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=== Biofilm === [[Biofilm]]s are groups of microorganisms, such as bacteria, that attach to each other and grow on wet surfaces.<ref name="Vidyasagar, A. 2016">Vidyasagar, A. (2016). What Are Biofilms? ''Live Science.''</ref> The ''S. aureus'' biofilm is embedded in a [[glycocalyx]] slime layer and can consist of [[teichoic acid]]s, host proteins, [[extracellular DNA]] (eDNA) and sometimes polysaccharide intercellular antigen (PIA). S. aureus biofilms are important in disease pathogenesis, as they can contribute to antibiotic resistance and immune system evasion.<ref name="Archer_2011" /> ''S. aureus'' biofilm has high resistance to antibiotic treatments and host immune response.<ref name="Vidyasagar, A. 2016"/> One hypothesis for explaining this is that the biofilm matrix protects the embedded cells by acting as a barrier to prevent antibiotic penetration. However, the biofilm matrix is composed with many water channels, so this hypothesis is becoming increasingly less likely, but a biofilm matrix possibly contains antibiotic‐degrading enzymes such as β-lactamases, which can prevent antibiotic penetration.<ref>{{cite journal | vauthors = de la Fuente-Núñez C, Reffuveille F, Fernández L, Hancock RE | title = Bacterial biofilm development as a multicellular adaptation: antibiotic resistance and new therapeutic strategies | journal = Current Opinion in Microbiology | volume = 16 | issue = 5 | pages = 580–9 | date = October 2013 | pmid = 23880136 | doi = 10.1016/j.mib.2013.06.013 }}</ref> Another hypothesis is that the conditions in the biofilm matrix favor the formation of [[persister cell]]s, which are highly antibiotic-resistant, dormant bacterial cells.<ref name="Archer_2011" /> ''S. aureus'' biofilms also have high resistance to host immune response. Though the exact mechanism of resistance is unknown, ''S. aureus'' biofilms have increased growth under the presence of [[cytokine]]s produced by the host immune response.<ref>{{cite journal | vauthors = McLaughlin RA, Hoogewerf AJ | title = Interleukin-1beta-induced growth enhancement of ''Staphylococcus aureus'' occurs in biofilm but not planktonic cultures | journal = Microbial Pathogenesis | volume = 41 | issue = 2–3 | pages = 67–79 | date = August 2006 | pmid = 16769197 | doi = 10.1016/j.micpath.2006.04.005 }}</ref> Host antibodies are less effective for ''S. aureus'' biofilm due to the heterogeneous [[antigen]] distribution, where an antigen may be present in some areas of the biofilm, but completely absent from other areas.<ref name="Archer_2011" /> Studies in biofilm development have shown to be related to changes in gene expression. There are specific genes that were found to be crucial in the different biofilm growth stages. Two of these genes include rocD and gudB, which encode for the enzyme's [[ornithine-oxo-acid transaminase]] and [[glutamate dehydrogenase]], which are important for amino acid metabolism. Studies have shown biofilm development rely on amino acids [[glutamine]] and [[glutamate]] for proper metabolic functions.<ref>{{cite journal | vauthors = Nassar R, Hachim M, Nassar M, Kaklamanos EG, Jamal M, Williams D, Senok A | title = Microbial Metabolic Genes Crucial for ''S. aureus'' Biofilms: An Insight From Re-analysis of Publicly Available Microarray Datasets | language = English | journal = Frontiers in Microbiology | volume = 11 | pages = 607002 | date = 2021 | pmid = 33584569 | pmc = 7876462 | doi = 10.3389/fmicb.2020.607002 | doi-access = free }}</ref>
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