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Moreover, concerns regarding adverse effects limit their clinical implementation. We investigated the antibacterial efficacy of human recombinant histone H1 subtypes against\n                      <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                      PAO1, both planktonic and in biofilms. After the\n                      <jats:italic>in vitro<\/jats:italic>\n                      tests, toxicity and efficacy were assessed in a\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      PAO1 infection model using\n                      <jats:italic>Galleria mellonella<\/jats:italic>\n                      larvae. Histones were also evaluated in combination with ciprofloxacin (Cpx) and gentamicin (Gm). Our results demonstrate antimicrobial activity of all three histones against\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      PAO1, with H1.0 and H1.4 showing efficacy at lower concentrations. The bactericidal effect was associated with a mechanism of membrane disruption.\n                      <jats:italic>In vitro<\/jats:italic>\n                      studies using static and dynamic models showed that H1.4 had antibiofilm potential by reducing cell biomass. Neither H1.0 nor H1.4 showed toxicity in\n                      <jats:italic>G. mellonella<\/jats:italic>\n                      larvae, and both increased larvae survival when infected with\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      PAO1. Although\n                      <jats:italic>in vitro<\/jats:italic>\n                      synergism was observed between ciprofloxacin and H1.0, no improvement over the antibiotic alone was noted\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Differences in antibacterial and antibiofilm activity were attributed to sequence and structural variations among histone subtypes. Moreover, the efficacy of H1.0 and H1.4 was influenced by the presence and strength of the extracellular matrix. These findings suggest histones hold promise for combating acute and chronic infections caused by pathogens such as\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      .\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The constant increase of multidrug-resistant bacteria is a critical global concern. The inefficacy of current therapies to treat bacterial infections is attributed to multiple mechanisms of resistance, including the capacity to form biofilms. Therefore, the identification of novel and safe therapeutic strategies is imperative. This study confirms the antimicrobial potential of three histone H1 subtypes against both Gram-negative and Gram-positive bacteria. Furthermore, histones H1.0 and H1.4 demonstrated\n                        <jats:italic>in vivo<\/jats:italic>\n                        efficacy without associated toxicity in an acute infection model of\n                        <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                        PAO1 in\n                        <jats:italic>Galleria mellonella<\/jats:italic>\n                        larvae. The bactericidal effect of these proteins also resulted in biomass reduction of\n                        <jats:italic>P. aeruginosa<\/jats:italic>\n                        PAO1 biofilms. Given the clinical significance of this opportunistic pathogen, our research provides a comprehensive initial evaluation of the efficacy, toxicity, and mechanism of action of a potential new therapeutic approach against acute and chronic bacterial infections.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msystems.00704-24","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T09:01:48Z","timestamp":1730192508000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Antimicrobial and antibiofilm activity of human recombinant H1 histones against bacterial infections"],"prefix":"10.1128","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3363-5403","authenticated-orcid":false,"given":"Betsy Ver\u00f3nica","family":"Ar\u00e9valo-Jaimes","sequence":"first","affiliation":[{"name":"Bacterial infections and antimicrobial therapies group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology","place":["Barcelona, Spain"]},{"name":"Microbiology Section, Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Salinas-Pena","sequence":"additional","affiliation":[{"name":"Molecular Biology Institute of Barcelona (IBMB-CSIC)","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9448-6915","authenticated-orcid":false,"given":"Inmaculada","family":"Ponte","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Department, Universitat Aut\u00f2noma de Barcelona","place":["Bellaterra, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3970-8693","authenticated-orcid":true,"given":"Albert","family":"Jordan","sequence":"additional","affiliation":[{"name":"Molecular Biology Institute of Barcelona (IBMB-CSIC)","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6206-6481","authenticated-orcid":false,"given":"Alicia","family":"Roque","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Department, Universitat Aut\u00f2noma de Barcelona","place":["Bellaterra, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3010-1609","authenticated-orcid":true,"given":"Eduard","family":"Torrents","sequence":"additional","affiliation":[{"name":"Bacterial infections and antimicrobial therapies group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science 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