{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:18:56Z","timestamp":1792603136034,"version":"4.5.0"},"reference-count":78,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Port Said University"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Microbiol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Infections affecting neonates caused by\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      are widespread in healthcare facilities; hence, novel strategies are needed to fight this pathogen. In this study, we aimed to investigate the effectiveness of the FDA-approved medications ascorbic acid, dexamethasone, and sodium bicarbonate to reduce the virulence of the resistant\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      bacteria that causes neonatal sepsis and seek out suitable alternatives to the problem of multi-drug resistance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Tested drugs were assessed phenotypically and genotypically for their effects on virulence factors and virulence-encoding genes in\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      . Furthermore, drugs were tested in vivo for their ability to reduce\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sub-inhibitory concentrations (1\/8 MIC) of ascorbic acid, dexamethasone, and sodium bicarbonate reduced the production of\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      virulence factors, including biofilm formation, staphyloxanthin, proteases, and hemolysin production, as well as resistance to oxidative stress. At the molecular level, qRT-PCR was used to assess the relative expression levels of\n                      <jats:italic>crtM<\/jats:italic>\n                      ,\n                      <jats:italic>sigB<\/jats:italic>\n                      ,\n                      <jats:italic>sarA<\/jats:italic>\n                      ,\n                      <jats:italic>agrA<\/jats:italic>\n                      ,\n                      <jats:italic>hla<\/jats:italic>\n                      ,\n                      <jats:italic>fnbA<\/jats:italic>\n                      , and\n                      <jats:italic>icaA<\/jats:italic>\n                      genes regulating virulence factors production and showed a significant reduction in the relative expression levels of all the tested genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The current findings reveal that ascorbic acid, dexamethasone, and sodium bicarbonate have strong anti-virulence effects against\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      . Thus, suggesting that they might be used as adjuvants to treat infections caused by\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      in combination with conventional antimicrobials or as alternative therapies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12866-022-02684-x","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T20:02:39Z","timestamp":1667937759000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Attenuating the virulence of the resistant superbug Staphylococcus aureus bacteria isolated from neonatal sepsis by ascorbic acid, dexamethasone, and sodium bicarbonate"],"prefix":"10.1186","volume":"22","author":[{"given":"Moustafa M.","family":"Saleh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nehal","family":"Yousef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shokri M.","family":"Shafik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisham A.","family":"Abbas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,9]]},"reference":[{"key":"2684_CR1","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1128\/CMR.00134-14","volume":"28","author":"SYC Tong","year":"2015","unstructured":"Tong SYC, Davis JS, Eichenberger E, Holland TL, Fowler VG. Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev. 2015;28:603\u201361.","journal-title":"Clin Microbiol Rev"},{"key":"2684_CR2","doi-asserted-by":"publisher","first-page":"5520","DOI":"10.1016\/j.idc.2021.11.006","volume":"36","author":"IC Kalu","year":"2022","unstructured":"Kalu IC, Kao CM, Fritz SA. Management and prevention of Staphylococcus aureus infections in children. Infect Dis Clin N Am. 2022;36:5520.","journal-title":"Infect Dis Clin N Am"},{"key":"2684_CR3","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.mib.2013.11.004","volume":"17","author":"M Otto","year":"2014","unstructured":"Otto M. Staphylococcus aureus toxins. Curr Opin Microbiol. 2014;17:32\u20137.","journal-title":"Curr Opin Microbiol"},{"key":"2684_CR4","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1080\/21505594.2021.1878688","volume":"12","author":"GYC Cheung","year":"2021","unstructured":"Cheung GYC, Bae JS, Otto M. Pathogenicity and virulence of Staphylococcus aureus. Virulence. 2021;12:547\u201369.","journal-title":"Virulence"},{"key":"2684_CR5","first-page":"66","volume":"7","author":"P Sharma","year":"2013","unstructured":"Sharma P, Kaur P, Aggarwal A. Staphylococcus aureus- the predominant pathogen in the neonatal ICU of a tertiary care hospital in Amritsar. India J Clin Diagn Res. 2013;7:66\u20139.","journal-title":"India J Clin Diagn Res"},{"key":"2684_CR6","doi-asserted-by":"publisher","first-page":"20307","DOI":"10.1038\/srep20307","volume":"6","author":"Y Yang","year":"2016","unstructured":"Yang Y, Li H, Sun H, Gong L, Guo L, Shi Y, et al. A novel nitro-dexamethasone inhibits agr system activity and improves therapeutic effects in MRSA sepsis models without antibiotics. Sci Rep. 2016;6:20307.","journal-title":"Sci Rep"},{"key":"2684_CR7","doi-asserted-by":"publisher","first-page":"e0211845","DOI":"10.1371\/journal.pone.0211845","volume":"15","author":"W Geng","year":"2020","unstructured":"Geng W, Qi Y, Li W, McConville TH, Hill-Ricciuti A, Grohs EC, et al. Epidemiology of Staphylococcus aureus in neonates on admission to a Chinese neonatal intensive care unit. PLoS One. 2020;15:e0211845.","journal-title":"PLoS One"},{"key":"2684_CR8","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.mib.2020.02.005","volume":"53","author":"JM Kwiecinski","year":"2020","unstructured":"Kwiecinski JM, Horswill AR. Staphylococcus aureus bloodstream infections: pathogenesis and regulatory mechanisms. Curr Opin Microbiol. 2020;53:51\u201360.","journal-title":"Curr Opin Microbiol"},{"key":"2684_CR9","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1080\/17512433.2016.1241141","volume":"9","author":"J Rello","year":"2016","unstructured":"Rello J, Bunsow E, Perez A. What if there were no new antibiotics? A look at alternatives. Expert Rev Clin Pharmacol. 2016;9:1547\u201355.","journal-title":"Expert Rev Clin Pharmacol"},{"key":"2684_CR10","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1111\/j.1469-0691.2011.03570.x","volume":"18","author":"A-P Magiorakos","year":"2012","unstructured":"Magiorakos A-P, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18:268\u201381.","journal-title":"Clin Microbiol Infect"},{"key":"2684_CR11","doi-asserted-by":"publisher","first-page":"2384","DOI":"10.1128\/JCM.43.5.2384-2390.2005","volume":"43","author":"A Holmes","year":"2005","unstructured":"Holmes A, Ganner M, McGuane S, Pitt TL, Cookson BD, Kearns AM. Staphylococcus aureus isolates carrying Panton-valentine leucocidin genes in England and Wales: frequency, characterization, and association with clinical disease. J Clin Microbiol. 2005;43:2384\u201390.","journal-title":"J Clin Microbiol"},{"key":"2684_CR12","doi-asserted-by":"crossref","unstructured":"Selvaraj A, Jayasree T, Valliammai A, Pandian SK. Myrtenol attenuates MRSA biofilm and virulence by suppressing sarA expression dynamism. Front Microbiol 2019;10 September:1\u201315.","DOI":"10.3389\/fmicb.2019.02027"},{"key":"2684_CR13","doi-asserted-by":"publisher","first-page":"3255","DOI":"10.2147\/IDR.S272733","volume":"13","author":"AM Algammal","year":"2020","unstructured":"Algammal AM, Hetta HF, Elkelish A, Alkhalifah DHH, Hozzein WN, Batiha GE-S, et al. Methicillin-resistant Staphylococcus aureus (MRSA): one health perspective approach to the bacterium epidemiology, virulence factors, antibiotic-resistance, and zoonotic impact. Infect Drug Resist. 2020;13:3255\u201365.","journal-title":"Infect Drug Resist"},{"key":"2684_CR14","doi-asserted-by":"publisher","first-page":"e1004870","DOI":"10.1371\/journal.ppat.1004870","volume":"11","author":"L Tuchscherr","year":"2015","unstructured":"Tuchscherr L, Bischoff M, Lattar SM, Noto Llana M, Pf\u00f6rtner H, Niemann S, et al. Sigma factor SigB is crucial to mediate Staphylococcus aureus adaptation during chronic infections. PLoS Pathog. 2015;11:e1004870.","journal-title":"PLoS Pathog"},{"key":"2684_CR15","doi-asserted-by":"publisher","first-page":"e11071","DOI":"10.1371\/journal.pone.0011071","volume":"5","author":"K Burnside","year":"2010","unstructured":"Burnside K, Lembo A, de Los RM, Iliuk A, Binhtran N-T, Connelly JE, et al. Regulation of hemolysin expression and virulence of Staphylococcus aureus by a serine\/threonine kinase and phosphatase. PLoS One. 2010;5:e11071.","journal-title":"PLoS One"},{"key":"2684_CR16","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1007\/s00284-017-1331-x","volume":"74","author":"S Yeswanth","year":"2017","unstructured":"Yeswanth S, Chaudhury A, Sarma PVGK. Quantitative expression analysis of SpA, FnbA and Rsp genes in Staphylococcus aureus: actively associated in the formation of biofilms. Curr Microbiol. 2017;74:1394\u2013403.","journal-title":"Curr Microbiol"},{"key":"2684_CR17","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1111\/j.1462-5822.2012.01832.x","volume":"14","author":"M Otto","year":"2012","unstructured":"Otto M. MRSA virulence and spread. Cell Microbiol. 2012;14:1513\u201321.","journal-title":"Cell Microbiol"},{"key":"2684_CR18","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1186\/s12866-022-02515-z","volume":"22","author":"FAA Yehia","year":"2022","unstructured":"Yehia FAA, Yousef N, Askoura M. Celastrol mitigates staphyloxanthin biosynthesis and biofilm formation in Staphylococcus aureus via targeting key regulators of virulence; in vitro and in vivo approach. BMC Microbiol. 2022;22:106.","journal-title":"BMC Microbiol"},{"key":"2684_CR19","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1016\/j.chembiol.2020.06.017","volume":"27","author":"MH Lee","year":"2020","unstructured":"Lee MH, Nuccio S-P, Raffatellu M. Pathogen interference: targeting virulence factors to tackle intracellular microbes. Cell Chem Biol. 2020;27:765\u20137.","journal-title":"Cell Chem Biol"},{"key":"2684_CR20","first-page":"e01296","volume":"62","author":"F D\u2019Angelo","year":"2018","unstructured":"D\u2019Angelo F, Baldelli V, Halliday N, Pantalone P, Polticelli F, Fiscarelli E, et al. Identification of FDA-approved drugs as Antivirulence agents targeting the pqs quorum-sensing system of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2018;62:e01296\u201318.","journal-title":"Antimicrob Agents Chemother"},{"key":"2684_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ph13120443","volume":"13","author":"A Mostafa","year":"2020","unstructured":"Mostafa A, Kandeil A, Elshaier YAMM, Kutkat O, Moatasim Y, Rashad AA, et al. Fda-approved drugs with potent in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2. Pharmaceuticals. 2020;13:1\u201324.","journal-title":"Pharmaceuticals"},{"key":"2684_CR22","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1097\/MOP.0000000000000463","volume":"29","author":"AM Smith","year":"2017","unstructured":"Smith AM, Davis JM. Challenges and opportunities to enhance global drug development in neonates. Curr Opin Pediatr. 2017;29:149\u201352.","journal-title":"Curr Opin Pediatr"},{"key":"2684_CR23","doi-asserted-by":"publisher","first-page":"3734","DOI":"10.1128\/JCM.42.8.3734-3738.2004","volume":"42","author":"M de Cueto","year":"2004","unstructured":"de Cueto M, Ceballos E, Martinez-Martinez L, Perea EJ, Pascual A. Use of positive blood cultures for direct identification and susceptibility testing with the Vitek 2 system. J Clin Microbiol. 2004;42:3734\u20138.","journal-title":"J Clin Microbiol"},{"key":"2684_CR24","volume-title":"Clinical and laboratory standards institute (CLSI). Performance standards for antimicrobial susceptibility testing","author":"CLSI","year":"2020","unstructured":"CLSI. Clinical and laboratory standards institute (CLSI). Performance standards for antimicrobial susceptibility testing. 30th ed: CLSI supplement M100; 2020.","edition":"30"},{"key":"2684_CR25","doi-asserted-by":"publisher","first-page":"1680","DOI":"10.1128\/AAC.50.5.1680-1688.2006","volume":"50","author":"Y Nalca","year":"2006","unstructured":"Nalca Y, J\u00e4nsch L, Bredenbruch F, Geffers R, Buer J, H\u00e4ussler S. Quorum-sensing antagonistic activities of azithromycin in Pseudomonas aeruginosa PAO1: a global approach. Antimicrob Agents Chemother. 2006;50:1680\u20138.","journal-title":"Antimicrob Agents Chemother"},{"key":"2684_CR26","doi-asserted-by":"publisher","first-page":"e9736","DOI":"10.1371\/journal.pone.0009736","volume":"5","author":"J Qiu","year":"2010","unstructured":"Qiu J, Wang D, Xiang H, Feng H, Jiang Y, Xia L, et al. Subinhibitory concentrations of Thymol reduce enterotoxins a and B and \u03b1-Hemolysin production in Staphylococcus aureus isolates. PLoS One. 2010;5:e9736.","journal-title":"PLoS One"},{"key":"2684_CR27","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1111\/j.1600-0463.2007.apm_630.x","volume":"115","author":"S Stepanovic","year":"2007","unstructured":"Stepanovic S, Vukovic D, Hola V, Giovanni Di Bonaventura SD, And ICI, Ruzicka Fi. Quantification of biofilm in microtiter plates\u00a0: overview of testing conditions and practical recommendations for assessment of biofilm ... Quantification of biofilm in microtiter plates\u00a0: overview of testing conditions and practical recommendations for a. Apmis 2007;115:231\u2013241.","journal-title":"Apmis"},{"key":"2684_CR28","first-page":"1823","volume":"55","author":"EJ Al-kazaz","year":"2014","unstructured":"Al-kazaz EJ, Melconian AK, Kandela NJ. Extraction of Staphyloxanthin from Staphylococcus aureus isolated from clinical sources to determine its antibacterial activity against other Bacteria. Iraqi J Sci. 2014;55:1823\u201332.","journal-title":"Iraqi J Sci"},{"key":"2684_CR29","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.micpath.2014.07.008","volume":"74","author":"SA El-Mowafy","year":"2014","unstructured":"El-Mowafy SA, Abd El Galil KH, El-Messery SM, Shaaban MI. Aspirin is an efficient inhibitor of quorum sensing, virulence and toxins in Pseudomonas aeruginosa. Microb Pathog. 2014;74:25\u201332.","journal-title":"Microb Pathog"},{"key":"2684_CR30","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.3390\/molecules15031679","volume":"15","author":"H Xiang","year":"2010","unstructured":"Xiang H, Qiu J, Wang D, Jiang Y, Xia L, Deng X. Influence of Magnolol on the secretion of \u03b1-toxin by Staphylococcus aureus. Molecules. 2010;15:1679\u201389.","journal-title":"Molecules"},{"key":"2684_CR31","doi-asserted-by":"publisher","first-page":"6330","DOI":"10.1128\/jb.177.22.6330-6337.1995","volume":"177","author":"DJ Hassett","year":"1995","unstructured":"Hassett DJ, Schweizer HP, Ohman DE. Pseudomonas aeruginosa sodA and sodB mutants defective in manganese- and iron-cofactored superoxide dismutase activity demonstrate the importance of the iron-cofactored form in aerobic metabolism. J Bacteriol. 1995;177:6330\u20137.","journal-title":"J Bacteriol"},{"key":"2684_CR32","first-page":"175","volume":"6","author":"V Antonic","year":"2013","unstructured":"Antonic V, Stojadinovic A, Zhang B, Izadjoo MJ, Alavi M. Pseudomonas aeruginosa induces pigment production and enhances virulence in a white phenotypic variant of Staphylococcus aureus. Infect Drug Resist. 2013;6:175\u201386.","journal-title":"Infect Drug Resist"},{"key":"2684_CR33","first-page":"2559","volume":"152","author":"K Sambanthamoorthy","year":"2006","unstructured":"Sambanthamoorthy K, Smeltzer MS, Elasri MO. Identification and characterization of msa (SA 1233), a gene involved in expression of SarA and several virulence factors in Staphylococcus aureus. Microbiology (N Y). 2006;152:2559\u201372.","journal-title":"Microbiology (N Y)"},{"key":"2684_CR34","doi-asserted-by":"crossref","unstructured":"Kot B, Sytykiewicz H, Sprawka I. Expression of the biofilm-associated genes in methicillin-resistant Staphylococcus aureus in biofilm and planktonic conditions. Int J Mol Sci. 2018;19.","DOI":"10.3390\/ijms19113487"},{"key":"2684_CR35","doi-asserted-by":"publisher","first-page":"4543","DOI":"10.1007\/s00253-012-4674-z","volume":"97","author":"JH Lee","year":"2013","unstructured":"Lee JH, Cho HS, Kim Y, Kim JA, Banskota S, Cho MH, et al. Indole and 7-benzyloxyindole attenuate the virulence of Staphylococcus aureus. Appl Microbiol Biotechnol. 2013;97:4543\u201352.","journal-title":"Appl Microbiol Biotechnol"},{"key":"2684_CR36","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(\u2212Delta Delta C(T)) method. Methods. 2001;25:402\u20138.","journal-title":"Methods"},{"key":"2684_CR37","doi-asserted-by":"publisher","first-page":"8656","DOI":"10.1038\/srep08656","volume":"5","author":"H-S Kim","year":"2015","unstructured":"Kim H-S, Lee S-H, Byun Y, Park H-D. 6-Gingerol reduces Pseudomonas aeruginosa biofilm formation and virulence via quorum sensing inhibition. Sci Rep. 2015;5:8656.","journal-title":"Sci Rep"},{"key":"2684_CR38","first-page":"4","volume":"58","author":"P Ferrara","year":"2022","unstructured":"Ferrara P, Albano L. Azithromycin Has Been Flying Off the Shelves\u00a0: The Italian Lesson Learnt from Improper Use of Antibiotics against COVID-19. Medicina (Kaunas). 2022;58:4\u20136.","journal-title":"Medicina (Kaunas)"},{"key":"2684_CR39","doi-asserted-by":"publisher","first-page":"40","DOI":"10.3390\/antibiotics9020040","volume":"9","author":"LL Newstead","year":"2020","unstructured":"Newstead LL, Varjonen K, Nuttall T, Paterson GK. Staphylococcal-produced Bacteriocins and antimicrobial peptides: their potential as alternative treatments for Staphylococcus aureus infections. Antibiotics (Basel). 2020;9:40.","journal-title":"Antibiotics (Basel)"},{"key":"2684_CR40","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1093\/jac\/dkab468","volume":"77","author":"CA Darlow","year":"2022","unstructured":"Darlow CA, Hope W. Flomoxef for neonates: extending options for treatment of neonatal sepsis caused by ESBL-producing Enterobacterales. J Antimicrob Chemother. 2022;77:711\u20138.","journal-title":"J Antimicrob Chemother"},{"key":"2684_CR41","doi-asserted-by":"publisher","first-page":"41","DOI":"10.3389\/fmicb.2019.00041","volume":"10","author":"A Mir\u00f3-canturri","year":"2019","unstructured":"Mir\u00f3-canturri A, Ayerbe-algaba R, Smani Y. Drug Repurposing for the Treatment of Bacterial and Fungal Infections. Front Microbiol. 2019;10:41.","journal-title":"Front Microbiol"},{"key":"2684_CR42","first-page":"140","volume-title":"Phenolic Compounds - Biological Activity","author":"N Mu\u00f1oz-Cazares","year":"2017","unstructured":"Mu\u00f1oz-Cazares N, Garc\u00eda-Contreras R, P\u00e9rez-L\u00f3pez M, Castillo-Ju\u00e1rez I. Phenolic compounds with anti-virulence properties. In:  Phenolic Compounds - Biological Activity; 2017. p. 140\u201367."},{"key":"2684_CR43","doi-asserted-by":"publisher","first-page":"6377","DOI":"10.1073\/pnas.86.16.6377","volume":"86","author":"B Frei","year":"1989","unstructured":"Frei B, England L, Ames BN. Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci. 1989;86:6377\u201381.","journal-title":"Proc Natl Acad Sci"},{"key":"2684_CR44","first-page":"Doc03","volume":"5","author":"KK Abdul-Razzak","year":"2007","unstructured":"Abdul-Razzak KK, Nusier MK, Obediat AD, Salim AM. Antioxidant vitamins and hyperbilirubinemia in neonates. Ger. Med Sci. 2007;5:Doc03.","journal-title":"Med Sci"},{"key":"2684_CR45","doi-asserted-by":"publisher","first-page":"315642","DOI":"10.1155\/2012\/315642","volume":"2012","author":"S Gupta","year":"2012","unstructured":"Gupta S, Prasanth K, Chen C-M, Yeh TF. Postnatal corticosteroids for prevention and treatment of chronic lung disease in the preterm newborn. Int J Pediatr. 2012;2012:315642.","journal-title":"Int J Pediatr"},{"key":"2684_CR46","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1136\/bmj.319.7222.1385","volume":"319","author":"W Tarnow-Mordi","year":"1999","unstructured":"Tarnow-Mordi W, Mitra A. Postnatal dexamethasone in preterm infants is potentially lifesaving, but follow up studies are urgently needed. BMJ. 1999;319:1385\u20136.","journal-title":"BMJ"},{"key":"2684_CR47","first-page":"63","volume":"47","author":"L Massenzi","year":"2021","unstructured":"Massenzi L, Aufieri R, Donno S, Agostino R, Dotta A, (SIN) NPSG of the IS of N. Use of intravenous sodium bicarbonate in neonatal intensive care units in Italy: a nationwide survey. Ital. J Pediatr. 2021;47:63.","journal-title":"J Pediatr"},{"key":"2684_CR48","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1542\/peds.91.2.496","volume":"91","author":"HA Hein","year":"1993","unstructured":"Hein HA. The use of sodium bicarbonate in neonatal resuscitation: help or harm? Pediatrics. 1993;91:496\u20137.","journal-title":"Pediatrics"},{"key":"2684_CR49","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1586\/14787210.2015.1100533","volume":"13","author":"M Bhattacharya","year":"2015","unstructured":"Bhattacharya M, Wozniak DJ, Stoodley P, Hall-Stoodley L. Prevention and treatment of Staphylococcus aureus biofilms. Expert Rev Anti-Infect Ther. 2015;13:1499\u2013516.","journal-title":"Expert Rev Anti-Infect Ther"},{"key":"2684_CR50","doi-asserted-by":"publisher","first-page":"100739","DOI":"10.1016\/j.genrep.2020.100739","volume":"20","author":"R Parastan","year":"2020","unstructured":"Parastan R, Kargar M, Solhjoo K, Kafilzadeh F. Staphylococcus aureus biofilms: structures, antibiotic resistance, inhibition, and vaccines. Gene Rep. 2020;20:100739.","journal-title":"Gene Rep"},{"key":"2684_CR51","doi-asserted-by":"publisher","first-page":"4950","DOI":"10.1128\/IAI.00204-06","volume":"74","author":"A Clauditz","year":"2006","unstructured":"Clauditz A, Resch A, Wieland K-P, Peschel A, G\u00f6tz F. Staphyloxanthin plays a role in the fitness of Staphylococcus aureus and its ability to cope with oxidative stress. Infect Immun. 2006;74:4950\u20133.","journal-title":"Infect Immun"},{"key":"2684_CR52","first-page":"467","volume":"49","author":"FAZA Yehia","year":"2021","unstructured":"Yehia FAZA, Yousef N, Askoura M. Exploring Staphylococcus aureus virulence factors; special emphasis on Staphyloxanthin. Microbiol Biotechnol Lett. 2021;49:467\u201377.","journal-title":"Microbiol Biotechnol Lett"},{"issue":"Pt 1","key":"2684_CR53","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1099\/mic.0.26634-0","volume":"150","author":"L Shaw","year":"2004","unstructured":"Shaw L, Golonka E, Potempa J, Foster SJ. The role and regulation of the extracellular proteases of Staphylococcus aureus. Microbiology (Reading). 2004;150(Pt 1):217\u201328.","journal-title":"Microbiology (Reading)"},{"key":"2684_CR54","doi-asserted-by":"crossref","unstructured":"Murphy J, Ramezanpour M, Stach N, Dubin G, Psaltis AJ, Wormald PJ, et al. Staphylococcus Aureus V8 protease disrupts the integrity of the airway epithelial barrier and impairs IL-6 production in vitro. Laryngoscope. 2018;128.","DOI":"10.1002\/lary.26949"},{"key":"2684_CR55","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1111\/jam.12631","volume":"117","author":"SA El-Mowafy","year":"2014","unstructured":"El-Mowafy SA, Shaaban MI, Abd El Galil KH. Sodium ascorbate as a quorum sensing inhibitor of Pseudomonas aeruginosa. J Appl Microbiol. 2014;117:1388\u201399.","journal-title":"J Appl Microbiol"},{"key":"2684_CR56","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.3389\/fmicb.2020.01054","volume":"11","author":"B Han","year":"2020","unstructured":"Han B, Zheng X, Baruah K, Bossier P. Sodium Ascorbate as a quorum-sensing inhibitor leads to decreased virulence in Vibrio campbellii. Front Microbiol. 2020;11:1054.","journal-title":"Front Microbiol"},{"key":"2684_CR57","doi-asserted-by":"publisher","first-page":"103894","DOI":"10.1016\/j.isci.2022.103894","volume":"25","author":"C Xu","year":"2022","unstructured":"Xu C, Dong N, Chen K, Yang X, Zeng P, Hou C, et al. Bactericidal, anti-biofilm, and anti-virulence activity of vitamin C against carbapenem-resistant hypervirulent Klebsiella pneumoniae. iScience. 2022;25:103894.","journal-title":"iScience"},{"key":"2684_CR58","doi-asserted-by":"crossref","unstructured":"Pandit S, Ravikumar V, Abdel-Haleem AM, Derouiche A, Mokkapati VRSS, Sihlbom C, et al. Low concentrations of vitamin C reduce the synthesis of extracellular polymers and destabilize bacterial biofilms. Front Microbiol. 2017:8.","DOI":"10.3389\/fmicb.2017.02599"},{"key":"2684_CR59","doi-asserted-by":"publisher","first-page":"607","DOI":"10.2217\/fmb-2021-0146","volume":"17","author":"LJ Silva","year":"2022","unstructured":"Silva LJ, Silva CR, S\u00e1 LG, Barroso FD, C\u00e2ndido TM, Queiroz HA, et al. Antifungal activity of dexamethasone against fluconazole-resistant Candida albicans and its activity against biofilms. Future Microbiol. 2022;17:607\u201320.","journal-title":"Future Microbiol"},{"key":"2684_CR60","doi-asserted-by":"publisher","first-page":"468","DOI":"10.3390\/microorganisms8040468","volume":"8","author":"A Vollaro","year":"2020","unstructured":"Vollaro A, Esposito A, Antonaki E, Iula VD, D\u2019Alonzo D, Guaragna A, et al. Steroid derivatives as potential antimicrobial agents against Staphylococcus aureus planktonic cells. Microorganisms. 2020;8:468.","journal-title":"Microorganisms"},{"key":"2684_CR61","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1002\/art.1780390921","volume":"39","author":"E Sakiniene","year":"1996","unstructured":"Sakiniene E, Bremell T, Tarkowski A. Addition of corticosteroids to antibiotic treatment ameliorates the course of experimental Staphylococcus aureus arthritis. Arthritis Rheum. 1996;39:1596\u2013605.","journal-title":"Arthritis Rheum"},{"key":"2684_CR62","doi-asserted-by":"publisher","first-page":"2245","DOI":"10.3389\/fmicb.2018.02245","volume":"9","author":"O Dobay","year":"2018","unstructured":"Dobay O, Laub K, Stercz B, K\u00e9ri A, Bal\u00e1zs B, T\u00f3thp\u00e1l A, et al. Bicarbonate inhibits bacterial growth and biofilm formation of prevalent cystic fibrosis pathogens. Front Microbiol. 2018;9:2245.","journal-title":"Front Microbiol"},{"key":"2684_CR63","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1093\/jac\/dkab421","volume":"77","author":"M Holland","year":"2022","unstructured":"Holland M, Bjanes E, Nizet V, Dillon N. Bicarbonate modulates delafloxacin activity against MDR Staphylococcus aureus and Pseudomonas aeruginosa. J Antimicrob Chemother. 2022;77:433\u201342.","journal-title":"J Antimicrob Chemother"},{"key":"2684_CR64","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s42770-021-00655-4","volume":"53","author":"AM El-Ganiny","year":"2022","unstructured":"El-Ganiny AM, Gad AI, El-Sayed MA, Shaldam MA, Abbas HA. The promising anti-virulence activity of candesartan, domperidone, and miconazole on Staphylococcus aureus. Braz J Microbiol. 2022;53:1\u201318.","journal-title":"Braz J Microbiol"},{"key":"2684_CR65","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1007\/s11274-022-03232-5","volume":"38","author":"K Vijayakumar","year":"2022","unstructured":"Vijayakumar K, Muhilvannan S, Arun VM. Hesperidin inhibits biofilm formation, virulence and staphyloxanthin synthesis in methicillin resistant Staphylococcus aureus by targeting sarA and crtM: an in vitro and in silico approach. World J Microbiol Biotechnol. 2022;38:44.","journal-title":"World J Microbiol Biotechnol"},{"key":"2684_CR66","doi-asserted-by":"publisher","first-page":"2751","DOI":"10.1007\/s00203-020-01992-y","volume":"202","author":"HA Abbas","year":"2020","unstructured":"Abbas HA, Atallah H, El-Sayed MA, El-Ganiny AM. Diclofenac mitigates virulence of multidrug-resistant Staphylococcus aureus. Arch Microbiol. 2020;202:2751\u201360.","journal-title":"Arch Microbiol"},{"key":"2684_CR67","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.4314\/ahs.v19i1.10","volume":"19","author":"HA Abbas","year":"2019","unstructured":"Abbas HA, Elsherbini AM, Shaldam MA. Glyceryl trinitrate blocks staphyloxanthin and biofilm formation in Staphylococcus aureus. Afr Health Sci. 2019;19:1376\u201384.","journal-title":"Afr Health Sci"},{"key":"2684_CR68","doi-asserted-by":"publisher","first-page":"111933","DOI":"10.1016\/j.biopha.2021.111933","volume":"141","author":"A Valliammai","year":"2021","unstructured":"Valliammai A, Selvaraj A, Muthuramalingam P, Priya A, Ramesh M, Pandian SK. Staphyloxanthin inhibitory potential of thymol impairs antioxidant fitness, enhances neutrophil mediated killing and alters membrane fluidity of methicillin resistant Staphylococcus aureus. Biomed Pharmacother. 2021;141:111933.","journal-title":"Biomed Pharmacother"},{"key":"2684_CR69","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1128\/JB.185.2.610-619.2003","volume":"185","author":"B Sa\u00efd-Salim","year":"2003","unstructured":"Sa\u00efd-Salim B, Dunman PM, McAleese FM, Macapagal D, Murphy E, McNamara PJ, et al. Global regulation of Staphylococcus aureus genes by rot. J Bacteriol. 2003;185:610\u20139.","journal-title":"J Bacteriol"},{"key":"2684_CR70","doi-asserted-by":"publisher","first-page":"32493","DOI":"10.1074\/jbc.M505070200","volume":"280","author":"A Pelz","year":"2005","unstructured":"Pelz A, Wieland K-P, Putzbach K, Hentschel P, Albert K, G\u00f6tz F. Structure and biosynthesis of staphyloxanthin from Staphylococcus aureus. J Biol Chem. 2005;280:32493\u20138.","journal-title":"J Biol Chem"},{"key":"2684_CR71","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.3389\/fmicb.2017.01290","volume":"8","author":"P Balamurugan","year":"2017","unstructured":"Balamurugan P, Praveen Krishna V, Bharath D, Lavanya R, Vairaprakash P, Adline PS. Staphylococcus aureus quorum regulator SarA targeted compound, 2-[(Methylamino)methyl] phenol inhibits biofilm and down-regulates virulence genes. Front Microbiol. 2017;8:1290.","journal-title":"Front Microbiol"},{"key":"2684_CR72","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/microbiolspec.GPP3-0031-2018","volume":"7","author":"C Jenul","year":"2019","unstructured":"Jenul C, Horswill AR. Regulation of Staphylococcus aureus virulence. Microbiol Spectr. 2019;7:1.","journal-title":"Microbiol Spectr"},{"key":"2684_CR73","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1016\/S0196-9781(01)00495-8","volume":"22","author":"M Otto","year":"2001","unstructured":"Otto M. Staphylococcus aureus and Staphylococcus epidermidis peptide pheromones produced by the accessory gene regulator agr system. Peptides (NY). 2001;22:1603\u20138.","journal-title":"Peptides (NY)"},{"key":"2684_CR74","doi-asserted-by":"publisher","first-page":"e0149112","DOI":"10.1371\/journal.pone.0149112","volume":"11","author":"M Xiao","year":"2016","unstructured":"Xiao M, Zhao R, Zhang Q, Fan X, O\u2019Sullivan MVN, Li D-F, et al. Genotypic diversity of Staphylococcus aureus \u03b1-Hemolysin gene (hla) and its association with clonal background: implications for vaccine development. PLoS One. 2016;11:e0149112.","journal-title":"PLoS One"},{"key":"2684_CR75","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1111\/1348-0421.12377","volume":"60","author":"M Murai","year":"2016","unstructured":"Murai M, Moriyama H, Hata E, Takeuchi F, Amemura-Maekawa J. Variation and association of fibronectin-binding protein genes fnbA and fnbB in Staphylococcus aureus Japanese isolates. Microbiol Immunol. 2016;60:312\u201325.","journal-title":"Microbiol Immunol"},{"key":"2684_CR76","doi-asserted-by":"crossref","unstructured":"Bernab\u00e8 G, Dal Pra M, Ronca V, Pauletto A, Marzaro G, Saluzzo F, et al. A novel Aza-derivative inhibits agr quorum sensing signaling and synergizes methicillin-resistant Staphylococcus aureus to clindamycin. Front Microbiol. 2021:12, 610859.","DOI":"10.3389\/fmicb.2021.610859"},{"key":"2684_CR77","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1517\/13543784.2015.1019062","volume":"24","author":"BA Khan","year":"2015","unstructured":"Khan BA, Yeh AJ, Cheung GYC, Otto M. Investigational therapies targeting quorum-sensing for the treatment of Staphylococcus aureus infections. Expert Opin Investig Drugs. 2015;24:689\u2013704.","journal-title":"Expert Opin Investig Drugs"},{"key":"2684_CR78","doi-asserted-by":"publisher","first-page":"e0234021","DOI":"10.1128\/spectrum.02340-21","volume":"10","author":"S Jing","year":"2022","unstructured":"Jing S, Kong X, Wang L, Wang H, Feng J, Wei L, et al. Quercetin reduces the virulence of S. aureus by targeting ClpP to protect mice from MRSA-induced lethal pneumonia. Microbiol Spectr. 2022;10:e0234021.","journal-title":"Microbiol Spectr"}],"container-title":["BMC Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12866-022-02684-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12866-022-02684-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12866-022-02684-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T05:32:31Z","timestamp":1668144751000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmicrobiol.biomedcentral.com\/articles\/10.1186\/s12866-022-02684-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,9]]},"references-count":78,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["2684"],"URL":"https:\/\/doi.org\/10.1186\/s12866-022-02684-x","relation":{},"ISSN":["1471-2180"],"issn-type":[{"value":"1471-2180","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,9]]},"assertion":[{"value":"14 July 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 November 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All mentioned procedures in the animal study section were in accordance with Guide for the Care and Use of Laboratory Animals (8th edition, National Academies Press) and the ethical standards of the Zagazig University Institutional Animal Care and Use Committee (ZU-IACUC) with approval number ZU-IACUC\/3\/F\/141\/2022; and all experimental protocols were approved by Zagazig University Institutional Animal Care and Use Committee. The study is reported in accordance with ARRIVE guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"NA.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"268"}}