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Biomedical subjects

Henk J Busscher

Publications and source records attributed to Henk J Busscher.

At least 19 recordsLinked to original sources

Transfer of bacteria between biomaterials surfaces in the operating room--an experimental study.

Bacterial adhesion to and transfer between surfaces is a complicated process. With regard to the success of biomaterials implants, studies on bacterial adhesion and transfer should not be confined to biomaterials surfaces in the human body, but also encompass surfaces in the operating room, where the origin of many biomaterials related infections is found. The purpose of this study was to quantify the transfer of Staphylococcus aureus, Staphylococcus epidermidis, and Propionibacterium acnes from one operating room material to another, while accounting for surface hydrophobicity and roughness, moistness and application of friction during transfer. The tested operating room materials were gloves, broaches (orthopaedic drills), theatre gowns, and light handles. As a possible clinical intervention method to prevent transfer, it was investigated whether dipping the gloves in a chlorhexidine splash-basin affected the viability of the transferred bacteria. Transfer (moist and without friction) was demonstrated to some extent with all bacterial strains and with every material, ranging from 17% to 71%, and was influenced by the bacterial strain, moistness of the inoculum, the application of friction, and the characteristics of both the donating and the receiving surface. Dipping the glove material in 4% or 0.4% chlorhexidine solutions killed all bacteria present, regardless of whether surfaces were dried or moist and thus prevented transfer.

Bacteria↗

Biofilm formation on surface characterized micro-implants for skeletal anchorage in orthodontics.

Micro-implants are increasingly popular in clinical orthodontics to effect skeletal anchorage. However, biofilm formation on their surfaces and subsequent infection of peri-implant tissues can result in either exfoliation or surgical removal of these devices. The present study aimed to assess biofilm formation on five commercially available, surface characterized micro-implant systems in vitro. The elemental surface compositions of as-received and autoclave-sterilized micro-implants were characterized by X-ray photoelectron spectroscopy. High carbon contamination was detected on the oxide surfaces, along with traces of inorganic elements (Ca, Cu, Cr, Pb, Zn, and P) which disappeared after Ar(+) ion sputtering. The mean surface roughnesses (R(a)) were around 182nm for titanium micro-implants, and 69nm for stainless steel micro-implants, as measured by atomic force microscopy. Scanning electron microscopy revealed different surface topographies between manufacturers, varying from typical machined grooves to structural defects like pores and pits. Overnight biofilms were grown on micro-implant surfaces by immersion in pooled human whole saliva. Biofilms on micro-implants treated with chlorhexidine and fluoride mouthrinses contained comparable numbers of viable organisms, but significantly less than did untreated micro-implants. Comparison of different implant systems using multiple linear regression analysis indicated that biofilm formation was governed by roughness of the implant surface and the prevalence of carbon- and oxygen-rich components.

Argon↗

Efficacy and mechanisms of non-antibacterial, chemical plaque control by dentifrices--an in vitro study.

OBJECTIVES: The provision of antiplaque benefits to dentifrices assists patients in improving hygiene and reducing susceptibility to gingivitis and caries. Chemical plaque control involves different mechanisms and is mostly associated with antibacterial effects, but also includes effects on pellicle surface chemistry to improve cleansing or discourage renewed plaque formation. It is the aim of this paper to analyze in vitro detachment of co-aggregating oral actinomyces and streptococci from pellicle surfaces by dentifrice supernates and to study subsequent de novo streptococcal deposition. METHODS: Detachment by dentifrices of a co-adhering bacterial pair was studied in the parallel plate flow chamber on a 16 h pellicle coated surface. After detachment by perfusing the chamber with a dentifrice, re-deposition was initiated by flowing with a fresh streptococcal suspension. The dentifrices included both a regular, SLS-fluoride based formulation as well a pyrophosphate, anticalculus and antimicrobial formulations. RESULTS: All dentifrice supernates containing SLS were effective in detaching co-adhering bacteria from pellicles surfaces, except in combination with SnF(2). When hexametaphosphate was added immediate detachment was relatively low, but continued even during re-deposition. The re-deposition of streptococci after detachment by other, NaF containing dentifrices involved relatively few large aggregates, presumably because fluoride was able to block bi-dentate calcium binding sites on the bacterial cell surfaces, mediating co-adhesion. When pyrophosphate was present in addition to NaF, re-deposition involved significantly more large aggregates, likely because pyrophosphate served as a bi-dentate bridge between calcium bound on the bacterial cell surfaces. CONCLUSION: Commercially available dentifrice formulations differ in their ability to stimulate bacterial detachment from pellicles and dependent on their composition yield the formation of large co-adhering aggregates of actinomyces and streptococci in de novo deposition.

Actinomyces↗

Removal of two waterborne pathogenic bacterial strains by activated carbon particles prior to and after charge modification.

Waterborne diseases constitute a threat to public health despite costly treatment measures aimed at removing pathogenic microorganisms from potable water supplies. This paper compared the removal of Raoultella terrigena ATCC 33257 and Escherichia coli ATCC 25922 by negatively and positively charged types of activated carbon particles. Both strains display bimodal negative zeta-potential distributions in stabilized water. Carbon particles were suspended to an equivalent external geometric surface area of 700 cm2 in 250 mL of a bacterial suspension, with shaking. Samples were taken after different durations for plate counting. Initial removal rates were less elevated for the positively charged carbon particle than expected, yielding the conclusion that bacterial adhesion under shaking is mass-transport limited. After 360 min, however, the log-reduction of the more negatively charged R. terrigena in suspension was largest for the positively charged carbon particles as compared with the negatively charged ones, although conditioning in ultrapure or tap water of positively charged carbon particles for 21 days eliminated the favorable effect of the positive charge due to counterion adsorption from the water. Removal of the less negatively charged E. coli was less affected by aging of the (positively charged) carbon particles, confirming the role of electrostatic interactions in bacterial removal by activated carbon particles. The microporous, negatively charged coconut carbon performed less than the mesoporous, positively charged carbon particle prior to conditioning but did not suffer from loss of effect after conditioning in ultrapure or tap water.

Bacteria↗

Calorimetric comparison of the interactions between salivary proteins and Streptococcus mutans with and without antigen I/II.

Antigen I/II can be found on streptococcal cell surfaces and is involved in their interaction with salivary proteins. In this paper, we determine the adsorption enthalpies of salivary proteins to Streptococcus mutans LT11 and S. mutans IB03987 with and without antigen I/II, respectively, using isothermal titration calorimetry. In addition, protein adsorption to the cell surfaces was determined spectrophotometrically. S. mutans LT11 with antigen I/II, yielded a much higher, exothermic adsorption enthalpy at pH 6.8 (ranging from -2073 x 10(-9) to -31707 x 10(-9) microJ per bacterium) when mixed with saliva than did S. mutans IB03987 (-165 x 10(-9) to -1107 x 10(-9) microJ per bacterium) at all bacterial concentrations studied (5 x 10(9), 5 x 10(8), and 5 x 10(7) ml(-1)), largest effects per bacterium being observed for the lowest concentration. However, the enthalpy of salivary protein adsorption to S. mutans LT11 became smaller at pH 5.8. Adsorption isotherms for the S. mutans LT11 showed considerable protein adsorption at pH 6.8 (1.2 - 2.1 mg/m(2)), that decreased only slightly at pH 5.8 (1.1 - 1.6 mg/m(2)), with the largest amount adsorbed at the lowest bacterial concentration. This suggests that the protein(s) in the saliva with the strongest affinity for antigen I/II is (are) readily depleted from saliva. In conclusion, antigen I/II surface proteins on S. mutans play a determinant role in adsorption of salivary proteins through the creation of enthalpically favorable adsorption sites.

Antigens, Bacterial↗

The combination of ultrasound with antibiotics released from bone cement decreases the viability of planktonic and biofilm bacteria: an in vitro study with clinical strains.

OBJECTIVES: Antibiotic-loaded bone cements are used for the permanent fixation of joint prostheses. Antibiotic-loaded cements significantly decrease the incidence of infection. The objective of this study was to investigate whether the viability of bacteria derived from patients with a prosthesis-related infection could be further decreased when antibiotic release from bone cements was combined with application of pulsed ultrasound. METHODS: Escherichia coli ATCC 10798, Staphylococcus aureus 7323, coagulase-negative staphylococci (CoNS 7368 and CoNS 7391) and Pseudomonas aeruginosa 5148 were grown planktonically in suspension and as a biofilm on three different bone cements: Palacos R without gentamicin as control, gentamicin-loaded Palacos R-G and gentamicin/clindamycin-loaded Copal. The viability of planktonic and biofilm bacteria was measured in the absence and presence of pulsed ultrasound for 40 h. RESULTS: Ultrasound itself did not affect bacterial viability. However, application of pulsed ultrasound in combination with antibiotic release by antibiotic-loaded bone cements yielded a reduction of both planktonic and biofilm bacterial viability compared with antibiotic release without application of ultrasound. CONCLUSIONS: This study shows that antibiotic release in combination with ultrasound increases the antimicrobial efficacy further than antibiotic release alone against a variety of clinical isolates. Application of ultrasound in combination with antibiotic release in clinical practice could therefore lead to better prevention or treatment of prosthesis-related infections.

Anti-Bacterial Agents↗

Development of an accommodating intra-ocular lens--in vitro prevention of re-growth of pig and rabbit lens capsule epithelial cells.

Cataract surgery is routinely performed to replace the clouded lens by a rigid polymeric intra-ocular lens unable to accommodate. By implanting a silicone gel into an intact capsular bag the accommodating properties of the natural lens can be maintained or enhanced. The implantation success of accommodating lenses is hampered by the occurrence of capsular opacification (PCO) due to lens epithelial cell (LEC) growth. In order to prevent LEC proliferation, a treatment regime using actinomycin D, cycloheximide and water was developed. The effectiveness of treatment was analyzed using an in vitro, MTT-based cell culture system and an ex vivo pig eye model in which the implanted lens-in-the-bag is cultured as a whole. LEC were exposed to treatment solutions for 5 min, then the cells were allowed to recover and to re-colonize the substratum. MTT conversion by cells was transiently inhibited by cycloheximide dissolved in water and by water alone. Exposure to actinomycin D resulted in a lasting inhibition of MTT conversion and consequently cell proliferation. These in vitro data could not be fully reproduced in the ex vivo pig eye model due to essential differences between both models. Treatment with actinomycin D containing solutions, however, resulted in a nearly complete absence of cells on the capsular wall. The pig eye model is a promising approach to further evaluate the effects of peri-surgical treatment during the accommodating intra-ocular lens implantation.

Animals↗

Resistance to a polyquaternium-1 lens care solution and isoelectric points of Pseudomonas aeruginosa strains.

OBJECTIVES: The aim of this study was to correlate the cell surface hydrophobicity and charge of various strains of Pseudomonas aeruginosa with their resistance to a polyquaternium-1 lens care solution. METHODS: The 11 P. aeruginosa strains included were isolated from eyes, contact lenses, lens cases and lens care solutions. Cell surface hydrophobicities were determined from water contact angle measurements and surface charges were measured as a function of pH using particulate micro-electrophoresis. RESULTS: Strains resistant to polyquaternium-1 had an isoelectric point (IEP; pH where the bacterial zeta potential is zero) ranging from 4.0 to 5.5, whereas susceptible strains were more negatively charged than resistant strains and had an IEP between 1.3 and 1.9. Water contact angles ranged from hydrophilic (34 degrees) to hydrophobic (124 degrees), without showing a relation with antimicrobial resistance. CONCLUSIONS: Results suggest that electrostatic repulsion between cationic molecules on the cell surface and quaternary ammonium compounds impedes the antimicrobial entering the cell.

Contact Lens Solutions↗

Multivariate analysis of surface physico-chemical properties controlling biofilm formation on orthodontic adhesives prior to and after fluoride and chlorhexidine treatment.

Biofilm formation on orthodontic adhesives is a serious clinical problem, as it leads to enamel demineralization around fixed orthodontic appliances, often leaving white spot lesions after their removal. The aim of this work was to determine the influence of surface physico-chemical properties of four commonly used orthodontic adhesives (Concise, Fuji ORTHO LC, Ketac Cem mu, and Transbond XT) on early bacterial biofilm formation. In addition, effects of two commercially available mouthrinses (0.05% sodium fluoride and 0.2% chlorhexidine gluconate) on these properties and biofilm formation were determined. Water contact angles on the adhesives decreased after fluoride and chlorhexidine treatment, concurrent with an increase in carbon and a decrease in oxygen surface concentrations, except for Transbond, as determined by X-ray photoelectron spectroscopy. No fluorine was detected on any of the adhesive surfaces after fluoride treatment, while all surfaces showed chlorine after chlorhexidine treatment. Surface roughness of the adhesives measured using three-dimensional optical profilometry was around 4 microm and found not to be a factor governing early biofilm formation. Multiple linear regression analysis indicated that early biofilm formation by Streptococcus sanguis could be explained in a model comprising hydrophobicity and the prevalence of oxygen- and nitrogen-rich components on the adhesive surfaces.

Bacterial Adhesion↗

Biomechanical and surface physico-chemical analyses of used osteosynthesis plates and screws--potential for reuse in developing countries?

Reprocessing of single-use devices is an upcoming issue in the Western world, but has been for many years in developing countries. In developing countries, the number of bone fractures due to traffic or industrial accidents is high. Patients often need an osteosynthesis with plates and screws, but most patients, however, cannot afford this because of the costs involved and have to rely on the application of used plates and screws. This study aims to determine whether used plates can be safely reused in another patient from a biomechanical, surface physico-chemical, and biological point-of-view. Osteosynthesis plates weakened in a predictable way during use, regardless of the history, presumably because tests were conducted under extreme conditions in the absence of clinically applied load-sharing between bone and plate. Surface physico-chemical analyses indicated that used plates and screws were more hydrophilic than new ones; had increased amounts of calcium-phosphates at their surfaces; and possessed higher number of scratches. Pitting corrosion could be seen on SEM micrographs. Simple cleaning methods, as available in developing countries, including toothbrush, water, detergent and bleach yielded elemental surface compositions, and hydrophobicities similar to those of new ones, while biologically thus cleaned screws were not cytotoxic according to ISO-10993-5 and endotoxin release according to USP-27-NF-22 was within the requirements of the FDA. It is concluded that the reuse of osteosynthesis plates and screws is not necessarily unsafe, although preferably a register should be kept of all previous users to limit the number of reuses as mechanical weakening does occur.

Adolescent↗

Antimicrobial efficacy of gentamicin-loaded acrylic bone cements with fusidic acid or clindamycin added.

The increasing gentamicin resistance among bacteria in septic joint arthroplasty has stimulated interest in adding a second antibiotic into gentamicin-loaded bone cement. A first aim of this in vitro study is to investigate whether addition of fusidic acid or clindamycin to gentamicin-loaded bone cement has an additional antimicrobial effect against a collection of 38 clinical isolates, including 16 gentamicin-resistant strains. A modified Kirby-Bauer test, involving measurement of the inhibition zone around antibiotic-loaded bone cement discs on agar plates, was used to investigate whether adding a second antibiotic has an additional antimicrobial effect. Second, a selected number of strains was used to study their survival in an interfacial gap made in the different bone cements to mimic the gap between bone and cement as existing near a prosthesis. Gentamicin-loaded bone cement had an antimicrobial activity against 58% of the 38 bacterial strains included in this study, while 68% of the strains were affected by bone cement loaded with a combination of gentamicin and clindamycin. Bone cement loaded with the combination of gentamicin and fusidic acid had antimicrobial activity against 87% of the bacterial strains. In the prosthesis-related gap model, there was a clear trend toward less bacterial survival for gentamicin-loaded bone cement after adding clindamycin or fusidic acid. Addition of clindamycin or fusidic acid into gentamicin-loaded bone cement yields an additional antimicrobial effect. The combination gentamicin and fusidic acid was effective against a higher number of clinical isolates than the combination of gentamicin with clindamycin, including gentamicin-resistant strains.

Anti-Bacterial Agents↗

Intraoperative contamination influences wound discharge and periprosthetic infection.

Intraoperative bacterial contamination increases risk for postoperative wound-healing problems and periprosthetic infection, but to what extent remains unclear. We asked whether bacterial contamination of the instruments and bone during primary prosthesis insertion was associated with prolonged wound discharge and subsequent periprosthetic infection. During 100 total hip arthroplasties, four intraoperative cultures were taken from the instruments and two portions of removed bone. Postoperatively, the duration of wound discharge was monitored, with Day 5 as the cut-off point. All patients were followed for 2 years to determine whether periprosthetic infection occurred. Bacterial contamination occurred in 36 operative procedures (36%). We found an association between intraoperative contamination and prolonged wound discharge, with a relative risk of 2.5. The culturing of removed bone had a positive predictive value of 81% to 90%. Other factors associated with prolonged wound discharge were rheumatoid arthritis (relative risk, 6.4), use of cement (relative risk, 1.6), and increased blood loss (relative risk, 1.5).

Adult↗

Influence of day and night wear on surface properties of silicone hydrogel contact lenses and bacterial adhesion.

PURPOSE: The aim of this study was to determine the effect of continuous wear on physicochemical surface properties of silicone hydrogel (S-H) lenses and their susceptibility to bacterial adhesion. METHODS: In this study, volunteers wore 2 pairs of either "lotrafilcon A" or "balafilcon A" S-H contact lenses. The first pair was worn continuously for a week and the second pair for 4 weeks. One lens of each pair was used for surface characterization and the other one for bacterial adhesion experiments. Lens surfaces were characterized by examination of their wettability, roughness, elemental composition, and proteins attached to their surfaces. Adhesion of Staphylococcus aureus 835 and Pseudomonas aeruginosa #3 to a lens was studied using a parallel plate flow chamber. RESULTS: Before use, the lotrafilcon A lens was rougher than the balafilcon A lens and had a lower water contact angle and a higher affinity for S. aureus 835. After wear, both lens types had similar water contact angles, whereas the differences in elemental surface composition decreased as well. S. aureus 835 adhered in higher numbers to worn balafilcon A lenses, whereas the opposite was seen for P. aeruginosa #3. The initial deposition rates of both bacterial strains to lotrafilcon A lenses decreased by wearing and were found to correlate significant (P < 0.001) with the surface roughness of worn lenses. CONCLUSIONS: In this study, the differences in surface properties between 2 types of S-H lenses were found to change after 1 week of continuous wear. Generally, bacteria adhered in lower numbers and less tenaciously to worn lenses, except S. aureus 835, adhering in higher numbers to worn balafilcon A lenses.

Bacterial Adhesion↗

Enterococcus faecalis strains show culture heterogeneity in cell surface charge.

Adhesion of micro-organisms to biotic and abiotic surfaces is an important virulence factor and involves different types of interactions. Enterococcus faecalis, a human commensal and an important opportunistic pathogen, has the ability to adhere to surfaces. Biliary stents frequently become clogged with bacterial biofilms, with E. faecalis as one of the predominant species. Six E. faecalis strains isolated from clogged biliary stents were investigated for the presence of specific biochemical factors involved in their adhesion: aggregation substances (Aggs) and the enterococcal surface protein (encoded by the esp gene). In addition, physico-chemical factors involved in adhesion (zeta potential and cell surface hydrophobicity) were determined, as well as the influence of ox bile on these properties. Two-thirds of the biliary stent isolates displayed culture heterogeneity in the pH dependence of their zeta potentials. Moreover, 24 out of 46 clinical isolates of E. faecalis, including 11 laboratory strains, also displayed such heterogeneity. The culture heterogeneity was demonstrated to be a stable trait, not caused by quorum sensing, not plasmid mediated, and independent of the presence of esp and Agg. Data presented show that culture heterogeneity in zeta potential enhances adhesion to an abiotic surface. A higher prevalence of culture heterogeneity in zeta potential in pathogenic as compared to non-pathogenic isolates could indicate that this phenomenon might play a role in virulence and putatively in pathogenesis.

Animals↗

Bacterial factors influencing adhesion of Pseudomonas aeruginosa strains to a poly(ethylene oxide) brush.

Most bacterial strains adhere poorly to poly(ethylene oxide) (PEO)-brush coatings, with the exception of a Pseudomonas aeruginosa strain. The aim of this study was to find factors determining whether P. aeruginosa strains do or do not adhere to a PEO-brush coating in a parallel plate flow chamber. On the basis of their adhesion, a distinction could be made between three adhesive and three non-adhesive strains of P. aeruginosa, while bacterial motilities and zeta potentials were comparable for all six strains. However, water contact angles indicated that the adhesive strains were much more hydrophobic than the non-adhesive strains. Furthermore, only adhesive strains released surfactive extracellular substances, which may be engaged in attractive interactions with the PEO chains. Atomic force microscopy showed that the adhesion energy, measured from the retract curves of a bacterial-coated cantilever from a brush coating, was significantly more negative for adhesive strains than for non-adhesive strains (P<0.001). Through surface thermodynamic and extended-DLVO (Derjaguin, Landau, Verwey, Overbeek) analyses, these stronger adhesion energies could be attributed to acid-base interactions. However, the energies of adhesion of all strains to a brush coating were small when compared with their energies of adhesion to a glass surface. Accordingly, even the adhesive P. aeruginosa strains could be easily removed from a PEO-brush coating by the passage of a liquid-air interface. In conclusion, cell surface hydrophobicity and surfactant release are the main factors involved in adhesion of P. aeruginosa strains to PEO-brush coatings.

Bacterial Adhesion↗

Effects of quaternary ammonium silane coatings on mixed fungal and bacterial biofilms on tracheoesophageal shunt prostheses.

Two quaternary ammonium silanes (QAS) were used to coat silicone rubber tracheoesophageal shunt prostheses, yielding a positively charged surface. One QAS coating [(trimethoxysilyl)-propyldimethyloctadecylammonium chloride] was applied through chemical bonding, while the other coating, Biocidal ZF, was sprayed onto the silicone rubber surface. The sprayed coating lost its stability within an hour, while the chemically bonded coating appeared stable. Upon incubation in an artificial throat model, allowing simultaneous adhesion and growth of yeast and bacteria, all coated prostheses showed significant reductions in the numbers of viable yeast (to 12% to 16%) and bacteria (to 27% to 36%) compared with those for silicone rubber controls, as confirmed using confocal laser scanning microscopy after live/dead staining of the biofilms. In situ hybridization with fluorescently labeled oligonucleotide probes showed that yeasts expressed hyphae on the untreated and Biocidal ZF-coated prostheses but not on the QAS-coated prostheses. Whether this is a result of the positive QAS coating or is due to the reduced number of bacteria is currently unknown. In summary, this is the first report on the inhibitory effects of positively charged coatings on the viability of yeasts and bacteria in mixed biofilms. Although the study initially aimed at reducing voice prosthetic biofilms, its relevance extends to all biomedical and environmental surfaces where mixed biofilms develop and present a problem.

Anti-Bacterial Agents↗

Microbial adhesion in flow displacement systems.

Flow displacement systems are superior to many other (static) systems for studying microbial adhesion to surfaces because mass transport and prevailing shear conditions can be adequately controlled and notoriously ill-defined slight rinsing steps to remove so-called "loosely adhering organisms" can be avoided. In this review, we present the basic background required to calculate mass transport and shear rates in flow displacement systems, focusing on the parallel plate flow chamber as an example. Critical features in the design of flow displacement systems are discussed, as well as different strategies for data analysis. Finally, selected examples of working with flow displacement systems are given for diverse biomedical applications.

Bacteria↗

Influence of culture heterogeneity in cell surface charge on adhesion and biofilm formation by Enterococcus faecalis.

Biofilm formation is an increasing problem in medicine, due to the intrinsic resistance of microorganisms in the biofilm mode of growth against the host immune system and antimicrobial therapy. Adhesion is an important step in biofilm formation, influenced, among other factors, by the surface hydrophobicities and charges of both the substratum and the adhering microorganisms. Enterococcus faecalis strains generally display subpopulations with different surface charges, expressed as bimodal zeta potential distributions. Two-thirds of E. faecalis strains isolated from clogged biliary stents displayed such heterogeneity of surface charges in culture. In this study, the influence of this culture heterogeneity on initial adhesion and subsequent biofilm formation was investigated. Heterogeneous strains were retained in higher numbers on polystyrene than homogeneous strains. Also, biofilm formation was much more pronounced for heterogeneous strains than for homogeneous strains. In a population enriched to display only one subpopulation, fewer bacteria were retained than in its original heterogeneous culture. Also, the enriched subpopulation formed less biofilm than its original heterogeneous culture. The presence of ox bile during adhesion resulted in fewer retained bacteria, although heterogeneous strains were still retained in significantly higher numbers than were homogeneous strains, and, in general, the presence of ox bile reduced biofilm formation. The initial adhesion and biofilm formation were independent of the presence of the gene encoding the enterococcal surface protein (esp) or the expression of gelatinase (GelE). It is concluded that heterogeneity in cell surface charge represents an advantage for bacteria in the colonization of surfaces.

Bacterial Adhesion↗