Bacterial Biofilm Inhibition: A Focused Review on Recent Therapeutic Strategies for Combating the Biofilm Mediated Infections

Biofilm formation is a major concern in various sectors and cause severe problems to public health, medicine, and industry. Bacterial biofilm formation is a major persistent threat, as it increases morbidity and mortality, thereby imposing heavy economic pressure on the healthcare sector. Bacterial biofilms also strengthen biofouling, affecting shipping functions, and the offshore industries in their natural environment. Besides, they accomplish harsh roles in the corrosion of pipelines in industries. At biofilm state, bacterial pathogens are significantly resistant to external attack like antibiotics, chemicals, disinfectants, etc. Within a cell, they are insensitive to drugs and host immune responses. The development of intact biofilms is very critical for the spreading and persistence of bacterial infections in the host. Further, bacteria form biofilms on every probable substratum, and their infections have been found in plants, livestock, and humans. The advent of novel strategies for treating and preventing biofilm formation has gained a great deal of attention. To prevent the development of resistant mutants, a feasible technique that may target adhesive properties without affecting the bacterial vitality is needed. This stimulated research is a rapidly growing field for applicable control measures to prevent biofilm formation. Therefore, this review discusses the current understanding of antibiotic resistance mechanisms in bacterial biofilm and intensely emphasized the novel therapeutic strategies for combating biofilm mediated infections. The forthcoming experimental studies will focus on these recent therapeutic strategies that may lead to the development of effective biofilm inhibitors than conventional treatments.

Download Full-text

Antibiotics Application Strategies to Control Biofilm Formation in Pathogenic Bacteria

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666191112155905 ◽

2020 ◽

Vol 21 (4) ◽

pp. 270-286 ◽

Cited By ~ 2

Author(s):

Fazlurrahman Khan ◽

Dung T.N. Pham ◽

Sandra F. Oloketuyi ◽

Young-Mog Kim

Keyword(s):

Biofilm Formation ◽

Pathogenic Bacteria ◽

Extracellular Polymeric Substances ◽

Quorum Quenching ◽

Resistance Mechanisms ◽

Bacterial Biofilm ◽

Bacterial Cells ◽

High Concentration ◽

Biofilm Inhibition ◽

Abiotic Surfaces

Background: The establishment of a biofilm by most pathogenic bacteria has been known as one of the resistance mechanisms against antibiotics. A biofilm is a structural component where the bacterial community adheres to the biotic or abiotic surfaces by the help of Extracellular Polymeric Substances (EPS) produced by bacterial cells. The biofilm matrix possesses the ability to resist several adverse environmental factors, including the effect of antibiotics. Therefore, the resistance of bacterial biofilm-forming cells could be increased up to 1000 times than the planktonic cells, hence requiring a significantly high concentration of antibiotics for treatment. Methods: Up to the present, several methodologies employing antibiotics as an anti-biofilm, antivirulence or quorum quenching agent have been developed for biofilm inhibition and eradication of a pre-formed mature biofilm. Results: Among the anti-biofilm strategies being tested, the sub-minimal inhibitory concentration of several antibiotics either alone or in combination has been shown to inhibit biofilm formation and down-regulate the production of virulence factors. The combinatorial strategies include (1) combination of multiple antibiotics, (2) combination of antibiotics with non-antibiotic agents and (3) loading of antibiotics onto a carrier. Conclusion: The present review paper describes the role of several antibiotics as biofilm inhibitors and also the alternative strategies adopted for applications in eradicating and inhibiting the formation of biofilm by pathogenic bacteria.

Download Full-text

Superhydrophobic Nanocoatings as Intervention against Biofilm-Associated Bacterial Infections

Nanomaterials ◽

10.3390/nano11041046 ◽

2021 ◽

Vol 11 (4) ◽

pp. 1046

Author(s):

Yinghan Chan ◽

Xun Hui Wu ◽

Buong Woei Chieng ◽

Nor Azowa Ibrahim ◽

Yoon Yee Then

Keyword(s):

Biofilm Formation ◽

Bacterial Infections ◽

Therapeutic Strategies ◽

Public Healthcare ◽

Persistent Infections ◽

Promising Strategy ◽

Antimicrobial Interventions ◽

Novel Therapeutic Strategies ◽

Insight Into ◽

Microbial Attachment

Biofilm formation represents a significant cause of concern as it has been associated with increased morbidity and mortality, thereby imposing a huge burden on public healthcare system throughout the world. As biofilms are usually resistant to various conventional antimicrobial interventions, they may result in severe and persistent infections, which necessitates the development of novel therapeutic strategies to combat biofilm-based infections. Physicochemical modification of the biomaterials utilized in medical devices to mitigate initial microbial attachment has been proposed as a promising strategy in combating polymicrobial infections, as the adhesion of microorganisms is typically the first step for the formation of biofilms. For instance, superhydrophobic surfaces have been shown to possess substantial anti-biofilm properties attributed to the presence of nanostructures. In this article, we provide an insight into the mechanisms underlying biofilm formation and their composition, as well as the applications of nanomaterials as superhydrophobic nanocoatings for the development of novel anti-biofilm therapies.

Download Full-text

Blocking of Bacterial Biofilm Formation by a Fish Protein Coating

Applied and Environmental Microbiology ◽

10.1128/aem.00279-08 ◽

2008 ◽

Vol 74 (11) ◽

pp. 3551-3558 ◽

Cited By ~ 16

Author(s):

Rebecca Munk Vejborg ◽

Per Klemm

Keyword(s):

Biofilm Formation ◽

Fish Muscle ◽

Physicochemical Characteristics ◽

Economic Problem ◽

Bacterial Attachment ◽

Bacterial Biofilm ◽

Adhesive Properties ◽

Muscle Extract ◽

Wide Range ◽

Inert Surfaces

ABSTRACT Bacterial biofilm formation on inert surfaces is a significant health and economic problem in a wide range of environmental, industrial, and medical areas. Bacterial adhesion is generally a prerequisite for this colonization process and, thus, represents an attractive target for the development of biofilm-preventive measures. We have previously found that the preconditioning of several different inert materials with an aqueous fish muscle extract, composed primarily of fish muscle α-tropomyosin, significantly discourages bacterial attachment and adhesion to these surfaces. Here, this proteinaceous coating is characterized with regards to its biofilm-reducing properties by using a range of urinary tract infectious isolates with various pathogenic and adhesive properties. The antiadhesive coating significantly reduced or delayed biofilm formation by all these isolates under every condition examined. The biofilm-reducing activity did, however, vary depending on the substratum physicochemical characteristics and the environmental conditions studied. These data illustrate the importance of protein conditioning layers with respect to bacterial biofilm formation and suggest that antiadhesive proteins may offer an attractive measure for reducing or delaying biofilm-associated infections.

Download Full-text

Antimicrobial Synergy of Silver-Platinum Nanohybrids With Antibiotics

Frontiers in Microbiology ◽

10.3389/fmicb.2020.610968 ◽

2021 ◽

Vol 11 ◽

Author(s):

Bansi Ranpariya ◽

Gayatri Salunke ◽

Srikanta Karmakar ◽

Kaushik Babiya ◽

Santosh Sutar ◽

...

Keyword(s):

Biofilm Formation ◽

Bacterial Infections ◽

Bacterial Biofilm ◽

Antimicrobial Drugs ◽

Mortality And Morbidity ◽

Green Route ◽

Antimicrobial Synergy ◽

First Time ◽

Tuber Extract ◽

Powerful Strategy

Various bacterial pathogens are responsible for nosocomial infections resulting in critical pathophysiological conditions, mortality, and morbidity. Most of the bacterial infections are associated with biofilm formation, which is resistant to the available antimicrobial drugs. As a result, novel bactericidal agents need to be fabricated, which can effectively combat the biofilm-associated bacterial infections. Herein, for the first time we report the antimicrobial and antibiofilm properties of silver-platinum nanohybrids (AgPtNHs), silver nanoparticles (AgNPs), and platinum nanoparticles (PtNPs) against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The AgPtNHs were synthesized by a green route using Dioscorea bulbifera tuber extract at 100°C for 5 h. The AgPtNHs ranged in size from 20 to 80 nm, with an average of ∼59 nm. AgNPs, PtNPs, and AgPtNHs showed a zeta potential of −14.46, −1.09, and −11.39 mV, respectively. High antimicrobial activity was observed against P. aeruginosa and S. aureus and AgPtNHs exhibited potent antimicrobial synergy in combination with antibiotics such as streptomycin, rifampicin, chloramphenicol, novobiocin, and ampicillin up to variable degrees. Interestingly, AgPtNHs could inhibit bacterial biofilm formation significantly. Hence, co-administration of AgPtNHs and antibiotics may serve as a powerful strategy to treat bacterial infections.

Download Full-text

Effects of vancomycin, daptomycin, and tigecycline on coagulase-negative staphylococcus biofilm and bacterial viability within biofilm: an in vitro biofilm model

Canadian Journal of Microbiology ◽

10.1139/cjm-2015-0855 ◽

2016 ◽

Vol 62 (9) ◽

pp. 735-743 ◽

Cited By ~ 5

Author(s):

Barcin Ozturk ◽

Necati Gunay ◽

Bulent M. Ertugrul ◽

Serhan Sakarya

Keyword(s):

Biofilm Formation ◽

Treatment Time ◽

Antimicrobial Effect ◽

Bacterial Biofilm ◽

Coagulase Negative Staphylococcus ◽

Biofilm Inhibition ◽

Major Barrier ◽

Biofilm Model ◽

Repeated Doses

Bacteria may hide in a hydrated polysaccharide matrix known as a biofilm. The structure of the bacterial biofilm renders phagocytosis difficult and increases antibiotic resistance. We hypothesized that repeated doses of antibiotics have an effect on bacteria within the biofilm and that it could inhibit or eradicate biofilm formation. Two clinical biofilm-positive coagulase-negative staphylococcus isolates were evaluated. The effects of antibiotics on preformed and nascent biofilm and on bacterial eradication within the biofilm were determined using different doses of vancomycin, daptomycin, and tigecycline for different durations in an in vitro biofilm model. Vancomycin neither penetrated the biofilm nor had any microbicidal effect on bacteria within the biofilm. Daptomycin had a microbicidal effect on bacteria within the biofilm but had no effect on biofilm inhibition and eradication (independent from dose and treatment time). Tigecycline inhibited and eradicated biofilm formation and had a microbicidal effect on bacteria within the biofilm. In conclusion, (i) biofilm formation appeared to be a major barrier to vancomycin activity, (ii) daptomycin had an antimicrobial effect on the bacteria within the biofilm but not on the biofilm burden, and (iii) tigecycline had effects both on bacteria within the biofilm and on biofilm burden. Thus, both tigecycline and daptomycin might be promising candidates for the treatment of biofilm infections.

Download Full-text

Deacetylation of Fungal Exopolysaccharide Mediates Adhesion and Biofilm Formation

mBio ◽

10.1128/mbio.00252-16 ◽

2016 ◽

Vol 7 (2) ◽

Cited By ~ 39

Author(s):

Mark J. Lee ◽

Alexander M. Geller ◽

Natalie C. Bamford ◽

Hong Liu ◽

Fabrice N. Gravelat ◽

...

Keyword(s):

Biofilm Formation ◽

Fungal Pathogens ◽

Molecular Mechanisms ◽

Pathogenic Fungi ◽

Gene Clusters ◽

Biosynthetic Gene Cluster ◽

Bacterial Biofilm ◽

Invasive Infection ◽

Biosynthetic Gene ◽

Adhesive Properties

ABSTRACTThe moldAspergillus fumigatuscauses invasive infection in immunocompromised patients. Recently, galactosaminogalactan (GAG), an exopolysaccharide composed of galactose andN-acetylgalactosamine (GalNAc), was identified as a virulence factor required for biofilm formation. The molecular mechanisms underlying GAG biosynthesis and GAG-mediated biofilm formation were unknown. We identified a cluster of five coregulated genes that were dysregulated in GAG-deficient mutants and whose gene products share functional similarity with proteins that mediate the synthesis of the bacterial biofilm exopolysaccharide poly-(β1-6)-N-acetyl-d-glucosamine (PNAG). Bioinformatic analyses suggested that the GAG cluster geneagd3encodes a protein containing a deacetylase domain. Because deacetylation ofN-acetylglucosamine residues is critical for the function of PNAG, we investigated the role of GAG deacetylation in fungal biofilm formation. Agd3 was found to mediate deacetylation of GalNAc residues within GAG and render the polysaccharide polycationic. As with PNAG, deacetylation is required for the adherence of GAG to hyphae and for biofilm formation. Growth of the Δagd3mutant in the presence of culture supernatants of the GAG-deficient Δuge3mutant rescued the biofilm defect of the Δagd3mutant and restored the adhesive properties of GAG, suggesting that deacetylation is an extracellular process. The GAG biosynthetic gene cluster is present in the genomes of members of thePezizomycotinasubphylum of theAscomycotaincluding a number of plant-pathogenic fungi and a single basidiomycete species,Trichosporon asahii, likely a result of recent horizontal gene transfer. The current study demonstrates that the production of cationic, deacetylated exopolysaccharides is a strategy used by both fungi and bacteria for biofilm formation.IMPORTANCEThis study sheds light on the biosynthetic pathways governing the synthesis of galactosaminogalactan (GAG), which plays a key role inA. fumigatusvirulence and biofilm formation. We find that bacteria and fungi use similar strategies to synthesize adhesive biofilm exopolysaccharides. The presence of orthologs of the GAG biosynthetic gene clusters in multiple fungi suggests that this exopolysaccharide may also be important in the virulence of other fungal pathogens. Further, these studies establish a molecular mechanism of adhesion in which GAG interacts via charge-charge interactions to bind to both fungal hyphae and other substrates. Finally, the importance of deacetylation in the synthesis of functional GAG and the extracellular localization of this process suggest that inhibition of deacetylation may be an attractive target for the development of novel antifungal therapies.

Download Full-text

Chitooligosaccharides as Antibacterial, Antibiofilm, Antihemolytic and Anti-Virulence Agent against Staphylococcus aureus

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666190902130722 ◽

2019 ◽

Vol 20 (14) ◽

pp. 1223-1233 ◽

Cited By ~ 3

Author(s):

Fazlurrahman Khan ◽

Jang-Won Lee ◽

Dung T.N. Pham ◽

Young-Mog Kim

Keyword(s):

Molecular Weight ◽

Staphylococcus Aureus ◽

Bactericidal Activity ◽

Biofilm Formation ◽

Cost Effective ◽

Bacterial Biofilm ◽

Water Soluble ◽

Dilution Method ◽

Low Molecular Weight ◽

Biofilm Inhibition

Background: Staphylococcus aureus nosocomial infections with a high mortality rate in human and animals have been reported to associate with bacterial biofilm formation, along with the secretion of numerous virulence factors. Therefore, the inhibition of biofilm formation and attenuation of virulence determinants are considered as a promising solution to combat the spread of S. aureus infections. Modern trends in antibiofilm therapies have opted for the active agents that are biocompatible, biodegradable, non-toxic and cost-effective. Owning the aforementioned properties, chitosan, a natural N-acetylated carbohydrate biopolymer derived from chitin, has been favorably employed. Recently, the chitosan structure has been chemically modified into Chitooligosaccharides (COS) to overcome its limited solubility in water, thus widening chitosan applications in modern antibiofilm research. In the present study, we have investigated the antibacterial, antibiofilm and anti-virulence activities against S. aureus of COS of different molecular weights dissolved in neutral water. Methods: The study of bactericidal activity was performed using the micro-dilution method while the biofilm inhibition assay was performed using crystal-violet staining method and confirmed by scanning electron microscopic analysis. The inhibition of amyloid protein production was confirmed by Congo Red staining. Results: Results showed that low molecular weight COS exhibited bactericidal activity and reduced the bacterial amylogenesis, hemolytic activity as well as H2O2 resistance properties, while slightly inhibiting biofilm formation. The present study provides a new insight for further applications of the water-soluble COS as a safe and cost-effective drug for the treatment of S. aureus biofilm-associated infections. Conclusion: Reducing the molecular weight of chitosan in the form of COS has become an effective strategy to maintain chitosan biological activity while improving its water solubility. The low molecular weight COS investigated in this study have effectively performed antibacterial, antibiofilm and antivirulence properties against S. aureus.

Download Full-text

The phycobiota-derived proteins Pµ84 and Pµ19 suppress bacterial biofilm formation in gram-negative pathogens

10.5194/biofilms9-63 ◽

2020 ◽

Author(s):

Yuchen Han ◽

Wolfgang R. Streit ◽

Ines Krohn

Keyword(s):

Biofilm Formation ◽

Pathogenic Bacteria ◽

Bacterial Biofilm ◽

Klebsiella Pneumonia ◽

Biofilm Inhibition ◽

Marine Systems ◽

Microtiter Plates ◽

Small Proteins ◽

Ongoing Work ◽

Growth Promoting

Microalgae are typically found in freshwater and marine systems and they harbor a mostly a beneficial growth promoting microbiota. We have recently isolated several small proteins from the microbiomes of microalga (Scenedesmus quadricauda, Microasterias crux-melintensis, Chlorella saccherophilia) and have tested them for their role in either inhibition of biofilm formation and/or biofilm degradation. Thereby we have identified two candidate proteins that showed promising activities on biofilm inhibition and degradation. These proteins were designated P&#181;84 and P&#181;19 and strongly affected biofilm formation in several human- and plant-pathogenic bacteria. Recombinant and purified P&#181;84 and P&#181;19 were applied in biofilm assays in microtiter plates and reduced biofilms formed by Stenotrophomonas maltophilia, Pseudomonas aeruginosa and Klebsiella pneumonia. If expressed in the different hosts, biofilms were reduced by a factor of 40% and if applied as exogenous proteins, biofilms were reduced up to 20%. P&#181;84 application also resulted in a delayed biofilm formation and biofilm formation was affected by a factor of 17%. The microprotein P&#181;19 consist of 57 aa and P&#181;84 consists of 49 aa. Ongoing work elucidates the mechanism of P&#181;84 and P&#181;19 on the reduction of biofilm in order to achieve the optimal activity.

Download Full-text

Immobilizing hydrolytic active Papain on biodegradable PLLA for biofilm inhibition in cardiovascular applications

Current Directions in Biomedical Engineering ◽

10.1515/cdbme-2020-3044 ◽

2020 ◽

Vol 6 (3) ◽

pp. 172-175

Author(s):

Michael Teske ◽

Tina Kießlich ◽

Niels Grabow ◽

Sabine Illner ◽

Julia Fischer ◽

...

Keyword(s):

Biofilm Formation ◽

Antimicrobial Agents ◽

Hydrolytic Enzyme ◽

Bacterial Biofilm ◽

Biofilm Inhibition ◽

Biofilm Growth ◽

Clostridioides Difficile ◽

Adhesive Surface

AbstractThe use of biomaterials in medicine is becoming increasingly important. One of the main concerns is the foreign body associated infection caused by direct microbial contamination or clinical infections. The bacterial biofilm formation on biomaterials depends on their surface properties. Therefore, several anti-adhesive surface modifications were developed. Nevertheless, the demand for antimicrobial agents that prevent bacterial colonisation is still largely unmet. The immobilization of active antimicrobial agents, such as antibacterial peptides or enzymes, offers a potential approach to achieve long-lasting effectiveness. In this investigation, the hydrolytic enzyme papain with its published antibacterial activity was covalently immobilized on the well-established biodegradable biomaterial poly-L-lactic acid (PLLA). For the characterization of the enzymes on the PLLA surfaces, the protein content and enzyme activity were determined. A biofilm assay was performed to test the effect of the papain-modified PLLA samples on the biofilm-forming bacterial strain Clostridioides difficile, one of the most frequently occurring human nosocomial pathogens. The investigated hydrolytic enzyme papain could be immobilized by coupling via the crosslinker EDC to the PLLA surface. Detection was performed by determination of the amount of protein and the reduced biofilm growth after 24 h and 72 h compared to the reference.

Download Full-text

In vitro Inhibition of Biofilm Formation on Silicon Rubber Voice Prosthesis: Α Systematic Review and Meta-Analysis

ORL ◽

10.1159/000516345 ◽

2021 ◽

pp. 1-20

Author(s):

Alexios Tsikopoulos ◽

Efi Petinaki ◽

Charalampos Festas ◽

Konstantinos Tsikopoulos ◽

Gabriele Meroni ◽

...

Keyword(s):

Surface Modification ◽

Silicone Rubber ◽

Subgroup Analysis ◽

Biofilm Formation ◽

Meta Analysis ◽

Bacterial Biofilm ◽

Biofilm Inhibition ◽

Voice Prostheses ◽

Significant Difference

Introduction: Biofilm formation on voice prostheses is the primary reason for their premature implant dysfunction. Multiple strategies have been proposed over the last decades to achieve inhibition of biofilm formation on these devices. The purpose of this study was to assess the results of the available in vitro biofilm inhibition modalities on silicone rubber voice prostheses. Methods: We conducted a systematic search in PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases up to February 29, 2020. A total of 33 in vitro laboratory studies investigating the efficacy of different coating methods against Candida, Staphylococcus, Streptococcus, Lactobacilli, and Rothia biofilm growth on silicone rubber medical devices were included. Subgroup analysis linked to the type of prevention modality was carried out, and quality assessment was performed with the use of the modified CONSORT tool. Results: Data from 33 studies were included in qualitative analysis, of which 12 qualified for quantitative analysis. For yeast biofilm formation assessment, there was a statistically significant difference in favor of the intervention group (standardized mean difference [SMD] = −1.20; 95% confidence interval [CI] [−1.73, −0.66]; p < 0.0001). Subgroup analysis showed that combined methods (active and passive surface modification) are the most effective for biofilm inhibition in yeast (SMD = −2.53; 95% CI [−4.02, −1.03]; p = 0.00001). No statistically significant differences between intervention and control groups were shown for bacterial biofilm inhibition (SMD = −0.09; 95% CI [−0.68, 0.46]; p = 0.65), and the results from the subgroup analysis found no notable differences between the surface modification methods. After analyzing data on polymicrobial biofilms, a statistically significant difference in favor of prevention methods in comparison with the control group was detected (SMD = −2.59; 95% CI [−7.48, 2.31]; p = 0.30). Conclusions: The meta-analysis on biofilm inhibition demonstrated significant differences in favor of yeast biofilm inhibition compared to bacteria. A stronger inhibition with the application of passive or combined active and passive surface modification techniques was reported.

Download Full-text