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Molecular Research of Biofilms in Microbial Infections
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Molecular Research of Biofilms in Microbial Infections

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: 20 February 2025 | Viewed by 10207

Special Issue Editors

Dr. Mara Di Giulio

E-Mail Website
Guest Editor
Department of Pharmacy, University of “G. d’Annunzio” Chieti-Pescara, Chieti, Italy
Interests: microbial biofilm; Helicobacter pylori; chronic wounds; microbial dormancy; chronic infections; innovative treatments; microbiota, probiotic prebiotics
Special Issues, Collections and Topics in MDPI journals
Dr. Silvia Di Lodovico

E-Mail Website
Guest Editor
Department of Pharmacy, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy
Interests: antimicrobial; anti-biofilm and anti-virulence activities of natural compounds alone and combined with antibiotics against multi drug-resistant strains (Helicobacter pylori, Staphylococcus spp., Pseudomonas aeruginosa, Candida albicans, Mycobacterium abscessus and other fast-growing mycobacteria)
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Microbial biofilms play an important role in persistent/chronic infections in humans. Inter-microbial interactions in biofilms, together with the presence of microorganisms resistant to conventional antimicrobials, make it necessary to study the mechanisms of bacteria–bacteria/bacteria–fungi interactions in detail, which involves exploring signal molecules related to biofilm maturation and planning innovative antimicrobial/antibiofilm sustainable approaches to potentiate conventional ones.

This Special Issue focuses on the polymicrobial nature of biofilms using in vitro, ex vivo, and in vivo studies, or innovative 3D models, on the molecular aspects of microbial biofilms and on new therapeutic agents to counteract microbial adhesion, biofilm formation, or the disaggregation of mature biofilms. In this Special Issue, original research articles and critical reviews on the molecular aspects of biofilms in microbial infections are welcome.

Dr. Mara Di Giulio
Dr. Silvia Di Lodovico
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
  • biofilm matrix
  • EPS
  • microbial interaction
  • antibiofilm agents
  • biofilm models

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Published Papers (6 papers)

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Research

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11 pages, 9701 KiB  
Article
Antibiofilm and Antivirulence Potentials of 3,2′-Dihydroxyflavone against Staphylococcus aureus
by Inji Park, Yong-Guy Kim, Jin-Hyung Lee and Jintae Lee
Int. J. Mol. Sci. 2024, 25(15), 8059; https://doi.org/10.3390/ijms25158059 - 24 Jul 2024
Cited by 1 | Viewed by 863
Abstract
Staphylococcus aureus, particularly drug-resistant strains, poses significant challenges in healthcare due to its ability to form biofilms, which confer increased resistance to antibiotics and immune responses. Building on previous knowledge that several flavonoids exhibit antibiofilm activity, this study sought to identify a [...] Read more.
Staphylococcus aureus, particularly drug-resistant strains, poses significant challenges in healthcare due to its ability to form biofilms, which confer increased resistance to antibiotics and immune responses. Building on previous knowledge that several flavonoids exhibit antibiofilm activity, this study sought to identify a novel flavonoid capable of effectively inhibiting biofilm formation and virulence factor production in S. aureus strains including MRSA. Among the 19 flavonoid-like compounds tested, 3,2′-dihydroxyflavone (3,2′-DHF) was identified for the first time as inhibiting biofilm formation and virulence factors in S. aureus with an MIC 75 µg/mL. The antibiofilm activity was further confirmed by microscopic methods. Notably, 3,2′-DHF at 5 µg/mL was effective in inhibiting both mono- and polymicrobial biofilms involving S. aureus and Candida albicans, a common co-pathogen. 3,2′-DHF reduces hemolytic activity, slime production, and the expression of key virulence factors such as hemolysin gene hla and nuclease gene nuc1 in S. aureus. These findings highlight the potential of 3,2′-DHF as a novel antibiofilm and antivirulence agent against both bacterial and fungal biofilms, offering a promising alternative to traditional antibiotics in the treatment of biofilm-associated infections. Full article
(This article belongs to the Special Issue Molecular Research of Biofilms in Microbial Infections)
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23 pages, 8940 KiB  
Article
Effect of Acetylsalicylic Acid on Biological Properties of Novel Cement Based on Calcium Phosphate Doped with Ions of Strontium, Copper, and Zinc
by Tamara Vlajić Tovilović, Sanja Petrović, Miloš Lazarević, Aleksandar Pavić, Nikola Plačkić, Aleksa Milovanović, Miloš Milošević, Vesna Miletic, Djordje Veljović and Milena Radunović
Int. J. Mol. Sci. 2024, 25(14), 7940; https://doi.org/10.3390/ijms25147940 - 20 Jul 2024
Viewed by 997
Abstract
This study aimed to compare the biological properties of newly synthesized cements based on calcium phosphate with a commercially used cement, mineral trioxide aggregate (MTA). Strontium (Sr)-, Copper (Cu)-, and Zinc (Zn)-doped hydroxyapatite (miHAp) powder was obtained through hydrothermal synthesis and characterized by [...] Read more.
This study aimed to compare the biological properties of newly synthesized cements based on calcium phosphate with a commercially used cement, mineral trioxide aggregate (MTA). Strontium (Sr)-, Copper (Cu)-, and Zinc (Zn)-doped hydroxyapatite (miHAp) powder was obtained through hydrothermal synthesis and characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy dispersive X-ray spectrometry (EDX). Calcium phosphate cement (CPC) was produced by mixing miHAp powder with a 20 wt.% citric acid solution, followed by the assessment of its compressive strength, setting time, and in vitro bioactivity. Acetylsalicylic acid (ASA) was added to the CPC, resulting in CPCA. Biological tests were conducted on CPC, CPCA, and MTA. The biocompatibility of the cement extracts was evaluated in vitro using human dental pulp stem cells (hDPSCs) and in vivo using a zebrafish model. Antibiofilm and antimicrobial effect (quantified by CFUs/mL) were assessed against Streptococcus mutans and Lactobacillus rhamnosus. None of the tested materials showed toxicity, while CPCA even increased hDPSCs proliferation. CPCA showed a better safety profile than MTA and CPC, and no toxic or immunomodulatory effects on the zebrafish model. CPCA exhibited similar antibiofilm effects against S. mutans and L. rhamnosus to MTA. Full article
(This article belongs to the Special Issue Molecular Research of Biofilms in Microbial Infections)
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15 pages, 2581 KiB  
Article
Quantifying the Dynamics of Bacterial Biofilm Formation on the Surface of Soft Contact Lens Materials Using Digital Holographic Tomography to Advance Biofilm Research
by Igor Buzalewicz, Aleksandra Kaczorowska, Wojciech Fijałkowski, Aleksandra Pietrowska, Anna Karolina Matczuk, Halina Podbielska, Alina Wieliczko, Wojciech Witkiewicz and Natalia Jędruchniewicz
Int. J. Mol. Sci. 2024, 25(5), 2653; https://doi.org/10.3390/ijms25052653 - 24 Feb 2024
Cited by 1 | Viewed by 2332
Abstract
The increase in bacterial resistance to antibiotics in recent years demands innovative strategies for the detection and combating of biofilms, which are notoriously resilient. Biofilms, particularly those on contact lenses, can lead to biofilm-related infections (e.g., conjunctivitis and keratitis), posing a significant risk [...] Read more.
The increase in bacterial resistance to antibiotics in recent years demands innovative strategies for the detection and combating of biofilms, which are notoriously resilient. Biofilms, particularly those on contact lenses, can lead to biofilm-related infections (e.g., conjunctivitis and keratitis), posing a significant risk to patients. Non-destructive and non-contact sensing techniques are essential in addressing this threat. Digital holographic tomography emerges as a promising solution. This allows for the 3D reconstruction of the refractive index distribution in biological samples, enabling label-free visualization and the quantitative analysis of biofilms. This tool provides insight into the dynamics of biofilm formation and maturation on the surface of transparent materials. Applying digital holographic tomography for biofilm examination has the potential to advance our ability to combat the antibiotic bacterial resistance crisis. A recent study focused on characterizing biofilm formation and maturation on six soft contact lens materials (three silicone hydrogels, three hydrogels), with a particular emphasis on Staphylococcus epidermis and Pseudomonas aeruginosa, both common culprits in ocular infections. The results revealed species- and time-dependent variations in the refractive indexes and volumes of biofilms, shedding light on cell dynamics, cell death, and contact lens material-related factors. The use of digital holographic tomography enables the quantitative analysis of biofilm dynamics, providing us with a better understanding and characterization of bacterial biofilms. Full article
(This article belongs to the Special Issue Molecular Research of Biofilms in Microbial Infections)
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16 pages, 7354 KiB  
Article
Acute Ammonia Causes Pathogenic Dysbiosis of Shrimp Gut Biofilms
by Ning Gao, Yi Shu, Yongming Wang, Meng Sun, Zhongcheng Wei, Chenxi Song, Weipeng Zhang, Yue Sun, Xiaoli Hu, Zhenmin Bao and Wei Ding
Int. J. Mol. Sci. 2024, 25(5), 2614; https://doi.org/10.3390/ijms25052614 - 23 Feb 2024
Viewed by 1608
Abstract
Acute ammonia exposure has detrimental effects on shrimp, but the underlying mechanisms remain to be fully explored. In the present study, we investigated the impact of acute ammonia exposure on the gut microbiota of the white shrimp Litopenaeus vannamei and its association with [...] Read more.
Acute ammonia exposure has detrimental effects on shrimp, but the underlying mechanisms remain to be fully explored. In the present study, we investigated the impact of acute ammonia exposure on the gut microbiota of the white shrimp Litopenaeus vannamei and its association with shrimp mortality. Exposure to a lethal concentration of ammonia for 48 h resulted in increased mortality in L. vannamei, with severe damage to the hepatopancreas. Ammonia exposure led to a significant decrease in gut microbial diversity, along with the loss of beneficial bacterial taxa and the proliferation of pathogenic Vibrio strains. A phenotypic analysis revealed a transition from the dominance of aerobic to facultative anaerobic strains due to ammonia exposure. A functional analysis revealed that ammonia exposure led to an enrichment of genes related to biofilm formation, host colonization, and virulence pathogenicity. A species-level analysis and experiments suggest the key role of a Vibrio harveyi strain in causing shrimp disease and specificity under distinct environments. These findings provide new information on the mechanism of shrimp disease under environmental changes. Full article
(This article belongs to the Special Issue Molecular Research of Biofilms in Microbial Infections)
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17 pages, 5336 KiB  
Article
Strong Activity and No Resistance Induction Exerted by Cell-Free Supernatants from Lacticaseibacillus rhamnosus against Mono-Species and Dual-Species Biofilms of Wound Pathogens in In Vivo-like Conditions
by Esingül Kaya, Marta Bianchi, Giuseppantonio Maisetta, Semih Esin and Giovanna Batoni
Int. J. Mol. Sci. 2024, 25(4), 2087; https://doi.org/10.3390/ijms25042087 - 8 Feb 2024
Cited by 1 | Viewed by 1422
Abstract
It is widely agreed that microbial biofilms play a major role in promoting infection and delaying healing of chronic wounds. In the era of microbial resistance, probiotic strains or their metabolic products are emerging as an innovative approach for the treatment of hard-to-heal [...] Read more.
It is widely agreed that microbial biofilms play a major role in promoting infection and delaying healing of chronic wounds. In the era of microbial resistance, probiotic strains or their metabolic products are emerging as an innovative approach for the treatment of hard-to-heal (chronic) wounds due to their antimicrobial, healing, and host immune-modulatory effects. In this study, we aimed to investigate the potential of cell-free supernatants (CFS) from Lacticaseibacillus rhamnosus GG against mono- and dual-species biofilms of wound pathogens in a 3D in vitro infection model. Mature biofilms of Pseudomonas aeruginosa and Staphylococcus aureus were obtained on collagen scaffolds in the presence of a simulant wound fluid (SWF) and treated with CFS at different doses and time intervals. At 1:4 dilution in SWF, CFS caused a marked reduction in the colony forming-unit (CFU) numbers of bacteria embedded in mono-species biofilms as well as bacteria released by the biofilms in the supernatant. CFU count and electron microscopy imaging also demonstrated a marked antibiofilm effect against dual-species biofilms starting from 8 h of incubation. Furthermore, CFS exhibited acceptable levels of cytotoxicity at 24 h of incubation against HaCaT cells and, differently from ciprofloxacin, failed to induce resistance after 15 passages at sub-inhibitory concentrations. Overall, the results obtained point to L. rhamnosus GG postbiotics as a promising strategy for the treatment of wound biofilms. Full article
(This article belongs to the Special Issue Molecular Research of Biofilms in Microbial Infections)
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Review

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17 pages, 923 KiB  
Review
Mycobacterial Biofilm: Mechanisms, Clinical Problems, and Treatments
by Xining Liu, Junxing Hu, Wenzhen Wang, Hanyu Yang, Erning Tao, Yufang Ma and Shanshan Sha
Int. J. Mol. Sci. 2024, 25(14), 7771; https://doi.org/10.3390/ijms25147771 - 16 Jul 2024
Cited by 1 | Viewed by 1590
Abstract
Tuberculosis (TB) remains a threat to human health worldwide. Mycobacterium tuberculosis (Mtb) and other nontuberculous mycobacteria (NTM) can form biofilms, and in vitro and animal experiments have shown that biofilms cause serious drug resistance and mycobacterial persistence. Deeper investigations into the mechanisms of [...] Read more.
Tuberculosis (TB) remains a threat to human health worldwide. Mycobacterium tuberculosis (Mtb) and other nontuberculous mycobacteria (NTM) can form biofilms, and in vitro and animal experiments have shown that biofilms cause serious drug resistance and mycobacterial persistence. Deeper investigations into the mechanisms of mycobacterial biofilm formation and, consequently, the exploration of appropriate antibiofilm treatments to improve the efficiency of current anti-TB drugs will be useful for curing TB. In this review, the genes and molecules that have been recently reported to be involved in mycobacterial biofilm development, such as ABC transporter, Pks1, PpiB, GroEL1, MprB, (p)ppGpp, poly(P), and c-di-GMP, are summarized. Biofilm-induced clinical problems, including biofilm-related infections and enhanced virulence, as well as their possible mechanisms, are also discussed in detail. Moreover, we also illustrate newly synthesized anti-TB agents that target mycobacterial biofilm, as well as some assistant methods with high efficiency in reducing biofilms in hosts, such as the use of nanoparticles. Full article
(This article belongs to the Special Issue Molecular Research of Biofilms in Microbial Infections)
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