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Novel and Improved Strategies for the Detection, Diagnosis and Treatment...
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Novel and Improved Strategies for the Detection, Diagnosis and Treatment of Biofilm-Associated Infections

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiofilm Strategies".

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 22477

Special Issue Editors

Dr. Celia Mayer

E-Mail Website
Guest Editor
Escherichia coli Reference Laboratory (LREC)-Fundación Instituto de Investigación Sanitaria Santiago de Compostela (FIDIS), 15706 Santiago de Compostela, Spain
Interests: biofilms; quorum sensing cell-to-cell communication system; anti-biofilm strategies; quorum-sensing inhibition; Escherichia coli; Acinetobacter baumannii
Dr. Saskia Camille Flament Simon

E-Mail Website
Guest Editor
Escherichia coli reference laboratory (LREC), Facultade de Veterinaria, Universidade de Santiago de Compostela, 27002 Lugo, Spain
Interests: Escherichia coli; biofilms; phage therapy; bacterial infections; antibiotic resistance; core genome; plasmidome; virulome; resistome; zoonotic potential

Special Issue Information

Dear Colleagues,

Several microorganisms are difficult to eradicate due to their ability to produce biofilm on several kinds of surfaces, protecting themselves from a wide range of antimicrobials. Since these complex communities have an impact on every aspect of our lives and can have a profound negative effect on human health by producing several infections, the study of biofilms requires special attention. To complicate this situation, the emergence of multidrug-resistant pathogens is one of the greatest challenges nowadays, representing a serious problem for public health worldwide. Currently, microbiology culturing and molecular techniques are the standard methods for identifying pathogens in clinical settings, however, they cannot distinguish biofilm in clinical samples. In fact, the diagnosis of clinically relevant biofilm infections is often difficult and inconsistent, as well as there are controversies and uncertainties concerning treatment or prophylactic approaches using antibiotics in clinical settings. Furthermore, conventional antibiotic therapies used to treat acute infections may not eliminate chronic biofilm infections and, in many cases, promote resistance and further biofilm formation. Therefore, the successful treatment of biofilm-associated infections requires novel and more effective anti-biofilm strategies. More targeted therapeutics for biofilm are also required for selecting the appropriate and specific treatment to achieve clinical efficacy. Aware of these facts, the main subject of this Special Issue includes any novel and new diagnostic tool to identify biofilms in infections and improved anti-biofilm strategies and therapies that could be used to control and treat relevant biofilm-based infections.

Dr. Celia Mayer
Dr. Saskia Camille Flament Simon
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • biofilm
  • biofilm diagnosis
  • biofilm infections
  • biofilm detection
  • biofilm treatment
  • biofilm-associated infections
  • biofilm therapies
  • anti-biofilm strategies
  • bacterial pathogens

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Published Papers (7 papers)

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Research

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17 pages, 7141 KiB  
Article
FTY720 Reduces the Biomass of Biofilms in Pseudomonas aeruginosa in a Dose-Dependent Manner
by Abdurahman A. Niazy, Rhodanne Nicole A. Lambarte, Terrence S. Sumague, Mary Grace B. Vigilla, Najla M. Bin Shwish, Ranan Kamalan, Eid Khulaif Daeab and Nami M. Aljehani
Antibiotics 2024, 13(7), 621; https://doi.org/10.3390/antibiotics13070621 - 4 Jul 2024
Cited by 1 | Viewed by 1379
Abstract
Pseudomonas aeruginosa, a nosocomial pathogen, has strong biofilm capabilities, representing the main source of infection in the human body. Repurposing existing drugs has been explored as an alternative strategy to combat emerging antibiotic-resistant pathogens. Fingolimod hydrochloride (FTY720), an immunomodulatory drug for multiple [...] Read more.
Pseudomonas aeruginosa, a nosocomial pathogen, has strong biofilm capabilities, representing the main source of infection in the human body. Repurposing existing drugs has been explored as an alternative strategy to combat emerging antibiotic-resistant pathogens. Fingolimod hydrochloride (FTY720), an immunomodulatory drug for multiple sclerosis, has shown promising antimicrobial effects against some ESKAPE pathogens. Therefore, the effects of FTY720 on the biofilm capabilities of Pseudomonas aeruginosa were investigated in this study. It was determined that FTY720 inhibited the growth of P. aeruginosa PAO1 at 100 µM. The significant reduction in PAO1 cell viability was observed to be dose-dependent. Additional cytotoxicity analysis on human cell lines showed that FTY720 significantly reduced viabilities at sub-inhibitory concentrations of 25–50 µM. Microtiter assays and confocal analysis confirmed reductions in biofilm mass and thickness and the cell survivability ratio in the presence of FTY720. Similarly, virulence production and biofilm-related gene expression (rhlA, rhlB, pilA, pilI, fliC, fliD and algR) were determined. The results demonstrate that pigment production was affected and quantitative real-time PCR analysis showed a variable degree of reduced gene expression in response to FTY720 at 12.5–50 µM. These findings suggest that FTY720 could be repurposed as an alternative antibiofilm agent against Pseudomonas aeruginosa. Full article
(This article belongs to the Special Issue Novel and Improved Strategies for the Detection, Diagnosis and Treatment of Biofilm-Associated Infections)
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15 pages, 3867 KiB  
Article
New Preventive Strategy against Oral Biofilm Formation in Caries-Active Children: An In Vitro Study
by Ana Parga, Sabela Balboa, Paz Otero-Casal and Ana Otero
Antibiotics 2023, 12(8), 1263; https://doi.org/10.3390/antibiotics12081263 - 31 Jul 2023
Cited by 4 | Viewed by 1803
Abstract
Quorum quenching (QQ) is the inhibition of bacterial communication, i.e., quorum sensing (QS). QS is a key mechanism in regulating biofilm formation and phenotype in complex bacterial communities, such as those found within cariogenic biofilms. Whereas QQ approaches were shown to effectively reduce [...] Read more.
Quorum quenching (QQ) is the inhibition of bacterial communication, i.e., quorum sensing (QS). QS is a key mechanism in regulating biofilm formation and phenotype in complex bacterial communities, such as those found within cariogenic biofilms. Whereas QQ approaches were shown to effectively reduce biomass, knowledge of their impact on the taxonomic composition of oral polymicrobial biofilms remains scarce. Here, we investigate the effect of the QQ lactonase Aii20J on biomass production and taxonomical composition of biofilms. We collected supragingival plaque samples from 10 caries-free and 10 caries-active children and cultured them to generate in vitro biofilms. We describe significant biomass reductions upon Aii20J exposure, as assessed by crystal violet assays. Taxonomical profiling using 16S rRNA gene amplicon sequencing revealed no significant changes in bacterial composition at the genus level. Interestingly, at the species level Aii20J-treatment increased the abundance of Streptococcus cristatus and Streptococcus salivarius. Both S. cristatus and S. salivarius express pH-buffering enzymes (arginine deiminase and urease, respectively) that catalyze ammonia production, thereby potentially raising local pH and counteracting the biofilm’s cariogenic potential. Within the limitations of the study, our findings provide evidence of the biofilm-modulating ability of QQ and offer novel insights into alternative strategies to restore homeostasis within dysbiotic ecosystems. Full article
(This article belongs to the Special Issue Novel and Improved Strategies for the Detection, Diagnosis and Treatment of Biofilm-Associated Infections)
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10 pages, 1996 KiB  
Article
Activity of Delafloxacin and Comparator Fluoroquinolones against Multidrug-Resistant Pseudomonas aeruginosa in an In Vitro Cystic Fibrosis Sputum Model
by Vaughn D. Craddock, Evan L. Steere, Hannah Harman and Nicholas S. Britt
Antibiotics 2023, 12(6), 1078; https://doi.org/10.3390/antibiotics12061078 - 20 Jun 2023
Viewed by 1824
Abstract
Delafloxacin (DLX) is a recently approved fluoroquinolone with broad activity against common cystic fibrosis (CF) pathogens, including multidrug-resistant Pseudomonas aeruginosa (MDR-Psa). Delafloxacin has been previously shown to have excellent lung and biofilm penetration and enhanced activity at lower pH environments, such as those [...] Read more.
Delafloxacin (DLX) is a recently approved fluoroquinolone with broad activity against common cystic fibrosis (CF) pathogens, including multidrug-resistant Pseudomonas aeruginosa (MDR-Psa). Delafloxacin has been previously shown to have excellent lung and biofilm penetration and enhanced activity at lower pH environments, such as those that would be observed in the CF lung. We analyzed six Psa strains isolated from CF sputum and compared DLX to ciprofloxacin (CPX) and levofloxacin (LVX). Minimum inhibitory concentrations (MICs) were determined for DLX using standard culture media (pH 7.3) and artificial sputum media (ASM), a physiologic media recapitulating the CF lung microenvironment (pH 6.9). Delafloxacin activity was further compared to CPX and LVX in an in vitro CF sputum time-kill model at physiologically relevant drug concentrations (Cmax, Cmed, Cmin). Delafloxacin exhibited 2- to 4-fold MIC reductions in ASM, which corresponded with significant improvements in bacterial killing in the CF sputum time-kill model between DLX and LVX at Cmed (p = 0.033) and Cmin (p = 0.004). Compared to CPX, DLX demonstrated significantly greater killing at Cmin (p = 0.024). Overall, DLX demonstrated favorable in vitro activity compared to alternative fluoroquinolones against MDR-Psa. Delafloxacin may be considered as an option against MDR-Psa pulmonary infections in CF. Full article
(This article belongs to the Special Issue Novel and Improved Strategies for the Detection, Diagnosis and Treatment of Biofilm-Associated Infections)
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12 pages, 3129 KiB  
Article
The Combination of Low-Frequency Ultrasound and Antibiotics Improves the Killing of In Vitro Staphylococcus aureus and Pseudomonas aeruginosa Biofilms
by Lasse Kvich, Mads H. Christensen, Malgorzata K. Pierchala, Konstantin Astafiev, Rasmus Lou-Moeller and Thomas Bjarnsholt
Antibiotics 2022, 11(11), 1494; https://doi.org/10.3390/antibiotics11111494 - 28 Oct 2022
Cited by 6 | Viewed by 3857
Abstract
Due to an increase in underlying predisposing factors, chronic wounds have become an increasing burden on healthcare systems worldwide. Chronic infections often contain biofilm-forming bacteria, which are challenging to eradicate due to increased antibiotic tolerance; thus, new and improved therapeutic strategies are warranted. [...] Read more.
Due to an increase in underlying predisposing factors, chronic wounds have become an increasing burden on healthcare systems worldwide. Chronic infections often contain biofilm-forming bacteria, which are challenging to eradicate due to increased antibiotic tolerance; thus, new and improved therapeutic strategies are warranted. One such strategy is the combination of ultrasound and antibiotics. Therefore, this study aimed to investigate the combinatory effects of low-frequency (50 kHz) ultrasound delivered by specially designed ultrasound patches using flexible piezoelectric material, PiezoPaint™, in combination with antibiotics against biofilms with Staphylococcus aureus and Pseudomonas aeruginosa. The reduction in viable cells in S. aureus and P. aeruginosa biofilms was evaluated post-treatment with fusidic acid, clindamycin, ciprofloxacin, and colistin in combination with ultrasound treatment. Two-hour ultrasound treatment significantly increased the bactericidal effect of all four antibiotics, resulting in a 96–98% and 90–93% reduction in P. aeruginosa and S. aureus, respectively. In addition, an additive effect was observed when extending treatment to 4 h, resulting in >99% and 95–97% reduction in P. aeruginosa and S. aureus, respectively. These results contrasted the lack of effect observed when treating filter-biofilms with antibiotics alone. The combined effect of ultrasound and antibiotic treatment resulted in a synergistic effect, reducing the viability of the clinically relevant pathogens S. aureus and P. aeruginosa. The modularity of the specially designed patches intended for topical treatment holds promising applications as a supplement in chronic wound therapy. Further studies are warranted with clinically isolated strains and other clinically relevant antibiotics before proceeding to studies where safety and applicability are investigated. Full article
(This article belongs to the Special Issue Novel and Improved Strategies for the Detection, Diagnosis and Treatment of Biofilm-Associated Infections)
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11 pages, 1118 KiB  
Article
Anticandidal and Antibiofilm Effect of Synbiotics including Probiotics and Inulin-Type Fructans
by Ricardo García-Gamboa, Miguel Domínguez-Simi, Misael S. Gradilla-Hernández, Jorge Bravo, Andrés Moya, Blanca Ruiz-Álvarez and Marisela González-Avila
Antibiotics 2022, 11(8), 1135; https://doi.org/10.3390/antibiotics11081135 - 21 Aug 2022
Cited by 7 | Viewed by 2596
Abstract
Background: There is great interest in the search for new alternatives to antimicrobial drugs, and the use of synbiotics is a promising approach to this problem. This study evaluated the growth inhibition and antibiofilm activity of the short-chain fatty acids produced by Lacticaseibacillus [...] Read more.
Background: There is great interest in the search for new alternatives to antimicrobial drugs, and the use of synbiotics is a promising approach to this problem. This study evaluated the growth inhibition and antibiofilm activity of the short-chain fatty acids produced by Lacticaseibacillus rhamnosus and Pediococcus acidilactici in combination with inulin-type fructans against Candida albicans. Methods: The growth inhibition of Candida was evaluated using microdilution analysis in 96-well microtiter plates; different concentrations of cell-free supernatants of Lacticaseibacillus rhamnosus and Pediococcus acidilactici were exposed to Candida albicans. The antibiofilm assessment was carried out using the crystal violet staining assay. The short-chain fatty acids were analyzed by gas chromatography. Results: The clinically isolated Candida albicans interacted with supernatants from Lacticaseibacillus rhamnosus and Pediococcus acidilactici and showed significant growth inhibition and antibiofilm formation versus the controls. Lactate and acetic acid were elevated in the supernatants. The results suggest that the supernatants obtained from the synbiotic combinations of Lacticaseibacillus rhamnosus and Pediococcus acidilactici with inulin-type fructans can inhibit the growth and biofilm formation against a clinically isolated Candida albicans strain. Conclusions: These results suggest that synbiotic formulations could be a promising alternative to antifungal drugs in candidiasis therapy. Full article
(This article belongs to the Special Issue Novel and Improved Strategies for the Detection, Diagnosis and Treatment of Biofilm-Associated Infections)
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20 pages, 3689 KiB  
Article
Biofilm Formation of Staphylococcus aureus from Pets, Livestock, and Wild Animals: Relationship with Clonal Lineages and Antimicrobial Resistance
by Vanessa Silva, Elisete Correia, José Eduardo Pereira, Camino González-Machado, Rosa Capita, Carlos Alonso-Calleja, Gilberto Igrejas and Patrícia Poeta
Antibiotics 2022, 11(6), 772; https://doi.org/10.3390/antibiotics11060772 - 4 Jun 2022
Cited by 13 | Viewed by 4278
Abstract
This study aimed to compare the biofilm formation ability of Staphylococcus aureus isolated from a wide range of animals and study the association between biofilm formation and antimicrobial resistance and genetic lineages. A total of 214 S. aureus strains isolated from pets, livestock, [...] Read more.
This study aimed to compare the biofilm formation ability of Staphylococcus aureus isolated from a wide range of animals and study the association between biofilm formation and antimicrobial resistance and genetic lineages. A total of 214 S. aureus strains isolated from pets, livestock, and wild animals were evaluated regarding their ability to form biofilms by the microtiter biofilm assay and their structure via confocal scanning laser microscopy. Statistical analysis was used to find an association between biofilm formation and antimicrobial resistance, multidrug resistance, sequence types (STs), spa and agr-types of the isolates. The antimicrobial susceptibility of 24 h-old biofilms was assessed against minimum inhibitory concentrations (MIC) and 10× MIC of amikacin and tetracycline, and the biomass reduction was measured. The metabolic activity of biofilms after antimicrobial treatment was evaluated by the XTT assay. All isolates were had the ability to form biofilms. Yet, significant differences in biofilm biomass production were detected among animal species. Multidrug resistance had a positive association with biofilm formation as well as methicillin-resistance. Significant differences were also detected among the clonal lineages of the isolates. Both tetracycline and amikacin were able to significantly reduce the biofilm mass. However, none of the antimicrobials were able to eradicate the biofilm at the maximum concentration used. Our results provide important information on the biofilm-forming capacity of animal-adapted S. aureus isolates, which may have potential implications for the development of new biofilm-targeted therapeutics. Full article
(This article belongs to the Special Issue Novel and Improved Strategies for the Detection, Diagnosis and Treatment of Biofilm-Associated Infections)
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Review

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42 pages, 4428 KiB  
Review
Strategies to Mitigate and Treat Orthopaedic Device-Associated Infections
by Darragh G. Kennedy, Aoife M. O’Mahony, Eamonn P. Culligan, Caitriona M. O’Driscoll and Katie B. Ryan
Antibiotics 2022, 11(12), 1822; https://doi.org/10.3390/antibiotics11121822 - 15 Dec 2022
Cited by 14 | Viewed by 5445
Abstract
Orthopaedic device implants play a crucial role in restoring functionality to patients suffering from debilitating musculoskeletal diseases or to those who have experienced traumatic injury. However, the surgical implantation of these devices carries a risk of infection, which represents a significant burden for [...] Read more.
Orthopaedic device implants play a crucial role in restoring functionality to patients suffering from debilitating musculoskeletal diseases or to those who have experienced traumatic injury. However, the surgical implantation of these devices carries a risk of infection, which represents a significant burden for patients and healthcare providers. This review delineates the pathogenesis of orthopaedic implant infections and the challenges that arise due to biofilm formation and the implications for treatment. It focuses on research advancements in the development of next-generation orthopaedic medical devices to mitigate against implant-related infections. Key considerations impacting the development of devices, which must often perform multiple biological and mechanical roles, are delineated. We review technologies designed to exert spatial and temporal control over antimicrobial presentation and the use of antimicrobial surfaces with intrinsic antibacterial activity. A range of measures to control bio-interfacial interactions including approaches that modify implant surface chemistry or topography to reduce the capacity of bacteria to colonise the surface, form biofilms and cause infections at the device interface and surrounding tissues are also reviewed. Full article
(This article belongs to the Special Issue Novel and Improved Strategies for the Detection, Diagnosis and Treatment of Biofilm-Associated Infections)
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