Tendencia a la asimetría funcional y quiralidad helicoidal inducida por microsatélites en Staphylococcus aureus
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Staphylococcus aureus presenta una distribución genómica rica en microsatélites, lo que puede inducir asimetrías funcionales y sesgos de quiralidad helicoidal. Se analizaron cuatro genomas reportados en la base de datos NCBI y se cuantificaron los motivos repetitivos ATAT, ACAC y AGAG en todos los genes mediante la herramienta MFind y los gráficos de superficie. Se observaron diferencias reproducibles en la topografía de picos y valles entre genomas, con un patrón consistente de similitud en Gn2–Gn4 y un marcado desvío en Gn1. Mientras que ATAT predominó en Gn2–Gn4, Gn1 mostró un enriquecimiento atípico de ACAC. Este cambio en el motivo dominante, junto con el desplazamiento de máximos entre genomas, sugiere una variación en la disposición local de las repeticiones compatible con efectos quirales (asimetrías entre hebras, repeticiones invertidas y posibles transiciones entre patrones en espejo). Tales configuraciones son plausibles moduladoras de la direccionalidad regulatoria, de la formación de estructuras secundarias y de la propensión a la recombinación. Metodológicamente, se destaca que la métrica empleada puede verse influida por la longitud de las regiones y de los genes analizados. En el análisis de tres motivos en cuatro genomas, los patrones observados ofrecen un mapa comparativo inicial de la dimensión quiral en la arquitectura repetitiva de S. aureus y motivan análisis mecanísticos que integren evidencia estructural y funcional para cuantificar la contribución de la quiralidad a la variación genómica entre linajes. Se ponen a disposición los genomas, las tablas de cuantificación de microsatélites y los cálculos del índice propuesto de tendencia al cambio de quiralidad: https://www.usegalaxy.org/u/rioswillars/h/s-aureus-microsatellite.
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Referencias
Ahmad-Mansour, N., Loubet, P., Pouget, C., Dunyach-Remy, C., Sotto, A., Lavigne, J.-P. and Molle, V. (2021) ‘Staphylococcus aureus toxins: An update on their pathogenic properties and potential treatments’, Toxins, 13(10), 677. https://doi.org/10.3390/toxins13100677
Archer, G.L. (1998) ‘Staphylococcus aureus: A well-armed pathogen’, Clinical Infectious Diseases, 26(5), pp. 1179–1181. https://doi.org/10.1086/520289
Bacolla, A., Larson, J.E., Collins, J.R., Li, J., Milosavljevic, A., Stenson, P.D., Cooper, D.N. and Wells, R.D. (2008) ‘Abundance and length of simple repeats in vertebrate genomes are determined by their structural properties’, Genome Research, 18(10), pp. 1545–1553. https://doi.org/10.1101/gr.078303.108
Bagshaw, A.T.M. (2017) ‘Functional mechanisms of microsatellite ADN in eukaryotic genomes’, Genome Biology and Evolution, 9(9), pp. 2428–2443. https://doi.org/10.1093/gbe/evx164
Brooks, J. and Jefferson, K. (2014) ‘Phase variation of poly-N-acetylglucosamine expression in Staphylococcus aureus’, PLoS Pathogens, 10(7), e1004292. https://doi.org/10.1371/journal.ppat.1004292
Crespo-Piazuelo, D. and Lawlor, P.G. (2021) ‘Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) prevalence in humans in close contact with animals and measures to reduce on-farm colonisation’, Irish Veterinary Journal, 74(1), 21. https://doi.org/10.1186/s13620-021-00200-7
Dunyach-Remy, C., Ngba Essebe, C., Sotto, A. and Lavigne, J.-P. (2016) ‘Staphylococcus aureus toxins and diabetic foot ulcers: Role in pathogenesis and interest in diagnosis’, Toxins, 8(7), 209. https://doi.org/10.3390/toxins8070209
Essien, U.C., Boswihi, S.S., Agbakoba, N.R. and Udo, E.E. (2022) ‘Description of methicillin-susceptible Staphylococcus aureus clonal complex 30 related to the pandemic phage type 80/81 isolated from patients in three tertiary hospitals in Jos, North Central Nigeria’, Medical Principles and Practice, 31, pp. 269–275. https://doi.org/10.1159/000524755
Gadgil, R.Y., Romer, E.J., Goodman, C.C., Rider, S.D., Damewood, F.J., Barthelemy, J.R., Shin-ya, K., Hanenberg, H. and Leffak, M. (2020) ‘Replication stress at microsatellites causes DNA double-strand breaks and break-induced replication’, Journal of Biological Chemistry, 295(45), pp. 15378–15397. https://doi.org/10.1074/jbc.RA120.013495
George, A.N., Stewart, J.R., Evans, J.C. and Gibson, J.M. (2020) ‘Risk of antibiotic-resistant Staphylococcus aureus dispersion from hog farms: A critical review’, Risk Analysis, 40(8), pp. 1645–1665. https://doi.org/10.1111/risa.13495
Gherardi, G. (2023) ‘Staphylococcus aureus infection: Pathogenesis and antimicrobial resistance’, International Journal of Molecular Sciences, 24(9), 8182. https://doi.org/10.3390/ijms24098182
Gladding, T.L., Rolph, C.A., Gwyther, C.L., Kinnersley, R., Walsh, K. and Tyrrel, S. (2020) ‘Concentration and composition of bioaerosol emissions from intensive farms: Pig and poultry livestock’, Journal of Environmental Management, 272, 111052. https://doi.org/10.1016/j.jenvman.2020.111052
Gor, V., Ohniwa, R. and Morikawa, K. (2021) ‘No change, no life? What we know about phase variation in Staphylococcus aureus’, Microorganisms, 9(2), 244. https://doi.org/10.3390/microorganisms9020244
Guillén, R., Salinas, C., Mendoza-Álvarez, A., Rubio Rodríguez, L.A., Díaz-de Usera, A., Lorenzo-Salazar, J.M., González-Montelongo, R., Flores, C. and Rodríguez, F. (2024) ‘Genomic epidemiology of the primary methicillin-resistant Staphylococcus aureus clones causing invasive infections in Paraguayan children’, Microbiology Spectrum, 12(2), e03012-23. https://doi.org/10.1128/spectrum.03012-23
Harhay, G., Harhay, D., Bono, J., Capik, S., Dedonder, K., Apley, M., Lubbers, B., White, B., Larson, R. and Smith, T. (2019) ‘A computational method to quantify the effects of slipped strand mispairing on bacterial tetranucleotide repeats’, Scientific Reports, 9, 17192. https://doi.org/10.1038/s41598-019-53866-z
Heaton, C.J., Gerbig, G.R., Sensius, L.D., Patel, V. and Smith, T.C. (2020) ‘Staphylococcus aureus epidemiology in wildlife: A systematic review’, Antibiotics, 9(2), 89. https://doi.org/10.3390/antibiotics9020089
Holden, M.T.G., Feil, E.J., Lindsay, J.A., Peacock, S.J., Day, N.P.J., Enright, M.C., Foster, T.J., Moore, C.E., Hurst, L., Atkin, R., Barron, A., Bason, N., Bentley, S.D., Chillingworth, C., Chillingworth, T., Churcher, C., Clark, L., Corton, C., Cronin, A. and Parkhill, J. (2004) ‘Complete genomes of two clinical Staphylococcus aureus strains: Evidence for the rapid evolution of virulence and drug resistance’, Proceedings of the National Academy of Sciences, 101(26), pp. 9786–9791. https://doi.org/10.1073/pnas.0402521101
Idrees, M., Sawant, S., Karodia, N. and Rahman, A. (2021) ‘Staphylococcus aureus biofilm: Morphology, genetics, pathogenesis and treatment strategies’, International Journal of Environmental Research and Public Health, 18(14), 7602. https://doi.org/10.3390/ijerph18147602
Kwiecinski, J.M. and Horswill, A.R. (2020) ‘Staphylococcus aureus bloodstream infections: Pathogenesis and regulatory mechanisms’, Current Opinion in Microbiology, 53, pp. 51–60. https://doi.org/10.1016/j.mib.2020.02.005
Larkin, E., Carman, R., Krakauer, T. and Stiles, B. (2009) ‘Staphylococcus aureus: The toxic presence of a pathogen extraordinaire’, Current Medicinal Chemistry, 16(30), pp. 4003–4019. https://doi.org/10.2174/092986709789352321
Martin, P., Makepeace, K., Hill, S.A., Hood, D.W. and Moxon, E.R. (2005) ‘Microsatellite instability regulates transcription factor binding and gene expression’, Proceedings of the National Academy of Sciences, 102(10), pp. 3800–3804. https://doi.org/10.1073/pnas.0406805102
Metzgar, D., Liu, L., Hansen, C., Dybvig, K. and Wills, C. (2002) ‘Domain-level differences in microsatellite distribution and content result from different relative rates of insertion and deletion mutations’, Genome Research, 12(3), pp. 408–413. https://doi.org/10.1101/gr.198602
Monecke, S., Akpaka, P.E., Smith, M.R., Unakal, C.G., Thoms Rodriguez, C.-A., Ashraph, K., Müller, E., Braun, S.D., Diezel, C., Reinicke, M. and Ehricht, R. (2023) ‘Clonal complexes distribution of Staphylococcus aureus isolates from clinical samples from the Caribbean Islands’, Antibiotics, 12(6), 1050. https://doi.org/10.3390/antibiotics12061050
Narechania, A., Baker, R., DeSalle, R., Mathema, B., Kolokotronis, S.-O., Kreiswirth, B. and Planet, P.J. (2016) ‘Clusterflock: A flocking algorithm for isolating congruent phylogenomic datasets’, GigaScience, 5(1), 43. https://doi.org/10.1186/s13742-016-0152-3
Oliveira, D., Borges, A. and Simões, M. (2018) ‘Staphylococcus aureus toxins and their molecular activity in infectious diseases’, Toxins, 10(6), 252. https://doi.org/10.3390/toxins10060252
Pedersen, K., Nielsen, M.W., Fertner, M.E., Espinosa-Gongora, C. and Bækbo, P. (2024) ‘Development of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) loads in pigs and pig stables during the fattening period’, Veterinary Sciences, 11(11), 558. https://doi.org/10.3390/vetsci11110558
Ramirez, H.A., Pastar, I., Jozic, I., Stojadinovic, O., Stone, R.C., Ojeh, N., Gil, J., Davis, S.C., Kirsner, R.S. and Tomic-Canic, M. (2018) ‘Staphylococcus aureus triggers induction of miR-15B-5P to diminish DNA repair and deregulate inflammatory response in diabetic foot ulcers’, Journal of Investigative Dermatology, 138(5), pp. 1187–1196. https://doi.org/10.1016/j.jid.2017.11.038
Ramos, B., Rosalino, L.M., Palmeira, J.D., Torres, R.T. and Cunha, M.V. (2022) ‘Antimicrobial resistance in commensal Staphylococcus aureus from wild ungulates is driven by agricultural land cover and livestock farming’, Environmental Pollution, 303, 119116. https://doi.org/10.1016/j.envpol.2022.119116
Rios-Willars, E. and Chirinos-Arias, M.C. (2024) ‘Mfind: A tool for DNA barcode analysis in angiosperms and its relationship with microsatellites using a sliding window algorithm’, Planta, 259(6), 134. https://doi.org/10.1007/s00425-024-04420-3
Saeed, A.F., Wang, R. and Wang, S. (2016) ‘Microsatellites in pursuit of microbial genome evolution’, Frontiers in Microbiology, 6, 1462. https://doi.org/10.3389/fmicb.2015.01462
Sayers, E.W., Beck, J., Bolton, E.E., Brister, J.R., Chan, J., Connor, R., Feldgarden, M., Fine, A.M., Funk, K., Hoffman, J., Kannan, S., Kelly, C., Klimke, W., Kim, S., Lathrop, S., Marchler-Bauer, A., Murphy, T.D., O’Sullivan, C., Schmieder, E. and Pruitt, K.D. (2025) ‘Database resources of the National Center for Biotechnology Information in 2025’, Nucleic Acids Research, 53(D1), pp. D20–D29. https://doi.org/10.1093/nar/gkae979
Sayhood, M.H., Mohammed, A.L., Abdulhameed, M.F. and Jori, M.M. (2022) ‘Classical and molecular identification of Staphylococcus aureus isolated from infestation cattle wounds with myiasis in Basrah governorate, Iraq’, Iraqi Journal of Veterinary Sciences, 36(3), pp. 641–646. https://doi.org/10.33899/ijvs.2021.131196.1930
Shettigar, K. and Murali, T.S. (2020) ‘Virulence factors and clonal diversity of Staphylococcus aureus in colonization and wound infection with emphasis on diabetic foot infection’, European Journal of Clinical Microbiology & Infectious Diseases, 39(12), pp. 2235–2246. https://doi.org/10.1007/s10096-020-03984-8
Song, X., Yang, T., Zhang, X., Yuan, Y., Yan, X., Wei, Y., Zhang, J. and Zhou, C. (2021) ‘Comparison of the microsatellite distribution patterns in the genomes of Euarchontoglires at the taxonomic level’, Frontiers in Genetics, 12, 622724. https://doi.org/10.3389/fgene.2021.622724
Srivastava, D., Ahmad, M.M., Shamim, M., Maurya, R., Srivastava, N., Pandey, P., Siddiqui, S. and Siddiqui, M.H. (2019) ‘Modulation of gene expression by microsatellites in microbes’, in New and Future Developments in Microbial Biotechnology and Bioengineering. Elsevier, pp. 209–218. https://doi.org/10.1016/B978-0-444-63503-7.00012-7
Tatusova, T., Ciufo, S., Fedorov, B., O’Neill, K. and Tolstoy, I. (2015) ‘RefSeq microbial genomes database: New representation and annotation strategy’, Nucleic Acids Research, 43(7), p. 3872. https://doi.org/10.1093/nar/gkv278
Timsit, Y. and Várnai, P. (2010) ‘Helical chirality: A link between local interactions and global topology in DNA’, PLoS ONE, 5(2), e9326. https://doi.org/10.1371/journal.pone.0009326
Tong, S.Y.C., Davis, J.S., Eichenberger, E., Holland, T.L. and Fowler, V.G. (2015) ‘Staphylococcus aureus infections: Epidemiology, pathophysiology, clinical manifestations, and management’, Clinical Microbiology Reviews, 28(3), pp. 603–661. https://doi.org/10.1128/CMR.00134-14
Vayssières, M., Marechal, N., Yun, L., Lopez Duran, B., Murugasamy, N.K., Fogg, J.M., Zechiedrich, L., Nadal, M. and Lamour, V. (2024) ‘Structural basis of DNA crossover capture by Escherichia coli DNA gyrase’, Science, 384(6692), pp. 227–232. https://doi.org/10.1126/science.adl5899
Wang, Y., Zhang, P., Wu, J., Chen, S., Jin, Y., Long, J., Duan, G. and Yang, H. (2023) ‘Transmission of livestock-associated methicillin-resistant Staphylococcus aureus between animals, environment, and humans in the farm’, Environmental Science and Pollution Research, 30(37), pp. 86521–86539. https://doi.org/10.1007/s11356-023-28532-7
Winogradoff, D., Li, P., Joshi, H., Quednau, L., Maffeo, C. and Aksimentiev, A. (2021) ‘Chiral systems made from DNA’, Advanced Science, 8(5), 2003113. https://doi.org/10.1002/advs.202003113
Wu, Y., Chen, T., Wang, Y., Huang, M., Wang, Y. and Luo, Z. (2023) ‘New insight into the virulence and inflammatory response of Staphylococcus aureus strains isolated from diabetic foot ulcers’, Frontiers in Cellular and Infection Microbiology, 13, 1234994. https://doi.org/10.3389/fcimb.2023.1234994
Yu, S., Xie, Y., Jiao, Y., Li, N. and Ding, B. (2025) ‘Nucleic acid-based chiral nanostructures and their biomedical applications’, Nanoscale Horizons, 10(9), pp. 1802–1814. https://doi.org/10.1039/D5NH00140D
Zhou, K., Aertsen, A. and Michiels, C. (2014) ‘The role of variable DNA tandem repeats in bacterial adaptation’, FEMS Microbiology Reviews, 38(1), pp. 119–141. https://doi.org/10.1111/1574-6976.12036