Biofilm formation is an important physiological process in Staphylococcus aureus (S. aureus) that can cause infections in humans. In this study, the ability of 36 methicillin-resistant S. aureus (MRSA) clinical isolates to form biofilm was studied based on genotypic and phenotypic approaches. These isolates were genotyped based on the microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) and biofilm-associated genes (icaAD) via polymerase chain reactions. Phenotyping was performed based on the determination of the strength of biofilm formation of MRSA isolates in vitro. The most prevalent MSCRAMMs and biofilm-associated genes were clfA, eno, and icaD, followed by clfB. The fnbB (38.9%) and ebpS (11.1%) occurred less frequently among the MRSA isolates, while bbp and fnbA genes were absent from all isolates. The MRSA isolates were mostly moderate to strong biofilm formers, despite the heterogeneity of the MSCRAMM profiles. MRSA isolates from different infection sources (primary, catheter-related bloodstream, or secondary infections) were capable of forming strong biofilms. However, persistent bacteraemia was observed only in 19.4% of the MRSA-infected individuals. This study suggested that persistent MRSA bacteraemia in patients might not be associated with the biofilm-forming ability of the isolates.

Department of Medical Microbiology Faculty of Medicine Universiti Malaya 50603 Kuala Lumpur Malaysia

Department of Medicine Faculty of Medicine Universiti Malaya 50603 Kuala Lumpur Malaysia

Nanotechnology and Catalysis Research Centre Universiti Malaya 50603 Kuala Lumpur Malaysia

Zobrazit více v PubMed

Archer NK, Mazaitis MJ, Costerton JW, Leid JG, Powers ME, Shirtliff ME (2011) Staphylococcus Aureus Biofilms Virulence 2:445–459 PubMed

Arciola CR, Baldassarri L, Montanaro L (2001) Presence of icaA and icaD genes and slime production in a collection of staphylococcal strains from catheter-associated infections. J Clin Microbiol 39:2151–2156 DOI

Arvidson S, Tegmark K (2001) Regulation of virulence determinants in Staphylococcus aureus. Int J Med Microbiol 291:159–170 DOI

Boles BR, Horswill AR (2008) agr-Mediated dispersal of Staphylococcus aureus biofilms. PLOS Pathog 4:e1000052 DOI

Cascioferro S, Carbone D, Parrino B, Pecoraro C, Giovannetti E, Cirrincione G, Diana P (2020a) Therapeutic strategies to counteract antibiotic resistance in MRSA biofilm-associated infections. ChemMedChem 16:65–80 DOI

Cascioferro S, Parrino B, Carbone D, Schillaci D, Giovannetti E, Cirrincione G, Diana P (2020b) Thiazoles, their benzofused systems, and thiazolidinone derivatives: Versatile and promising tools to combat antibiotic resistance. J Med Chem 63:7923–7956 DOI

Cha J-O, Yoo JI, Yoo JS, Chung H-S, Park S-H, Kim HS et al (2013) Investigation of biofilm formation and its association with the molecular and clinical characteristics of methicillin-resistant Staphylococcus aureus. Osong Public Health Res Perspect 4:225–232 DOI

Choe D, Szubin R, Dahesh S, Cho S, Nizet V, Palsson B et al (2018) Genome-scale analysis of methicillin-resistant Staphylococcus aureus USA300 reveals a tradeoff between pathogenesis and drug resistance. UK-Sci Rep 8:2215 DOI

Costerton JW, Montanaro L, Arciola CR (2005) Biofilm in implant infections: its production and regulation. Int J Artif Organs 28:1062–1068 DOI

Costerton JW, Stewart PS, Greenberg EP (1999) Bacterial biofilms: a common cause of persistent infections. Science (new York, NY) 284:1318–1322 DOI

Croes S, Deurenberg RH, Boumans M-LL, Beisser PS, Neef C, Stobberingh EE (2009) Staphylococcus aureus biofilm formation at the physiologic glucose concentration depends on the S. aureus lineage. BMC Microbiol 9:229.

Cue D, Lei M, Lee C (2012) Genetic regulation of the intercellular adhesion locus in staphylococci. Front Cell Infect Microbiol 2:38 DOI

Eseonu KC, Middleton SD, Eseonu CC (2011) A retrospective study of risk factors for poor outcomes in methicillin-resistant Staphylococcus aureus (MRSA) infection in surgical patients. J Orthop Surg Res 6:25 DOI

Fluit AC (2012) Livestock-associated Staphylococcus aureus. Clin Microbiol Infect 18:735–744 DOI

Foster TJ, Geoghegan JA, Ganesh VK, Höök M (2014) Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus. Nat Rev Microbiol 12:49–62 DOI

Francois P, Schrenzel J, Stoerman-Chopard C, Favre H, Herrmann M, Foster TJ et al (2000) Identification of plasma proteins adsorbed on hemodialysis tubing that promote Staphylococcus aureus adhesion. J Lab Clin Med 135:32–42 DOI

Jones SM, Morgan M, Humphrey TJ, Lappin-Scott H (2001) Effect of vancomycin and rifampicin on methicillin-resistant Staphylococcus aureus biofilms. Lancet 357:40–41 DOI

Kawamura H, Nishi J, Imuta N, Tokuda K, Miyanohara H, Hashiguchi T et al (2011) Quantitative analysis of biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA) strains from patients with orthopaedic device-related infections. FEMS Immunol Med Microbiol 63:10–15 DOI

Kiedrowski MR, Horswill AR (2011) New approaches for treating staphylococcal biofilm infections. Ann NY Acad Sci 1241:104–121 DOI

Kwiecinski JM, Jacobsson G, Horswill AR, Josefsson E, Jin T (2019) Biofilm formation by Staphylococcus aureus clinical isolates correlates with the infection type. Infect Dis 51:446–451 DOI

Kwon AS, Park GC, Ryu SY, Lim DH, Lim DY, Choi CH et al (2008) Higher biofilm formation in multidrug-resistant clinical isolates of Staphylococcus aureus. Int J Antimicrob Ag 32:68–72 DOI

Lebeaux D, Ghigo J-M, Beloin C (2014) Biofilm-related infections: Bridging the gap between clinical management and fundamental aspects of recalcitrance toward antibiotics. Microbiol Mol Biol Rev 78:510–543 DOI

Lewis K (2010) Persister Cells Ann Rev Microbiol 64:357–372 DOI

McCarthy H, Rudkin JK, Black NS, Gallagher L, O’Neill E, O’Gara JP (2015) Methicillin resistance and the biofilm phenotype in Staphylococcus aureus. Front Cell Infect Microbiol 5:1 DOI

McCourt J, O’Halloran DP, McCarthy H, O’Gara JP, Geoghegan JA (2014) Fibronectin-binding proteins are required for biofilm formation by community-associated methicillin-resistant Staphylococcus aureus strain LAC. FEMS Microbiol Lett 353:157–164 DOI

Montanaro L, Poggi A, Visai L, Ravaioli S, Campoccia D, Speziale P et al (2011) Extracellular DNA in biofilms. Int J Artif Organs 34:824–831 DOI

Niek WK, Teh CSJ, Idris N, Thong KL, Ponnampalavanar S (2019) Predominance of ST22-MRSA-IV clone and emergence of clones for methicillin-resistant Staphylococcus aureus clinical isolates collected from a tertiary teaching hospital over a two-year period. Jpn J Infect Dis 72:228–236 DOI

O’Gara JP (2007) ica and beyond: Biofilm mechanisms and regulation in Staphylococcus epidermidis and Staphylococcus aureus. FEMS Microbiol Lett 270:179–188 DOI

Ok HS, Lee HS, Park MJ, Kim KH, Kim BK, Wi YM et al (2013) Predictors and clinical outcomes of persistent methicillin-resistant Staphylococcus aureus bacteremia: a prospective observational study. Korean J Intern Med 28:678–686 DOI

O’Neill E, Pozzi C, Houston P, Humphreys H, Robinson DA, Loughman A et al (2008) A novel Staphylococcus aureus biofilm phenotype mediated by the fibronectin-binding proteins, FnBPA and FnBPB. J Bacteriol 190:3835–3850 DOI

O’Toole GA (2011) Microtiter dish biofilm formation assay. J vis Exp 2011:2437

Parrino B, Carbone D, Cirrincione G, Diana P, Cascioferro S (2020) Inhibitors of antibiotic resistance mechanisms: clinical applications and future perspectives. Future Med Chem 12:357–359 DOI

Parrino B, Schillaci D, Carnevale I, Giovannetti E, Diana P, Cirrincione G, Cascioferro S (2019) Synthetic small molecules as anti-biofilm agents in the struggle against antibiotic resistance. Eur J Med Chem 161:154–178 DOI

Stepanović S, Vuković D, Hola V, Bonaventura GD, Djukić S, Ćirković I et al (2007) Quantification of biofilm in microtiter plates: overview of testing conditions and practical recommendations for assessment of biofilm production by staphylococci. APMIS 115:891–899 DOI

Szabó J (2009) hVISA/VISA: Diagnostic and therapeutic problems. Expert Rev Anti-Infe 7:1–3 DOI

Szczuka E, Urbańska K, Pietryka M, Kaznowski A (2013) Biofilm density and detection of biofilm-producing genes in methicillin-resistant Staphylococcus aureus strains. Folia Microbiol 58:47–52 DOI

Tristan A, Ying L, Bes M, Etienne J, Vandenesch F, Lina G (2003) Use of multiplex PCR to identify Staphylococcus aureus adhesins involved in human hematogenous infections. J Clin Microbiol 41:4465–4467 DOI

Vasudevan P, Nair MKM, Annamalai T, Venkitanarayanan KS (2003) Phenotypic and genotypic characterization of bovine mastitis isolates of Staphylococcus aureus for biofilm formation. Vet Microbiol 92:179–185 DOI

Yahav D, Yassin S, Shaked H, Goldberg E, Bishara J, Paul M et al (2016) Risk factors for long-term mortality of Staphylococcus aureus bacteremia. Eur J Clin Microbiol 35:785–790 DOI