{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:16:43Z","timestamp":1785331003328,"version":"3.55.0"},"reference-count":50,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,30]],"date-time":"2022-04-30T00:00:00Z","timestamp":1651276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003069","name":"Instituto Polit\u00e9cnico Nacional","doi-asserted-by":"publisher","award":["20221352SIP"],"award-info":[{"award-number":["20221352SIP"]}],"id":[{"id":"10.13039\/501100003069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003069","name":"Instituto Polit\u00e9cnico Nacional","doi-asserted-by":"publisher","award":["20221193SIP"],"award-info":[{"award-number":["20221193SIP"]}],"id":[{"id":"10.13039\/501100003069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neutrophils play a crucial role in eliminating bacteria that invade the human body; however, cathepsin G can induce biofilm formation in a non-biofilm-forming Staphylococcus epidermidis 1457 strain, suggesting that neutrophil proteases may be involved in biofilm formation. Cathepsin G, cathepsin B, proteinase-3, and metalloproteinase-9 (MMP-9) from neutrophils were tested on the biofilm induction in commensal (skin isolated) and clinical non-biofilm-forming S. epidermidis isolates. From 81 isolates, 53 (74%) were aap+, icaA\u2212, icaD\u2212 genotype, and without the capacity of biofilm formation under conditions of 1% glucose, 4% ethanol or 4% NaCl, but these 53 non-biofilm-forming isolates induced biofilm by the use of different neutrophil proteases. Of these, 62.3% induced biofilm with proteinase-3, 15% with cathepsin G, 10% with cathepsin B and 5% with MMP -9, where most of the protease-induced biofilm isolates were commensal strains (skin). In the biofilm formation kinetics analysis, the addition of phenylmethylsulfonyl fluoride (PMSF; a proteinase-3 inhibitor) showed that proteinase-3 participates in the cell aggregation stage of biofilm formation. A biofilm induced with proteinase-3 and DNAse-treated significantly reduced biofilm formation at an early time (initial adhesion stage of biofilm formation) compared to untreated proteinase-3-induced biofilm (p &lt; 0.05). A catheter inoculated with a commensal (skin) non-biofilm-forming S. epidermidis isolate treated with proteinase-3 and another one without the enzyme were inserted into the back of a mouse. After 7 days of incubation period, the catheters were recovered and the number of grown bacteria was quantified, finding a higher amount of adhered proteinase-3-treated bacteria in the catheter than non-proteinase-3-treated bacteria (p &lt; 0.05). Commensal non-biofilm-forming S. epidermidis in the presence of neutrophil cells significantly induced the biofilm formation when multiplicity of infection (MOI) 1:0.01 (neutrophil:bacteria) was used, but the addition of a cocktail of protease inhibitors impeded biofilm formation. A neutrophil:bacteria assay did not induce neutrophil extracellular traps (NETs). Our results suggest that neutrophils, in the presence of commensal non-biofilm-forming S. epidermidis, do not generate NETs formation. The effect of neutrophils is the production of proteases, and proteinase-3 releases bacterial DNA at the initial adhesion, favoring cell aggregation and subsequently leading to biofilm formation.<\/jats:p>","DOI":"10.3390\/ijms23094992","type":"journal-article","created":{"date-parts":[[2022,4,30]],"date-time":"2022-04-30T05:44:07Z","timestamp":1651297447000},"page":"4992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Low Concentration of the Neutrophil Proteases Cathepsin G, Cathepsin B, Proteinase-3 and Metalloproteinase-9 Induce Biofilm Formation in Non-Biofilm-Forming Staphylococcus epidermidis Isolates"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9894-3298","authenticated-orcid":false,"given":"Itzia S.","family":"G\u00f3mez-Alonso","sequence":"first","affiliation":[{"name":"Laboratorio de Inmunomicrobiolog\u00eda, Departamento de Microbiolog\u00eda, Escuela 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Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9036-004X","authenticated-orcid":false,"given":"Esmeralda","family":"Ju\u00e1rez","sequence":"additional","affiliation":[{"name":"Departamento de Investigaci\u00f3n en Microbiolog\u00eda, Instituto Nacional de Enfermedades Respiratorias \u201cIsmael Cosi\u00f3 Villegas\u201d, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda C.","family":"Sarabia-Le\u00f3n","sequence":"additional","affiliation":[{"name":"Departamento de Investigaci\u00f3n en Microbiolog\u00eda, Instituto Nacional de Enfermedades Respiratorias \u201cIsmael Cosi\u00f3 Villegas\u201d, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7941-5468","authenticated-orcid":false,"given":"Mar\u00eda Teresa","family":"Herrera","sequence":"additional","affiliation":[{"name":"Departamento de Investigaci\u00f3n en Microbiolog\u00eda, Instituto Nacional de Enfermedades Respiratorias \u201cIsmael Cosi\u00f3 Villegas\u201d, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5050-2143","authenticated-orcid":false,"given":"Fernando","family":"G\u00f3mez-Ch\u00e1vez","sequence":"additional","affiliation":[{"name":"Laboratorio de Enfermedades Osteoarticulares e Inmunol\u00f3gicas, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Nacional de Medicina y Homeopat\u00eda, Instituto Polit\u00e9cnico Nacional, Mexico City 073240, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7128-849X","authenticated-orcid":false,"given":"Luvia","family":"Sanchez-Torres","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunidad Innata, Departamento de Inmunolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Rodr\u00edguez-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunidad Innata, Departamento de Inmunolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0271-7892","authenticated-orcid":false,"given":"Mario E.","family":"Cancino-Diaz","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunidad Innata, Departamento de Inmunolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3287-3060","authenticated-orcid":false,"given":"Jorge","family":"Cancino","sequence":"additional","affiliation":[{"name":"Programa Moscafrut 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