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Clinical Implications of Microbial Biofilm

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A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Biofilm".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 32670

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Special Issue Editors

Prof. Dr. Giovanni Di Bonaventura

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Department of Medical, Oral and Biotechnological Sciences, Center for Advanced Studies and Technology (CAST), Gabriele d’Annunzio University of Chieti-Pescara, 66100 Chieti, Italy
Interests: biofilm formation; cystic fibrosis; lung infections; antibiotic resistance; antimicrobial compounds; Pseudomonas aeruginosa
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Dr. Arianna Pompilio

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Guest Editor

Department of Medical, Oral and Biotechnological Sciences, Center for Advanced Studies and Technology (CAST), Gabriele d’Annunzio University of Chieti-Pescara, 66100 Chieti, Italy
Interests: biofilm formation; cystic fibrosis; lung infections; probiotics; antibiotic resistance; antimicrobial compounds; Pseudomonas aeruginosa; Stenotrophomonas maltophilia; bacterial pathogenesis; microbial cooperation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The concept that microbial biofilms can enable the survival of microorganisms in various compartments of the human body, as well as on the surface of prostheses and therapeutic devices, is strongly supported by in vitro studies, which have increased exponentially over the past two decades.

However, our understanding of the natural history of this important bacterial growth phenotype remains limited. While biofilms have been demonstrated in vitro in numerous studies, it is worth noting that, with rare exceptions, biofilms were not perfectly correlated with disease.

Most of these studies consist, in fact, of basic science investigation, surveys of clinical isolate collections, with limited clinical relevance, as they do not shed light on the influence of the biofilm phenotype on the clinical outcomes of infected human patients. Furthermore, they suffer from a lack of standardization in biofilm laboratory methods, which makes it difficult to make a meaningful comparison of data across studies and species, and is probably the reason that conflicting results arose from studies looking for an association between biofilm-forming bacteria and more severe clinical outcomes.

More informative clinical studies correlating biofilm formation to patient data, and indicating biofilm phenotype as a risk factor for adverse clinical outcomes are needed, both to advance our understanding of the role of biofilms in human disease and to identify new therapeutic strategies/targets.

For these reasons, this Special Issue welcomes research articles, review articles, short communications and case reports focused mainly (but not only) on the following:

mechanisms underlying the antimicrobial tolerance of biofilm communities;
mechanisms in which bacterial biofilms evade, dampen, or actively counterattack the host immune response;
definition of clinical indicators for biofilm formation (i.e., failure of appropriate antibiotic treatment, recalcitrance to appropriate antibiotic treatment, recurrence of delayed healing on cessation of antibiotic treatment, and unresponsiveness to antimicrobial therapy);
in vitro predictors of biofilm formation and therapeutic outcomes for biofilm-related infections;
non-device-related chronic biofilm disease;
device-related biofilm disease;
biofilm-related device malfunction;
classic (antibiotic treatment) and alternative therapeutic strategies to combat biofilm-related infections;
evaluation of the clinical impact of biofilm formation in human and animal studies;
standardization of in vitro and in vivo models that allow for biofilm formation under environmental conditions similar to the infection site.

Prof. Giovanni Di Bonaventura
Dr. Arianna Pompilio
Guest Editor

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. Microorganisms 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 2700 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

Biofilms
Clinical studies
Biofilm microbial interaction
Biofilm-related infections
Device-related biofilm diseases
Antibiotic tolerance
Host immune response evasion
Biofilm clinical indicators

Published Papers (8 papers)

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Research

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14 pages, 841 KiB

Open AccessArticle

In Vivo Biofilm Formation of Pathogenic Leptospira spp. in the Vitreous Humor of Horses with Recurrent Uveitis

by Kerstin Ackermann, Rebecca Kenngott, Monica Settles, Hartmut Gerhards, Johann Maierl and Bettina Wollanke

Microorganisms 2021, 9(9), 1915; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9091915 - 09 Sep 2021

Cited by 12 | Viewed by 2523

Abstract

Equine recurrent uveitis (ERU) causes painful inflammatory attacks and oftentimes blindness in the affected eyes. The disease is considered a late sequela of systemic leptospirosis. The most effective therapy is the surgical removal of the vitreous (vitrectomy), which is not only therapeutic, but provides vitreous material that can be assessed diagnostically. For example, the lipL32 gene, culturable Leptospira spp., and anti-Leptospira antibodies have all been detected in vitreous samples obtained from eyes with chronic ERU. Despite this clear evidence of leptospiral involvement, the systemic administration of antibiotics in infected horses is ineffective at resolving ERU. This syndrome of chronic recurrent inflammation, which is unresponsive to antibiotic therapy, combined with apparent bacteria evading the immune response, is consistent with a biofilm-associated infection. The purpose of this study, therefore, was to detect the in vivo biofilm formation of Leptospira spp. in vitreous samples collected during vitrectomy and examined using a Warthin-Starry silver stain and immunohistochemistry. All known steps of biofilm formation were visualized in these samples, including individual Leptospira spp., leptospiral microcolonies and dense roundish accumulations of Leptospira spp. In many instances spirochetes were surrounded by an extracellular substance. Taken together, data from the present study show that ERU is a biofilm-associated intraocular leptospiral infection, which best explains the typical clinical course. Full article

(This article belongs to the Special Issue Clinical Implications of Microbial Biofilm)

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10 pages, 1583 KiB

Open AccessArticle

Device Design Modifications Informed by In Vitro Testing of Bacterial Attachment Reduce Infection Rates of Cochlear Implants in Clinical Practice

by Lynne Turnbull, Roger Leigh, Rosalia Cavaliere, Sarah R. Osvath, Laura M. Nolan, Daniel Smyth, Kristien Verhoeven, Richard A. Chole and Cynthia B. Whitchurch

Microorganisms 2021, 9(9), 1809; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9091809 - 25 Aug 2021

Cited by 3 | Viewed by 2360

Abstract

Recalcitrant chronic infections of implanted medical devices are often linked to the presence of biofilms. The prevention and treatment of medical device-associated infections is a major source of antibiotic use and driver of antimicrobial resistance globally. Lowering the incidence of infection in patients that receive implanted medical devices could therefore significantly improve antibiotic stewardship and reduce patient morbidity. Here we determined if modifying the design of an implantable medical device to reduce bacterial attachment, impacted the incidence of device-associated infections in clinical practice. Since the 1980s cochlear implants have provided long-term treatment of sensorineural hearing deficiency in hundreds of thousands of patients world-wide. Nonetheless, a relatively small number of devices are surgically explanted each year due to unresolvable infections. Features associated with the accumulation of bacteria on the Cochlear™ Nucleus^® CI24RE™ model of cochlear implant devices were identified using both in vitro bacterial attachment assays and examination of explanted devices. Macro-scale design modifications that reduced bacterial attachment in vitro were incorporated into the design of the CI500™ and Profile™ series of Nucleus implant. Analyses of mandatory post-market vigilance data of 198,757 CI24RE and 123,084 CI500/Profile series implantation surgeries revealed that these design modifications correlated with significantly reduced infection rates. This study demonstrates that a design-centric approach aimed at mitigating bacterial attachment was a simple, and effective means of reducing infections associated with Cochlear Nucleus devices. This approach is likely to be applicable to improving the designs of other implantable medical devices to reduce device-associated infections. Full article

(This article belongs to the Special Issue Clinical Implications of Microbial Biofilm)

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23 pages, 3846 KiB

Open AccessArticle

Actinotignum schaalii: Relation to Concomitants and Connection to Patients’ Conditions in Polymicrobial Biofilms of Urinary Tract Catheters and Urines

by Iva Kotásková, Vít Syrovátka, Hana Obručová, Petra Vídeňská, Barbora Zwinsová, Veronika Holá, Eva Blaštíková, Filip Růžička and Tomáš Freiberger

Microorganisms 2021, 9(3), 669; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9030669 - 23 Mar 2021

Cited by 3 | Viewed by 4470

Abstract

Actinotignum schaalii is an emerging, opportunistic pathogen and its connection to non-infectious diseases and conditions, such as prostate or bladder cancer, or chronic inflammation has been proposed. Here, we analyzed 297 urine, ureteral and urinary catheter samples from 128 patients by Polymerase Chain Reaction followed by Denaturing Gradient Gel Electrophoresis and Sequencing (PCR-DGGE-S), and culture, and 29 of these samples also by 16S rRNA Illumina sequencing, to establish A. schaalii’s prevalence in urinary tract-related samples, its relation to other bacteria, and its potential association with patients’ conditions and samples’ characteristics. A. schaalii-positive samples were significantly more diverse than A. schaalii negative and between-group diversity was higher than intra-group. Propionimicrobium lymphophilum, Fusobacterium nucleatum, Veillonella sp., Morganella sp., and Aerococcus sp. were significantly more often present in A. schaalii-positive samples; thus, we suggest these species are A. schaalii’s concomitants, while Enterobacter and Staphylococcaceae were more often identified in A. schaalii-negative samples; therefore, we propose A. schaalii and these species are mutually exclusive. Additionally, a significantly higher A. schaalii prevalence in patients with ureter stricture associated hydronephrosis (p = 0.020) was noted. We suggest that A. schaalii could be an early polybacterial biofilm colonizer, together with concomitant species, known for pro-inflammatory features. Full article

(This article belongs to the Special Issue Clinical Implications of Microbial Biofilm)

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17 pages, 5081 KiB

Open AccessArticle

Genomic Characterization of a New Biofilm-Forming and Adhesive ST398 Human-Adapted MSSA Lineage Causing Septic Knee Arthritis Following Surgical Reconstruction

by Viviana Cafiso, Flavia Lo Verde, Alessandra Zega, Giuseppe Pigola, Roberto Rostagno, Silvio Borrè and Stefania Stefani

Microorganisms 2021, 9(2), 305; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9020305 - 02 Feb 2021

Cited by 6 | Viewed by 2529

Abstract

Methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen commonly found in bone and joint infections, including septic arthritis. S. aureus virulence and the frailty of affected patients can cause several complications; a prompt and specific antibiotic treatment can positively affect the outcome of patients. We carried out an in-depth genomic characterization by Illumina whole genome sequencing and bioinformatics of two biofilm-producing M1 and M2 ST398 MSSA causing septic knee arthritis not-responding to antimicrobial therapy. The strains were characterized for antibiotic resistance, biofilm and adhesive properties as well as genomics, single nucleotide polymorphism phylogeny, resistomics and virulomics. Our results showed that M1 and M2 MSSA were ST398-t1451-agrI-Cap5, susceptible to cefoxitin and resistant to erythromycin and clindamycin, traits consistent with the lack of the SCCmec-locus and the presence of the sole blaZ and ermT. Furthermore, M1 and M2 were biofilm-producing and largely potentially adhesive strains, as indicated by the adhesion gene profile. Our data characterized a new human-adapted ST398 MSSA lineage, representing a “fusion” between the human-animal independent ST398 and the Livestock Associated (LA) ST398 lineages, forming biofilm and genomically predicted high adhesive, characterized by different genomic adaptation conferring a great ability to adhere to the host’s extracellular matrix causing septic knee arthritis. Full article

(This article belongs to the Special Issue Clinical Implications of Microbial Biofilm)

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25 pages, 5458 KiB

Open AccessArticle

Biofilm Formation among Stenotrophomonas maltophilia Isolates Has Clinical Relevance: The ANSELM Prospective Multicenter Study

by Arianna Pompilio, Marco Ranalli, Alessandra Piccirilli, Mariagrazia Perilli, Dragana Vukovic, Branislava Savic, Marcela Krutova, Pavel Drevinek, Daniel Jonas, Ersilia V. Fiscarelli, Vanessa Tuccio Guarna Assanti, María M. Tavío, Fernando Artiles and Giovanni Di Bonaventura

Microorganisms 2021, 9(1), 49; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9010049 - 27 Dec 2020

Cited by 19 | Viewed by 3235

Abstract

The ability to form biofilms is a recognized trait of Stenotrophomonas maltophilia, but the extent of its clinical relevance is still unclear. The present multicenter prospective study (ANSELM) aims at investigating the association between biofilm formation and clinical outcomes of S. maltophilia infections. One hundred and nine isolates were collected from various geographical origins and stratified according to their clinical relevance. Biofilm formation was evaluated by the microtiter plate assay and correlated with microbiological and clinical data from the associated strains. Antibiotic susceptibility of the planktonic cells was tested by the disk diffusion technique, while antibiotic activity against mature biofilms was spectrophotometrically assessed. Most strains (91.7%) were able to form biofilm, although bloodborne strains produced biofilm amounts significantly higher than strains causing hospital- rather than community-acquired infections, and those recognized as “definite” pathogens. Biofilm formation efficiency was positively correlated with mechanical ventilation (p = 0.032), whereas a negative relationship was found with antibiotic resistance (r² = 0.107; p < 0.001), specifically in the case of the pathogenic strains. Mature S. maltophilia biofilms were markedly more resistant (up to 128 times) to cotrimoxazole and levofloxacin compared with their planktonic counterparts, especially in the case of bloodborne strains. Our findings indicate that biofilm formation by S. maltophilia is obviously a contributing factor in the pathogenesis of infections, especially in deep ones, thus warranting additional studies with larger cohort of patients and isolates. Full article

(This article belongs to the Special Issue Clinical Implications of Microbial Biofilm)

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15 pages, 954 KiB

Open AccessArticle

Biofilm Formation Reducing Properties of Manuka Honey and Propolis in Proteus mirabilis Rods Isolated from Chronic Wounds

by Joanna Kwiecińska-Piróg, Jana Przekwas, Michał Majkut, Krzysztof Skowron and Eugenia Gospodarek-Komkowska

Microorganisms 2020, 8(11), 1823; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8111823 - 19 Nov 2020

Cited by 14 | Viewed by 3480

Abstract

Chronic wound infections are difficult to manage because of the biofilm formation in the wound environment. New measures for eliminating infections are necessary to increase the chance of wound healing. Apitherapy may be the new solution. The aim of this study was to assess the prevalence of wound infection factors and to examine the impact of Manuka honey and ethanol extract of propolis on biofilm formation of Proteus mirabilis isolated from chronic wound infections. According to the findings, the most frequent factors of infection are Staphylococcus aureus (46.1%), Pseudomonas aeruginosa (35.0%), and Proteus mirabilis (10.6%). Minimal inhibitory concentration and minimal bactericidal concentration values were assigned using the microbroth dilution test according to the Clinical and Laboratory Standards Institute. Biofilm of Proteus mirabilis isolates was formed in 96-well polystyrene plates and treated with Manuka honey (concentrations from 1.88% to 30.0%) and ethanol extract of propolis (1.0% to 40.0%). After 24 h, the biofilm viability was expressed by formazan absorbance (λ = 470 nm). Manuka honey reduced the biofilm viability in all, and ethanol extract of propolis in most, of the concentrations tested. Ethanol extract of propolis at the concentrations of 20.0% and 40.0%, reduced biofilm viability stronger than ethanol itself. With these results comes the conclusion that these substances can reduce biofilm formation. Full article

(This article belongs to the Special Issue Clinical Implications of Microbial Biofilm)

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Review

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33 pages, 1241 KiB

Open AccessReview

Gram-Negative Bacteria Holding Together in a Biofilm: The Acinetobacter baumannii Way

by Arianna Pompilio, Daniela Scribano, Meysam Sarshar, Giovanni Di Bonaventura, Anna Teresa Palamara and Cecilia Ambrosi

Microorganisms 2021, 9(7), 1353; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9071353 - 22 Jun 2021

Cited by 37 | Viewed by 5893

Abstract

Bacterial biofilms are a serious public-health problem worldwide. In recent years, the rates of antibiotic-resistant Gram-negative bacteria associated with biofilm-forming activity have increased worrisomely, particularly among healthcare-associated pathogens. Acinetobacter baumannii is a critically opportunistic pathogen, due to the high rates of antibiotic resistant strains causing healthcare-acquired infections (HAIs). The clinical isolates of A. baumannii can form biofilms on both biotic and abiotic surfaces; hospital settings and medical devices are the ideal environments for A. baumannii biofilms, thereby representing the main source of patient infections. However, the paucity of therapeutic options poses major concerns for human health infections caused by A. baumannii strains. The increasing number of multidrug-resistant A. baumannii biofilm-forming isolates in association with the limited number of biofilm-eradicating treatments intensify the need for effective antibiofilm approaches. This review discusses the mechanisms used by this opportunistic pathogen to form biofilms, describes their clinical impact, and summarizes the current and emerging treatment options available, both to prevent their formation and to disrupt preformed A. baumannii biofilms. Full article

(This article belongs to the Special Issue Clinical Implications of Microbial Biofilm)

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15 pages, 719 KiB

Open AccessReview

Biofilms in Diabetic Foot Ulcers: Significance and Clinical Relevance

by Cassandra Pouget, Catherine Dunyach-Remy, Alix Pantel, Sophie Schuldiner, Albert Sotto and Jean-Philippe Lavigne

Microorganisms 2020, 8(10), 1580; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8101580 - 14 Oct 2020

Cited by 92 | Viewed by 6997

Abstract

Foot infections are the main disabling complication in patients with diabetes mellitus. These infections can lead to lower-limb amputation, increasing mortality and decreasing the quality of life. Biofilm formation is an important pathophysiology step in diabetic foot ulcers (DFU)—it plays a main role in the disease progression and chronicity of the lesion, the development of antibiotic resistance, and makes wound healing difficult to treat. The main problem is the difficulty in distinguishing between infection and colonization in DFU. The bacteria present in DFU are organized into functionally equivalent pathogroups that allow for close interactions between the bacteria within the biofilm. Consequently, some bacterial species that alone would be considered non-pathogenic, or incapable of maintaining a chronic infection, could co-aggregate symbiotically in a pathogenic biofilm and act synergistically to cause a chronic infection. In this review, we discuss current knowledge on biofilm formation, its presence in DFU, how the diabetic environment affects biofilm formation and its regulation, and the clinical implications. Full article

(This article belongs to the Special Issue Clinical Implications of Microbial Biofilm)

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