Special Issue "Clinical Implications of Microbial Biofilm"

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

Deadline for manuscript submissions: closed (31 July 2021).

Special Issue Editors

Prof. Dr. Giovanni Di Bonaventura
E-Mail Website
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: microbial biofilm; cystic fibrosis lung infection; Stenotrophomonas maltophilia; Pseudomonas aeruginosa; microbial interactions; antimicrobial peptides; antibiotics; antibiotic resistance; bacterial virulence
Dr. Arianna Pompilio
E-Mail Website
Guest Editor
Department of Medical, Oral and Biotechnological Sciences, School of Medicine, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
Interests: biofilm-related infections; cystic fibrosis infections; antibiotic-resistance; wastewater microbiology; repurposing strategy; hypogean microbiology
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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

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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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Article
In Vivo Biofilm Formation of Pathogenic Leptospira spp. in the Vitreous Humor of Horses with Recurrent Uveitis
Microorganisms 2021, 9(9), 1915; https://doi.org/10.3390/microorganisms9091915 - 09 Sep 2021
Cited by 1 | Viewed by 555
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 [...] Read more.
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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Article
Device Design Modifications Informed by In Vitro Testing of Bacterial Attachment Reduce Infection Rates of Cochlear Implants in Clinical Practice
Microorganisms 2021, 9(9), 1809; https://doi.org/10.3390/microorganisms9091809 - 25 Aug 2021
Viewed by 806
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 [...] Read more.
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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Article
Actinotignum schaalii: Relation to Concomitants and Connection to Patients’ Conditions in Polymicrobial Biofilms of Urinary Tract Catheters and Urines
Microorganisms 2021, 9(3), 669; https://doi.org/10.3390/microorganisms9030669 - 23 Mar 2021
Viewed by 1235
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 [...] Read more.
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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Article
Genomic Characterization of a New Biofilm-Forming and Adhesive ST398 Human-Adapted MSSA Lineage Causing Septic Knee Arthritis Following Surgical Reconstruction
Microorganisms 2021, 9(2), 305; https://doi.org/10.3390/microorganisms9020305 - 02 Feb 2021
Cited by 1 | Viewed by 898
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 [...] Read more.
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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Article
Biofilm Formation among Stenotrophomonas maltophilia Isolates Has Clinical Relevance: The ANSELM Prospective Multicenter Study
Microorganisms 2021, 9(1), 49; https://doi.org/10.3390/microorganisms9010049 - 27 Dec 2020
Cited by 1 | Viewed by 835
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 [...] Read more.
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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Article
Biofilm Formation Reducing Properties of Manuka Honey and Propolis in Proteus mirabilis Rods Isolated from Chronic Wounds
Microorganisms 2020, 8(11), 1823; https://doi.org/10.3390/microorganisms8111823 - 19 Nov 2020
Cited by 3 | Viewed by 767
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 [...] Read more.
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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Review
Gram-Negative Bacteria Holding Together in a Biofilm: The Acinetobacter baumannii Way
Microorganisms 2021, 9(7), 1353; https://doi.org/10.3390/microorganisms9071353 - 22 Jun 2021
Cited by 1 | Viewed by 915
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 [...] Read more.
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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Review
Biofilms in Diabetic Foot Ulcers: Significance and Clinical Relevance
Microorganisms 2020, 8(10), 1580; https://doi.org/10.3390/microorganisms8101580 - 14 Oct 2020
Cited by 12 | Viewed by 1536
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 [...] Read more.
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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