{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T00:39:54Z","timestamp":1794443994585,"version":"4.9.1"},"reference-count":136,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovation, Republic of Serbia","award":["451-03-137\/2025-03\/200110"],"award-info":[{"award-number":["451-03-137\/2025-03\/200110"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Otitis media is among the most common pediatric illnesses globally, constituting a leading cause of antimicrobial prescriptions, recurrent medical consultations, and preventable hearing loss in early childhood. Traditionally regarded as a sterile cavity intermittently invaded by pathogens, the middle ear is now recognized as a dynamic ecological niche influenced by anatomical immaturity of the Eustachian tube, host immune development, and the composition of resident microbial communities. Increasing evidence demonstrates that microbial dysbiosis and the establishment of biofilms are central to the persistence and recurrence of disease. This review synthesizes current knowledge of the pediatric middle ear microbiome, highlighting how commensal organisms contribute to mucosal resilience and colonization resistance, whereas pathogenic bacteria exploit ecological disruption to establish biofilm communities. Biofilm formation provides bacteria with enhanced survival through immune evasion, altered microenvironments, and antibiotic tolerance, thereby transforming acute otitis media into recurrent or chronic states. Furthermore, studies demonstrate how adenoids act as reservoirs of biofilm-forming organisms, seeding the middle ear and perpetuating infection. The emerging ecological perspective emphasizes the limitations of conventional antibiotic-centered management and directs attention toward innovative strategies, including microbiome-preserving interventions, probiotic or live biotherapeutic approaches, and antibiofilm agents. By defining pediatric otitis media as a disorder of disrupted host\u2013microbe equilibrium, future research may pave the way for precision-based preventive and therapeutic strategies aimed at reducing the global burden of this pervasive disease.<\/jats:p>","DOI":"10.3390\/microorganisms13122760","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T15:14:06Z","timestamp":1764861246000},"page":"2760","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Biofilm Formation and Its Relationship with the Microbiome in Pediatric Otitis Media"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9862-592X","authenticated-orcid":false,"given":"Ana","family":"Jotic","sequence":"first","affiliation":[{"name":"Clinic for Otorhinolaryngology and Maxillofacial Surgery, University Clinical Center of Serbia, Pasterova 2, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, Dr Subotica 4, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1515-1824","authenticated-orcid":false,"given":"Ivana","family":"Cirkovic","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Dr Subotica 1, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0786-2423","authenticated-orcid":false,"given":"Nevena","family":"Jovicic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, Dr Subotica 4, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University Children\u2019s Clinic, Tirsova 10, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bojana","family":"Bukurov","sequence":"additional","affiliation":[{"name":"Clinic for Otorhinolaryngology and Maxillofacial Surgery, University Clinical Center of Serbia, Pasterova 2, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, Dr Subotica 4, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalija","family":"Krca","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Dr Subotica 1, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Savic Vujovic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Dr Subotica 1, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Monasta, L., Ronfani, L., Marchetti, F., Montico, M., Vecchi Brumatti, L., Bavcar, A., Grasso, D., Barbiero, C., and Tamburlini, G. (2012). Burden of Disease Caused by Otitis Media: Systematic Review and Global Estimates. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0036226"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1097\/AUD.0000000000001453","article-title":"Global, Regional, and National Burdens of Otitis Media from 1990 to 2019: A Population Based Study","volume":"45","author":"Jin","year":"2024","journal-title":"Ear Hear."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2959","DOI":"10.1007\/s00405-024-09165-z","article-title":"Trends in the Incidence and Burden of Otitis Media in Children: A Global Analysis from 1990 to 2021","volume":"282","author":"Dong","year":"2025","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Alshehri, S., and Musleh, A. (2025). The Role of Eustachian Tube Dysfunction in Recurrent Chronic Otitis Media: A Cross-Sectional Study of Anatomical and Functional Variations. Healthcare, 13.","DOI":"10.3390\/healthcare13010077"},{"key":"ref_5","unstructured":"(2025, September 28). Is Allergic Rhinitis Related to Otitis Media with Effusion in Adults and Children? Applying Epidemiological Guidelines for Causation\u2014PubMed, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/40497981\/."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Huang, G.-J., Lin, B.-R., Li, P.-S., Tang, N., Fan, Z.-J., and Lu, B.-Q. (2024). The Global Burden of Otitis Media in 204 Countries and Territories from 1992 to 2021: A Systematic Analysis for the Global Burden of Disease Study 2021. Front. Public. Health, 12.","DOI":"10.3389\/fpubh.2024.1519623"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1097\/INF.0000000000004413","article-title":"Anticipated Effects of Higher-valency Pneumococcal Conjugate Vaccines on Colonization and Acute Otitis Media","volume":"43","author":"Kaur","year":"2024","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3201\/eid2801.210734","article-title":"SpIDnet group1. Serotype Replacement after Introduction of 10-Valent and 13-Valent Pneumococcal Conjugate Vaccines in 10 Countries, Europe","volume":"28","author":"Hanquet","year":"2022","journal-title":"Emerg. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s44197-025-00396-9","article-title":"Epidemiology of Chronic Suppurative Otitis Media: Systematic Review To Estimate Global Prevalence","volume":"15","author":"Onifade","year":"2025","journal-title":"J. Epidemiol. Glob. Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1136\/archdischild-2024-327454","article-title":"Modifiable Risk Factors for Developing Otitis Media with Effusion in Children under 12 Years in High-Income Countries: A Systematic Review","volume":"110","author":"Paing","year":"2024","journal-title":"Arch. Dis. Child."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.ijporl.2019.04.041","article-title":"A systematic review and meta-analysis of antimicrobial resistance in paediatric acute otitis media","volume":"123","author":"Mather","year":"2019","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/ped4.12364","article-title":"Can non-typeable Haemophilus influenzae carriage surveillance data infer antimicrobial resistance associated with otitis media?","volume":"7","author":"Harris","year":"2023","journal-title":"Pediatr Investig."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Folino, F., Ruggiero, L., Capaccio, P., Coro, I., Aliberti, S., Drago, L., Marchisio, P., and Torretta, S. (2020). Upper Respiratory Tract Microbiome and Otitis Media Intertalk: Lessons from the Literature. J. Clin. Med., 9.","DOI":"10.3390\/jcm9092845"},{"key":"ref_14","first-page":"e28019","article-title":"Etiology, Diagnosis, Complications, and Management of Acute Otitis Media in Children","volume":"14","author":"Jamal","year":"2022","journal-title":"Cureus"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/S0030-6665(02)00047-6","article-title":"The Eustachian Tube. Update on Anatomy, Development, and Function","volume":"35","author":"Licameli","year":"2002","journal-title":"Otolaryngol. Clin. N. Am."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1002\/lary.30113","article-title":"Measurements of The Pediatric Cartilaginous Eustachian Tube: Implications for Balloon Dilation","volume":"133","author":"Yu","year":"2023","journal-title":"Laryngoscope"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1177\/000348940311200510","article-title":"Difference in Attachment of the Tensor Veli Palatini Muscle to the Eustachian Tube Cartilage with Age","volume":"112","author":"Suzuki","year":"2003","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.ijporl.2010.05.021","article-title":"Eustachian Tube-Tensor Veli Palatini Muscle-Cranial Base Relationships in Children and Adults: An Osteological Study","volume":"74","author":"Doyle","year":"2010","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S223","DOI":"10.1016\/S0165-5876(99)00164-0","article-title":"Non-Specific and Specific Immunity to Bacterial Invasion of the Middle Ear Cavity","volume":"49","author":"Stenfors","year":"1999","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Massa, H.M., Spann, K.M., and Cripps, A.W. (2021). Innate Immunity in the Middle Ear Mucosa. Front. Cell Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.764772"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1128\/CVI.05443-11","article-title":"Antibody in Middle Ear Fluid of Children Originates Predominantly from Sera and Nasopharyngeal Secretions","volume":"19","author":"Kaur","year":"2012","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1007\/s00405-015-3683-9","article-title":"Pro-Inflammatory Interleukins in Middle Ear Effusions from Atopic and Non-Atopic Children with Chronic Otitis Media with Effusion","volume":"273","year":"2016","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Frey, A., Lunding, L.P., Ehlers, J.C., Weckmann, M., Zissler, U.M., and Wegmann, M. (2020). More Than Just a Barrier: The Immune Functions of the Airway Epithelium in Asthma Pathogenesis. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00761"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"109838","DOI":"10.1016\/j.ijporl.2019.109838","article-title":"Panel 7\u2014Pathogenesis of Otitis Media\u2014A Review of the Literature between 2015 and 2019","volume":"130","author":"Thornton","year":"2020","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e10","DOI":"10.1017\/erm.2021.10","article-title":"Dysregulation of Immune Response in Otitis Media","volume":"23","author":"Mather","year":"2021","journal-title":"Expert. Rev. Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1001\/archoto.2011.116","article-title":"The Otologic Microbiome: A Study of the Bacterial Microbiota in a Pediatric Patient with Chronic Serous Otitis Media Using 16SrRNA Gene-Based Pyrosequencing","volume":"137","author":"Liu","year":"2011","journal-title":"Arch. Otolaryngol. Head. Neck Surg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1002\/lio2.460","article-title":"Review of Otitis Media Microbiome Studies: What Do They Tell Us?","volume":"5","author":"Nogues","year":"2020","journal-title":"Laryngoscope Investig. Otolaryngol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"E371","DOI":"10.1002\/lary.26579","article-title":"Microbiomes of the Normal Middle Ear and Ears with Chronic Otitis Media","volume":"127","author":"Minami","year":"2017","journal-title":"Laryngoscope"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2844","DOI":"10.1002\/lary.26128","article-title":"The Microbiome of Otitis Media with Effusion","volume":"126","author":"Chan","year":"2016","journal-title":"Laryngoscope"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1016\/j.ijporl.2015.07.013","article-title":"The Microbiome of Otitis Media with Effusion in Indigenous Australian Children","volume":"79","author":"Rogers","year":"2015","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s40249-016-0189-7","article-title":"Middle Ear Microbiome Differences in Indigenous Filipinos with Chronic Otitis Media Due to a Duplication in the A2ML1 Gene","volume":"5","author":"Hutchinson","year":"2016","journal-title":"Infect. Dis. Poverty"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1007\/s10096-017-3178-2","article-title":"Characterization of the Nasopharyngeal and Middle Ear Microbiota in Gastroesophageal Reflux-Prone versus Gastroesophageal Reflux Non-Prone Children","volume":"37","author":"Boers","year":"2018","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Lappan, R., Imbrogno, K., Sikazwe, C., Anderson, D., Mok, D., Coates, H., Vijayasekaran, S., Bumbak, P., Blyth, C.C., and Jamieson, S.E. (2018). A Microbiome Case-Control Study of Recurrent Acute Otitis Media Identified Potentially Protective Bacterial Genera. BMC Microbiol., 18.","DOI":"10.1186\/s12866-018-1154-3"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1001\/jama.279.4.296","article-title":"Evidence of Bacterial Metabolic Activity in Culture-Negative Otitis Media with Effusion","volume":"279","author":"Rayner","year":"1998","journal-title":"JAMA"},{"key":"ref_35","unstructured":"Bluestone, C.D., and Klein, J.O. (2007). Otitis Media in Infants and Children, WB Saunders. [4th ed.]."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13073-025-01447-3","article-title":"Metatranscriptomic Profiling Reveals Pathogen and Host Response Signatures of Pediatric Acute Sinusitis and Upper Respiratory Infection","volume":"17","author":"Doxey","year":"2025","journal-title":"Genome Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e00245-00210","DOI":"10.1128\/mBio.00245-10","article-title":"Microbial Communities of the Upper Respiratory Tract and Otitis Media in Children","volume":"2","author":"Laufer","year":"2011","journal-title":"mBio"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Jo, J.-W., Kim, S.K., Byun, J.Y., Hong, S.M., and Kim, B.-S. (2025). The Association between the Adenoid Microbiome and Chronic Otitis Media with Effusion in Children Differs According to Age. Front. Cell Infect. Microbiol., 15.","DOI":"10.3389\/fcimb.2025.1660939"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e00009-16","DOI":"10.1128\/mBio.00009-16","article-title":"Unraveling the Molecular Mechanisms Underlying the Nasopharyngeal Bacterial Community Structure","volume":"7","author":"Bogaert","year":"2016","journal-title":"mBio"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.3201\/eid1811.111904","article-title":"Nasopharyngeal Bacterial Interactions in Children","volume":"18","author":"Xu","year":"2012","journal-title":"Emerg. Infect. Dis."},{"key":"ref_41","first-page":"e00056-21","article-title":"Case-Control Microbiome Study of Chronic Otitis Media with Effusion in Children Points at Streptococcus Salivarius as a Pathobiont-Inhibiting Species","volume":"6","author":"Wittouck","year":"2021","journal-title":"mSystems"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1016\/j.ijporl.2006.01.013","article-title":"Viral Upper Respiratory Tract Infections in Young Children with Emphasis on Acute Otitis Media","volume":"70","author":"Hovi","year":"2006","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/nrmicro821","article-title":"Bacterial Biofilms: From the Natural Environment to Infectious Diseases","volume":"2","author":"Costerton","year":"2004","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1128\/CMR.15.2.167-193.2002","article-title":"Biofilms: Survival Mechanisms of Clinically Relevant Microorganisms","volume":"15","author":"Donlan","year":"2002","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1146\/annurev.micro.56.012302.160705","article-title":"Biofilms as Complex Differentiated Communities","volume":"56","author":"Stoodley","year":"2002","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3868","DOI":"10.1128\/JB.01935-06","article-title":"Biofilms Formed by Nontypeable Haemophilus Influenzae in Vivo Contain Both Double-Stranded DNA and Type IV Pilin Protein","volume":"189","author":"Jurcisek","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mizrahi, A., Cohen, R., Varon, E., Bonacorsi, S., Bechet, S., Poyart, C., Levy, C., and Raymond, J. (2014). Non Typable-Haemophilus Influenzae Biofilm Formation and Acute Otitis Media. BMC Infect. Dis., 14.","DOI":"10.1186\/1471-2334-14-400"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6339","DOI":"10.1128\/IAI.70.11.6339-6345.2002","article-title":"Human Leukocytes Adhere to, Penetrate, and Respond to Staphylococcus Aureus Biofilms","volume":"70","author":"Leid","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Bair, K.L., and Campagnari, A.A. (2019). Moraxella Catarrhalis Promotes Stable Polymicrobial Biofilms With the Major Otopathogens. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.03006"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1111\/2049-632X.12129","article-title":"Residence of Streptococcus Pneumoniae and Moraxella Catarrhalis within Polymicrobial Biofilm Promotes Antibiotic Resistance and Bacterial Persistence in Vivo","volume":"70","author":"Perez","year":"2014","journal-title":"Pathog. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1177\/0022034509359403","article-title":"Biofilm Dispersal: Mechanisms, Clinical Implications, and Potential Therapeutic Uses","volume":"89","author":"Kaplan","year":"2010","journal-title":"J. Dent. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.prrv.2009.10.007","article-title":"Airway Clearance Modalities in Neuromuscular Disease","volume":"11","author":"Finder","year":"2010","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1099\/mic.0.042929-0","article-title":"Colonization of Healthy Children by Moraxella Catarrhalis Is Characterized by Genotype Heterogeneity, Virulence Gene Diversity and Co-Colonization with Haemophilus Influenzae","volume":"157","author":"Verhaegh","year":"2011","journal-title":"Microbiology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6262","DOI":"10.1128\/AEM.01051-12","article-title":"Upper Respiratory Tract Microbial Communities, Acute Otitis Media Pathogens, and Antibiotic Use in Healthy and Sick Children","volume":"78","author":"Pettigrew","year":"2012","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Swords, W.E. (2012). Quorum Signaling and Sensing by Nontypeable Haemophilus Influenzae. Front. Cell Infect. Microbiol., 2.","DOI":"10.3389\/fcimb.2012.00100"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1001\/jama.296.2.202","article-title":"Direct Detection of Bacterial Biofilms on the Middle-Ear Mucosa of Children with Chronic Otitis Media","volume":"296","author":"Hu","year":"2006","journal-title":"JAMA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1097\/INF.0000000000001493","article-title":"Relationship of the Middle Ear Effusion Microbiome to Secretory Mucin Production in Pediatric Patients with Chronic Otitis Media","volume":"36","author":"Krueger","year":"2017","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.3390\/s120302519","article-title":"Quorum Sensing and Bacterial Social Interactions in Biofilms","volume":"12","author":"Li","year":"2012","journal-title":"Sensors"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Khan, R., Petersen, F.C., and Shekhar, S. (2019). Commensal Bacteria: An Emerging Player in Defense Against Respiratory Pathogens. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01203"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1146\/annurev.micro.55.1.165","article-title":"Quorum Sensing in Bacteria","volume":"55","author":"Miller","year":"2001","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Szekely, D., Zara, F., Patrascu, R., Dumitru, C.S., Novacescu, D., Manole, A., Mogoanta, C.A., Iovanescu, D., and Iovanescu, G. (2025). Histopathological and Molecular Insights into Chronic Nasopharyngeal and Otic Disorders in Children: Structural and Immune Mechanisms Underlying Disease Chronicity. Life, 15.","DOI":"10.3390\/life15081228"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e00852-20","DOI":"10.1128\/mSphere.00852-20","article-title":"Dolosigranulum Pigrum Cooperation and Competition in Human Nasal Microbiota","volume":"5","author":"Brugger","year":"2020","journal-title":"mSphere"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Cisneros, M., Blanco-Fuertes, M., Lluans\u00ed, A., Brotons, P., Henares, D., P\u00e9rez-Arg\u00fcello, A., Gonz\u00e1lez-Comino, G., Ciruela, P., Mira, A., and Mu\u00f1oz-Almagro, C. (2025). Synergistic Inhibition of Pneumococcal Growth by Dolosigranulum Pigrum and Corynebacterium Pseudodiphtheriticum: Insights into Nasopharyngeal Microbial Interactions. Microbiol. Spectr., 13.","DOI":"10.1128\/spectrum.00138-25"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2252780","DOI":"10.1080\/19490976.2023.2252780","article-title":"Targeting Microbial Quorum Sensing: The next Frontier to Hinder Bacterial Driven Gastrointestinal Infections","volume":"15","author":"Su","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Ziegert, Z., Dietz, M., Hill, M., McBride, M., Painter, E., Elias, M.H., and Staley, C. (2024). Targeting Quorum Sensing for Manipulation of Commensal Microbiota. BMC Biotechnol., 24, Correction in BMC Biotechnol. 2025, 25, 14. https:\/\/doi.org\/10.1186\/s12896-025-00949-7.","DOI":"10.1186\/s12896-025-00949-7"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Verbeke, F., De Craemer, S., Debunne, N., Janssens, Y., Wynendaele, E., Van de Wiele, C., and De Spiegeleer, B. (2017). Peptides as Quorum Sensing Molecules: Measurement Techniques and Obtained Levels In Vitro and In Vivo. Front. Neurosci., 11.","DOI":"10.3389\/fnins.2017.00183"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Inagaki, R., Koshiba, A., Nasuno, E., and Kato, N. (2024). Eliminating Extracellular Autoinducing Peptide Signals Inhibits the Staphylococcus Aureus Quorum Sensing Agr System. Biochem. Biophys. Res. Commun., 711.","DOI":"10.1016\/j.bbrc.2024.149912"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e02539-19","DOI":"10.1128\/AEM.02539-19","article-title":"Small Molecules Produced by Commensal Staphylococcus Epidermidis Disrupt Formation of Biofilms by Staphylococcus aureus","volume":"86","author":"Glatthardt","year":"2020","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"109836","DOI":"10.1016\/j.ijporl.2019.109836","article-title":"Panel 4: Recent Advances in Understanding the Natural History of the Otitis Media Microbiome and Its Response to Environmental Pressures","volume":"130","author":"Marsh","year":"2020","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Yuan, V.G., Xia, A., and Santa Maria, P.L. (2025). Chronic Suppurative Otitis Media: Disrupted Host-Microbial Interactions and Immune Dysregulation. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1547206"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"110629","DOI":"10.1016\/j.ijporl.2021.110629","article-title":"Nasopharyngeal Microbiome Analyses in Otitis-Prone and Otitis-Free Children","volume":"143","author":"Xu","year":"2021","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Elgamal, Z., Singh, P., and Geraghty, P. (2021). The Upper Airway Microbiota, Environmental Exposures, Inflammation, and Disease. Medicina, 57.","DOI":"10.3390\/medicina57080823"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1093\/cid\/ciw347","article-title":"Impact of Widespread Introduction of Pneumococcal Conjugate Vaccines on Pneumococcal and Nonpneumococcal Otitis Media","volume":"63","author":"Leibovitz","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"394368","DOI":"10.1155\/2015\/394368","article-title":"Nasopharyngeal Bacterial Carriage in the Conjugate Vaccine Era with a Focus on Pneumococci","volume":"2015","author":"Devine","year":"2015","journal-title":"J. Immunol. Res."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Mika, M., Maurer, J., Korten, I., Allemann, A., Aebi, S., Brugger, S.D., Qi, W., Frey, U., Latzin, P., and Hilty, M. (2017). Influence of the Pneumococcal Conjugate Vaccines on the Temporal Variation of Pneumococcal Carriage and the Nasal Microbiota in Healthy Infants: A Longitudinal Analysis of a Case-Control Study. Microbiome, 5.","DOI":"10.1186\/s40168-017-0302-6"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"S321","DOI":"10.1093\/infdis\/jiaa537","article-title":"Hib Vaccines: Their Impact on Haemophilus Influenzae Type b Disease","volume":"224","author":"Gilsdorf","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1080\/14760584.2017.1333905","article-title":"Impact of Protein D-Containing Pneumococcal Conjugate Vaccines on Non-Typeable Haemophilus Influenzae Acute Otitis Media and Carriage","volume":"16","author":"Clarke","year":"2017","journal-title":"Expert. Rev. Vaccines"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1186\/s12967-025-06433-2","article-title":"The Intricate Interplay among Microbiota, Mucosal Immunity, and Viral Infection in the Respiratory Tract","volume":"23","author":"Li","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1002\/JLB.4RU0119-003R","article-title":"Subversion of Host Immune Responses by Otopathogens during Otitis Media","volume":"106","author":"Parrish","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Walker, R.E., Walker, C.G., Camargo, C.A., Bartley, J., Flint, D., Thompson, J.M.D., and Mitchell, E.A. (2019). Nasal Microbial Composition and Chronic Otitis Media with Effusion: A Case-Control Study. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0212473"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"101143","DOI":"10.1016\/j.mam.2022.101143","article-title":"The Subversion of Toll-like Receptor Signaling by Bacterial and Viral Proteases during the Development of Infectious Diseases","volume":"88","author":"Ciaston","year":"2022","journal-title":"Mol. Aspects Med."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez Montalvo, A., Gohy, S., Rombaux, P., Pilette, C., and Hox, V. (2022). The Role of IgA in Chronic Upper Airway Disease: Friend or Foe?. Front. Allergy, 3.","DOI":"10.3389\/falgy.2022.852546"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1146\/annurev-immunol-101320-011829","article-title":"T Cell Responses to the Microbiota","volume":"40","author":"Ivanov","year":"2022","journal-title":"Annu. Rev. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1128\/CVI.00194-10","article-title":"Serum Intercellular Adhesion Molecule 1 Variations in Young Children with Acute Otitis Media","volume":"17","author":"Liu","year":"2010","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.resp.2006.04.011","article-title":"Middle Ear Gas Loss in Inflammatory Conditions: The Role of Mucosa Thickness and Blood Flow","volume":"155","author":"Ar","year":"2007","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1128\/IAI.74.2.830-838.2006","article-title":"Nontypeable Haemophilus Influenzae Adheres to Intercellular Adhesion Molecule 1 (ICAM-1) on Respiratory Epithelial Cells and Upregulates ICAM-1 Expression","volume":"74","author":"Avadhanula","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e416","DOI":"10.1097\/INF.0000000000004028","article-title":"Moraxella Catarrhalis Infrequently Cultured from Middle Ear Fluid of Children with Acute Otitis Media","volume":"42","author":"Conway","year":"2023","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e0000624","DOI":"10.1128\/jb.00006-24","article-title":"Multitasking Functions of Bacterial Extracellular DNA in Biofilms","volume":"206","author":"Sharma","year":"2024","journal-title":"J. Bacteriol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Keller, L.E., Bradshaw, J.L., Pipkins, H., and McDaniel, L.S. (2016). Surface Proteins and Pneumolysin of Encapsulated and Nonencapsulated Streptococcus Pneumoniae Mediate Virulence in a Chinchilla Model of Otitis Media. Front. Cell Infect. Microbiol., 6.","DOI":"10.3389\/fcimb.2016.00055"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e00102-10","DOI":"10.1128\/mBio.00102-10","article-title":"Indirect Pathogenicity of Haemophilus Influenzae and Moraxella Catarrhalis in Polymicrobial Otitis Media Occurs via Interspecies Quorum Signaling","volume":"1","author":"Armbruster","year":"2010","journal-title":"mBio"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Yadav, M.K., Vidal, J.E., Go, Y.Y., Kim, S.H., Chae, S.-W., and Song, J.-J. (2018). The LuxS\/AI-2 Quorum-Sensing System of Streptococcus Pneumoniae Is Required to Cause Disease, and to Regulate Virulence- and Metabolism-Related Genes in a Rat Model of Middle Ear Infection. Front. Cell Infect. Microbiol., 8.","DOI":"10.3389\/fcimb.2018.00138"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Ioannidis, A., Chatzipanagiotou, S., Vassilaki, N., Giannakopoulos, P., Hatzaki, D., Magana, M., Sachlas, A., Mpekoulis, G., Radiotis, A., and Tsakanikos, M. (2023). Biofilm-Forming Bacteria Implicated in Complex Otitis Media in Children in the Post-Heptavalent Pneumococcal Conjugate Vaccine (PCV7) Era. Microorganisms, 11.","DOI":"10.3390\/microorganisms11030545"},{"key":"ref_93","first-page":"e57634","article-title":"A Comprehensive Review on Biofilms in Otorhinolaryngology: Understanding the Pathogenesis, Diagnosis, and Treatment Strategies","volume":"16","author":"Deshmukh","year":"2024","journal-title":"Cureus"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Lannes-Costa, P.S., Fernandes, I.R., Pena, J.M.S., Costa, B.R.F.V., da Cunha, M.M.L., Ferreira-Carvalho, B.T., and Nagao, P.E. (2024). Antibiotic Resistance and Presence of Persister Cells in the Biofilm-like Environments in Streptococcus Agalactiae. Antibiotics, 13.","DOI":"10.3390\/antibiotics13111014"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.micinf.2013.11.006","article-title":"Nontypeable Haemophilus Influenzae Inhibits Autolysis and Fratricide of Streptococcus Pneumoniae In Vitro","volume":"16","author":"Hong","year":"2014","journal-title":"Microbes Infect."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.ijmm.2015.09.003","article-title":"The Outcome of H. Influenzae and S. Pneumoniae Inter-Species Interactions Depends on pH, Nutrient Availability and Growth Phase","volume":"305","author":"Tikhomirova","year":"2015","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e27318","DOI":"10.1002\/ppul.27318","article-title":"Haemophilus Influenzae and Pneumococci: Co-Colonization, Interactions, Cooperation and Competition","volume":"60","author":"McMahon","year":"2025","journal-title":"Pediatr. Pulmonol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1086\/647933","article-title":"Acute Otitis Media Caused by Moraxella Catarrhalis: Epidemiologic and Clinical Characteristics","volume":"49","author":"Broides","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Neeff, M., Kimita, W., Waldvogel-Thurlow, S., Douglas, R.G., and Biswas, K. (2025). Host-Microbe Interactions in Healthy and CSOM-Affected Middle Ears. Microorganisms, 13.","DOI":"10.3390\/microorganisms13020339"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Gupta, P., Sumit Dutta, S., Chatterjee, D., Das, A., and Nandi, A. (2025). Nasal, Transdermal Delivery of Probiotics. Advances in Probiotic Delivery Systems, Academic Press.","DOI":"10.1016\/B978-0-443-27594-4.00012-7"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.ijporl.2018.10.023","article-title":"Probiotics in the Treatment of Otitis Media. The Past, the Present and the Future","volume":"116","author":"Coleman","year":"2019","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Mosquera, F.E.C., de la Rosa Caldas, M., Naranjo Rojas, A., Perlaza, C.L., and Liscano, Y. (2025). Probiotic, Prebiotic, and Synbiotic Supplementation for the Prevention and Treatment of Acute Otitis Media: A Systematic Review and Meta-Analysis. Children, 12.","DOI":"10.3390\/children12050591"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Malag\u00f3n-Rojas, J.N., Mantziari, A., Salminen, S., and Szajewska, H. (2020). Postbiotics for Preventing and Treating Common Infectious Diseases in Children: A Systematic Review. Nutrients, 12.","DOI":"10.3390\/nu12020389"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Kono, M., Umar, N.K., Takeda, S., Ohtani, M., Murakami, D., Sakatani, H., Kaneko, F., Nanushaj, D., and Hotomi, M. (2021). Novel Antimicrobial Treatment Strategy Based on Drug Delivery Systems for Acute Otitis Media. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.640514"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1016\/j.jfma.2018.08.011","article-title":"Fecal Microbiota Transplantation: Review and Update","volume":"118","author":"Wang","year":"2019","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.tim.2024.12.010","article-title":"Nasal Microbiota Transplantation: A Gateway to Novel Treatments","volume":"33","author":"Shekhar","year":"2025","journal-title":"Trends Microbiol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1038\/s41587-022-01584-9","article-title":"Engineered Live Bacteria Suppress Pseudomonas Aeruginosa Infection in Mouse Lung and Dissolve Endotracheal-Tube Biofilms","volume":"41","author":"Mazzolini","year":"2023","journal-title":"Nat. Biotechnol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"3184","DOI":"10.1021\/acssynbio.0c00444","article-title":"Living Therapeutics: The Next Frontier of Precision Medicine","volume":"9","author":"Kelly","year":"2020","journal-title":"ACS Synth. Biol."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Santos-Cortez, R.L.P., Ehrlich, G.D., and Ryan, A.F. (2021). Editorial: Otitis Media Genomics and the Middle Ear Microbiome. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.763688"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"112208","DOI":"10.1016\/j.ijporl.2024.112208","article-title":"Bacteriological Profile, Antibiotic Susceptibility, and Biofilm Formation in Children with Chronic Suppurative Otitis Media","volume":"188","author":"Taha","year":"2025","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1002\/lio2.934","article-title":"Cholesteatoma Has an Altered Microbiota with a Higher Abundance of Staphylococcus Species","volume":"7","author":"Fujikawa","year":"2022","journal-title":"Laryngoscope Investig. Otolaryngol."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Microbiome Therapeutics Innovation Group, and Barberio, D. (2024). Navigating Regulatory and Analytical Challenges in Live Biotherapeutic Product Development and Manufacturing. Front. Microbiomes, 3.","DOI":"10.3389\/frmbi.2024.1441290"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Al-Fakhrany, O.M., and Elekhnawy, E. (2024). Next-Generation Probiotics: The Upcoming Biotherapeutics. Mol. Biol. Rep., 51.","DOI":"10.1007\/s11033-024-09398-5"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1164\/rccm.202112-2704PP","article-title":"Therapeutic Targeting of the Respiratory Microbiome","volume":"206","author":"Chotirmall","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"3676","DOI":"10.1016\/j.tjnut.2025.09.009","article-title":"Postbiotics in Respiratory Health: Functional Components, Innovative Application, and Emerging Challenges","volume":"155","author":"Lan","year":"2025","journal-title":"J. Nutr."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s00408-024-00700-7","article-title":"Phage Therapy for Respiratory Infections: Opportunities and Challenges","volume":"202","author":"Khosravi","year":"2024","journal-title":"Lung"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1038\/s41467-020-15508-1","article-title":"Developing a New Class of Engineered Live Bacterial Therapeutics to Treat Human Diseases","volume":"11","author":"Charbonneau","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"100018","DOI":"10.1016\/j.premed.2025.100018","article-title":"Microbiome-Guided Precision Medicine: Mechanistic Insights, Multi-Omics Integration, and Translational Horizons","volume":"3","author":"Shahid","year":"2025","journal-title":"J. Precis. Med. Health Dis."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Jotic, A., Savic Vujovic, K., Cirkovic, A., Bo\u017ei\u0107, D.D., Brkic, S., Subotic, N., Bukurov, B., Korugic, A., and Cirkovic, I. (2024). Antibiofilm Effects of Novel Compounds in Otitis Media Treatment: Systematic Review. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252312841"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Bo\u017ei\u0107, D.D., \u0106irkovi\u0107, I., Milovanovi\u0107, J., Bufan, B., Foli\u0107, M., Savi\u0107 Vujovi\u0107, K., Pavlovi\u0107, B., and Joti\u0107, A. (2023). In Vitro Antibiofilm Effect of N-Acetyl-L-Cysteine\/Dry Propolis Extract Combination on Bacterial Pathogens Isolated from Upper Respiratory Tract Infections. Pharmaceuticals, 16.","DOI":"10.3390\/ph16111604"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Pakkulnan, R., Thonglao, N., and Chareonsudjai, S. (2023). DNase I and Chitosan Enhance Efficacy of Ceftazidime to Eradicate Burkholderia Pseudomallei Biofilm Cells. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-27790-2"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Principi, N., and Esposito, S. (2024). Biofilm Production and Its Implications in Pediatrics. Microorganisms, 12.","DOI":"10.3390\/microorganisms12081522"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Zeng, X., Zou, Y., Zheng, J., Qiu, S., Liu, L., and Wei, C. (2023). Quorum Sensing-Mediated Microbial Interactions: Mechanisms, Applications, Challenges and Perspectives. Microbiol. Res., 273.","DOI":"10.1016\/j.micres.2023.127414"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Vashistha, A., Sharma, N., Nanaji, Y., Kumar, D., Singh, G., Barnwal, R.P., and Yadav, A.K. (2023). Quorum Sensing Inhibitors as Therapeutics: Bacterial Biofilm Inhibition. Bioorg Chem., 136.","DOI":"10.1016\/j.bioorg.2023.106551"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.addr.2021.04.005","article-title":"Polymeric Nano- and Microparticulate Drug Delivery Systems for Treatment of Biofilms","volume":"174","author":"Birk","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"e2304713","DOI":"10.1002\/smll.202304713","article-title":"Charge-Reversible Nanoparticles: Advanced Delivery Systems for Therapy and Diagnosis","volume":"20","author":"Veider","year":"2024","journal-title":"Small"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Zafer, M.M., Mohamed, G.A., Ibrahim, S.R.M., Ghosh, S., Bornman, C., and Elfaky, M.A. (2024). Biofilm-Mediated Infections by Multidrug-Resistant Microbes: A Comprehensive Exploration and Forward Perspectives. Arch. Microbiol., 206.","DOI":"10.1007\/s00203-023-03826-z"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.ijmmb.2021.01.004","article-title":"Evaluation of Combined Ciprofloxacin and Azithromycin Free and Nano Formulations to Control Biofilm Producing Pseudomonas Aeruginosa Isolated from Burn Wounds","volume":"39","author":"Raouf","year":"2021","journal-title":"Indian. J. Med. Microbiol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s15010-018-1222-5","article-title":"A Review on Anti-Adhesion Therapies of Bacterial Diseases","volume":"47","author":"Asadi","year":"2019","journal-title":"Infection"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1007\/s42770-024-01363-5","article-title":"Lactobacillus Acidophilus VB1 Co-Aggregates and Inhibits Biofilm Formation of Chronic Otitis Media-Associated Pathogens","volume":"55","author":"Algburi","year":"2024","journal-title":"Braz. J. Microbiol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1111\/apm.12254","article-title":"Antiadhesive and Antibiofilm Activity of Hyaluronic Acid against Bacteria Responsible for Respiratory Tract Infections","volume":"122","author":"Drago","year":"2014","journal-title":"APMIS"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"63","DOI":"10.7150\/jbji.17705","article-title":"Hyaluronic Acid and Its Composites as a Local Antimicrobial\/Antiadhesive Barrier","volume":"2","author":"Bortolin","year":"2017","journal-title":"J. Bone Jt. Infect."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Ribi\u0107, R. (2025). Mannose Derivatives as Anti-Infective Agents. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262010230"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Qvortrup, K., Hultqvist, L.D., Nilsson, M., Jakobsen, T.H., Jansen, C.U., Uhd, J., Andersen, J.B., Nielsen, T.E., Givskov, M., and Tolker-Nielsen, T. (2019). Small Molecule Anti-Biofilm Agents Developed on the Basis of Mechanistic Understanding of Biofilm Formation. Front. Chem., 7.","DOI":"10.3389\/fchem.2019.00742"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s12250-019-00192-3","article-title":"Bacteriophages and Lysins in Biofilm Control","volume":"35","year":"2020","journal-title":"Virol. Sin."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.mib.2016.06.001","article-title":"Considerations and Caveats in Anti-Virulence Drug Development","volume":"33","author":"Maura","year":"2016","journal-title":"Curr. Opin. Microbiol."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/12\/2760\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T15:30:29Z","timestamp":1764862229000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/12\/2760"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,4]]},"references-count":136,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["microorganisms13122760"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms13122760","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,4]]}}}