{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T06:46:26Z","timestamp":1774939586350,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T00:00:00Z","timestamp":1626220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Urinary tract infections are often polymicrobial and are mainly due to uropathogenic Escherichia coli (UPEC). We previously demonstrated a link among clinical fluoroquinolone susceptible E. coli reducing in vitro urothelial interleukin-8 (CXCL8) induced by E. coli K-12, polymicrobial cystitis, and pyuria absence. Here, we evaluated whether fifteen clinical fluoroquinolone susceptible UPEC were able to reduce CXCL8 induced by Enterococcus faecalis that had been isolated from the same mixed urines, other than CXCL8 induced by E. coli K-12. We also evaluated the connection between fluoroquinolone susceptibility and pathogenicity by evaluating the immune modulation of isogenic gyrA, a mutant UPEC resistant to ciprofloxacin. Using the 5637 bladder epithelial cell line, we observed that lower CXCL8 induced the most UPEC isolates than K-12 and the corresponding E. faecalis. During coinfections of UPEC\/K-12 and UPEC\/E. faecalis, we observed lower CXCL8 than during infections caused by K-12 and E. faecalis alone. UPEC strains showed host\u2013pathogen and pathogen\u2013pathogen interaction, which in part explained their persistence in the human urinary tract and coinfections, respectively. Mutant UPEC showed lower modulating activity with respect to the wildtypes, confirming the connection between acquired fluoroquinolone resistance and the decrease of innate microbial properties.<\/jats:p>","DOI":"10.3390\/microorganisms9071501","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T10:13:42Z","timestamp":1626257622000},"page":"1501","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In Vitro Reduction of Interleukin-8 Response to Enterococcus faecalis by Escherichia coli Strains Isolated from the Same Polymicrobial Urines"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6517-0321","authenticated-orcid":false,"given":"Gabriella","family":"Piatti","sequence":"first","affiliation":[{"name":"Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, 16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"De Ferrari","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genoa, 16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Maria","family":"Schito","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, 16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Maria","family":"Riccio","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genoa, 16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanna","family":"Penco","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Genoa, 16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastiano","family":"Cassia","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genoa, 16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8821-4542","authenticated-orcid":false,"given":"Marco","family":"Bruzzone","sequence":"additional","affiliation":[{"name":"Unit of Clinical Epidemiology, Ospedale Policlinico San Martino-IRCCS per l\u2019Oncologia, 16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcello","family":"Ceppi","sequence":"additional","affiliation":[{"name":"Unit of Clinical Epidemiology, Ospedale Policlinico San Martino-IRCCS per l\u2019Oncologia, 16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nrmicro3432","article-title":"Urinary tract infections: Epidemiology, mechanisms of infection and treatment options","volume":"13","author":"Walker","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3355","DOI":"10.1016\/j.jmb.2016.05.006","article-title":"Polymicrobial-Host Interactions during infection","volume":"428","author":"Tay","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0140-6736(05)70155-0","article-title":"Human polymicrobial infections","volume":"365","author":"Brogden","year":"2005","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.jinf.2011.06.005","article-title":"The nature and consequences of coinfection in humans","volume":"63","author":"Griffiths","year":"2011","journal-title":"J. Infect."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nrmicro.2015.8","article-title":"The biogeography of polymicrobial infection","volume":"14","author":"Stacy","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.chom.2016.09.004","article-title":"Enterococcal metabolites cues facilitate interspecies niche modulation and polymicrobial infection","volume":"20","author":"Keogh","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e00146-19","DOI":"10.1128\/mBio.00146-19","article-title":"Quorum sensing selectivity and the potential for interspecies cross talk","volume":"10","author":"Wellington","year":"2019","journal-title":"mBio"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1038\/ismej.2012.69","article-title":"Acyl-omoserine lactone-dependent eavesdropping promotes competition in a laboratory co-colture model","volume":"6","author":"Chandler","year":"2012","journal-title":"ISME J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/nrurol.2010.190","article-title":"The epidemiology of urinary tract infection","volume":"7","author":"Foxman","year":"2010","journal-title":"Nat. Rev. Urol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1099\/jmm.0.068783-0","article-title":"Faecal Escherichia coli form patients with E. coli urinary tract infection and healthy controls who have never had a urinary tract infection","volume":"63","author":"Nielsen","year":"2014","journal-title":"J. Med. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1111\/j.1574-695X.2010.00751.x","article-title":"Quinolone\/Fuoroquinolone susceptibility in Escherichia coli correlates with human polymicrobial bacteriuria and with in vitro interleukin-8 suppression","volume":"61","author":"Saverino","year":"2010","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4218","DOI":"10.1128\/JCM.43.8.4218-4220.2005","article-title":"Decreased prevalence of virulence factors among ciprofloxacin-resistant uropathogenic Escherichia coli isolates","volume":"43","author":"Drew","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1128\/JCM.01740-08","article-title":"Genetic profiles of fluoroquinolone-resistant Escherichia coli isolates obtained from patients with cystitis: Phylogeny, virulence factors, PAIusp subtypes, and mutation patterns","volume":"47","author":"Takahashi","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1126\/science.277.5331.1453","article-title":"The complete genome sequence of Escherichia coli K-12","volume":"277","author":"Blattner","year":"1997","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3999","DOI":"10.1128\/IAI.73.7.3999-4006.2005","article-title":"Suppression of bladder epithelial cytokine responses by uropathogenic Escherichia coli","volume":"73","author":"Hunstad","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Cirz, R.T., Chin, J.K., Andes, D.R., de Cr\u00e9cy-Lagard, V., Craig, W.A., and Romesberg, F.E. (2005). Inhibition of mutation and combating the evolution of antibiotic resistance. PLoS Biol., 3.","DOI":"10.1371\/journal.pbio.0030176"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1093\/jac\/dkq496","article-title":"Effect of recA inactivation on mutagenesis of Escherichia coli exposed to sublethal concentrations of antimicrobials","volume":"66","author":"Thi","year":"2011","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4555","DOI":"10.1128\/AEM.66.10.4555-4558.2000","article-title":"Rapid and simple determination of the Escherichia coli phylogenetic group","volume":"66","author":"Clermont","year":"2000","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1086\/315217","article-title":"Extended virulence genotypes of Escherichia coli strains from patients with urosepsis in relation to phylogeny and host compromise","volume":"181","author":"Johnson","year":"2000","journal-title":"J. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1099\/mic.0.27499-0","article-title":"Comparison of Escherichia coli isolates implicated in human urinary tract infection and avian colibacillosis","volume":"151","author":"Giddings","year":"2005","journal-title":"Microbiology"},{"key":"ref_21","unstructured":"Bland, M. (2015). An Introduction to Medical Statistics, Oxford University Press. [4th ed.]."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"80","DOI":"10.2307\/3001968","article-title":"Individual comparisons by ranking methods","volume":"1","author":"Wilcoxon","year":"1945","journal-title":"Biometrics"},{"key":"ref_23","unstructured":"Altman, D.G. (1991). Practical Statistics for Medical Research, Chapman & Hall\/CRC."},{"key":"ref_24","unstructured":"Chambers, J.M., Cleveland, W.S., and Kleiner, B. (1983). Graphical Methods for Data Analysis, Wadsworth."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4186","DOI":"10.1128\/IAI.00684-12","article-title":"Immune modulation by Group B Streptococcus influences host susceptibility to urinary tract infection by uropathogenic Escherichia coli","volume":"80","author":"Kline","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e00378-17","DOI":"10.1128\/IAI.00378-17","article-title":"Enterococcus faecalis promotes innate immune suppression and polymicrobial catheter-associated urinary tract infection","volume":"85","author":"Tien","year":"2017","journal-title":"Infect. Immun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e00808-16","DOI":"10.1128\/IAI.00808-16","article-title":"The pathogenic potential of Proteus mirabilis is enhanced by other uropathogens during polymicrobial urinary tract infection","volume":"85","author":"Armbruster","year":"2017","journal-title":"Infect. Immun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen recognition and innate immunity","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.4049\/jimmunol.174.2.1020","article-title":"Bacterial lipoprotein induces resistance to Gram-negative sepsis in TLR4-deficient mice via enhanced bacterial clearance","volume":"174","author":"Wang","year":"2005","journal-title":"J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7096","DOI":"10.4049\/jimmunol.165.12.7096","article-title":"Synergy and cross-tolerance between Toll like receptor (TLR) 2- and TLR4-mediated signaling pathway","volume":"165","author":"Santo","year":"2000","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"14","DOI":"10.4049\/jimmunol.170.1.14","article-title":"Bacterial lip-oprotein induces endotoxin-independent tolerance to septic shock","volume":"170","author":"Wang","year":"2003","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5564","DOI":"10.4049\/jimmunol.164.11.5564","article-title":"Inhibition of lipopolysaccharide-induced signal transduc-tion in endotoxin tolerized mouse macrophages: Dysregulation of cytokine, chemokine, and Toll-like receptor 2 and 4 gene expression","volume":"164","author":"Medveded","year":"2000","journal-title":"J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1128\/IAI.71.3.1470-1480.2003","article-title":"CD14- and Toll-like receptor-dependent activation of bladder epithelial cells by lipopolysaccharide and Type 1 piliated Escherichia coli","volume":"71","author":"Schilling","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"36","DOI":"10.4161\/viru.25436","article-title":"Host innate immune responses to sepsis","volume":"5","author":"Wiersinga","year":"2014","journal-title":"Virulence"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6067","DOI":"10.1128\/IAI.67.11.6067-6075.1999","article-title":"Enterococcus faecalis bearing aggregation substance is resistant to killing by human neutrophils despite phagocytosis and neutrophil activation","volume":"67","author":"Rakita","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1038\/ncpuro1231","article-title":"Bacterial biofilms in patients with indwelling urinary catheters","volume":"5","author":"Stickler","year":"2008","journal-title":"Nat. Clin. Pract. Urol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4166","DOI":"10.1128\/IAI.00711-10","article-title":"Enterococcal biofilm formation and virulence in an optimized murine model of foreign body-associated urinary tract infections","volume":"78","author":"Guiton","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.3748\/wjg.14.1067","article-title":"Infant intestinal Enterococcus faecalis down-regulates inflammatory responses in human intestinal cell lines","volume":"14","author":"Wang","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1007\/s10156-012-0497-1","article-title":"Differences in cytokine stimulation between methicillin-susceptible and methicillin-resistant Staphylococcus aureus in an experimental endocarditis model","volume":"19","author":"Tsaganos","year":"2013","journal-title":"J. Infect. Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1159\/000326893","article-title":"Impact of multidrug resistance on experimental empyema by Pseudomonas aeruginosa","volume":"82","author":"Tzepi","year":"2011","journal-title":"Respiration"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.ijantimicag.2007.10.028","article-title":"The impact of multidrug resistance on the pathogenicity of Escherichia coli: An experimental study","volume":"31","author":"Bristianou","year":"2008","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1099\/jmm.0.000475","article-title":"Mechanisms of quinolone action and resistance: Where do we stand?","volume":"66","author":"Correia","year":"2017","journal-title":"J. Med. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nm1734","article-title":"Subversion of Toll-like receptor signaling by a unique family of bacterial Toll\/interleukin-1 receptor domain-containing proteins","volume":"14","author":"Cirl","year":"2008","journal-title":"Nat. Med."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Zou, J., Baghdayan, A.S., Payne, S.J., and Shankar, N. (2014). A TIR domain protein from E. faecalis attenuates MyD88-mediated signaling and NF-\u03baB activation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112010"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/7\/1501\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:30:18Z","timestamp":1760164218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/7\/1501"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,14]]},"references-count":44,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["microorganisms9071501"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms9071501","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,14]]}}}