{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:25:39Z","timestamp":1787613939234,"version":"build-2736575974"},"reference-count":132,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T00:00:00Z","timestamp":1609891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>It is widely recognized that many chronic infections of the human body have a polymicrobial etiology. These include diabetic foot ulcer infections, lung infections in cystic fibrosis patients, periodontitis, otitis, urinary tract infections and even a proportion of systemic infections. The treatment of mixed infections poses serious challenges in the clinic. First, polymicrobial communities of microorganisms often organize themselves as biofilms that are notoriously recalcitrant to antimicrobial therapy and clearance by the host immune system. Secondly, a plethora of interactions among community members may affect the expression of virulence factors and the susceptibility to antimicrobials of individual species in the community. Therefore, new strategies able to target multiple pathogens in mixed populations need to be urgently developed and evaluated. In this regard, antimicrobial or host defense peptides (AMPs) deserve particular attention as they are endowed with many favorable features that may serve to this end. The aim of the present review is to offer a comprehensive and updated overview of studies addressing the therapeutic potential of AMPs in mixed infections, highlighting the opportunities offered by this class of antimicrobials in the fight against polymicrobial infections, but also the limits that may arise in their use for this type of application.<\/jats:p>","DOI":"10.3390\/ijms22020482","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T09:15:16Z","timestamp":1609924516000},"page":"482","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":98,"title":["Therapeutic Potential of Antimicrobial Peptides in Polymicrobial Biofilm-Associated Infections"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4448-2385","authenticated-orcid":false,"given":"Giovanna","family":"Batoni","sequence":"first","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56123 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppantonio","family":"Maisetta","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56123 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4358-5294","authenticated-orcid":false,"given":"Semih","family":"Esin","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56123 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Maisetta, G., and Batoni, G. (2020). Editorial: Interspecies interactions: Effects on virulence and antimicrobial susceptibility of bacterial and fungal pathogens. Front. Microbiol.","DOI":"10.3389\/978-2-88966-097-1"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Filkins, L.M., and O\u2019Toole, G.A. (2015). Cystic fibrosis lung infections: Polymicrobial, complex, and hard to treat. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005258"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1136\/thoraxjnl-2018-212616","article-title":"Help, hinder, hide and harm: What can we learn from the interactions between Pseudomonas aeruginosa and Staphylococcus aureus during respiratory infections?","volume":"74","author":"Limoli","year":"2019","journal-title":"Thorax"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e00809-20","DOI":"10.1128\/mSystems.00809-20","article-title":"Ecological succession of polymicrobial communities in the cystic fibrosis airways","volume":"5","author":"Khanolkar","year":"2020","journal-title":"mSystems"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.ijpharm.2013.12.012","article-title":"Polymicrobial wound infections: Pathophysiology and current therapeutic approaches","volume":"463","author":"Bertesteanu","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1586\/14787210.2015.1023291","article-title":"Chronic wound infections: The role of Pseudomonas aeruginosa and Staphylococcus aureus","volume":"13","author":"Serra","year":"2015","journal-title":"Expert. Rev. Anti Infect. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"119659","DOI":"10.1016\/j.ijpharm.2020.119659","article-title":"Bacterial vaginosis: Standard treatments and alternative strategies","volume":"587","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"104588","DOI":"10.1016\/j.micpath.2020.104588","article-title":"Comparative analysis of bacterial vaginosis microbiota among pregnant and non-pregnant females and isolation of phages against Enterococcus faecalis, Enterococcus faecium, and Shigella flexneri strains","volume":"149","author":"Javed","year":"2020","journal-title":"Microb. Pathog."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/S0924-8579(02)00087-0","article-title":"Aetiology of chronic prostatitis","volume":"19","author":"Skerk","year":"2002","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.3389\/fmicb.2019.03006","article-title":"Moraxella catarrhalis promotes stable polymicrobial biofilms with the major otopathogens","volume":"10","author":"Bair","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1080\/1040841X.2016.1240656","article-title":"Impact of polymicrobial biofilms in catheter-associated urinary tract infections","volume":"43","author":"Azevedo","year":"2017","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_12","unstructured":"Mehrotra, N., and Singh, S. (2020). Periodontitis. StatPearls [Internet], StatPearls Publishing."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Dahlen, G., Basic, A., and Bylund, J. (2019). Importance of virulence factors for the persistence of oral bacteria in the inflamed gingival crevice and in the pathogenesis of periodontal disease. J. Clin. Med., 8.","DOI":"10.3390\/jcm8091339"},{"key":"ref_14","first-page":"911","article-title":"Association of Streptococcus mutans, Candida albicans and oral health practices with activity status of caries lesions among 5-year-old children with early childhood caries","volume":"18","author":"Sridhar","year":"2020","journal-title":"Oral Health Prev. Dent."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kaya, E., Tollapi, L., Pastore, A., Aringhieri, G., Maisetta, G., Barnini, S., Paolicchi, A., Batoni, G., and Esin, S. (2020). Comparison of methods for the microbiological diagnosis of totally implantable venous access port-related infections. J. Med. Microbiol.","DOI":"10.1099\/jmm.0.001263"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3201\/eid0702.010226","article-title":"Biofilms and device-associated infections","volume":"7","author":"Donlan","year":"2001","journal-title":"Emerg. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.biotechadv.2019.02.013","article-title":"A \u2018culture\u2019 shift: Application of molecular techniques for diagnosing polymicrobial infections","volume":"37","author":"Zhang","year":"2019","journal-title":"Biotechnol. Adv."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0732-8893(86)90001-5","article-title":"Clinical importance of polymicrobial bacteremia","volume":"5","author":"Weinstein","year":"1986","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.diagmicrobio.2007.07.001","article-title":"Polymicrobial bloodstream infections involving Candida species: Analysis of patients and review of the literature","volume":"59","author":"Klotz","year":"2007","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6141","DOI":"10.1007\/s00253-016-7596-3","article-title":"Interactions between Pseudomonas aeruginosa and Staphylococcus aureus during co-cultivations and polymicrobial infections","volume":"100","author":"Nguyen","year":"2016","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Dalton, T., Dowd, S.E., Wolcott, R.D., Sun, Y., Watters, C., Griswold, J.A., and Rumbaugh, K.P. (2011). An in vivo polymicrobial biofilm wound infection model to study interspecies interactions. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0027317"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4718","DOI":"10.1128\/IAI.02198-14","article-title":"Synergistic interactions of Pseudomonas aeruginosa and Staphylococcus aureus in an in vitro wound model","volume":"82","author":"DeLeon","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1007\/s10096-016-2621-0","article-title":"Staphylococcus aureus and Pseudomonas aeruginosa co-infection is associated with cystic fibrosis-related diabetes and poor clinical outcomes","volume":"35","author":"Limoli","year":"2016","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3389\/fcimb.2017.00106","article-title":"In vivo and in vitro interactions between Pseudomonas aeruginosa and Staphylococcus spp.","volume":"7","author":"Hotterbeekx","year":"2017","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lopez-Medina, E., Fan, D., Coughlin, L.A., Ho, E.X., Lamont, I.L., Reimmann, C., Hooper, L.V., and Koh, A.Y. (2015). Candida albicans inhibits Pseudomonas aeruginosa virulence through suppression of pyochelin and pyoverdine biosynthesis. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005129"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/j.1365-2958.2008.06132.x","article-title":"Interspecies signalling via the Stenotrophomonas maltophilia diffusible signal factor influences biofilm formation and polymyxin tolerance in Pseudomonas aeruginosa","volume":"68","author":"Ryan","year":"2008","journal-title":"Mol. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3914","DOI":"10.1128\/AAC.00657-09","article-title":"Candida albicans and Staphylococcus aureus form polymicrobial biofilms: Effects on antimicrobial resistance","volume":"53","author":"Harriott","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e00873-17","DOI":"10.1128\/mBio.00873-17","article-title":"Pseudomonas aeruginosa alters Staphylococcus aureus sensitivity to vancomycin in a biofilm model of cystic fibrosis infection","volume":"8","author":"Orazi","year":"2017","journal-title":"mBio"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"19890","DOI":"10.1073\/pnas.0606756104","article-title":"Selection for Staphylococcus aureus small-colony variants due to growth in the presence of Pseudomonas aeruginosa","volume":"103","author":"Hoffman","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1093\/jac\/dkt072","article-title":"Antibiotic activity against small-colony variants of Staphylococcus aureus: Review of in vitro, animal and clinical data","volume":"68","author":"Garcia","year":"2013","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Li, H., Li, X., Wang, Z., Fu, Y., Ai, Q., Dong, Y., and Ju, J. (2015). Autoinducer-2 regulates Pseudomonas aeruginosa PAO1 biofilm formation and virulence production in a dose-dependent manner. BMC Microbiol., 15.","DOI":"10.1186\/s12866-015-0529-y"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1128\/JB.187.2.554-566.2005","article-title":"Staphylococcus aureus serves as an iron source for Pseudomonas aeruginosa during in vivo coculture","volume":"187","author":"Mashburn","year":"2005","journal-title":"J. Bacteriol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e00530-19","DOI":"10.1128\/JB.00530-19","article-title":"\u201cIt takes a village\u201d: Mechanisms underlying antimicrobial recalcitrance of polymicrobial biofilms","volume":"202","author":"Orazi","year":"2019","journal-title":"J. Bacteriol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1099\/0022-1317-51-4-344","article-title":"Mixed species biofilms of Candida albicans and Staphylococcus epidermidis","volume":"51","author":"Adam","year":"2002","journal-title":"J. Med. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.3389\/fmicb.2019.02803","article-title":"Polymicrobial interactions induce multidrug tolerance in Staphylococcus aureus through energy depletion","volume":"10","author":"Nabb","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1080\/21505594.2018.1426520","article-title":"Polymicrobial infections: Do bacteria behave differently depending on their neighbors?","volume":"9","author":"Lasa","year":"2018","journal-title":"Virulence"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.bbamem.2015.10.013","article-title":"Antimicrobial peptides and their interaction with biofilms of medically relevant bacteria","volume":"1858","author":"Batoni","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3389\/fchem.2017.00063","article-title":"Antimicrobial peptides in biomedical device manufacturing","volume":"5","author":"Riool","year":"2017","journal-title":"Front Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1080\/08927014.2015.1021340","article-title":"BaAMPs: The database of biofilm-active antimicrobial peptides","volume":"31","author":"Maccari","year":"2015","journal-title":"Biofouling"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"949","DOI":"10.3389\/fmicb.2016.00949","article-title":"Prediction of biofilm inhibiting peptides: An in silico approach","volume":"7","author":"Gupta","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"21839","DOI":"10.1038\/srep21839","article-title":"DPABBs: A novel in silico approach for predicting and designing","volume":"6","author":"Sharma","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7290","DOI":"10.1021\/acsomega.9b04119","article-title":"BIPEP: Sequence-based prediction of biofilm inhibitory peptides using a combination of nmr and physicochemical descriptors","volume":"5","author":"Behrouzi","year":"2020","journal-title":"ACS Omega"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.3389\/fmicb.2017.01917","article-title":"Generation of persister cells of Pseudomonas aeruginosa and Staphylococcus aureus by chemical treatment and evaluation of their susceptibility to membrane-targeting agents","volume":"8","author":"Grassi","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"eaan4044","DOI":"10.1126\/scitranslmed.aan4044","article-title":"The antimicrobial peptide SAAP-148 combats drug-resistant bacteria and biofilms","volume":"10","author":"Riool","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/exd.12929","article-title":"Antimicrobial peptides and wound healing: Biological and therapeutic considerations","volume":"25","author":"Mangoni","year":"2016","journal-title":"Exp. Dermatol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Grassi, L., Pompilio, A., Kaya, E., Rinaldi, A.C., Sanjust, E., Maisetta, G., Crabb\u00e9, A., Di Bonaventura, G., Batoni, G., and Esin, S. (2020). The anti-microbial peptide (Lin-SB056-1)2-K reduces pro-inflammatory cytokine release through interaction with Pseudomonas aeruginosa lipopolysaccharide. Antibiotics, 9.","DOI":"10.3390\/antibiotics9090585"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"904","DOI":"10.2174\/1381612824666180213130318","article-title":"The Modification and design of antimicrobial peptide","volume":"24","author":"Gao","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"111814","DOI":"10.1016\/j.ejmech.2019.111814","article-title":"Development of a novel hybrid antimicrobial peptide for targeted killing of Pseudomonas aeruginosa","volume":"185","author":"Kim","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41522-017-0017-2","article-title":"Komodo dragon-inspired synthetic peptide DRGN-1 promotes wound-healing of a mixed-biofilm infected wound","volume":"3","author":"Chung","year":"2017","journal-title":"npj Biofilms Microbiomes"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Gomes, D., Santos, R., Soares, R.S., Reis, S., Carvalho, S., Rego, P., Peleteiro, M.C., Tavares, L., and Oliveira, M. (2020). Pexiganan in combination with nisin to control polymicrobial diabetic foot infections. Antibiotics, 9.","DOI":"10.3390\/antibiotics9030128"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Jorge, P., Grzywacz, D., Kamysz, W., Lourenc\u00cbo, A., and Pereira, M.O. (2017). Searching for new strategies against biofilm infections: Colistin-AMP combinations against Pseudomonas aeruginosa and Staphylococcus aureus single- and double-species biofilms. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0174654"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1093\/milmed\/usx135","article-title":"A novel peptide-based antimicrobial wound treatment is effective against biofilms of multi-drug resistant wound pathogens","volume":"183","author":"Bayramov","year":"2018","journal-title":"Mil. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.ijbiomac.2019.08.087","article-title":"Biofunctions of antimicrobial peptide-conjugated alginate\/hyaluronic acid\/collagen wound dressings promote wound healing of a mixed-bacteria-infected wound","volume":"140","author":"Lin","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.ijantimicag.2011.01.003","article-title":"Broad-spectrum antimicrobial efficacy of peptide A3-APO in mouse models of multidrug-resistant wound and lung infections cannot be explained by in vitro activity against the pathogens involved","volume":"37","author":"Ostorhazi","year":"2011","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.2147\/IDR.S217020","article-title":"Potential role of the antimicrobial peptide Tachyplesin III against multidrug-resistant P. aeruginosa and A. baumannii coinfection in an animal model","volume":"12","author":"Qi","year":"2019","journal-title":"Infect. Drug Resist."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.actbio.2015.07.031","article-title":"Efficacy of a novel antimicrobial peptide against periodontal pathogens in both planktonic and polymicrobial biofilm states","volume":"25","author":"Wang","year":"2015","journal-title":"Acta Biomater."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3028","DOI":"10.1016\/j.bbadis.2017.08.032","article-title":"Epinecidin-1 protects mice from LPS-induced endotoxemia and cecal ligation and puncture-induced polymicrobial sepsis","volume":"1863","author":"Su","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"R3","DOI":"10.1186\/cc11920","article-title":"The anti-inflammatory effect of the synthetic antimicrobial peptide 19-2.5 in a murine sepsis model: A prospective randomized study","volume":"17","author":"Schuerholz","year":"2013","journal-title":"Crit. Care"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"37277","DOI":"10.1038\/srep37277","article-title":"The synthetic antimicrobial peptide 19-2.5 attenuates septic cardiomyopathy and prevents down-regulation of SERCA2 in polymicrobial sepsis","volume":"6","author":"Martin","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3227","DOI":"10.2147\/IDR.S218778","article-title":"Functional synergy of antimicrobial peptides and chlorhexidine acetate against Gram-negative\/Gram-positive bacteria and a fungus in vitro and in vivo","volume":"12","author":"Zhu","year":"2019","journal-title":"Infect. Drug Resist."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.micpath.2018.09.027","article-title":"Polymicrobial antibiofilm activity of the membranotropic peptide gH625 and its analogue","volume":"125","author":"Lombardi","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e00520-19","DOI":"10.1128\/AAC.00520-19","article-title":"Cholic acid-peptide conjugates as potent antimicrobials against interkingdom polymicrobial biofilms","volume":"63","author":"Gupta","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e00083-16","DOI":"10.1128\/mSphere.00083-16","article-title":"Simultaneous antibiofilm and antiviral activities of an engineered antimicrobial peptide during virus-bacterium coinfection","volume":"1","author":"Melvin","year":"2016","journal-title":"mSphere"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Rollins-Smith, L.A., Smith, P.B., Ledeczi, A.M., Rowe, J.M., and Reinert, L.K. (2020). Caerin 1 antimicrobial peptides that inhibit HIV and Neisseria may spare protective Lactobacilli. Antibiotics, 9.","DOI":"10.3390\/antibiotics9100661"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Bessa, L.J., Manickchand, J.R., Eaton, P., Leite, J.R.S.A., Brand, G.D., and Gameiro, P. (2019). Intragenic antimicrobial peptide Hs02 hampers the proliferation of single- and dual-species biofilms of P. aeruginosa and S. aureus: A promising agent for mitigation of biofilm-associated infections. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20143604"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1093\/jac\/dkv334","article-title":"Searching for new strategies against polymicrobial biofilm infections: Guanylated polymethacrylates kill mixed fungal\/bacterial biofilms","volume":"71","author":"Qu","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/cbic.201600381","article-title":"Peptoid efficacy against polymicrobial biofilms determined by using propidium monoazide-modified quantitative PCR","volume":"18","author":"Luo","year":"2017","journal-title":"ChemBioChem"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/s13643-016-0329-y","article-title":"Prevalence and incidence of chronic wounds and related complications: A protocol for a systematic review","volume":"5","author":"Ni","year":"2016","journal-title":"Syst. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5","DOI":"10.4103\/2321-3868.113329","article-title":"Biofilm delays wound healing: A review of the evidence","volume":"1","author":"Metcalf","year":"2013","journal-title":"Burns Trauma"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"7","DOI":"10.12968\/jowc.2015.24.Sup4b.7","article-title":"Innovation and wound healing","volume":"24","author":"Harding","year":"2015","journal-title":"J. Wound Care"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1097\/00129334-200509000-00011","article-title":"A toxicity index of skin and wound cleansers used on in vitro fibroblasts and keratinocytes","volume":"18","author":"Wilson","year":"2005","journal-title":"Adv. SkinWound Care"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"516","DOI":"10.3389\/fbioe.2020.00516","article-title":"Functional biomaterials for treatment of chronic wound","volume":"8","author":"Zhang","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.cytogfr.2019.08.001","article-title":"Architecture of antimicrobial skin defense","volume":"49","author":"Kwiecien","year":"2019","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"R14","DOI":"10.1016\/j.cub.2015.11.017","article-title":"Antimicrobial peptides","volume":"26","author":"Zhang","year":"2016","journal-title":"Curr. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.actbio.2019.12.025","article-title":"Topical antimicrobial peptide formulations for wound healing: Current developments and future prospects","volume":"103","author":"Thapa","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.3389\/fmicb.2019.01688","article-title":"Evaluation of the antimicrobial peptide, RP557, for the broad-spectrum treatment of wound pathogens and biofilm","volume":"10","author":"Woodburn","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"143","DOI":"10.3389\/fimmu.2013.00143","article-title":"The human cathelicidin antimicrobial peptide LL-37 as a potential treatment for polymicrobial infected wounds","volume":"4","author":"Duplantier","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.3389\/fmicb.2017.02409","article-title":"Combination strategies to enhance the efficacy of antimicrobial peptides against bacterial biofilms","volume":"8","author":"Grassi","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.bbamem.2006.12.003","article-title":"The role of lipid II in membrane binding of and pore formation by nisin analyzed by two combined biosensor techniques","volume":"1768","author":"Christ","year":"2007","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.2217\/nnm-2016-0057","article-title":"Perspectives on polymeric nanostructures for the therapeutic application of antimicrobial peptides","volume":"11","author":"Sandreschi","year":"2016","journal-title":"Nanomedicine"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"372","DOI":"10.3389\/fmicb.2015.00372","article-title":"Chitosan nanoparticles loaded with the antimicrobial peptide temporin B exert a long-term antibacterial activity in vitro against clinical isolates of Staphylococcus epidermidis","volume":"6","author":"Piras","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jcf.2013.09.004","article-title":"Culture-based diagnostic microbiology in cystic fibrosis: Can we simplify the complexity?","volume":"13","author":"Burns","year":"2014","journal-title":"J. Cyst Fibros."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1080\/01902140701756687","article-title":"The role of epithelial beta-defensins and cathelicidins in host defense of the lung","volume":"33","author":"Hiemstra","year":"2007","journal-title":"Exp. Lung Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1159\/000354465","article-title":"Antimicrobial peptide LL-37 and IDR-1 ameliorate MRSA pneumonia in vivo","volume":"32","author":"Hou","year":"2013","journal-title":"Cell Physiol. Biochem."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Barlow, P.G., Svoboda, P., Mackellar, A., Nash, A.A., York, I.A., Pohl, J., Davidson, D.J., and Donis, R.O. (2011). Antiviral activity and increased host defense against influenza infection elicited by the human cathelicidin LL-37. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025333"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Beaumont, P.E., McHugh, B., Gwyer Findlay, E., Mackellar, A., Mackenzie, K.J., Gallo, R.L., Govan, J.R., Simpson, A.J., and Davidson, D.J. (2014). Cathelicidin host defence peptide augments clearance of pulmonary Pseudomonas aeruginosa infection by its influence on neutrophil function in vivo. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0099029"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/prd.12342","article-title":"Periodontitis is an inflammatory disease of oxidative stress: We should treat it that way","volume":"84","author":"Sczepanik","year":"2020","journal-title":"Periodontol 2000"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/S1532-3382(12)70013-1","article-title":"Local and systemic antimicrobial therapy in periodontics","volume":"12","author":"Herrera","year":"2012","journal-title":"J. Evid. Based Dent. Pract."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.jgar.2020.02.024","article-title":"Antimicrobial resistance of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Tannerella forsythia in periodontitis patients","volume":"22","author":"Ardila","year":"2020","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_90","first-page":"119","article-title":"Antimicrobial peptides in the oral environment: Expression and function in health and disease","volume":"7","author":"Dale","year":"2005","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1177\/0022034510385686","article-title":"Reduced human beta defensin 3 in individuals with periodontal disease","volume":"90","author":"Brancatisano","year":"2011","journal-title":"J. Dent. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3349","DOI":"10.1128\/AAC.47.10.3349-3351.2003","article-title":"Activity of human beta-defensin 3 alone or combined with other antimicrobial agents against oral bacteria","volume":"47","author":"Maisetta","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1128\/AAC.49.3.1245-1248.2005","article-title":"Susceptibility of Streptococcus mutans and Actinobacillus actinomycetemcomitans to bactericidal activity of human beta-defensin 3 in biological fluids","volume":"49","author":"Maisetta","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.2174\/1381612824666180403114615","article-title":"Human oral defensins antimicrobial peptides: A future promising antimicrobial drug","volume":"24","author":"Khurshid","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"4918","DOI":"10.1128\/AAC.00202-11","article-title":"Easy strategy to increase salt resistance of antimicrobial peptides","volume":"55","author":"Yu","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ijantimicag.2009.09.024","article-title":"Antibacterial and lipopolysaccharide (LPS)-neutralising activity of human cationic antimicrobial peptides against periodontopathogens","volume":"35","author":"Lee","year":"2010","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1164\/rccm.201504-0781OC","article-title":"International forum of acute care trialists. Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations","volume":"193","author":"Fleischmann","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1007\/s11908-001-0086-4","article-title":"The role of intravascular devices in sepsis","volume":"3","author":"Crnich","year":"2001","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_99","first-page":"25","article-title":"Long-term catheterization: Current approaches in the diagnosis and treatment of port-related infections","volume":"7","author":"Bustos","year":"2014","journal-title":"Infect Drug Resist."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13756-020-00741-6","article-title":"Clinical characteristics and risk factors of polymicrobial Staphylococcus aureus bloodstream infections","volume":"9","author":"Zheng","year":"2020","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.tim.2011.01.001","article-title":"Cecal ligation and puncture: The gold standard model for polymicrobial sepsis?","volume":"19","author":"Dejager","year":"2011","journal-title":"Trends Microbiol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Tidbury, F., Langhart, A., Weidlinger, S., and Stute, P. (2020). Non-antibiotic treatment of bacterial vaginosis-a systematic review. Arch. Gynecol. Obstet.","DOI":"10.1007\/s00404-020-05821-x"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Allison, D.L., Willems, H.M.E., Jayatilake, J.A.M.S., Bruno, V.M., Peters, B.M., and Shirtliff, M.E. (2016). Candida-bacteria interactions: Their impact on human disease. Microbiol. Spectr., 4.","DOI":"10.1128\/microbiolspec.VMBF-0030-2016"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/nrmicro2313","article-title":"Medically important bacterial\u2013fungal interactions","volume":"8","author":"Peleg","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1128\/iai.52.1.200-204.1986","article-title":"Increased susceptibility to lethal Candida infections in burned mice preinfected with Pseudomonas aeruginosa or pretreated with proteolytic enzymes","volume":"52","author":"Neely","year":"1986","journal-title":"Infect. Immun."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1093\/jac\/dkt322","article-title":"De novo generation of short antimicrobial peptides with enhanced stability and cell specificity","volume":"69","author":"Kim","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"6319","DOI":"10.3390\/molecules20046319","article-title":"Insights into the antimicrobial properties of hepcidins: Advantages and drawbacks as potential therapeutic agents","volume":"20","author":"Lombardi","year":"2015","journal-title":"Molecules"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"544","DOI":"10.3389\/fmicb.2017.00544","article-title":"The naturally occurring host defense peptide, LL-37, and its truncated mimetics KE-18 and KR-12 have selected biocidal and antibiofilm activities against Candida albicans, Staphylococcus aureus, and Escherichia coli in vitro","volume":"8","author":"Luo","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.nano.2011.04.009","article-title":"A peptide derived from herpes simplex virus type 1 glycoprotein H: Membrane translocation and applications to the delivery of quantum dots","volume":"7","author":"Falanga","year":"2011","journal-title":"Nanomedicine"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Neu, U., and Mainou, B.A. (2020). Virus interactions with bacteria: Partners in the infectious dance. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008234"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jcf.2005.05.011","article-title":"Viral respiratory infections in cystic fibrosis","volume":"4","author":"Wolfs","year":"2005","journal-title":"J. Cyst. Fibros."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1073\/pnas.1516979113","article-title":"Respiratory syncytial virus infection enhances Pseudomonas aeruginosa biofilm growth through dysregulation of nutritional immunity","volume":"113","author":"Hendricks","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/1097-0282(2000)55:1<4::AID-BIP30>3.0.CO;2-M","article-title":"Amphipathic, alpha-helical antimicrobial peptides","volume":"55","author":"Tossi","year":"2000","journal-title":"Biopolymers"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"5777","DOI":"10.1021\/bi0100384","article-title":"Design of Gram-negative selective antimicrobial peptides","volume":"40","author":"Muhle","year":"2001","journal-title":"Biochemistry"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1007\/s00726-015-2136-5","article-title":"Rational modification of a dendrimeric peptide with antimicrobial activity: Consequences on membrane-binding and biological properties","volume":"48","author":"Batoni","year":"2016","journal-title":"Amino Acids"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1038\/s41598-018-37630-3","article-title":"Minor sequence modifications in temporin B cause drastic changes in antibacterial potency and selectivity by fundamentally altering membrane activity","volume":"9","author":"Manzo","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"3651","DOI":"10.1128\/AAC.00622-06","article-title":"Targeted killing of Streptococcus mutans by a pheromone-guided \u201cSmart\u201d antimicrobial peptide","volume":"50","author":"Eckert","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1159\/000330510","article-title":"Clinical efficacy of a specifically targeted antimicrobial peptide mouth rinse: Targeted elimination of Streptococcus mutans and prevention of demineralization","volume":"45","author":"Sullivan","year":"2011","journal-title":"Caries Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1128\/AAC.50.4.1480-1488.2006","article-title":"Adding selectivity to antimicrobial peptides: Rational design of a multidomain peptide against Pseudomonas spp.","volume":"50","author":"Eckert","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.ijantimicag.2008.11.013","article-title":"Design and activity of a \u2018dual-targeted\u2019 antimicrobial peptide","volume":"33","author":"He","year":"2009","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_121","first-page":"299","article-title":"Peptoids as potential therapeutics","volume":"11","author":"Zuckermann","year":"2009","journal-title":"Curr. Opin. Mol. Ther."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1002\/ddr.430350105","article-title":"Comparison of the proteolytic susceptibilities of homologous L-Amino Acid, D-Amino Acid, and N-Substituted glycine peptide and peptoid oligomers","volume":"35","author":"Miller","year":"1995","journal-title":"Drug Develop. Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"951","DOI":"10.3389\/fmicb.2015.00951","article-title":"Cooperative pathogenicity in cystic fibrosis: Stenotrophomonas maltophilia modulates Pseudomonas aeruginosa virulence in mixed biofilm","volume":"6","author":"Pompilio","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"e00275-18","DOI":"10.1128\/mBio.00275-18","article-title":"Mixed communities of mucoid and non-mucoid Pseudomonas aeruginosa exhibit enhanced resistance to host antimicrobials","volume":"9","author":"Malhotra","year":"2018","journal-title":"mBio"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Billings, N., Millan, M., Caldara, M., Rusconi, R., Tarasova, Y., Stocker, R., and Ribbeck, K. (2013). The extracellular matrix component Psl provides fast-acting antibiotic defense in Pseudomonas aeruginosa biofilms. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003526"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1038\/jid.2014.176","article-title":"Decreased susceptibility of Staphylococcus aureus small-colony variants toward human antimicrobial peptides","volume":"134","author":"Becker","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Campa, M., Bendinelli, M., and Friedman, H. (1993). The role of proteases in the pathogenesis of Pseudomonas aeruginosa infections. Pseudomonas aeruginosa as an Opportunistic Pathogen. Infectious Agents and Pathogenesis, Springer.","DOI":"10.1007\/978-1-4615-3036-7"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1111\/j.1399-302X.1998.tb00706.x","article-title":"Proteases of Porphyromonas gingivalis: What don\u2019t they do?","volume":"13","author":"Kuramitsu","year":"1998","journal-title":"Oral Microbiol. Immunol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"20150292","DOI":"10.1098\/rstb.2015.0292","article-title":"Bacterial strategies of resistance to antimicrobial peptides","volume":"371","author":"Joo","year":"2016","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1586\/14787210.2014.976613","article-title":"Antimicrobial peptides: Therapeutic potentials","volume":"12","author":"Kang","year":"2014","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Ron\u010devi\u0107, T., Puizina, J., and Tossi, A. (2019). Antimicrobial peptides as anti-infective agents in pre-post-antibiotic era?. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225713"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Browne, K., Chakraborty, S., Chen, R., Willcox, M.D., Black, D.S., Walsh, W.R., and Kumar, N. (2020). A new era of antibiotics: The clinical potential of antimicrobial peptides. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197047"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/2\/482\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:07:29Z","timestamp":1760159249000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/2\/482"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,6]]},"references-count":132,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["ijms22020482"],"URL":"https:\/\/doi.org\/10.3390\/ijms22020482","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,6]]}}}