Editing Biofilm (section)

== Infectious diseases ==
Biofilms have been found to be involved in a wide variety of microbial infections in the body, by one estimate 80% of all infections.<ref>{{cite web | title=Research on microbial biofilms (PA-03-047) | url=http://grants.nih.gov/grants/guide/pa-files/PA-03-047.html | date=20 December 2002 | publisher=NIH, National Heart, Lung, and Blood Institute | access-date=12 October 2006 | archive-date=10 December 2006 | archive-url=https://web.archive.org/web/20061210052551/http://grants.nih.gov/grants/guide/pa-files/PA-03-047.html | url-status=live }}</ref> Infectious processes in which biofilms have been implicated include common problems such as [[List of bacterial vaginosis microbiota|bacterial vaginosis]], [[urinary tract infections]], [[Urinary catheterization|catheter]] infections, [[otitis media|middle-ear infections]], formation of [[dental plaque]],<ref name=Rogers2008>{{cite book| vauthors = Rogers A |title=Molecular Oral Microbiology|date=2008|publisher=Caister Academic Press|isbn=978-1-904455-24-0|pages=88–91}}</ref> [[gingivitis]], coating [[contact lenses]],<ref>{{cite journal | vauthors = Imamura Y, Chandra J, Mukherjee PK, Lattif AA, Szczotka-Flynn LB, Pearlman E, Lass JH, O'Donnell K, Ghannoum MA | title = Fusarium and Candida albicans biofilms on soft contact lenses: model development, influence of lens type, and susceptibility to lens care solutions | journal = Antimicrobial Agents and Chemotherapy | volume = 52 | issue = 1 | pages = 171–82 | date = January 2008 | pmid = 17999966 | pmc = 2223913 | doi = 10.1128/AAC.00387-07 }}</ref> and less common but more lethal processes such as [[endocarditis]], infections in [[cystic fibrosis]], and infections of permanent indwelling devices such as joint [[prosthesis|prostheses]], [[Heart valve prosthesis|heart valves]], and intervertebral disc.<ref>{{cite journal | vauthors = Capoor MN, Ruzicka F, Schmitz JE, James GA, Machackova T, Jancalek R, Smrcka M, Lipina R, Ahmed FS, Alamin TF, Anand N, Baird JC, Bhatia N, Demir-Deviren S, Eastlack RK, Fisher S, Garfin SR, Gogia JS, Gokaslan ZL, Kuo CC, Lee YP, Mavrommatis K, Michu E, Noskova H, Raz A, Sana J, Shamie AN, Stewart PS, Stonemetz JL, Wang JC, Witham TF, Coscia MF, Birkenmaier C, Fischetti VA, Slaby O | title = Propionibacterium acnes biofilm is present in intervertebral discs of patients undergoing microdiscectomy | journal = PLOS ONE | volume = 12 | issue = 4 | pages = e0174518 | date = 3 April 2017 | pmid = 28369127 | pmc = 5378350 | doi = 10.1371/journal.pone.0174518 | bibcode = 2017PLoSO..1274518C | doi-access = free }}</ref><ref>{{cite journal | vauthors = Lewis K | title = Riddle of biofilm resistance | journal = Antimicrobial Agents and Chemotherapy | volume = 45 | issue = 4 | pages = 999–1007 | date = April 2001 | pmid = 11257008 | pmc = 90417 | doi = 10.1128/AAC.45.4.999-1007.2001 }}</ref><ref>{{cite journal | vauthors = Parsek MR, Singh PK | title = Bacterial biofilms: an emerging link to disease pathogenesis | journal = Annual Review of Microbiology | volume = 57 | pages = 677–701 | year = 2003 | pmid = 14527295 | doi = 10.1146/annurev.micro.57.030502.090720 }}</ref> The first visual evidence of a biofilm was recorded after spine surgery.<ref name="Agarwal_2020">{{cite journal | vauthors = Agarwal A, Mooney M, Agarwal AG, Jayaswal D, Saakyan G, Goel V, Wang JC, Anand N, Garfin S, Shendge V, Elgafy H | title = High Prevalence of Biofilms on Retrieved Implants from Aseptic Pseudarthrosis Cases | journal = Spine Surgery and Related Research | volume = 5 | issue = 2 | pages = 104–108 | date = 2020 | pmid = 33842718 | pmc = 8026210 | doi = 10.22603/ssrr.2020-0147 | doi-access = free }}</ref> It was found that in the absence of clinical presentation of infection, impregnated bacteria could form a biofilm around an implant, and this biofilm can remain undetected via contemporary diagnostic methods, including swabbing. Implant biofilm is frequently present in "aseptic" pseudarthrosis cases.<ref name="Agarwal_2020" /><ref name="niamhcurran">{{Cite web|vauthors=Curran N|date=20 November 2020|title=New study first to visually capture biofilm architecture in retrieved implants from live patients|url=https://spinalnewsinternational.com/new-study-first-to-visually-capture-biofilm-architecture-in-retrieved-implants-from-live-patients/|access-date=24 November 2020|website=Spinal News International|language=en-GB|archive-date=23 November 2020|archive-url=https://web.archive.org/web/20201123193152/https://spinalnewsinternational.com/new-study-first-to-visually-capture-biofilm-architecture-in-retrieved-implants-from-live-patients/|url-status=live}}</ref><ref>{{Cite web|title=biofilm|date=22 December 2020|url=https://orthospinenews.com/2020/12/22/first-study-to-visually-capture-biofilm-structure-of-retrieved-implants-from-spine-patients-with-pseudarthrosis/|access-date=22 December 2020|archive-date=22 January 2021|archive-url=https://web.archive.org/web/20210122061753/https://orthospinenews.com/2020/12/22/first-study-to-visually-capture-biofilm-structure-of-retrieved-implants-from-spine-patients-with-pseudarthrosis/|url-status=live}}</ref> Furthermore, it has been noted that bacterial biofilms may impair cutaneous wound healing and reduce topical antibacterial efficiency in healing or treating infected skin wounds.<ref>{{cite journal | vauthors = Davis SC, Ricotti C, Cazzaniga A, Welsh E, Eaglstein WH, Mertz PM | title = Microscopic and physiologic evidence for biofilm-associated wound colonization in vivo | journal = Wound Repair and Regeneration | volume = 16 | issue = 1 | pages = 23–9 | year = 2008 | pmid = 18211576 | doi = 10.1111/j.1524-475X.2007.00303.x | s2cid = 205669081 }}</ref> The diversity of ''P. aeruginosa'' cells within a biofilm is thought to make it harder to treat the infected lungs of people with cystic fibrosis.<ref name="Labor"/> Early detection of biofilms in wounds is crucial to successful chronic wound management. Although many techniques have developed to identify planktonic bacteria in viable wounds, few have been able to quickly and accurately identify bacterial biofilms. Future studies are needed to find means of identifying and monitoring biofilm colonization at the bedside to permit timely initiation of treatment.<ref>{{cite journal | vauthors = Vyas KS, Wong LK | title = Detection of Biofilm in Wounds as an Early Indicator for Risk for Tissue Infection and Wound Chronicity | journal = Annals of Plastic Surgery | volume = 76 | issue = 1 | pages = 127–31 | date = January 2016 | pmid = 25774966 | doi = 10.1097/SAP.0000000000000440 | s2cid = 42078581 }}</ref>

It has been shown that biofilms are present on the removed tissue of 80% of patients undergoing surgery for chronic [[sinusitis]]. The patients with biofilms were shown to have been denuded of [[cilium|cilia]] and [[goblet cells]], unlike the controls without biofilms who had normal cilia and goblet cell morphology.<ref>{{cite journal|vauthors=Sanclement J, Webster P, Thomas J, Ramadan H |title=Bacterial biofilms in surgical specimens of patients with chronic rhinosinusitis |journal=The Laryngoscope |volume=115 |issue=4 |pages=578–82 |year=2005 |pmid=15805862 |doi=10.1097/01.mlg.0000161346.30752.18|s2cid=25830188 }}</ref> Biofilms were also found on samples from two of 10 healthy controls mentioned. The species of bacteria from intraoperative cultures did not correspond to the bacteria species in the biofilm on the respective patient's tissue. In other words, the cultures were negative though the bacteria were present.<ref>{{cite journal|vauthors=Sanderson AR, Leid JG, Hunsaker D |title=Bacterial biofilms on the sinus mucosa of human subjects with chronic rhinosinusitis |journal=The Laryngoscope |volume=116 |issue=7 |pages=1121–6 |date=July 2006 |pmid=16826045 |doi=10.1097/01.mlg.0000221954.05467.54|s2cid=24785016 |doi-access=free }}</ref> New staining techniques are being developed to differentiate bacterial cells growing in living animals, e.g. from tissues with allergy-inflammations.<ref>{{cite journal | vauthors = Leevy WM, Gammon ST, Jiang H, Johnson JR, Maxwell DJ, Jackson EN, Marquez M, Piwnica-Worms D, Smith BD | title = Optical imaging of bacterial infection in living mice using a fluorescent near-infrared molecular probe | journal = Journal of the American Chemical Society | volume = 128 | issue = 51 | pages = 16476–7 | date = December 2006 | pmid = 17177377 | pmc = 2531239 | doi = 10.1021/ja0665592 }}</ref>

Research has shown that sub-therapeutic levels of [[β-lactam antibiotics]] induce biofilm formation in ''[[Staphylococcus aureus]]''. This sub-therapeutic level of [[antibiotic]] may result from the use of antibiotics as growth promoters in agriculture, or during the normal course of antibiotic therapy. The biofilm formation induced by low-level methicillin was inhibited by DNase, suggesting that the sub-therapeutic levels of antibiotic also induce extracellular DNA release.<ref>{{cite journal | vauthors = Kaplan JB, Izano EA, Gopal P, Karwacki MT, Kim S, Bose JL, Bayles KW, Horswill AR | title = Low levels of β-lactam antibiotics induce extracellular DNA release and biofilm formation in Staphylococcus aureus | journal = mBio | volume = 3 | issue = 4 | pages = e00198-12 | year = 2012 | pmid = 22851659 | pmc = 3419523 | doi = 10.1128/mBio.00198-12 }}</ref> Moreover, from an evolutionary point of view, the creation of the [[tragedy of the commons]] in pathogenic microbes may provide advanced therapeutic ways for chronic infections caused by biofilms via genetically engineered invasive cheaters who can invade wild-types 'cooperators' of pathogenic bacteria until cooperator populations go to extinction or overall population 'cooperators and cheaters ' go to extinction.<ref>{{cite report | vauthors = Ibrahim AM | date = 2015 | title = The tragedy of the commons and prisoner's dilemma may improve our realization of the theory of life and provide us with advanced therapeutic ways | doi = 10.13140/RG.2.1.2327.9842 }}</ref>

=== ''Pseudomonas aeruginosa'' ===
''[[Pseudomonas aeruginosa|P. aeruginosa]]'' represents a commonly used biofilm [[model organism]] since it is involved in different types of biofilm-associated chronic infections.<ref name="JMB">{{cite journal | vauthors = Rybtke M, Hultqvist LD, Givskov M, Tolker-Nielsen T | title = Pseudomonas aeruginosa Biofilm Infections: Community Structure, Antimicrobial Tolerance and Immune Response | journal = Journal of Molecular Biology | volume = 427 | issue = 23 | pages = 3628–45 | date = November 2015 | pmid = 26319792 | doi = 10.1016/j.jmb.2015.08.016 }}</ref> Examples of such infections include chronic wounds, chronic otitis media, chronic prostatitis and chronic lung infections in [[cystic fibrosis]] (CF) patients. About 80% of CF patients have chronic lung infection, caused mainly by ''P. aeruginosa'' growing in a non-surface attached biofilms surround by [[Granulocyte|PMN]].<ref>{{cite journal | vauthors = Ciofu O, Tolker-Nielsen T, Jensen PØ, Wang H, Høiby N | title = Antimicrobial resistance, respiratory tract infections and role of biofilms in lung infections in cystic fibrosis patients | journal = Advanced Drug Delivery Reviews | volume = 85 | pages = 7–23 | date = May 2015 | pmid = 25477303 | doi = 10.1016/j.addr.2014.11.017 }}</ref> The infection remains present despite aggressive antibiotic therapy and is a common cause of death in CF patients due to constant inflammatory damage to the lungs.<ref name="JMB" /> In patients with CF, one therapy for treating early biofilm development is to employ [[DNase]] to structurally weaken the biofilm.<ref name="Aggarwal"/><ref>{{cite journal | vauthors = Whitchurch CB, Tolker-Nielsen T, Ragas PC, Mattick JS | title = Extracellular DNA required for bacterial biofilm formation | journal = Science | volume = 295 | issue = 5559 | pages = 1487 | date = February 2002 | pmid = 11859186 | doi = 10.1126/science.295.5559.1487 }}</ref>

Biofilm formation of ''[[Pseudomonas aeruginosa|P. aeruginosa]]'', along with other bacteria, is found in 90% of chronic wound infections, which leads to poor healing and high cost of treatment estimated at more than US$25 billion every year in the [[United States]].<ref>{{cite journal | vauthors = Sen CK, Gordillo GM, Roy S, Kirsner R, Lambert L, Hunt TK, Gottrup F, Gurtner GC, Longaker MT | title = Human skin wounds: a major and snowballing threat to public health and the economy | journal = Wound Repair and Regeneration | volume = 17 | issue = 6 | pages = 763–771 | date = November 2009 | pmid = 19903300 | pmc = 2810192 | doi = 10.1111/j.1524-475X.2009.00543.x }}</ref> In order to minimize the ''[[Pseudomonas aeruginosa|P. aeruginosa]]'' [[infection]], host epithelial cells secrete [[antimicrobial peptides]], such as [[lactoferrin]], to prevent the formation of the biofilms.<ref>{{cite journal | vauthors = Singh PK, Parsek MR, Greenberg EP, Welsh MJ | title = A component of innate immunity prevents bacterial biofilm development | journal = Nature | volume = 417 | issue = 6888 | pages = 552–555 | date = May 2002 | pmid = 12037568 | doi = 10.1038/417552a | bibcode = 2002Natur.417..552S | s2cid = 4423528 }}</ref>

=== ''Streptococcus pneumoniae'' ===
''[[Streptococcus pneumoniae]]'' is the main cause of community-acquired pneumonia and meningitis in children and the elderly, and of sepsis in HIV-infected persons. When ''S. pneumoniae'' grows in biofilms, genes are specifically expressed that respond to oxidative stress and induce competence.<ref name="pmid16925554">{{cite journal | vauthors = Oggioni MR, Trappetti C, Kadioglu A, Cassone M, Iannelli F, Ricci S, Andrew PW, Pozzi G | title = Switch from planktonic to sessile life: a major event in pneumococcal pathogenesis | journal = Molecular Microbiology | volume = 61 | issue = 5 | pages = 1196–210 | date = September 2006 | pmid = 16925554 | pmc = 1618759 | doi = 10.1111/j.1365-2958.2006.05310.x }}</ref> Formation of a biofilm depends on [[competence stimulating peptide]] (CSP). CSP also functions as a quorum-sensing peptide. It not only induces biofilm formation, but also increases virulence in pneumonia and meningitis.

It has been proposed that competence development and biofilm formation is an adaptation of ''S. pneumoniae'' to survive the defenses of the host.<ref name=Michod /> In particular, the host's polymorphonuclear leukocytes produce an oxidative burst to defend against the invading bacteria, and this response can kill bacteria by damaging their DNA. Competent ''S. pneumoniae'' in a biofilm have the survival advantage that they can more easily take up transforming DNA from nearby cells in the biofilm to use for recombinational repair of oxidative damages in their DNA. Competent ''S. pneumoniae'' can also secrete an enzyme (murein hydrolase) that destroys non-competent cells (fratricide) causing DNA to be released into the surrounding medium for potential use by the competent cells.<ref name="pmid22706053">{{cite journal |vauthors=Wei H, Håvarstein LS |title=Fratricide is essential for efficient gene transfer between pneumococci in biofilms |journal=Appl. Environ. Microbiol. |volume=78 |issue=16 |pages=5897–905 |date=August 2012 |pmid=22706053 |pmc=3406168 |doi=10.1128/AEM.01343-12 |bibcode=2012ApEnM..78.5897W }}</ref>

The insect antimicrobial peptide [[Cecropin#Members|cecropin A]] can destroy planktonic and sessile biofilm-forming [[Uropathogenic Escherichia coli|uropathogenic ''E. coli'']] cells, either alone or when combined with the antibiotic [[nalidixic acid]], synergistically clearing infection in vivo (in the insect host ''[[Galleria mellonella]]'') without off-target cytotoxicity. The multi-target mechanism of action involves outer membrane permeabilization followed by biofilm disruption triggered by the inhibition of efflux pump activity and interactions with extracellular and intracellular nucleic acids.<ref>{{cite journal | vauthors = Kalsy M, Tonk M, Hardt M, Dobrindt U, Zdybicka-Barabas A, Cytrynska M, Vilcinskas A, Mukherjee K | title = The insect antimicrobial peptide cecropin A disrupts uropathogenic Escherichia coli biofilms | journal = npj Biofilms and Microbiomes | volume = 6 | issue = 1 | pages = 6 | date = 2020 | pmid = 32051417 | doi = 10.1038/s41522-020-0116-3 | pmc = 7016129 | doi-access = free }}</ref>

=== ''Escherichia coli'' ===
''[[Escherichia coli]]'' biofilms are responsible for many intestinal infectious diseases.<ref>{{cite journal | vauthors = Sturbelle RT, de Avila LF, Roos TB, Borchardt JL, da Conceição R, Dellagostin OA, Leite FP | title = The role of quorum sensing in Escherichia coli (ETEC) virulence factors | journal = Veterinary Microbiology | volume = 180 | issue = 3–4 | pages = 245–252 | date = November 2015 | pmid = 26386492 | doi = 10.1016/j.vetmic.2015.08.015 }}</ref> The Extraintestinal group of ''E. coli'' (ExPEC) is the dominant bacterial group that attacks the [[urinary system]], which leads to [[urinary tract infection]]s.<ref>{{cite journal | vauthors = Vogeleer P, Tremblay YD, Mafu AA, Jacques M, Harel J | title = Life on the outside: role of biofilms in environmental persistence of Shiga-toxin producing Escherichia coli | journal = Frontiers in Microbiology | volume = 5 | pages = 317 | date = 2014 | pmid = 25071733 | doi = 10.3389/fmicb.2014.00317 | pmc = 4076661 | doi-access = free }}</ref> The biofilm formation of these pathogenic ''[[Escherichia coli|E. coli]]'' is hard to eradicate due to the complexity of its aggregation structure, and it has a significant contribution to developing aggressive medical complications, increase in hospitalization rate, and cost of treatment.<ref>{{cite journal | vauthors = Danese PN, Pratt LA, Kolter R | title = Exopolysaccharide production is required for development of Escherichia coli K-12 biofilm architecture | journal = Journal of Bacteriology | volume = 182 | issue = 12 | pages = 3593–3596 | date = June 2000 | pmid = 10852895 | pmc = 101973 | doi = 10.1128/JB.182.12.3593-3596.2000 }}</ref><ref>{{cite journal | vauthors = Niranjan V, Malini A | title = Antimicrobial resistance pattern in Escherichia coli causing urinary tract infection among inpatients | journal = The Indian Journal of Medical Research | volume = 139 | issue = 6 | pages = 945–948 | date = June 2014 | pmid = 25109731 | pmc = 4165009 }}</ref> The development of ''E. coli'' biofilm is a common leading cause of [[Urinary tract infection|urinary tract infections (UTI)]] in hospitals through its contribution to developing [[Hospital-acquired infection|medical device-associated infections]]. [[Catheter-associated urinary tract infection|Catheter-associated urinary tract infections (CAUTI)]] represent the most common [[hospital-acquired infection]] due to the formation of the pathogenic ''E. coli biofilm'' inside the catheters.<ref>{{cite journal | vauthors = Reisner A, Maierl M, Jörger M, Krause R, Berger D, Haid A, Tesic D, Zechner EL | title = Type 1 fimbriae contribute to catheter-associated urinary tract infections caused by Escherichia coli | journal = Journal of Bacteriology | volume = 196 | issue = 5 | pages = 931–939 | date = March 2014 | pmid = 24336940 | pmc = 3957706 | doi = 10.1128/JB.00985-13 }}</ref>

=== ''Staphylococcus aureus'' ===
''[[Staphylococcus aureus]]'' pathogen can attack skin and lungs, leading to [[skin infection]] and [[pneumonia]].<ref>{{cite journal | vauthors = Kobayashi SD, Malachowa N, Whitney AR, Braughton KR, Gardner DJ, Long D, Bubeck Wardenburg J, Schneewind O, Otto M, Deleo FR | title = Comparative analysis of USA300 virulence determinants in a rabbit model of skin and soft tissue infection | journal = The Journal of Infectious Diseases | volume = 204 | issue = 6 | pages = 937–941 | date = September 2011 | pmid = 21849291 | pmc = 3156927 | doi = 10.1093/infdis/jir441 }}</ref><ref>{{cite journal | vauthors = Kitur K, Parker D, Nieto P, Ahn DS, Cohen TS, Chung S, Wachtel S, Bueno S, Prince A | title = Toxin-induced necroptosis is a major mechanism of Staphylococcus aureus lung damage | journal = PLOS Pathogens | volume = 11 | issue = 4 | pages = e1004820 | date = April 2015 | pmid = 25880560 | pmc = 4399879 | doi = 10.1371/journal.ppat.1004820 | doi-access = free }}</ref> Moreover, the biofilm infections network of ''S. aureus'' plays a critical role in preventing immune cells, such as [[macrophage]]s from eliminating and destroying bacterial cells.<ref>{{cite journal | vauthors = Thurlow LR, Hanke ML, Fritz T, Angle A, Aldrich A, Williams SH, Engebretsen IL, Bayles KW, Horswill AR, Kielian T | title = Staphylococcus aureus biofilms prevent macrophage phagocytosis and attenuate inflammation in vivo | journal = Journal of Immunology | volume = 186 | issue = 11 | pages = 6585–6596 | date = June 2011 | pmid = 21525381 | pmc = 3110737 | doi = 10.4049/jimmunol.1002794 }}</ref> Furthermore, biofilm formation by bacteria, such as ''S. aureus'', not only develops [[Antimicrobial resistance|resistance against antibiotic]] medication but also develop internal resistance toward [[Antimicrobial peptides|antimicrobial peptides (AMPs)]], leading to preventing the inhibition of the pathogen and maintaining its survival.<ref>{{cite journal | vauthors = Craft KM, Nguyen JM, Berg LJ, Townsend SD | title = Methicillin-resistant ''Staphylococcus aureus'' (MRSA): antibiotic-resistance and the biofilm phenotype | journal = MedChemComm | volume = 10 | issue = 8 | pages = 1231–1241 | date = August 2019 | pmid = 31534648 | pmc = 6748282 | doi = 10.1039/c9md00044e }}</ref>

=== ''Serratia marcescens'' ===
''[[Serratia marcescens]]'' is a fairly common opportunistic pathogen that can form biofilms on various surfaces, including medical devices such as catheters and implants, as well as natural environments like soil and water. The formation of biofilms by ''S. marcescens'' is a serious concern because of its ability to adhere to and colonize surfaces, protecting itself from host immune responses and antimicrobial agents. This strength makes infections caused by ''S. marcescens'' challenging to treat, specifically in hospitals where the bacterium can cause severe, and specific, infections.

Research suggests that biofilm formation by S. marcescens is a process controlled by both nutrient cues and the quorum-sensing system.<ref>{{cite journal |vauthors=Rice SA, Koh KS, Queck SY, Labbate M, Lam KW, Kjelleberg S |date=2005 |title=Biofilm Formation and Sloughing in Serratia marcescens Are Controlled by Quorum Sensing and Nutrient Cues |journal=Journal of Bacteriology |volume=187 |issue=10 |pages=3477–3485 |doi=10.1128/JB.187.10.3477-3485.2005 |pmc=1111991 |pmid=15866935}}</ref> Quorum sensing influences the bacterium's ability to adhere to surfaces and establish mature biofilms, whereas the availability of specific nutrients can enhance or inhibit biofilm development.

''S. marcescens'' creates biofilms that ultimately develop into a highly porous, thread-like structure composed of chains of cells, filaments, and cell clusters. Research has shown that ''S. marcescens'' biofilms exhibit complex structural organization, including the formation of microcolonies and channels that facilitate nutrient and waste exchange. The production of extracellular polymeric substances (EPS) is a key factor in biofilm development, contributing to the bacterium's adhesion and resistance to antimicrobial agents. In addition to its role in healthcare-associated infections, ''S. marcescens'' biofilms have been implicated in the deterioration of industrial equipment and processes. For example, biofilm growth in cooling towers can lead to [[biofouling]] and reduced efficiency.

Efforts to control and prevent biofilm formation by ''S. marcescens'' involve the use of antimicrobial coatings on medical devices, the development of targeted biofilm disruptors, and improved sterilization protocols. Further research into the molecular mechanisms governing ''S. marcescens'' biofilm formation and persistence is crucial for developing effective strategies to combat its associated risks. The use of [[indole]] compounds has been studied to be used as protection against biofilm formation.<ref>{{cite journal |vauthors=Sethupathy S, Sathiyamoorthi E, Kim Y, Lee J, Lee J |date=2020 |title=Antibiofilm and Antivirulence Properties of Indoles Against Serratia marcescens |journal=Frontiers in Microbiology |volume=11 |doi=10.3389/fmicb.2020.584812 |pmc=7662412 |pmid=33193228 |doi-access=free}}</ref>