Biofilm prevention

Last updated April 12, 2023

Biofilm formation occurs when free floating microorganisms attach themselves to a surface. Although there are some beneficial uses of biofilms, they are generally considered undesirable, and means of biofilm prevention have been developed. Biofilms secrete extracellular polymeric substance that provides a structural matrix and facilitates adhesion for the microorganisms; the means of prevention have thus concentrated largely on two areas: killing the microbes that form the film, or preventing the adhesion of the microbes to a surface. Because biofilms protect the bacteria, they are often more resistant to traditional antimicrobial treatments, making them a serious health risk.^[1] For example, there are more than one million cases of catheter-associated urinary tract infections (CAUTI) reported each year, many of which can be attributed to bacterial biofilms.^[2] There is much research into the prevention of biofilms.

Methods

Biofilm prevention methods fall into two categories:

prevention of microbe growth; and
prevention of microbe surface attachment.

Prevention of microbe growth

Antimicrobial coatings

Chemical modifications are the main strategy for biofilm prevention on indwelling medical devices. Antibiotics, biocides, and ion coatings are commonly used chemical methods of biofilm prevention. They prevent biofilm formation by interfering with the attachment and expansion of immature biofilms. Typically, these coatings are effective only for a short time period (about 1 week), after which leaching of the antimicrobial agent reduces the effectiveness of the coating.^[3]

The medical uses of silver and silver ions have been known for some time; its use can be traced to the Phoenicians, who would store their water, wine, and vinegar in silver bottles to keep them from spoiling. There has been renewed interest in silver coatings for antimicrobial purposes. The antimicrobial property of silver is known as an oligodynamic effect, a process in which metal ions interfere with the growth and function of bacteria.^[4] Several in vitro studies have confirmed the effectiveness of silver at preventing infection, both in coating form and as nanoparticles dispersed in a polymer matrix. However, concerns remain over the use of silver in vivo. Considering the mechanism by which silver interferes with bacterial cell function, some fear that silver may have a similarly toxic effect on human tissue. For this reason, there has been limited use of silver coatings in vivo. Despite this, silver coatings are commonly used on devices such as catheters.^[5]

Water purification

When this technique was studied two purification methods were used to treat water. The first was a typical reverse osmosis technique used for pure water. The other was a double reverse osmosis technique with electric deionization which was continuously disinfected with UV light and disinfected weekly with ozone. The tubing it ran through was tested weekly for bacterial colonies. The highly purified water showed a sharp decrease in bacteria colony adherence. Water purification methods are being scrutinized here because it is in this state that contamination is thought to occur and biofilms are formed.^[6]

Prevention of microbes' surface attachment

Chemical

Polymer modification

To avoid the undesirable effects of leaching, antimicrobial agents can be immobilized on device surfaces using long, flexible polymeric chains. These chains are anchored to the device surface by covalent bonds, producing non-leaching, contact-killing surfaces. One in vitro study found that when N-alkylpyridinium bromide, an antimicrobial agent, was attached to a poly(4-vinyl-N-hexylpyridine), the polymer was capable of inactivating ≥ 99% of Staphylococcus epidermidis , Escherichia coli , and Pseudomonas aeruginosa bacteria.^[7]

Dispersion forces between the polymer chains and the bacterial cells prevent bacteria from binding to the surface and initiating biofilm growth. The concept is similar to that of steric stabilization of colloids. Polymer chains are grafting to a surface via covalent bonding or adsorption. The solubility of these polymers stems from the high conformational entropy of polymer chains in solution. The Χ (Chi) parameter is used to determine whether a polymer will be soluble in a given solution. Χ is given by the equation:

\chi ={\frac {{(\delta _{1}-\delta _{2}})^{2}\times {\bar {V}}}{RT}}.\

where $\delta _{1}$ and $\delta _{2}$ are the cohesive energy densities of the polymer and solvent, respectively, ${\bar {V}}$ is the molar volume of the solution (assuming ${\bar {V_{1}}}={\bar {V_{2}}}$ ), R is the ideal gas constant, and T is temperature in Kelvins. If 0 < $\chi$ < 2, the polymer will be soluble.

Ozonation

Biofilms form as a way of survival for bacteria in aqueous situations. Ozone targets extracellular polysaccharides, a group of bacterial colonies on a surface, and cleaves them. The ozone cuts through the skeleton of the biofilm at a rapid pace thus dissolving it back to harmless microscopic fragments. Ozone is so effective because it is a very strong oxidant and it encounters biofilms in much larger concentrations than most disinfectants like chlorine. This technique has been employed mainly in the spa and pool industry as a way to purify water.^[8]

Surface charge

Modification of the surface charge of polymers has also proven to be an effective means of biofilm prevention. Based on the principles of electrostatics charged particles will repel other particles of like charge. The hydrophobicity and the charge of polymeric chains can be controlled by using several backbone compounds and antimicrobial agents. Positively charged polycationic chains enables the molecule to stretch out and generate bactericidal activity.^[7]

Mechanical

Hydrophobicity

The ability of bacteria to adhere to a surface and begin the formation of a biofilm is determined in part by the enthalpy of adhesion of the surface. Adherence is thermodynamically favored if the free enthalpy of adhesion is negative and decreases with increasing free enthalpy values.^[7] The free energy of adhesion can be determined by measuring the contact angles of the substances in question. Young's Equation can be used to determine whether if adhesion is favorable or unfavorable:

\gamma _{\mathrm {SL} }+\gamma _{\mathrm {LV} }\cos {\theta _{\mathrm {c} }}=\gamma _{\mathrm {SV} }\,

where $\gamma _{\mathrm {SL} }$ , $\gamma _{\mathrm {LV} }$ , and $\gamma _{\mathrm {SV} }$ are the interfacial energies of the solid–liquid, the liquid–vapor, and the solid–vapor interfaces, respectively. Using this equation, $\theta _{\mathrm {c} }$ can be determined.

Surface roughness

Surface roughness can also affect biofilm adhesion. Rough, high-energy surfaces are more conducive to biofilm formation and maturation, while smooth surfaces are less susceptible to biofilm adhesion. The roughness of a surface can affect the hydrophobicity or hydrophilicity of the contacting substance, which in turn affects its ability to adhere. The Wenzel equation can be used to estimate the observed contact angle:

\cos \,{\theta _{obs}}=R\cos \,{\theta }

where $\theta _{obs}$ is the apparent contact angle and R is the roughness parameter of the surface. R is the ratio of actual surface area over projected surface area. The Wenzel equation predicts that a hydrophilic surface will have a lower $\theta _{obs}$ , thus making it easier for bacteria to adhere.^[9]

It is thus desirable to maintain a smooth surface on any products that may come in contact with bacteria. Studies have shown that there is a threshold value of surface roughness (Ra = 2 μm) below which biofilm adhesion will reduce no further.^[10]

Low-energy surface acoustic waves

This technique uses low-energy waves produced from a battery powered device. The device delivers periodic rectangular pulses through an actuator holding a thin piezo plate. The waves spread to the surface, in this case a catheter, creating horizontal waves that prevent the adhesion of planktonic bacteria to surfaces. This technique has been tested on white rabbits and guinea pigs. The results showed a lowered biofilm growth.^[11]

Examples of antibiofilm agents

Antibiofilm agents are the nontoxic molecules which have moieties such as: imidazole, indole, sulfide peptides, and triazole; and other moieties which give it a characteristic to disperse or inhibit biofilm formation.^[12] There are many antibiofilm agents such as: Aryl rhodanines, Cis-2-Decenoic acid (C2DA) and ionic liquid.^[13]

Aryl rhodanines

Aryl rhodanines chemical structure is [(Z)-3-(4-fluorophenyl)-5-(3-ethoxy-4-hydroxybenzylidene)-2-thioxothiazolidin-4-one]. Aryl rhodanines inhibit the adhesion of bacterial cell such as: staphylococcus aureus and enterococci in the first step of biofilm formation, because it prevents the initial interaction between bacterial cells and adhesion surface, the mechanism of inhibit biofilm by these molecules exhibit the physical interaction between aryl rhodanine and adhesine which are located on the bacterial cell surface. These molecules don't have any antimicrobial effect against any type of bacteria.^[14]

Cis-2-Decenoic acid (C2DA)

The C2DA inhibit methicillin resistant staphylococcus biofilm, but don't eliminate it. The mechanism of the biofilm inhibition by these molecules is still unknown. C2D is a medium of fatty acid chain that effect on staphylococcus aureus biofilm and dispersion of these biofilm. Pseudomonas aeruginosa is the main source for these molecules.^[15]

Ionic liquid

Ionic liquid is a group of low melting point salts containing anions and cations. It has flexibility to exhibit antibiofilm activity and has antimicrobial activity, it has many antibiofilm activities and prevents the biofilm formation for many gram-positive and gram-negative bacteria.^[16]

Glycosidase or glycosyl hydrolase

Other than chemicals, enzymes have been used to degrade the biofilm matrix and eject biofilm cells forcibly. First shown in P. aeruginosa, a glycosyl hydrolase PslG can trigger biofilm disassembly by disrupting exopolysaccharide matrix in biofilms effectively and can be used in combination with antibiotics to kill the cells released from biofilms.^[17]

Related Research Articles

A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular polymeric substances (EPSs). The cells within the biofilm produce the EPS components, which are typically a polymeric conglomeration of extracellular polysaccharides, proteins, lipids and DNA. Because they have three-dimensional structure and represent a community lifestyle for microorganisms, they have been metaphorically described as "cities for microbes".

Staphylococcus aureus is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive for catalase and nitrate reduction and is a facultative anaerobe that can grow without the need for oxygen. Although S. aureus usually acts as a commensal of the human microbiota, it can also become an opportunistic pathogen, being a common cause of skin infections including abscesses, respiratory infections such as sinusitis, and food poisoning. Pathogenic strains often promote infections by producing virulence factors such as potent protein toxins, and the expression of a cell-surface protein that binds and inactivates antibodies. S. aureus is one of the leading pathogens for deaths associated with antimicrobial resistance and the emergence of antibiotic-resistant strains, such as methicillin-resistant S. aureus (MRSA), is a worldwide problem in clinical medicine. Despite much research and development, no vaccine for S. aureus has been approved.

In surface science, surface free energy quantifies the disruption of intermolecular bonds that occurs when a surface is created. In solid-state physics, surfaces must be intrinsically less energetically favorable than the bulk of the material, otherwise there would be a driving force for surfaces to be created, removing the bulk of the material. The surface energy may therefore be defined as the excess energy at the surface of a material compared to the bulk, or it is the work required to build an area of a particular surface. Another way to view the surface energy is to relate it to the work required to cut a bulk sample, creating two surfaces. There is "excess energy" as a result of the now-incomplete, unrealized bonding between the two created surfaces.

A slime layer in bacteria is an easily removable, unorganized layer of extracellular material that surrounds bacteria cells. Specifically, this consists mostly of exopolysaccharides, glycoproteins, and glycolipids. Therefore, the slime layer is considered as a subset of glycocalyx.

Biofouling or biological fouling is the accumulation of microorganisms, plants, algae, or small animals where it is not wanted on surfaces such as ship and submarine hulls, devices such as water inlets, pipework, grates, ponds, and rivers that cause degradation to the primary purpose of that item. Such accumulation is referred to as epibiosis when the host surface is another organism and the relationship is not parasitic. Since biofouling can occur almost anywhere water is present, biofouling poses risks to a wide variety of objects such as boat hulls and equipment, medical devices and membranes, as well as to entire industries, such as paper manufacturing, food processing, underwater construction, and desalination plants.

Wetting is the ability of a liquid to maintain contact with a solid surface, resulting from intermolecular interactions when the two are brought together. This happens in presence of a gaseous phase or another liquid phase not miscible with the first one. The degree of wetting (wettability) is determined by a force balance between adhesive and cohesive forces.

<span class="mw-page-title-main">Langmuir–Blodgett trough</span> Laboratory equipment

A Langmuir–Blodgett trough is a laboratory apparatus that is used to compress monolayers of molecules on the surface of a given subphase and measures surface phenomena due to this compression. It can also be used to deposit single or multiple monolayers on a solid substrate.

The contact angle is the angle, conventionally measured through the liquid, where a liquid–vapor interface meets a solid surface. It quantifies the wettability of a solid surface by a liquid via the Young equation. A given system of solid, liquid, and vapor at a given temperature and pressure has a unique equilibrium contact angle. However, in practice a dynamic phenomenon of contact angle hysteresis is often observed, ranging from the advancing (maximal) contact angle to the receding (minimal) contact angle. The equilibrium contact is within those values, and can be calculated from them. The equilibrium contact angle reflects the relative strength of the liquid, solid, and vapour molecular interaction.

Staphylococcus epidermidis is a Gram-positive bacterium, and one of over 40 species belonging to the genus Staphylococcus. It is part of the normal human microbiota, typically the skin microbiota, and less commonly the mucosal microbiota and also found in marine sponges. It is a facultative anaerobic bacteria. Although S. epidermidis is not usually pathogenic, patients with compromised immune systems are at risk of developing infection. These infections are generally hospital-acquired. S. epidermidis is a particular concern for people with catheters or other surgical implants because it is known to form biofilms that grow on these devices. Being part of the normal skin microbiota, S. epidermidis is a frequent contaminant of specimens sent to the diagnostic laboratory.

Lysostaphin is a Staphylococcus simulans metalloendopeptidase. It can function as a bacteriocin (antimicrobial) against Staphylococcus aureus.

Extracellular polymeric substances (EPSs) are natural polymers of high molecular weight secreted by microorganisms into their environment. EPSs establish the functional and structural integrity of biofilms, and are considered the fundamental component that determines the physicochemical properties of a biofilm. EPS in the matrix of biofilms provides compositional support and protection of microbial communities from the harsh environments. Components of EPS can be of different classes of polysaccharides, lipids, nucleic acids, proteins, Lipopolysaccharides, and minerals.

<span class="mw-page-title-main">Dispersin B</span>

Dispersin B is a 40 kDa glycoside hydrolase produced by the periodontal pathogen, Aggregatibacter actinomycetemcomitans. The bacteria secrete Dispersin B to release adherent cells from a mature biofilm colony by disrupting biofilm formation. The enzyme catalyzes the hydrolysis of linear polymers of N-acetyl-D-glucosamines found in the biofilm matrices. Poly-acetyl glucosamines are integral to the structural integrity of the biofilms of various Gram-positive bacteria and Gram-negative bacteria and are referred to as PIA (PNAG,PS/A) in Staphylococcus species and PGA in Escherichia coli. By degrading the biofilm matrix, Dispersin B allows for the release of bacterial cells that can adhere to new surfaces close by and extend the biofilm or start new colonies. Currently there is interest in Dispersin B as a commercial anti-biofilm agent that could be combined with antibiotics for the treatment of bacterial infections.

Polymers with the ability to kill or inhibit the growth of microorganisms such as bacteria, fungi, or viruses are classified as antimicrobial agents. This class of polymers consists of natural polymers with inherent antimicrobial activity and polymers modified to exhibit antimicrobial activity. Polymers are generally nonvolatile, chemically stable, and can be chemically and physically modified to display desired characteristics and antimicrobial activity. Antimicrobial polymers are a prime candidate for use in the food industry to prevent bacterial contamination and in water sanitation to inhibit the growth of microorganisms in drinking water.

Sharklet, manufactured by Sharklet Technologies, is a bio-inspired plastic sheet product structured to impede microorganism growth, particularly bacterial growth. It is marketed for use in hospitals and other places with a relatively high potential for bacteria to spread and cause infections. Coating surfaces with Sharklet work due to the nano-scale texture of the product's surface.

Adsorption is the adhesion of ions or molecules onto the surface of another phase. Adsorption may occur via physisorption and chemisorption. Ions and molecules can adsorb to many types of surfaces including polymer surfaces. A polymer is a large molecule composed of repeating subunits bound together by covalent bonds. The adsorption of ions and molecules to polymer surfaces plays a role in many applications including: biomedical, structural, coatings, environmental and petroleum.

An antimicrobial surface is coated by an antimicrobial agent that inhibits the ability of microorganisms to grow on the surface of a material. Such surfaces are becoming more widely investigated for possible use in various settings including clinics, industry, and even the home. The most common and most important use of antimicrobial coatings has been in the healthcare setting for sterilization of medical devices to prevent hospital associated infections, which have accounted for almost 100,000 deaths in the United States. In addition to medical devices, linens and clothing can provide a suitable environment for many bacteria, fungi, and viruses to grow when in contact with the human body which allows for the transmission of infectious disease.

Photolithography is a process in removing select portions of thin films used in microfabrication. Microfabrication is the production of parts on the micro- and nano- scale, typically on the surface of silicon wafers, for the production of integrated circuits, microelectromechanical systems (MEMS), solar cells, and other devices. Photolithography makes this process possible through the combined use of hexamethyldisilazane (HMDS), photoresist, spin coating, photomask, an exposure system and other various chemicals. By carefully manipulating these factors it is possible to create nearly any geometry microstructure on the surface of a silicon wafer. The chemical interaction between all the different components and the surface of the silicon wafer makes photolithography an interesting chemistry problem. Current engineering has been able to create features on the surface of silicon wafers between 1 and 100 μm.

The surface chemistry of paper is responsible for many important paper properties, such as gloss, waterproofing, and printability. Many components are used in the paper-making process that affect the surface.

Ultra-low fouling is a rating of a surface's ability to shed potential contamination. Surfaces are prone to contamination, which is a phenomenon known as fouling. Unwanted adsorbates caused by fouling change the properties of a surface, which is often counter-productive to the function of that surface. Consequently, a necessity for anti-fouling surfaces has arisen in many fields: blocked pipes inhibit factory productivity, biofouling increases fuel consumption on ships, medical devices must be kept sanitary, etc. Although chemical fouling inhibitors, metallic coatings, and cleaning processes can be used to reduce fouling, non-toxic surfaces with anti-fouling properties are ideal for fouling prevention. To be considered effective, an ultra-low fouling surface must be able to repel and withstand the accumulation of detrimental aggregates down to less than 5 ng/cm². A recent surge of research has been conducted to create these surfaces in order to benefit the biological, nautical, mechanical, and medical fields.

Antivirulence is the concept of blocking virulence factors. In regards to bacteria, the idea is to design agents that block virulence rather than kill bacteria en masse, as the current regime results in much more selective pressure.

References

↑ Donlan, Rodney (April 2001). "Biofilms and Device-Associated Infections". Emerging Infectious Diseases. 7 (2): 277–281. doi:10.3201/eid0702.010226. PMC 2631701 . PMID 11294723.
↑ Maki, Dennis; Tambyah, PA (April 2001). "Engineering out the Risk of Infection with Urinary Catheters". Emerging Infectious Diseases. 7 (2): 342–347. doi:10.3201/eid0702.010240. PMC 2631699 . PMID 11294737.
↑ Dror, Naama; Mandel, Mathilda; Hazan, Zadik; Lavie, Gad (14 April 2009). "Advances in Microbial Biofilm Prevention on Indwelling Medical Devices with Emphasis on Usage of Acoustic Energy". Sensors. 9 (4): 2538–2554. doi:10.3390/s90402538. PMC 3348827 . PMID 22574031.
↑ Antibacterial effects of Silver, Salt Lake Metals^{[ full citation needed ]}
↑ Vasilev, Krasimir; Cook, Jessica; Griesser, Hans J (September 2009). "Antibacterial surfaces for biomedical devices". Expert Review of Medical Devices. 6 (5): 553–567. doi:10.1586/erd.09.36. PMID 19751126. S2CID 27412917.
↑ Smeets, E.D.; Kooman, Jeroen; van der Sande, Frank; Stobberingh, Ellen; Frederik, Peter; Claessens, Piet; Grave, Willem; Schot, Arend; Leunissen, Karel (April 2003). "Prevention of biofilm formation in dialysis water treatment systems". Kidney International. 63 (4): 1574–1576. doi: 10.1046/j.1523-1755.2003.00888.x . PMID 12631375.
1 2 3 Jansen, B; Kohnen, W (October 1995). "Prevention of biofilm formation by polymer modification". Journal of Industrial Microbiology. 15 (4): 391–396. doi:10.1007/BF01569996. PMID 8605077. S2CID 1850834.
↑ Barnes, Ronald L., and D. Kevin Caskey. "Using Ozone in the Prevention of Bacterial Biofilm Forming and Scaling." Water Condition & Purification Magazine. 2002. Web. 20 May 2011. <http://www.prozoneint.com/pdf/biofilms.pdf>.
↑ Meiron, T.S.; Saguy, I.S. (November 2007). "Adhesion Modeling on Rough Low Linear Density Polyethylene". Journal of Food Science. 72 (9): E485–E491. doi:10.1111/j.1750-3841.2007.00523.x. PMID 18034717.
↑ Jass, Jana; Surman, Susanne; Walker, James (2 April 2003). Medical Biofilms: Detection, Prevention and Control. John Wiley & Sons. ISBN 978-0-471-98867-0.^{[ page needed ]}
↑ Hazan, Zadik; Zumeris, Jona; Jacob, Harold; Raskin, Hanan; Kratysh, Gera; Vishnia, Moshe; Dror, Naama; Barliya, Tilda; Mandel, Mathilda; Lavie, Gad (December 2006). "Effective Prevention of Microbial Biofilm Formation on Medical Devices by Low-Energy Surface Acoustic Waves". Antimicrobial Agents and Chemotherapy. 50 (12): 4144–4152. doi:10.1128/AAC.00418-06. PMC 1693972 . PMID 16940055.
↑ Yu, Miao; Chua, Song Lin (May 2020). "Demolishing the great wall of biofilms in Gram-negative bacteria: To disrupt or disperse?". Medicinal Research Reviews. 40 (3): 1103–1116. doi:10.1002/med.21647. hdl: 10397/88308 . PMID 31746489.
↑ Rabin, Nira; Zheng, Yue; Opoku-Temeng, Clement; Du, Yixuan; Bonsu, Eric; Sintim, Herman O (April 2015). "Agents that inhibit bacterial biofilm formation". Future Medicinal Chemistry. 7 (5): 647–671. doi:10.4155/fmc.15.7. PMID 25921403.
↑ Opperman, Timothy J.; Kwasny, Steven M.; Williams, John D.; Khan, Atiyya R.; Peet, Norton P.; Moir, Donald T.; Bowlin, Terry L. (October 2009). "Aryl Rhodanines Specifically Inhibit Staphylococcal and Enterococcal Biofilm Formation". Antimicrobial Agents and Chemotherapy. 53 (10): 4357–4367. doi:10.1128/AAC.00077-09. PMC 2764210 . PMID 19651903.
↑ Chung, Pooi Y.; Toh, Yien S. (1 April 2014). "Anti-biofilm agents: recent breakthrough against multi-drug resistant Staphylococcus aureus". Pathogens and Disease. 70 (3): 231–239. doi: 10.1111/2049-632X.12141 . PMID 24453168.
↑ Rabin, Nira; Zheng, Yue; Opoku-Temeng, Clement; Du, Yixuan; Bonsu, Eric; Sintim, Herman O (April 2015). "Agents that inhibit bacterial biofilm formation". Future Medicinal Chemistry. 7 (5): 647–671. doi:10.4155/fmc.15.7. PMID 25921403.
↑ Yu, Shan; Su, Tiantian; Wu, Huijun; Liu, Shiheng; Wang, Di; Zhao, Tianhu; Jin, Zengjun; Du, Wenbin; Zhu, Mei-Jun; Chua, Song Lin; Yang, Liang; Zhu, Deyu; Gu, Lichuan; Ma, Luyan Z. (December 2015). "PslG, a self-produced glycosyl hydrolase, triggers biofilm disassembly by disrupting exopolysaccharide matrix". Cell Research. 25 (12): 1352–1367. doi:10.1038/cr.2015.129. PMC 4670989 . PMID 26611635.

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.

[1] Donlan, Rodney (April 2001). "Biofilms and Device-Associated Infections". Emerging Infectious Diseases. 7 (2): 277–281. doi:10.3201/eid0702.010226. PMC 2631701 . PMID 11294723.

[2] Maki, Dennis; Tambyah, PA (April 2001). "Engineering out the Risk of Infection with Urinary Catheters". Emerging Infectious Diseases. 7 (2): 342–347. doi:10.3201/eid0702.010240. PMC 2631699 . PMID 11294737.

[3] Dror, Naama; Mandel, Mathilda; Hazan, Zadik; Lavie, Gad (14 April 2009). "Advances in Microbial Biofilm Prevention on Indwelling Medical Devices with Emphasis on Usage of Acoustic Energy". Sensors. 9 (4): 2538–2554. doi:10.3390/s90402538. PMC 3348827 . PMID 22574031.

[4] Antibacterial effects of Silver, Salt Lake Metals^{[ full citation needed ]}

[5] Vasilev, Krasimir; Cook, Jessica; Griesser, Hans J (September 2009). "Antibacterial surfaces for biomedical devices". Expert Review of Medical Devices. 6 (5): 553–567. doi:10.1586/erd.09.36. PMID 19751126. S2CID 27412917.

[6] Smeets, E.D.; Kooman, Jeroen; van der Sande, Frank; Stobberingh, Ellen; Frederik, Peter; Claessens, Piet; Grave, Willem; Schot, Arend; Leunissen, Karel (April 2003). "Prevention of biofilm formation in dialysis water treatment systems". Kidney International. 63 (4): 1574–1576. doi: 10.1046/j.1523-1755.2003.00888.x . PMID 12631375.

[Biofilm-7] 1 2 3 Jansen, B; Kohnen, W (October 1995). "Prevention of biofilm formation by polymer modification". Journal of Industrial Microbiology. 15 (4): 391–396. doi:10.1007/BF01569996. PMID 8605077. S2CID 1850834.

[8] Barnes, Ronald L., and D. Kevin Caskey. "Using Ozone in the Prevention of Bacterial Biofilm Forming and Scaling." Water Condition & Purification Magazine. 2002. Web. 20 May 2011. <http://www.prozoneint.com/pdf/biofilms.pdf>.

[9] Meiron, T.S.; Saguy, I.S. (November 2007). "Adhesion Modeling on Rough Low Linear Density Polyethylene". Journal of Food Science. 72 (9): E485–E491. doi:10.1111/j.1750-3841.2007.00523.x. PMID 18034717.

[10] Jass, Jana; Surman, Susanne; Walker, James (2 April 2003). Medical Biofilms: Detection, Prevention and Control. John Wiley & Sons. ISBN 978-0-471-98867-0.^{[ page needed ]}

[11] Hazan, Zadik; Zumeris, Jona; Jacob, Harold; Raskin, Hanan; Kratysh, Gera; Vishnia, Moshe; Dror, Naama; Barliya, Tilda; Mandel, Mathilda; Lavie, Gad (December 2006). "Effective Prevention of Microbial Biofilm Formation on Medical Devices by Low-Energy Surface Acoustic Waves". Antimicrobial Agents and Chemotherapy. 50 (12): 4144–4152. doi:10.1128/AAC.00418-06. PMC 1693972 . PMID 16940055.

[12] Yu, Miao; Chua, Song Lin (May 2020). "Demolishing the great wall of biofilms in Gram-negative bacteria: To disrupt or disperse?". Medicinal Research Reviews. 40 (3): 1103–1116. doi:10.1002/med.21647. hdl: 10397/88308 . PMID 31746489.

[13] Rabin, Nira; Zheng, Yue; Opoku-Temeng, Clement; Du, Yixuan; Bonsu, Eric; Sintim, Herman O (April 2015). "Agents that inhibit bacterial biofilm formation". Future Medicinal Chemistry. 7 (5): 647–671. doi:10.4155/fmc.15.7. PMID 25921403.

[14] Opperman, Timothy J.; Kwasny, Steven M.; Williams, John D.; Khan, Atiyya R.; Peet, Norton P.; Moir, Donald T.; Bowlin, Terry L. (October 2009). "Aryl Rhodanines Specifically Inhibit Staphylococcal and Enterococcal Biofilm Formation". Antimicrobial Agents and Chemotherapy. 53 (10): 4357–4367. doi:10.1128/AAC.00077-09. PMC 2764210 . PMID 19651903.

[15] Chung, Pooi Y.; Toh, Yien S. (1 April 2014). "Anti-biofilm agents: recent breakthrough against multi-drug resistant Staphylococcus aureus". Pathogens and Disease. 70 (3): 231–239. doi: 10.1111/2049-632X.12141 . PMID 24453168.

[16] Rabin, Nira; Zheng, Yue; Opoku-Temeng, Clement; Du, Yixuan; Bonsu, Eric; Sintim, Herman O (April 2015). "Agents that inhibit bacterial biofilm formation". Future Medicinal Chemistry. 7 (5): 647–671. doi:10.4155/fmc.15.7. PMID 25921403.

[17] Yu, Shan; Su, Tiantian; Wu, Huijun; Liu, Shiheng; Wang, Di; Zhao, Tianhu; Jin, Zengjun; Du, Wenbin; Zhu, Mei-Jun; Chua, Song Lin; Yang, Liang; Zhu, Deyu; Gu, Lichuan; Ma, Luyan Z. (December 2015). "PslG, a self-produced glycosyl hydrolase, triggers biofilm disassembly by disrupting exopolysaccharide matrix". Cell Research. 25 (12): 1352–1367. doi:10.1038/cr.2015.129. PMC 4670989 . PMID 26611635.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]