{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T11:10:49Z","timestamp":1785928249265,"version":"3.56.0"},"reference-count":49,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,14]],"date-time":"2022-04-14T00:00:00Z","timestamp":1649894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Fungal\u2013bacterial co-culturing is a potential technique for the production of secondary metabolites with antibacterial activity. Twenty-nine fungal species were screened in a co-culture with carbapenem-resistant Klebsiella pneumoniae at different temperatures. A temperature of 37 \u00b0 showed inhibition of bacterial growth. Antimicrobial susceptibility testing for K. pneumoniae was conducted to compare antibiotic resistance patterns before and after the co-culture. Genotypic comparison of the K. pneumonia was performed using next generation sequencing (NGS). It was shown that two out of five K. pneumoniae, with sequence type ST 101 isolates, lost bla-OXA48, bla-CTX-M-14, tir, strA and strB genes after the co-culture with Scopulariopsis brevicaulis fungus. The other three isolates (ST 383 and 147) were inhibited in the co-culture but did not show any changes in resistance. The total ethyl acetate extract of the fungal\u2013bacterial co-culture was tested against K. pneumoniae using a disc diffusion method. The concentration of the crude extract was 0.97 mg\/\u00b5L which resulted in total inhibition of the bacteria. Using chromatographic techniques, the purified compounds were identified as 11-octadecenoic acid, 2,4-Di-tert-butylphenol, 2,3-Butanediol and 9-octadecenamide. These were tested against K. pneumoniae using the well diffusion method at a concentration of 85 \u00b5g\/\u00b5L which resulted in total inhibition of bacteria. The co-culture results indicated that bacteria under chemical stress showed variable responses and induced fungal secondary metabolites with antibacterial activities.<\/jats:p>","DOI":"10.3390\/molecules27082541","type":"journal-article","created":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T01:03:01Z","timestamp":1650330181000},"page":"2541","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["In Vitro Investigation of the Impact of Bacterial\u2013Fungal Interaction on Carbapenem-Resistant Klebsiella pneumoniae"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1319-4698","authenticated-orcid":false,"given":"Hani","family":"Moubasher","sequence":"first","affiliation":[{"name":"Department of Botany and Microbiology, Faculty of Science, Cairo University, Giza 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0645-7664","authenticated-orcid":false,"given":"Amani","family":"Elkholy","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, Faculty of Medicine, Cairo University, Giza 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May","family":"Sherif","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, Faculty of Medicine, Cairo University, Giza 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Zahran","sequence":"additional","affiliation":[{"name":"Department of Botany and Microbiology, Faculty of Science, Cairo University, Giza 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1331-8977","authenticated-orcid":false,"given":"Sherif","family":"Elnagdy","sequence":"additional","affiliation":[{"name":"Department of Botany and Microbiology, Faculty of Science, Cairo University, Giza 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3389\/fmolb.2019.00071","article-title":"Bacterial Mechanisms of Antibiotic Resistance: A Structural Perspective","volume":"6","author":"Conn","year":"2019","journal-title":"Front. Mol. Biosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15422","DOI":"10.1038\/s41598-019-51969-1","article-title":"Broad and Efficient Control of Klebsiella Pathogens by Peptidoglycan-Degrading and Pore-Forming Bacteriocins Klebicins","volume":"9","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_3","unstructured":"(2016, September 30). Current State of Resistance to Antibiotics of Last-Resort in South Africa: A Review from a Public Health Perspective, Available online: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5042966\/."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1093\/jac\/dkg101","article-title":"Antimicrobial resistance in Cairo, Egypt 1999\u20132000: A survey of five hospitals","volume":"51","author":"Kholy","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.4065\/mcp.2011.0358","article-title":"Antimicrobial Stewardship","volume":"86","author":"Doron","year":"2011","journal-title":"Mayo Clin. Proc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1089\/sur.2018.088","article-title":"High Prevalence of VIM, K. PNEUMONIAEC, and NDM Expression among Surgical Site Infection Pathogens in Patients Having Emergency Surgery","volume":"19","author":"Elanany","year":"2018","journal-title":"Surg. Infect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1007\/s10096-020-03812-z","article-title":"Molecular characterization of multidrug-resistant Gram-negative pathogens in three tertiary hospitals in Cairo, Egypt","volume":"39","author":"Girgis","year":"2020","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1128\/AAC.05289-11","article-title":"Genetic Features of the Widespread Plasmid Coding for the Carbapenemase OXA-48","volume":"56","author":"Poirel","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1007\/s10096-021-04177-7","article-title":"Whole-genome sequencing of Egyptian multidrug-resistant Klebsiella pneumoniae isolates: A multi-center pilot study","volume":"40","author":"Sherif","year":"2021","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis. Off. Publ. Eur. Soc. Clin. Microbiol."},{"key":"ref_10","unstructured":"Baron, S. (2019, December 28). Bacterial Pathogenesis, Medical Microbiology [Internet], Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK8526\/."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1159\/000494627","article-title":"The Iron Tug-of-War between Bacterial Siderophores and Innate Immunity","volume":"11","author":"Golonka","year":"2019","journal-title":"J. Innate Immun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.micinf.2011.04.008","article-title":"Yersiniabactin iron uptake: Mechanisms and role in Yersinia pestis pathogenesis","volume":"13","author":"Perry","year":"2011","journal-title":"Microbes Infect. Inst. Pasteur"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1093\/infdis\/jiu157","article-title":"Carbapenem-resistant Klebsiella pneumoniae exhibit variability in capsular polysaccharide and capsule associated virulence traits","volume":"210","author":"Chen","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3389\/fcimb.2018.00021","article-title":"Biofilm Formation in Klebsiella pneumoniae Bacteremia Strains Was Found to be Associated with CC23 and the Presence of wcaG","volume":"8","author":"Zheng","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1099\/mic.0.2007\/011981-0","article-title":"The ferric yersiniabactin uptake receptor FyuA is required for efficient biofilm formation by urinary tract infectious Escherichia coli in human urine","volume":"154","author":"Hancock","year":"2008","journal-title":"Microbiol Read. Engl."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1038\/nrmicro1286","article-title":"Fungal secondary metabolism\u2014From biochemistry to genomics","volume":"3","author":"Keller","year":"2005","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"915","DOI":"10.3389\/fmicb.2019.00915","article-title":"New Metabolites From the Co-culture of Marine-Derived Actinomycete Streptomyces rochei MB037 and Fungus Rhinocladiella similis 35","volume":"10","author":"Yu","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1016\/j.biotechadv.2014.03.001","article-title":"Metabolite induction via microorganism co-culture: A potential way to enhance chemical diversity for drug discovery","volume":"32","author":"Bertrand","year":"2014","journal-title":"Biotechnol. Adv."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.sajb.2017.10.001","article-title":"Microbial communication: A significant approach for new leads","volume":"113","author":"Abdalla","year":"2017","journal-title":"S. Afr. J. Bot."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1111\/1758-2229.12346","article-title":"Disturbance of the bacterial cell wall specifically interferes with biofilm formation","volume":"7","author":"Bucher","year":"2015","journal-title":"Environ. Microbiol. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1345\/aph.1R020","article-title":"Echinocandin resistance in Candida species: Mechanisms of reduced susceptibility and therapeutic approaches","volume":"46","author":"Beyda","year":"2012","journal-title":"Ann. Pharmacother."},{"key":"ref_22","first-page":"1","article-title":"Anticancer Compounds from Chaetomium globosum","volume":"4","author":"Moubasher","year":"2015","journal-title":"Biochem. Anal. Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-0463.2009.02563.x","article-title":"Beta-lactam Antibiotics: From Antibiosis to Resistance and Bacteriology","volume":"118","author":"Kong","year":"2010","journal-title":"APMIS Acta Pathol. Microbiol. Immunol. Scand."},{"key":"ref_24","first-page":"713","article-title":"Isolation and Identification of Non-pathogenic and Pathogenic Fungi from the Soil of Greater Tunb, Abu-Musa and Sirri Islands, Persian Gulf, Iran","volume":"4","author":"Nosratabadi","year":"2017","journal-title":"J. Appl. Biotechnol. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Napoli, C., Marcotrigiano, V., and Montagna, M.T. (2012). Air sampling procedures to evaluate microbial contamination: A comparison between active and passive methods in operating theatres. BMC Public Health, 12.","DOI":"10.1186\/1471-2458-12-594"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"18","DOI":"10.2174\/1874070701913010018","article-title":"Co-Culture Systems for the Production of Secondary Metabolites: Current and Future Prospects","volume":"13","author":"Tan","year":"2019","journal-title":"Open Biotechnol. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1128\/AAC.47.7.2339-2341.2003","article-title":"Scopulariopsis brevicaulis, a Fungal Pathogen Resistant to Broad-Spectrum Antifungal Agents","volume":"47","author":"Mellado","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"871947","DOI":"10.1155\/2015\/871947","article-title":"Emergence of Carbapenem-Resistant Klebsiella pneumoniae: Progressive Spread and Four-Year Period of Observation in a Cardiac Surgery Division","volume":"2015","author":"Lombardi","year":"2015","journal-title":"BioMed Res. International."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1093\/bioinformatics\/btt314","article-title":"Ultra-fast whole-genome secondary analysis on Illumina sequencing platforms","volume":"29","author":"Raczy","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ragheb, S.M., Tawfick, M.M., El-Kholy, A.A., and Abdulall, A.K. (2020). Phenotypic and Genotypic Features of Klebsiella pneumoniae Harboring Carbapenemases in Egypt: OXA-48-Like Carbapenemases as an Investigated Model. Antibiotics, 9.","DOI":"10.3390\/antibiotics9120852"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrd4510","article-title":"The re-emergence of natural products for drug discovery in the genomics era","volume":"14","author":"Harvey","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_32","first-page":"9","article-title":"Klebsiella pneumoniae prevents spore germination and hyphal development of Aspergillus species","volume":"18","author":"Nogueira","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1016\/j.cub.2014.08.057","article-title":"Anaerobic bacteria grow within Candida albicans biofilms and induce biofilm formation in suspension cultures","volume":"24","author":"Fox","year":"2014","journal-title":"Curr. Biol. CB"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.femsec.2004.10.002","article-title":"Comparison of temperature effects on soil respiration and bacterial and fungal growth rates","volume":"52","author":"Pettersson","year":"2005","journal-title":"FEMS Microbiol. Ecol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"198","DOI":"10.2174\/1874609811003030198","article-title":"Aging in bacteria, immortality or not-a critical review","volume":"3","year":"2010","journal-title":"Curr. Aging Sci."},{"key":"ref_36","first-page":"13","article-title":"A functional perspective on phenotypic heterogeneity in microorganisms","volume":"6","author":"Ackermann","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.resmic.2018.05.005","article-title":"Molecular mechanisms of AcrB-mediated multidrug export","volume":"169","author":"Zwama","year":"2018","journal-title":"Res. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1111\/j.1574-6976.2011.00290.x","article-title":"Broad-specificity efflux pumps and their role in multidrug resistance of Gram-negative bacteria","volume":"36","author":"Nikaido","year":"2012","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1126\/science.aav6390","article-title":"Role of AcrAB-TolC multidrug efflux pump in drug-resistance acquisition by plasmid transfer","volume":"364","author":"Nolivos","year":"2019","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1126\/science.aaf4762","article-title":"Biased partitioning of the multidrug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity","volume":"356","author":"Bergmiller","year":"2017","journal-title":"Science"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"335","DOI":"10.21608\/ejbo.2017.775.1045","article-title":"Purification and Characterization of Lignin Peroxidase Isozymes from Humicola grisea (Traaen) and Its Application in Bioremediation of Textile Dyes","volume":"57","author":"Moubasher","year":"2017","journal-title":"Egypt J. Bot."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.3389\/fmicb.2017.01284","article-title":"Dual Induction of New Microbial Secondary Metabolites by Fungal Bacterial Co-cultivation","volume":"8","author":"Wakefield","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1128\/AAC.01344-13","article-title":"Derepressed Transfer Properties Leading to the Efficient Spread of the Plasmid Encoding Carbapenemase OXA-48","volume":"58","author":"Potron","year":"2014","journal-title":"Antimicrob Agents Chemother."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1021\/np200470u","article-title":"Diverse metabolic profiles of a Streptomyces strain isolated from a hyper-arid environment","volume":"74","author":"Rateb","year":"2011","journal-title":"J. Nat. Prod."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3620","DOI":"10.1046\/j.1432-1327.2001.02265.x","article-title":"The drug\/metabolite transporter superfamily","volume":"268","author":"Jack","year":"2001","journal-title":"Eur. J. Biochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1146\/annurev.bi.50.070181.003435","article-title":"Microbial iron compounds","volume":"50","author":"Neilands","year":"1981","journal-title":"Annu. Rev. Biochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1086\/315831","article-title":"High-pathogenicity island of Yersinia pestis in enterobacteriaceae isolated from blood cultures and urine samples: Prevalence and functional expression","volume":"182","author":"Schubert","year":"2000","journal-title":"J. Infect. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0882-4010(03)00125-6","article-title":"Occurrence of the Yersinia high-pathogenicity island and iron uptake systems in clinical isolates of Klebsiella pneumoniae","volume":"35","author":"Koczura","year":"2003","journal-title":"Microb. Pathog."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1128\/IAI.00372-06","article-title":"Yersiniabactin Is a Virulence Factor for Klebsiella pneumoniae during Pulmonary Infection","volume":"75","author":"Lawlor","year":"2007","journal-title":"Infect. Immun."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/8\/2541\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:54:18Z","timestamp":1760136858000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/8\/2541"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,14]]},"references-count":49,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["molecules27082541"],"URL":"https:\/\/doi.org\/10.3390\/molecules27082541","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,14]]}}}