{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T23:31:15Z","timestamp":1785713475572,"version":"3.56.0"},"reference-count":73,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University - Sofia","award":["Grant No D-121\/29.05.2024"],"award-info":[{"award-number":["Grant No D-121\/29.05.2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Acute otitis media (AOM) is one of the most common pediatric infections. We aimed to investigate the bacterial profile of AOM in children, the serotype distribution, and the main genetic virulence factors involved in adhesion, immune evasion, and tissue spread. Methods: In total, 121 AOM cases involving children aged 0 to 14 years were studied. Middle ear fluids (MEF) (n = 42) and nasopharyngeal samples (n = 79) were collected. All strains were identified using routine microbiological tests, conventional PCRs and real-time PCR methods. Molecular serotyping was performed for S. pneumoniae and H. influenzae isolates. An immunofluorescence serotyping technique was employed for M. catarrhalis. Target genetic factors were determined for all involved bacterial agents using singleplex or multiplex PCRs. Results: We analyzed 148 nasopharyngeal and MEF. Among 121 AOM cases, a total of 127 bacterial agents were identified, including S. aureus (n = 41), S. pneumoniae (n = 28), H. influenzae (n = 23), M. catarrhalis (n = 19), and S. pyogenes (n = 16). The leading three serotypes among S. pneumoniae were: 19A (18.0%), 6A (14.3%), and 15B (14.3%). 91.3% of H. influenzae isolates were non-typeable (lacking a capsule\u2014NTHi). The M. catarrhalis isolates were distributed in serotypes A (57.9%), B (26.3%), and C (15.8%). Presence of pili type 1 was detected in 21.4% pneumococci, and the fimbrial gene hifA was found in 34.8% of the H. influenzae strains. In 73.6% of the M. catarrhalis strains, ompCD was identified, while 84.2% contained ompE. 62.5% of the S. pyogenes isolates harbored the sdc gene, and 56.2% possessed the sdaD gene, predominantly in the MEF isolates. The cna adhesin was found in 28.0% of the S. aureus strains. Conclusions: The monitoring of bacterial pathogens responsible for otitis media, along with their serotype distribution and the prevalence of genetic factors involved in disease pathogenesis, is essential for public health and can help predict disease severity and treatment options.<\/jats:p>","DOI":"10.3390\/genes16121512","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T08:32:27Z","timestamp":1765960347000},"page":"1512","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bacterial Profile, Molecular Serotyping, and Key Genetic Determinants for Adhesion, Immune Evasion, and Tissue Spread Among Bulgarian Children with Acute Otitis Media"],"prefix":"10.3390","volume":"16","author":[{"given":"Alexandra S.","family":"Alexandrova","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Medical Faculty, Medical University of Sofia, Zdrave Str. 2, 1431 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0429-9252","authenticated-orcid":false,"given":"Vasil S.","family":"Boyanov","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Medical Faculty, Medical University of Sofia, Zdrave Str. 2, 1431 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3605-6447","authenticated-orcid":false,"given":"Raina T.","family":"Gergova","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Medical Faculty, Medical University of Sofia, Zdrave Str. 2, 1431 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dermawan, A., Ropii, B., Lasminingrum, L., Hasansulama, W., and Setiabudiawan, B. (2025). Determinants of acute otitis media in children: A case-control study in West Java, Indonesia. Medicina, 61.","DOI":"10.3390\/medicina61020197"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1128\/JCM.01146-16","article-title":"Moraxella catarrhalis might be more common than expected in acute otitis media in young finnish children","volume":"54","author":"Oikarinen","year":"2016","journal-title":"J. Clin. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Im\u00f6hl, M., Perniciaro, S., Busse, A., and van der Linden, M. (2021). Bacterial spectrum of spontaneously ruptured otitis media in a 7-Year, longitudinal, multicenter, epidemiological cross-sectional study in Germany. Front. Med., 8.","DOI":"10.3389\/fmed.2021.675225"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13052-025-01894-z","article-title":"Antibiotic treatment of acute and recurrent otitis media in children: An Italian intersociety Consensus","volume":"51","author":"Gattinara","year":"2025","journal-title":"Ital. J. Pediatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S39","DOI":"10.5694\/j.1326-5377.2009.tb02925.x","article-title":"Natural history, definitions, risk factors and burden of otitis media","volume":"191","author":"Kong","year":"2009","journal-title":"Med. J. Aust."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"16063","DOI":"10.1038\/nrdp.2016.63","article-title":"Otitis media","volume":"2","author":"Schilder","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"594","DOI":"10.3390\/applmicrobiol2030046","article-title":"Recurrent acute otitis media environmental risk factors: A literature review from the microbiota point of view","volume":"2","author":"Folino","year":"2022","journal-title":"Appl. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.micpath.2011.03.008","article-title":"Bacterial adherence in otitis media: Determination of N-acetylgalactosamine (GalNAc) residues in the submucosal glands and surface epithelium of the normal and diseased Eustachian tube","volume":"51","author":"Kirkeby","year":"2011","journal-title":"Microb. Pathog."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e00010-18","DOI":"10.1128\/CMR.00010-18","article-title":"Translating recent microbiome insights in otitis media into probiotic strategies","volume":"32","author":"Kiekens","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_10","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_11","doi-asserted-by":"crossref","unstructured":"Zahid, A., Wilson, J.C., Grice, I.D., and Peak, I.R. (2024). Otitis media: Recent advances in otitis media vaccine development and model systems. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1345027"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3342\/ceo.2008.1.3.117","article-title":"The role of inflammatory mediators in the pathogenesis of otitis media and sequelae","volume":"1","author":"Juhn","year":"2008","journal-title":"Clin. Exp. Otorhinolaryngol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Muhtarova, A.A., Boyanov, V.S., Alexandrova, A.S., and Gergova, R.T. (2025). Molecular characterization of Streptococcus pyogenes isolates recovered from hospitalized patients during the years 2023\u20132024. Microorganisms, 13.","DOI":"10.3390\/microorganisms13092148"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.arcmed.2010.10.003","article-title":"Distribution of genes encoding virulence factors ompB2, ompCD, ompE, \u03b2-lactamase and serotype in pathogenic and colonizing strains of Moraxella catarrhalis","volume":"41","author":"Mitov","year":"2010","journal-title":"Arch. Med. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1080\/23744235.2019.1638964","article-title":"Relation between emm types and virulence gene profiles among Bulgarian Streptococcus pyogenes clinical isolates","volume":"51","author":"Gergova","year":"2019","journal-title":"Infect. Dis."},{"key":"ref_16","first-page":"133","article-title":"Streptococcus pyogenes strains associated with invasive and non-invasive infections present possible links with emm types and superantigens","volume":"23","author":"Khan","year":"2020","journal-title":"Iran J. Basic. Med. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ness, S., and Hilleringmann, M. (2021). Streptococcus pneumoniae type 1 pilus\u2014A multifunctional tool for optimized host interaction. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.615924"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1556\/030.2022.01816","article-title":"Association of pili with widespread multidrug-resistant genetic lineages of non-invasive pediatric Streptococcus pneumoniae isolates","volume":"69","author":"Alexandrova","year":"2022","journal-title":"Acta Microbiol. Immunol. Hung."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Miao, C., Cui, Y., Yan, Z., and Jiang, Y. (2023). Pilus of Streptococcus pneumoniae: Structure, function and vaccine potential. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1270848"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.micinf.2005.06.009","article-title":"The role of Streptococcus pneumoniae sortase A in colonisation and pathogenesis","volume":"8","author":"Paterson","year":"2006","journal-title":"Microbes Infect."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"114918","DOI":"10.1016\/j.intimp.2025.114918","article-title":"Type I and II pili mediate Streptococcus pneumoniae invasion into human blood-brain barrier-derived cells through extracellular matrix protein receptors and different endocytosis pathways","volume":"160","author":"Chen","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1128\/IAI.66.2.406-417.1998","article-title":"The fimbria gene cluster of nonencapsulated Haemophilus influenzae","volume":"66","author":"Geluk","year":"1998","journal-title":"Infect. Immun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.ijmm.2018.07.004","article-title":"Capsule and fimbriae modulate the invasion of Haemophilus influenzae in a human blood-cerebrospinal fluid barrier model","volume":"308","author":"Wegele","year":"2018","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"121928","DOI":"10.1016\/j.carbpol.2024.121928","article-title":"Formation and immunological evaluation of Moraxella catarrhalis glycoconjugates based on synthetic oligosaccharides","volume":"332","author":"Anderson","year":"2024","journal-title":"Carbohydr. Polym."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Chen, M., Wang, W., Tu, L., Zheng, Y., Pan, H., Wang, G., Chen, Y., Zhang, X., Zhu, L., and Chen, J. (2017). An emm5 group A streptococcal outbreak among workers in a factory manufacturing telephone accessories. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.01156"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Gergova, R., Boyanov, V., Muhtarova, A., and Alexandrova, A. (2024). A Review of the impact of streptococcal infections and antimicrobial resistance on human health. Antibiotics, 13.","DOI":"10.3390\/antibiotics13040360"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Madani, A., Garakani, K., and Mofrad, M.R.K. (2017). Molecular mechanics of Staphylococcus aureus adhesin, CNA, and the inhibition of bacterial adhesion by stretching collagen. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179601"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.tim.2019.06.007","article-title":"The MSCRAMM family of cell-wall-anchored surface proteins of gram-positive cocci","volume":"27","author":"Foster","year":"2019","journal-title":"Trends Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1469-0691.2007.01786.x","article-title":"Guidelines for the validation and application of typing methods for use in bacterial epidemiology","volume":"13","author":"Tassios","year":"2007","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"101675","DOI":"10.1016\/j.genrep.2022.101675","article-title":"A Bacterial typing methods from past to present: A comprehensive overview","volume":"29","author":"Ramadan","year":"2022","journal-title":"Gene Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1128\/jcm.29.11.2539-2542.1991","article-title":"Biotypes of Haemophilus influenzae that are associated with noninvasive infections","volume":"11","author":"Harper","year":"1991","journal-title":"J. Clin. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"559","DOI":"10.3897\/folmed.61.e47941","article-title":"Molecular-genetic method for fast direct detection of Staphylococcus Aureus and methicillin resistance in blood cultures and punctures","volume":"61","author":"Gergova","year":"2019","journal-title":"Folia Med."},{"key":"ref_33","first-page":"1410","article-title":"Comparison of cultural, immunological and new PCR techniques for detection of Streptococcus pyogenes","volume":"71","author":"Gergova","year":"2018","journal-title":"Comptes Rendus Acad. Bulg. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.1128\/JCM.00484-09","article-title":"Simple, accurate, serotype-specific PCR assay to differentiate Streptococcus pneumoniae serotypes 6A, 6B, and 6C","volume":"47","author":"Jin","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1128\/JCM.02509-10","article-title":"Use of bexB to detect the capsule locus in Haemophilus influenzae","volume":"7","author":"Davis","year":"2011","journal-title":"J. Clin. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.1128\/jcm.32.10.2382-2386.1994","article-title":"PCR for capsular typing of Haemophilus influenzae","volume":"32","author":"Falla","year":"1994","journal-title":"J. Clin. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s00284-005-0463-6","article-title":"Bactericidal monoclonal antibody against Moraxella catarrhalis lipooligosaccharide cross-reacts with Haemophilus spp.","volume":"54","author":"Gergova","year":"2007","journal-title":"Curr. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Aguiar, S., Serrano, I., Pinto, F., Melo-Christino, J., and Ramirez, M. (2008). The presence of the pilus locus is a clonal property among pneumococcal invasive isolates. BMC Microbiol., 28.","DOI":"10.1186\/1471-2180-8-41"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5480","DOI":"10.1128\/JB.00384-08","article-title":"A second pilus type in Streptococcus pneumoniae is prevalent in emerging serotypes and mediates adhesion to host cells","volume":"190","author":"Bagnoli","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_40","first-page":"359","article-title":"A polymerase chain reaction (PCR) method for the identification of collagen adhesin gene (CNA) in Staphylococcus-induced prosthesis infections","volume":"21","author":"Montanaro","year":"1998","journal-title":"New Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"111552","DOI":"10.1016\/j.ijporl.2023.111552","article-title":"Otopathogens in the middle ear and nasopharynx of children with recurrent acute otitis media","volume":"169","author":"Pereira","year":"2023","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Paton, J.C., and Trappetti, C. (2019). Streptococcus pneumoniae capsular polysaccharide. Microbiol. Spectr., 7.","DOI":"10.1128\/microbiolspec.GPP3-0019-2018"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"105085","DOI":"10.1016\/j.jbc.2023.105085","article-title":"Novel pneumococcal capsule type 33E results from the inactivation of glycosyltransferase WciE in vaccine type 33F","volume":"299","author":"Ganaie","year":"2023","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Alexandrova, A.S., Boyanov, V.S., Mihova, K.Y., Hristova, P.M., Hitkova, H.Y., Marteva-Proevska, Y., and Gergova, R.T. (2025). Population genetic structure of invasive and non-invasive Streptococcus pneumoniae isolates after fifteen years of routine PCV10 vaccination in Bulgaria. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26189028"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1093\/jpids\/piac117","article-title":"Serotype 19A and 6C account for one-third of pneumococcal carriage among Belgian day-care children four years after a shift to a lower-valent PCV","volume":"12","author":"Ekinci","year":"2023","journal-title":"J. Pediatr. Infect. Dis. Soc."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2497611","DOI":"10.1080\/21645515.2025.2497611","article-title":"The microbiological characteristics and diagnosis of Streptococcus pneumoniae infection in the conjugate vaccine era","volume":"21","author":"Chen","year":"2025","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Izurieta, P., AbdelGhany, M., and Borys, D. (2025). Serotype distribution of invasive and non-invasive pneumococcal disease in children \u22645 years of age following the introduction of 10- and 13-valent pneumococcal conjugate vaccines in infant national immunization programs: A systematic literature review. Front. Public Health, 13.","DOI":"10.3389\/fpubh.2025.1544359"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Bano, S., Hassan, N., Rafiq, M., Hassan, F., Rehman, M., Iqbal, N., Ali, H., Hasan, F., and Kang, Y.-Q. (2023). Biofilms as battlefield armor for bacteria against antibiotics: Challenges and combating strategies. Microorganisms, 11.","DOI":"10.3390\/microorganisms11102595"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s00203-023-03826-z","article-title":"Biofilm-mediated infections by multidrug-resistant microbes: A comprehensive exploration and forward perspectives","volume":"206","author":"Zafer","year":"2024","journal-title":"Arch. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S1473-3099(24)00588-7","article-title":"Serotype distribution of remaining invasive pneumococcal disease after extensive use of ten-valent and 13-valent pneumococcal conjugate vaccines (the PSERENADE project): A global surveillance analysis","volume":"25","author":"Quesada","year":"2025","journal-title":"Lancet Infect. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/s41579-018-0001-8","article-title":"Streptococcus pneumoniae: Transmission, colonization and invasion","volume":"16","author":"Weiser","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e0002821","DOI":"10.1128\/CMR.00028-21","article-title":"Invasive Haemophilus influenzae infections after 3 decades of Hib protein conjugate vaccine use","volume":"34","author":"Slack","year":"2021","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Huska, B., and Ulanova, M. (2025). Inflammatory responses to non-typeable Haemophilus influenzae clinical isolates from invasive and non-invasive infections. Pathogens, 14.","DOI":"10.3390\/pathogens14030210"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1155\/2013\/828730","article-title":"Emergence of non-serotype b encapsulated Haemophilus influenzae as a cause of pediatric meningitis in northwestern Ontario","volume":"24","author":"Tsang","year":"2013","journal-title":"Can. J. Infect. Dis. Med. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"001606","DOI":"10.1099\/jmm.0.001606","article-title":"Haemophilus influenzae type f in the post-Haemophilus influenzae type b vaccination era: A systematic review","volume":"71","author":"Reilly","year":"2022","journal-title":"J. Med. Microbiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e34","DOI":"10.1086\/525856","article-title":"Association of nasopharyngeal bacterial colonization during upper respiratory tract infection and the development of acute otitis media","volume":"46","author":"Revai","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.resmic.2012.10.012","article-title":"Pili of gram-positive bacteria: Roles in host colonization","volume":"163","author":"Danne","year":"2012","journal-title":"Res. Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2857","DOI":"10.1073\/pnas.0511017103","article-title":"A pneumococcal pilus influences virulence and host inflammatory responses","volume":"103","author":"Barocchi","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/j.1365-2958.2007.05908.x","article-title":"RrgA is a pilus-associated adhesin in Streptococcus pneumoniae","volume":"66","author":"Nelson","year":"2007","journal-title":"Mol. Microbiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5359","DOI":"10.2147\/IDR.S424468","article-title":"Epidemic trends and biofilm formation mechanisms of Haemophilus influenzae: Insights into clinical implications and prevention strategies","volume":"16","author":"Xiao","year":"2023","journal-title":"Infect. Drug. Resist."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Alexandrova, A.S., Boyanov, V.S., Mihova, K.Y., and Gergova, R.T. (2024). Phylogenetic Lineages and Diseases Associated with Moraxella catarrhalis Isolates Recovered from Bulgarian Patients. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25189769"},{"key":"ref_62","first-page":"514","article-title":"Bacteria-mucin interaction in the upper aerodigestive tract shows striking heterogeneity: Implications in otitis media, rhinosinusitis, and pneumonia","volume":"122","author":"Bernstein","year":"2000","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"6250","DOI":"10.1128\/IAI.68.11.6250-6256.2000","article-title":"Antigenic structure of outer membrane protein E of Moraxella catarrhalis and construction and characterization of mutants","volume":"68","author":"Murphy","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1111\/j.1348-0421.2005.tb03685.x","article-title":"Role of lipooligosaccharide in the attachment of Moraxella catarrhalis to human pharyngeal epithelial cells","volume":"49","author":"Akgul","year":"2005","journal-title":"Microbiol. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Zhao, N., Ren, H., Deng, J., Du, Y., Li, Q., Zhou, P., Zhou, H., Jiang, X., and Qin, T. (2022). Genotypic and Phenotypic Characteristics of Moraxella catarrhalis from Patients and Healthy Asymptomatic Participants among Preschool Children. Pathogens, 11.","DOI":"10.3390\/pathogens11090984"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1128\/IAI.72.4.1906-1913.2004","article-title":"The Moraxella catarrhalis porin-like outer membrane protein CD is an adhesin for human lung cells","volume":"72","author":"Holm","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_67","first-page":"001488","article-title":"A global perspective on the genomics of Moraxella catarrhalis","volume":"11","author":"Ugalde","year":"2025","journal-title":"Microb. Genom."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1128\/MMBR.00007-09","article-title":"Molecular aspects of Moraxella catarrhalis pathogenesis","volume":"73","author":"Bootsma","year":"2009","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"201991","DOI":"10.1098\/rsos.201991","article-title":"A brief review on Group A Streptococcus pathogenesis and vaccine development","volume":"8","author":"Castro","year":"2021","journal-title":"R. Soc. Open Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"111677","DOI":"10.1016\/j.isci.2024.111677","article-title":"The burden of group A Streptococcus (GAS) infections: The challenge continues in the twenty-first century","volume":"28","author":"Thacharodi","year":"2024","journal-title":"iScience"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1099\/mic.0.031955-0","article-title":"Characterization of a virulence-associated and cell-wall-located DNase of Streptococcus pyogenes","volume":"156","author":"Hasegawa","year":"2010","journal-title":"Microbiology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1099\/mic.0.000612","article-title":"The DNases of pathogenic Lancefield streptococci","volume":"164","author":"Remmington","year":"2018","journal-title":"Microbiology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1111\/j.1365-2958.2004.04255.x","article-title":"Post-proteomic identification of a novel phage-encoded streptodornase, Sda1, in invasive M1T1 Streptococcus pyogenes","volume":"54","author":"Aziz","year":"2004","journal-title":"Mol. Microbiol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/12\/1512\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T05:24:44Z","timestamp":1766121884000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/12\/1512"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,17]]},"references-count":73,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["genes16121512"],"URL":"https:\/\/doi.org\/10.3390\/genes16121512","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,17]]}}}