was supported by the Inter-ministerial Commission for Science and Technology (CICYT) of the Spanish Government (AGL2011-30170-C02-02 and AGL2014-53405-C2-2-P). The authors acknowledge Dr. E. A. Gomez for the statistical analysis and Prof. Sean (J.J) Callanan for revision of the manuscript.Selva Martinez, L.; Viana, D.; Corpa Arenas, JM. (2015). Staphylococcus aureus nasal carriage could be a risk for development of clinical infections in rabbits. World Rabbit Science. 23(3):181-184. https://doi.org/10.4995/wrs.2015.3960SWORD181184233Burton S., Reid-Smith R., McClure J.T., Weese J.S. 2008. Staphylococcus aureus colonization in healthy horses in Atlantic Canada. Can. Vet. J., 49: 797-799

Growth performance of three paternal rabbit lines with different potential for growth rate and resilience

[EN] This experiment aimed to compare the growth performance, digestive efficiency and health status of three paternal lines for growing rabbits. The R line was selected by growth rate during the growing period for 37 generations; the RF line was founded by selecting a population of elite R animals (average daily gain>60 g/d); and the RFLP line was founded by backcrossing males from the RF line with females from the LP maternal line. A total of 387 weaned rabbits were used to evaluate growing performance from weaning until 63 d of age in individual cages, in three batches. Additionally, 33 animals were used to determine nutrient digestive efficiency in a digestibility trial. Body weight and feed intake were controlled at weaning (28 d), 46 and 63 d of age. Mortality and morbidity were also monitored daily. During the digestibility trial, feed intake and faeces excretion were controlled daily. Results showed no significant effects of genetic type on body weight, daily feed intake and feed conversion ratio throughout the experiment. However, RF animals had a higher average daily gain from 28 to 46 d of age (+4.4%; P<0.05) compared with R animals, but lower from 46 to 63 d of age (–4.3%; P<0.05). Regarding digestive efficiency, RF and RFLP lines showed slightly higher faecal digestibility for dry matter and gross energy of the diet compared with the R line (+1.3 percentage points; P<0.05). Mortality was higher in animals from R and RF lines compared with RFLP (on av. 25.40 vs. 14.06%; P<0.05). Our results suggest that the RFLP genetic line could be a suitable alternative to the R line, as it shows a similar growth performance but a lower incidence of digestive disorders.This study was funded by the Ministry of Science, Innovation and Universities of the Government of Spain (AGL2017-85162-C2-1-R) and the General Direction of Science and Research of the Generalitat Valenciana (AICO/2012/256). The grantfor Catarina Peixoto Gonçalves is also gratefully acknowledged (GRISOLIAP/2019/149; from the General Direction of Science andResearch of the Generalitat Valenciana).Peixoto-Gonçalves, C.; Martínez-Paredes, E.; Ródenas, L.; Corpa, JM.; Blas, E.; Cambra-López, M.; Pascual, JJ. (2023). Growth performance of three paternal rabbit lines with different potential for growth rate and resilience. World Rabbit Science. 31(4):221-228. https://doi.org/10.4995/wrs.2023.1984122122831

Long-term implications of feed energy source in different genetic types of reproductive rabbit females. II.Immunologic status

[EN] Genetic selection and nutrition management have played a central role in the development of commercial rabbitry industry over the last few decades, being able to affect productive and immunological traits of the animals. However, the implication of different energy sources in animals from diverse genetic lines achieving such evolutionary success remains still unknown. Therefore, in this work, 203 female rabbits housed and bred in the same conditions were used from their first artificial insemination until their fifth weaning. The animals belonged to three different genetic types diverging greatly on breeding goals (H line, hyper-prolific (n=66); LP line, robust (n=67) and R line, selected for growth rate (n=67), and were assigned to two experimental diets, promoting major differences in energy source (cereal starch or animal fat)). The aims of this work were to: (1) characterize and describe blood leucocyte populations of three lines of rabbit does in different physiological stages during their reproductive period: first artificial insemination, first weaning, second parturition and fifth weaning; and (2) study the possible influence of two different experimental diets on the leucocyte populations in peripheral blood. Flow cytometry analyses were performed on blood samples taken from females at each different sampling stade. Lymphocyte populations at both weanings were characterized by significantly lower counts of total, CD5(+) and CD8(+) lymphocytes (-19.8, -21.7 and -44.6%; P<0.05), and higher counts of monocytes and granulocytes (+49.2 and +26.2%; P<0.05) than in the other stages. Females had higher blood counts of lymphocytes B, CD8(+) and CD25(+) and lower counts of CD4(+) at first than at fifth weaning (+55.6, +85.8, +57.5, -14.5%; P<0.05). G/L ratio was higher at both weanings (P<0.05), and CD4(+)/CD8(+) ratio increased progressively from the 1AI to the 5 W (P<0.001). Regarding the effect of genetic type in blood leucocyte counts, LP animals presented the highest counts for total, B, CD5(+) and CD8(+) lymphocytes (+16.7, +31.8, +24.5 and +38.7; P<0.05), but R rabbits showed the highest counts for monocytes and granulocytes (+25.3 and +27.6; P<0.05). The type of diet given during the reproductive life did not affect the leucocyte population counts. These results indicate that there are detectable variations in the leucocyte profile depending on the reproductive stage of the animal (parturition, weaning or none of them). Moreover, foundation for reproductive longevity criteria allows animals to be more capable of adapting to the challenges of the reproductive cycle from an immunological viewpoint.This study was supported by the Interministerial Commission for Science and Technology (CICYT) of the Spanish Government (AGL2014-53405-C2-1-P; AGL2014-53405-C2-2-P). The authors thank Juan Carlos Moreno for his technical support. Grants for Ana Garcia-Quiros from Universidad CEU-Cardenal Herrera, and Mariola Penades and Alberto Arnau from the Ministerio de Educacion, Cultura y Deporte (AP2010-3907 and BES-2012-052345, respectively) are also gratefully acknowledged.Penadés, M.; Arnau-Bonachera, A.; García-Quirós, A.; Viana, D.; Selva, L.; Corpa, JM.; Pascual Amorós, JJ. (2018). Long-term implications of feed energy source in different genetic types of reproductive rabbit females. II.Immunologic status. Animal. 12(9):1877-1885. https://doi.org/10.1017/S1751731117003299S18771885129Cifre, J., Baselga, M., García-Ximénez, F., & Vicente, J. S. (1998). Performance of a hyperprolific rabbit line I. Litter size traits. Journal of Animal Breeding and Genetics, 115(1-6), 131-138. doi:10.1111/j.1439-0388.1998.tb00336.xFranceschi, C., Valensin, S., Bonafè, M., Paolisso, G., Yashin, A. ., Monti, D., & De Benedictis, G. (2000). The network and the remodeling theories of aging: historical background and new perspectives. Experimental Gerontology, 35(6-7), 879-896. doi:10.1016/s0531-5565(00)00172-8Al-Murrani, W. K., Al-Rawi, I. K., & Raof, N. M. (2002). Genetic resistance to Salmonella typhimurium in two lines of chickens selected as resistant and sensitive on the basis of heterophil/lymphocyte ratio. British Poultry Science, 43(4), 501-507. doi:10.1080/0007166022000004408Savietto, D., Friggens, N. C., & Pascual, J. (2015). Reproductive robustness differs between generalist and specialist maternal rabbit lines: the role of acquisition and allocation of resources. Genetics Selection Evolution, 47(1), 2. doi:10.1186/s12711-014-0073-5Kilgas, P., Tilgar, V., & Mänd, R. (2006). Hematological Health State Indices Predict Local Survival in a Small Passerine Bird, the Great Tit (Parus major). Physiological and Biochemical Zoology, 79(3), 565-572. doi:10.1086/502817Hulstaert, F., Hannet, I., Deneys, V., Munhyeshuli, V., Reichert, T., De Bruyere, M., & Strauss, K. (1994). Age-Related Changes in Human Blood Lymphocyte Subpopulations. Clinical Immunology and Immunopathology, 70(2), 152-158. doi:10.1006/clin.1994.1023HÕrak, P., Ots, I., & Murumägi, A. (1998). Haematological health state indices of reproducing Great Tits: a response to brood size manipulation. Functional Ecology, 12(5), 750-756. doi:10.1046/j.1365-2435.1998.00244.xSakaguchi, S. (2005). Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nature Immunology, 6(4), 345-352. doi:10.1038/ni1178Kampen, A. H., Olsen, I., Tollersrud, T., Storset, A. K., & Lund, A. (2006). Lymphocyte subpopulations and neutrophil function in calves during the first 6 months of life. Veterinary Immunology and Immunopathology, 113(1-2), 53-63. doi:10.1016/j.vetimm.2006.04.001Blas, C. de, & Mateos, G. G. (s. f.). Feed formulation. Nutrition of the rabbit, 222-232. doi:10.1079/9781845936693.0222Jeklova, E., Leva, L., Knotigova, P., & Faldyna, M. (2009). Age-related changes in selected haematology parameters in rabbits. Research in Veterinary Science, 86(3), 525-528. doi:10.1016/j.rvsc.2008.10.007Arnau-Bonachera, A., Savietto, D., & Pascual, J. J. (2017). Long-term implications of feed energy source in different genetic types of reproductive rabbit females: III. Fitness and productivity. animal, 12(9), 1886-1894. doi:10.1017/s1751731117003305Davis, W. C., & Hamilton, M. J. (2008). Use of flow cytometry to develop and characterize a set of monoclonal antibodies specific for rabbit leukocyte differentiation molecules. Journal of Veterinary Science, 9(1), 51. doi:10.4142/jvs.2008.9.1.51Ferrian, S., Guerrero, I., Blas, E., García-Diego, F. J., Viana, D., Pascual, J. J., & Corpa, J. M. (2012). How selection for reproduction or foundation for longevity could have affected blood lymphocyte populations of rabbit does under conventional and heat stress conditions. Veterinary Immunology and Immunopathology, 150(1-2), 53-60. doi:10.1016/j.vetimm.2012.08.007Pascual, J. J., Savietto, D., Cervera, C., & Baselga, M. (2013). Resources allocation in reproductive rabbit does: a review of feeding and genetic strategies for suitable performance. World Rabbit Science, 21(3). doi:10.4995/wrs.2013.1236Pascual JJ 2010. The role of body condition on new feeding and breeding programmes for reproductive rabbit does. Proceedings of the 22nd Hungarian Conference on Rabbit Production, Kaposvár, Hungary, pp. 11–32.Sánchez, J. P., Theilgaard, P., Mínguez, C., & Baselga, M. (2008). Constitution and evaluation of a long-lived productive rabbit line1. Journal of Animal Science, 86(3), 515-525. doi:10.2527/jas.2007-0217Guerrero, I., Ferrian, S., Blas, E., Pascual, J. J., Cano, J. L., & Corpa, J. M. (2011). Evolution of the peripheral blood lymphocyte populations in multiparous rabbit does with two reproductive management rhythms. Veterinary Immunology and Immunopathology, 140(1-2), 75-81. doi:10.1016/j.vetimm.2010.11.017Kotani, M., Yamamura, Y., Tamatani, T., Kitamura, F., & Miyasaka, M. (1993). Generation and characterization of monoclomal antibodies against rabbit CD4, CD5 and CD11a antigens. Journal of Immunological Methods, 157(1-2), 241-252. doi:10.1016/0022-1759(93)90093-mArnau-Bonachera, A., Cervera, C., Blas, E., Larsen, T., Martínez-Paredes, E., Ródenas, L., & Pascual, J. J. (2017). Long-term implications of feed energy source in different genetic types of reproductive rabbit females: I. Resource acquisition and allocation. animal, 12(9), 1867-1876. doi:10.1017/s1751731117003287Chen, X., Du, Y., Lin, X., Qian, Y., Zhou, T., & Huang, Z. (2016). CD4 + CD25 + regulatory T cells in tumor immunity. International Immunopharmacology, 34, 244-249. doi:10.1016/j.intimp.2016.03.009Kotani, M., Yamamura, Y., Tsudo, M., Tamatani, T., Kitamura, F., & Miyasaka, M. (1993). Generation of Monoclonal Antibodies to the Rabbit Interleukin-2 ReceptoraChain (CD25) and Its Distribution in HTLV-1-transformed Rabbit T Cells. Japanese Journal of Cancer Research, 84(7), 770-775. doi:10.1111/j.1349-7006.1993.tb02042.xAyoub, I. A., & Yang, T. J. (1996). Age-dependent changes in peripheral blood lymphocyte subpopulations in cattle: A longitudinal study. Developmental & Comparative Immunology, 20(5), 353-363. doi:10.1016/s0145-305x(96)00024-9Davis, A. K., Maney, D. L., & Maerz, J. C. (2008). The use of leukocyte profiles to measure stress in vertebrates: a review for ecologists. Functional Ecology, 22(5), 760-772. doi:10.1111/j.1365-2435.2008.01467.xCastelo-Branco, C., & Soveral, I. (2013). The immune system and aging: a review. Gynecological Endocrinology, 30(1), 16-22. doi:10.3109/09513590.2013.852531Estany, J., Camacho, J., Baselga, M., & Blasco, A. (1992). Selection response of growth rate in rabbits for meat production. Genetics Selection Evolution, 24(6), 527. doi:10.1186/1297-9686-24-6-527García-Quirós, A., Arnau-Bonachera, A., Penadés, M., Cervera, C., Martínez-Paredes, E., Ródenas, L., … Pascual, J. J. (2014). A robust rabbit line increases leucocyte counts at weaning and reduces mortality by digestive disorder during fattening. Veterinary Immunology and Immunopathology, 161(3-4), 123-131. doi:10.1016/j.vetimm.2014.07.005Jeklova, E., Leva, L., & Faldyna, M. (2007). Lymphoid organ development in rabbits: Major lymphocyte subsets. Developmental & Comparative Immunology, 31(6), 632-644. doi:10.1016/j.dci.2006.10.002Jacobsen, C. N., Aasted, B., Broe, M. K., & Petersen, J. L. (1993). Reactivities of 20 anti-human monoclonal antibodies with leucocytes from ten different animal species. Veterinary Immunology and Immunopathology, 39(4), 461-466. doi:10.1016/0165-2427(93)90075-fMacIver, N. J., Jacobs, S. R., Wieman, H. L., Wofford, J. A., Coloff, J. L., & Rathmell, J. C. (2008). Glucose metabolism in lymphocytes is a regulated process with significant effects on immune cell function and survival. Journal of Leukocyte Biology, 84(4), 949-957. doi:10.1189/jlb.0108024Knap, P. W. (2005). Breeding robust pigs. Australian Journal of Experimental Agriculture, 45(8), 763. doi:10.1071/ea05041Meglia, G. E., Johannisson, A., Agenäs, S., Holtenius, K., & Waller, K. P. (2005). Effects of feeding intensity during the dry period on leukocyte and lymphocyte sub-populations, neutrophil function and health in periparturient dairy cows. The Veterinary Journal, 169(3), 376-384. doi:10.1016/j.tvjl.2004.02.003Nussey, D. H., Watt, K., Pilkington, J. G., Zamoyska, R., & McNeilly, T. N. (2011). Age‐related variation in immunity in a wild mammal population. Aging Cell, 11(1), 178-180. doi:10.1111/j.1474-9726.2011.00771.xPlowden, J., Renshaw-Hoelscher, M., Engleman, C., Katz, J., & Sambhara, S. (2004). Innate immunity in aging: impact on macrophage function. Aging Cell, 3(4), 161-167. doi:10.1111/j.1474-9728.2004.00102.xPlowden, J., Renshaw-Hoelscher, M., Gangappa, S., Engleman, C., Katz, J. M., & Sambhara, S. (2004). Impaired antigen-induced CD8+ T cell clonal expansion in aging is due to defects in antigen presenting cell function. Cellular Immunology, 229(2), 86-92. doi:10.1016/j.cellimm.2004.07.001Rosell, J. M., & de la Fuente, L. F. (2009). Culling and mortality in breeding rabbits. Preventive Veterinary Medicine, 88(2), 120-127. doi:10.1016/j.prevetmed.2008.08.003Dejaco, C., Duftner, C., Grubeck-Loebenstein, B., & Schirmer, M. (2006). Imbalance of regulatory T cells in human autoimmune diseases. Immunology, 117(3), 289-300. doi:10.1111/j.1365-2567.2005.02317.xWells, M. Y., Decobecq, C. P.-M., Decouvelaere, D. M., Justice, C., & Guittin, P. (1999). Changes in Clinical Pathology Parameters During Gestation in the New Zealand White Rabbit. Toxicologic Pathology, 27(3), 370-379. doi:10.1177/01926233990270031

Screening of virulence genes in Staphylococcus aureus isolates from rabbits

[EN] Staphylococcus aureus is a versatile pathogen able to cause disease in both humans and animals. In rabbits, this bacterium infects animals of different ages, producing several purulent lesions. The ability of S. aureus to cause disease depends on a combination of virulence factors. The aim of this study was therefore to investigate the distribution of bacterial virulence determinants in 69 S. aureus isolates from rabbits. Some virulence factors (7 adhesins, 1 toxin and 1 protease) were positive in all rabbit S. aureus isolates analysed, while others (1 adhesin and 10 toxins) were always negative. The remaining virulence factors were more variable among isolates. An association between genotype and the different profiles of virulence factors was observed, but not with the type of lesion (P<0.05). One strain of each genotype was further analysed by multilocus sequence typing, generating ST121, ST96 and ST2951, determining a greater number of enterotoxins in ST121 isolates compared to ST96 and ST2951 isolates, which could justify the different pathogenicity between strains. This study was supported by the Inter-ministerial Commission for Science and Technology (CICYT) of the Spanish Government (AGL2011-30170-C02-02 and AGL2014-53405-C2-2-P). The fellowship support for MP from Ministry of Education, Culture and Sports, Spain (AP2010-3907) is gratefully acknowledged.Viana Martín, D.; Selva, L.; Penadés, M.; Corpa, JM. (2015). Screening of virulence genes in Staphylococcus aureus isolates from rabbits. World Rabbit Science. 23(3):185-195. https://doi.org/10.4995/wrs.2015.3961SWORD18519523

First molecular detection and characterization of herpesvirus and poxvirus in a Pacific walrus (Odobenus rosmarus divergens)

BACKGROUND Herpesvirus and poxvirus can infect a wide range of species: herpesvirus genetic material has been detected and amplified in five species of the superfamily Pinnipedia; poxvirus genetic material, in eight species of Pinnipedia. To date, however, genetic material of these viruses has not been detected in walrus (Odobenus rosmarus), another marine mammal of the Pinnipedia clade, even though anti-herpesvirus antibodies have been detected in these animals. CASE PRESENTATION In February 2013, a 9-year-old healthy captive female Pacific walrus died unexpectedly at L'Oceanografic (Valencia, Spain). Herpesvirus was detected in pharyngeal tonsil tissue by PCR. Phylogenetic analysis revealed that the virus belongs to the subfamily Gammaherpesvirinae. Poxvirus was also detected by PCR in skin, pre-scapular and tracheobronchial lymph nodes and tonsils. Gross lesions were not detected in any tissue, but histopathological analyses of pharyngeal tonsils and lymph nodes revealed remarkable lymphoid depletion and lymphocytolysis. Similar histopathological lesions have been previously described in bovine calves infected with an alphaherpesvirus, and in northern elephant seals infected with a gammaherpesvirus that is closely related to the herpesvirus found in this case. Intracytoplasmic eosinophilic inclusion bodies, consistent with poxviral infection, were also observed in the epithelium of the tonsilar mucosa. CONCLUSION To our knowledge, this is the first molecular identification of herpesvirus and poxvirus in a walrus. Neither virus was likely to have contributed directly to the death of our animal

Pathogenesis of Intradermal Staphylococcal Infections Rabbit Experimental Approach to Natural Staphylococcus aureus Skin Infections

[EN] Despite the enormous efforts made to achieve effective tools that fight against Staphylococcus aureus, the results have not been successful. This failure may be due to the absence of truly representative experimental models. To overcome this deficiency, the present work describes and immunologically characterizes the infection for 28 days, in an experimental low-dose (300 colony-forming units) intradermal model of infection in rabbits, which reproduces the characteristic staphylococcal abscess. Surprisingly, when mutant strains in the genes involved in virulence (J Delta agr, J Delta coa Delta vwb, J Delta hla, and J Delta psm alpha) were inoculated, no strong effect on the severity of lesions was observed, unlike other models that use high doses of bacteria. The inoculation of a human rabbitized (FdltB(r)) strain demonstrated its capacity to generate a similar inflammatory response to a wild-type rabbit strain and, therefore, validated this model for conducting these experimental studies with human strains. To conclude, this model proved reproducible and may be an option of choice to check both wild-type and mutant strains of different origins.Supported by the Spanish Ministry of Economy and Competitiveness (MINECO) grant AGL2014-53405-C2-2-P, the Universidad CEU Cardenal Herrera, and European Union Development Fund (FEDER) Programme PO FEDER 2007-2013. A.M.-S., A.G.-Q., and E.M.-G. receive fellowship support from the Universidad CEU Cardenal Herrera; S.P.-F. receives fellowship support from the Generalitat Valenciana ACIF/2016/085; and M.P. and E.M.-G. receive fellowship support from the Spanish Ministry of Education, Culture, and Sport AP2010-3907 and FPU17/02708, respectively.Muñoz-Silvestre, A.; Penadés, M.; Selva, L.; Pérez-Fuentes, S.; Moreno Grua, E.; García-Quirós, A.; Pascual Amorós, JJ.... (2020). Pathogenesis of Intradermal Staphylococcal Infections Rabbit Experimental Approach to Natural Staphylococcus aureus Skin Infections. The American Journal of Pathology. 190(6):1188-1210. https://doi.org/10.1016/j.ajpath.2020.01.019S118812101906Kobayashi, S. D., Malachowa, N., & DeLeo, F. R. (2015). Pathogenesis of Staphylococcus aureus Abscesses. The American Journal of Pathology, 185(6), 1518-1527. doi:10.1016/j.ajpath.2014.11.030Lowy, F. D. (2011). HowStaphylococcus aureusAdapts to Its Host. New England Journal of Medicine, 364(21), 1987-1990. doi:10.1056/nejmp1100251Peschel, A., & Otto, M. (2013). Phenol-soluble modulins and staphylococcal infection. Nature Reviews Microbiology, 11(10), 667-673. doi:10.1038/nrmicro3110Von Eiff, C., Becker, K., Machka, K., Stammer, H., & Peters, G. (2001). Nasal Carriage as a Source ofStaphylococcus aureusBacteremia. New England Journal of Medicine, 344(1), 11-16. doi:10.1056/nejm200101043440102Saïd-Salim, B., Dunman, P. M., McAleese, F. M., Macapagal, D., Murphy, E., McNamara, P. J., … Kreiswirth, B. N. (2003). Global Regulation of Staphylococcus aureus Genes by Rot. Journal of Bacteriology, 185(2), 610-619. doi:10.1128/jb.185.2.610-619.2003Gao, J., & Stewart, G. C. (2004). Regulatory Elements of the Staphylococcus aureus Protein A (Spa) Promoter. Journal of Bacteriology, 186(12), 3738-3748. doi:10.1128/jb.186.12.3738-3748.2004Fridkin, S. K., Hageman, J. C., Morrison, M., Sanza, L. T., Como-Sabetti, K., Jernigan, J. A., … Farley, M. M. (2005). Methicillin-ResistantStaphylococcus aureusDisease in Three Communities. New England Journal of Medicine, 352(14), 1436-1444. doi:10.1056/nejmoa043252DeLeo, F. R., Otto, M., Kreiswirth, B. N., & Chambers, H. F. (2010). Community-associated meticillin-resistant Staphylococcus aureus. The Lancet, 375(9725), 1557-1568. doi:10.1016/s0140-6736(09)61999-1Talan, D. A., Krishnadasan, A., Gorwitz, R. J., Fosheim, G. E., Limbago, B., … Albrecht, V. (2011). Comparison of Staphylococcus aureus From Skin and Soft-Tissue Infections in US Emergency Department Patients, 2004 and 2008. Clinical Infectious Diseases, 53(2), 144-149. doi:10.1093/cid/cir308Bae, I.-G., Tonthat, G. T., Stryjewski, M. E., Rude, T. H., Reilly, L. F., Barriere, S. L., … Fowler, V. G. (2009). Presence of Genes Encoding the Panton-Valentine Leukocidin Exotoxin Is Not the Primary Determinant of Outcome in Patients with Complicated Skin and Skin Structure Infections Due to Methicillin-Resistant Staphylococcus aureus  : Results of a Multinational Trial. Journal of Clinical Microbiology, 47(12), 3952-3957. doi:10.1128/jcm.01643-09Kennedy, A. D., Wardenburg, J. B., Gardner, D. J., Long, D., Whitney, A. R., Braughton, K. R., … DeLeo, F. R. (2010). Targeting of Alpha‐Hemolysin by Active or Passive Immunization Decreases Severity of USA300 Skin Infection in a Mouse Model. The Journal of Infectious Diseases, 202(7), 1050-1058. doi:10.1086/656043Viana, D., Selva, L., Segura, P., Penadés, J. R., & Corpa, J. M. (2007). Genotypic characterization of Staphylococcus aureus strains isolated from rabbit lesions. Veterinary Microbiology, 121(3-4), 288-298. doi:10.1016/j.vetmic.2006.12.003Viana, D., Comos, M., McAdam, P. R., Ward, M. J., Selva, L., Guinane, C. M., … Penadés, J. R. (2015). A single natural nucleotide mutation alters bacterial pathogen host tropism. Nature Genetics, 47(4), 361-366. doi:10.1038/ng.3219Jung, E. C., & Maibach, H. I. (2014). Animal models for percutaneous absorption. Journal of Applied Toxicology, 35(1), 1-10. doi:10.1002/jat.3004Malachowa, N., Kobayashi, S. D., Porter, A. R., Braughton, K. R., Scott, D. P., Gardner, D. J., … DeLeo, F. R. (2016). Contribution of Staphylococcus aureus Coagulases and Clumping Factor A to Abscess Formation in a Rabbit Model of Skin and Soft Tissue Infection. PLOS ONE, 11(6), e0158293. doi:10.1371/journal.pone.0158293Le, V. T. M., Tkaczyk, C., Chau, S., Rao, R. L., Dip, E. C., Pereira-Franchi, E. P., … Diep, B. A. (2016). Critical Role of Alpha-Toxin and Protective Effects of Its Neutralization by a Human Antibody in Acute Bacterial Skin and Skin Structure Infections. Antimicrobial Agents and Chemotherapy, 60(10), 5640-5648. doi:10.1128/aac.00710-16Otto, M. (2014). Staphylococcus aureus toxins. Current Opinion in Microbiology, 17, 32-37. doi:10.1016/j.mib.2013.11.004Collins, L. V., Kristian, S. A., Weidenmaier, C., Faigle, M., van Kessel, K. P. M., van Strijp, J. A. G., … Peschel, A. (2002). Staphylococcus aureusStrains Lackingd‐Alanine Modifications of Teichoic Acids Are Highly Susceptible to Human Neutrophil Killing and Are Virulence Attenuated in Mice. The Journal of Infectious Diseases, 186(2), 214-219. doi:10.1086/341454Novick, R. P. (1991). [27] Genetic systems in Staphylococci. Bacterial Genetic Systems, 587-636. doi:10.1016/0076-6879(91)04029-nLindsay, J. A., Ruzin, A., Ross, H. F., Kurepina, N., & Novick, R. P. (1998). The gene for toxic shock toxin is carried by a family of mobile pathogenicity islands inStaphylococcus aureus. Molecular Microbiology, 29(2), 527-543. doi:10.1046/j.1365-2958.1998.00947.xArnaud, M., Chastanet, A., & Débarbouillé, M. (2004). New Vector for Efficient Allelic Replacement in Naturally Nontransformable, Low-GC-Content, Gram-Positive Bacteria. Applied and Environmental Microbiology, 70(11), 6887-6891. doi:10.1128/aem.70.11.6887-6891.2004Úbeda, C., Maiques, E., Knecht, E., Lasa, Í., Novick, R. P., & Penadés, J. R. (2005). Antibiotic-induced SOS response promotes horizontal dissemination of pathogenicity island-encoded virulence factors in staphylococci. Molecular Microbiology, 56(3), 836-844. doi:10.1111/j.1365-2958.2005.04584.xLi, M., Cheung, G. Y. C., Hu, J., Wang, D., Joo, H., DeLeo, F. R., & Otto, M. (2010). Comparative Analysis of Virulence and Toxin Expression of Global Community‐Associated Methicillin‐ResistantStaphylococcus aureusStrains. The Journal of Infectious Diseases, 202(12), 1866-1876. doi:10.1086/657419Bunce, C., Wheeler, L., Reed, G., Musser, J., & Barg, N. (1992). Murine model of cutaneous infection with gram-positive cocci. Infection and Immunity, 60(7), 2636-2640. doi:10.1128/iai.60.7.2636-2640.1992Voyich, J. M., Otto, M., Mathema, B., Braughton, K. R., Whitney, A. R., Welty, D., … DeLeo, F. R. (2006). Is Panton‐Valentine Leukocidin the Major Virulence Determinant in Community‐Associated Methicillin‐ResistantStaphylococcus aureusDisease? The Journal of Infectious Diseases, 194(12), 1761-1770. doi:10.1086/509506Jeklova, E., Leva, L., & Faldyna, M. (2007). Lymphoid organ development in rabbits: Major lymphocyte subsets. Developmental & Comparative Immunology, 31(6), 632-644. doi:10.1016/j.dci.2006.10.002Guerrero, I., Ferrian, S., Blas, E., Pascual, J. J., Cano, J. L., & Corpa, J. M. (2011). Evolution of the peripheral blood lymphocyte populations in multiparous rabbit does with two reproductive management rhythms. Veterinary Immunology and Immunopathology, 140(1-2), 75-81. doi:10.1016/j.vetimm.2010.11.017Hulstaert, F., Hannet, I., Deneys, V., Munhyeshuli, V., Reichert, T., De Bruyere, M., & Strauss, K. (1994). Age-Related Changes in Human Blood Lymphocyte Subpopulations. Clinical Immunology and Immunopathology, 70(2), 152-158. doi:10.1006/clin.1994.1023Armand-Lefevre, L., Ruimy, R., & Andremont, A. (2005). Clonal Comparison ofStaphylococcus aureusIsolates from Healthy Pig Farmers, Human Controls, and Pigs. Emerging Infectious Diseases, 11(5), 711-714. doi:10.3201/eid1105.040866Graveland, H., Duim, B., van Duijkeren, E., Heederik, D., & Wagenaar, J. A. (2011). Livestock-associated methicillin-resistant Staphylococcus aureus in animals and humans. International Journal of Medical Microbiology, 301(8), 630-634. doi:10.1016/j.ijmm.2011.09.004Aires-de-Sousa, M. (2017). Methicillin-resistant Staphylococcus aureus among animals: current overview. Clinical Microbiology and Infection, 23(6), 373-380. doi:10.1016/j.cmi.2016.11.002Moreno-Grúa, E., Pérez-Fuentes, S., Muñoz-Silvestre, A., Viana, D., Fernández-Ros, A. B., Sanz-Tejero, C., … Selva, L. (2018). Characterization of Livestock-Associated Methicillin-Resistant Staphylococcus aureus Isolates Obtained From Commercial Rabbitries Located in the Iberian Peninsula. Frontiers in Microbiology, 9. doi:10.3389/fmicb.2018.01812Viana, D., Selva, L., Callanan, J. J., Guerrero, I., Ferrian, S., & Corpa, J. M. (2011). Strains of Staphylococcus aureus and pathology associated with chronic suppurative mastitis in rabbits. The Veterinary Journal, 190(3), 403-407. doi:10.1016/j.tvjl.2010.11.022Cheng, A. G., DeDent, A. C., Schneewind, O., & Missiakas, D. (2011). A play in four acts: Staphylococcus aureus abscess formation. Trends in Microbiology, 19(5), 225-232. doi:10.1016/j.tim.2011.01.007Chen, X., Du, Y., Lin, X., Qian, Y., Zhou, T., & Huang, Z. (2016). CD4 + CD25 + regulatory T cells in tumor immunity. International Immunopharmacology, 34, 244-249. doi:10.1016/j.intimp.2016.03.009Bekeredjian-Ding, I. (2017). Deciphering the significance of the T-cell response to Staphylococcus aureus. Future Microbiology, 12(12), 1023-1026. doi:10.2217/fmb-2017-0138Krishna, S., & Miller, L. S. (2011). Innate and adaptive immune responses against Staphylococcus aureus skin infections. Seminars in Immunopathology, 34(2), 261-280. doi:10.1007/s00281-011-0292-6Liu, Q., Mazhar, M., & Miller, L. S. (2018). Immune and Inflammatory Reponses to Staphylococcus aureus Skin Infections. Current Dermatology Reports, 7(4), 338-349. doi:10.1007/s13671-018-0235-8Miller, L. S., & Cho, J. S. (2011). Immunity against Staphylococcus aureus cutaneous infections. Nature Reviews Immunology, 11(8), 505-518. doi:10.1038/nri3010Terada, M., Tsutsui, H., Imai, Y., Yasuda, K., Mizutani, H., Yamanishi, K., … Nakanishi, K. (2006). Contribution of IL-18 to atopic-dermatitis-like skin inflammation induced by Staphylococcus aureus product in mice. Proceedings of the National Academy of Sciences, 103(23), 8816-8821. doi:10.1073/pnas.0602900103Syed, A. K., Reed, T. J., Clark, K. L., Boles, B. R., & Kahlenberg, J. M. (2015). Staphlyococcus aureus Phenol-Soluble Modulins Stimulate the Release of Proinflammatory Cytokines from Keratinocytes and Are Required for Induction of Skin Inflammation. Infection and Immunity, 83(9), 3428-3437. doi:10.1128/iai.00401-15Laouini, D., Kawamoto, S., Yalcindag, A., Bryce, P., Mizoguchi, E., Oettgen, H., & Geha, R. S. (2003). Epicutaneous sensitization with superantigen induces allergic skin inflammation. Journal of Allergy and Clinical Immunology, 112(5), 981-987. doi:10.1016/j.jaci.2003.07.007Holtfreter, S., Radcliff, F. J., Grumann, D., Read, H., Johnson, S., Monecke, S., … Wiles, S. (2013). Characterization of a Mouse-Adapted Staphylococcus aureus Strain. PLoS ONE, 8(9), e71142. doi:10.1371/journal.pone.0071142Kobayashi, S. D., Malachowa, N., Whitney, A. R., Braughton, K. R., Gardner, D. J., Long, D., … DeLeo, F. R. (2011). Comparative Analysis of USA300 Virulence Determinants in a Rabbit Model of Skin and Soft Tissue Infection. The Journal of Infectious Diseases, 204(6), 937-941. doi:10.1093/infdis/jir441Schmid-Hempel, P., & Frank, S. A. (2007). Pathogenesis, Virulence, and Infective Dose. PLoS Pathogens, 3(10), e147. doi:10.1371/journal.ppat.0030147Inoshima, N., Wang, Y., & Bubeck Wardenburg, J. (2012). Genetic Requirement for ADAM10 in Severe Staphylococcus aureus Skin Infection. Journal of Investigative Dermatology, 132(5), 1513-1516. doi:10.1038/jid.2011.462Tkaczyk, C., Hamilton, M. M., Datta, V., Yang, X. P., Hilliard, J. J., Stephens, G. L., … Sellman, B. R. (2013). Staphylococcus aureus Alpha Toxin Suppresses Effective Innate and Adaptive Immune Responses in a Murine Dermonecrosis Model. PLoS ONE, 8(10), e75103. doi:10.1371/journal.pone.0075103Wang, R., Braughton, K. R., Kretschmer, D., Bach, T.-H. L., Queck, S. Y., Li, M., … Otto, M. (2007). Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA. Nature Medicine, 13(12), 1510-1514. doi:10.1038/nm1656Recsei, P., Kreiswirth, B., O’Reilly, M., Schlievert, P., Gruss, A., & Novick, R. P. (1986). Regulation of exoprotein gene expression in Staphylococcus aureus by agr. Molecular and General Genetics MGG, 202(1), 58-61. doi:10.1007/bf00330517Rainard, P., Gitton, C., Chaumeil, T., Fassier, T., Huau, C., Riou, M., … Martin, P. (2018). Host factors determine the evolution of infection with Staphylococcus aureus to gangrenous mastitis in goats. Veterinary Research, 49(1). doi:10.1186/s13567-018-0564-4Salam, A. M., & Quave, C. L. (2018). Targeting Virulence in Staphylococcus aureus by Chemical Inhibition of the Accessory Gene Regulator System In Vivo. mSphere, 3(1). doi:10.1128/msphere.00500-17Cheng, A. G., Kim, H. K., Burts, M. L., Krausz, T., Schneewind, O., & Missiakas, D. M. (2009). Genetic requirements forStaphylococcus aureusabscess formation and persistence in host tissues. The FASEB Journal, 23(10), 3393-3404. doi:10.1096/fj.09-135467Cheng, A. G., McAdow, M., Kim, H. K., Bae, T., Missiakas, D. M., & Schneewind, O. (2010). Contribution of Coagulases towards Staphylococcus aureus Disease and Protective Immunity. PLoS Pathogens, 6(8), e1001036. doi:10.1371/journal.ppat.1001036Kim, H. K., Missiakas, D., & Schneewind, O. (2014). Mouse models for infectious diseases caused by Staphylococcus aureus. Journal of Immunological Methods, 410, 88-99. doi:10.1016/j.jim.2014.04.00

Smart Tree: An Architectural, Greening and ICT Multidisciplinary Approach to Smart Campus Environments.

At present, climate change, pollution, and uncontrolled urbanism threaten not only natural ecosystems, but also the urban environment. Approaches to mitigate these challenges and able to provide an alternative for the use of the space are deemed to be multidisciplinary, combining architecture, vegetation integration, circular economy and information and communications technologies (ICT). University campuses are a key scenario to evaluate such solutions as their student and research community is intrinsically willing to support these experiences and provide a wide knowledge on the fields necessary for their design and implementation. However, the creation of areas combining usability and sustainability is commonly lacking a multidisciplinary approach combining all these different perspectives. Hence, the present work aims to overcome this limitation by the development of a novel integrated approach for campus spaces for co-working and leisure, namely a “Smart Tree”, where novel architecture, furniture design, flora integration, environmental sensoring and communications join together. To this end, a survey of the literature is provided, covering related approaches as well as general principles behind them. From this, the general requirements and constraints for the development of the Smart Tree area are identified, establishing the main interactions between the architecture, greening and ICT perspectives. Such requirements guide the proposed system design and implementation, whose impact on the environment is analyzed

Killing niche competitors by remote-control bacteriophage induction

A surprising example of interspecies competition is the production by certain bacteria of hydrogen peroxide at concentrations that are lethal for others. A case in point is the displacement of Staphylococcus aureus by Streptococcus pneumoniae in the nasopharynx, which is of considerable clinical significance. How it is accomplished, however, has been a great mystery, because H2O2 is a very well known disinfectant whose lethality is largely due to the production of hyperoxides through the abiological Fenton reaction. In this report, we have solved the mystery by showing that H2O2 at the concentrations typically produced by pneumococci kills lysogenic but not nonlysogenic staphylococci by inducing the SOS response. The SOS response, a stress response to DNA damage, not only invokes DNA repair mechanisms but also induces resident prophages, and the resulting lysis is responsible for H2O2 lethality. Because the vast majority of S. aureus strains are lysogenic, the production of H2O2 is a very widely effective antistaphylococcal strategy. Pneumococci, however, which are also commonly lysogenic and undergo SOS induction in response to DNA-damaging agents such as mitomycin C, are not SOS-induced on exposure to H2O2. This is apparently because they are resistant to the DNAdamaging effects of the Fenton reaction. The production of an SOS-inducing signal to activate prophages in neighboring organisms is thus a rather unique competitive strategy, which we suggest may be in widespread use for bacterial interference. However, this strategy has as a by-product the release of active phage, which can potentially spread mobile genetic elements carrying virulence genes.This work was supported by Comisión Interministerial de Ciencia y Tecnología Grants BIO2005-08399-C02-02, BIO2008-05284-C02-02, and BIO2008-00642-E/C; Cardenal Herrera-CEU University Grants PRCEUUCH25/ 08 and Copernicus program; and by Conselleria de Agricultura, Pesca i Alimentació (CAPiA), and from the Generalitat Valenciana (ACOMP07/258) (J.R.P.). L.S. and D.V. were supported by Cardenal Herrera-CEU University fellowships