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Antibiotics
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Nature Inspired Antibiotic Adjuvants to Face the Problem of Multidrug...
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Nature Inspired Antibiotic Adjuvants to Face the Problem of Multidrug Resistance and Biofilm Infections

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

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 23656

Special Issue Editors

Dr. Anabela Borges

E-Mail Website
Guest Editor
Laboratory for Process Engineering, Environment, Biotechnology and Energy (LEPABE), Department of Chemical Engineering, Faculty of Engineering, University of Porto, 4099-002 Porto, Portugal
Interests: bacterial infection; multidrug-resistance; biofilms; phytochemicals; strategies of biofilm prevention and control; quorum-sensing; quorum-quenching; virulence attenuators; drug-repurposing; molecular docking
Special Issues, Collections and Topics in MDPI journals
Dr. Manuel Simões

grade E-Mail Website
Guest Editor
LEPABE, Department of Chemical Engineering, Faculty of Engineering, University of Porto, Rua Roberto Frias, s/n, 4200-465 Porto, Portugal
Interests: antimicrobial agents; emerging antimicrobial strategies; antimicrobial resistance; biofilms; plant secondary metabolites
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Multidrug resistance to antibiotics has reached a large scale, threatening the effective prevention and treatment of an ever-increasing range of infectious diseases. Biofilm-related infections are one of the leading reasons for the increased antibiotic resistance. Several systematic investigations have tried to develop effective strategies for biofilm control. However, no antibiofilm molecule directed for the treatment of infectious diseases has yet been approved. Despite the global concern and actions to counteract this significant problem, the World Health Organization is warning about a lack of innovation and investment for R&D in antimicrobial chemotherapy. In addition, innovative directions are needed to bring both “fresh impetus” and new alternatives, which include, among other things, the use of antibiotic potentiators or enablers, nature-based products, antivirulence agents, biofilm inhibitors/disruptors, repurposing non-antibiotic drugs, and the combination of therapies. This Special Issue aims to gather original research papers or high-quality reviews on these subjects. Contributions of interest include (but are not restricted to) the identification and development (extraction/design/synthesis) of new nature-based products (particularly from the secondary metabolism of plants—phytochemicals) to improve/maintain antibiotic activity against microorganisms in the planktonic state and in biofilms, the antimicrobial modes of action of nature-based products; antivirulence mechanisms for controlling infections through non-antimicrobial effects, drug-repurposing strategies for antimicrobial chemotherapy, and bioinformatics in antibiotic development.

Dr. Anabela Portela Borges
Prof. Dr. Manuel Simões
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

  • Antibiotic resistance
  • Biofilms
  • Persister cells
  • Regrowth events
  • Antibiotic adjuvants
  • Resistance modifiers
  • Natural products
  • Phytochemicals
  • Drug discovery and development
  • Drug-repurposing
  • Antimicrobial mode of action
  • Virulence atenuators
  • Quorum-sensing inhibitors
  • Methal chelators
  • Virtual screening
  • Molecular docking

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Published Papers (5 papers)

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Research

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17 pages, 3828 KiB  
Article
Screening of Natural Molecules as Adjuvants to Topical Antibiotics to Treat Staphylococcus aureus from Diabetic Foot Ulcer Infections
by Diana Oliveira, Anabela Borges, Maria J. Saavedra, Fernanda Borges and Manuel Simões
Antibiotics 2022, 11(5), 620; https://doi.org/10.3390/antibiotics11050620 - 4 May 2022
Cited by 8 | Viewed by 3254
Abstract
Diabetic foot ulcers (DFUs) are a common result of a complex secondary complication of diabetes mellitus. More than half of DFUs become infected due to frequent colonization with Staphylococcus aureus. The use of topical antibiotics is proposed, especially in combination with [...] Read more.
Diabetic foot ulcers (DFUs) are a common result of a complex secondary complication of diabetes mellitus. More than half of DFUs become infected due to frequent colonization with Staphylococcus aureus. The use of topical antibiotics is proposed, especially in combination with natural adjuvants, to minimize the negative impacts caused by generalized use of systemic antibiotics. In this study, 13 different phytochemicals—namely chalcone, juglone, cinnamic acid, trigonelline, Furvina—and four nitrovinylfuran derivatives—guaiazulene, α-bisabolol, farnesol and nerolidol—were selected to be tested as antibiotic enhancers. After minimum inhibitory and bactericidal concentration (MIC and MBC) determination of each molecule against different strains of S. aureus, including clinical isolates from diabetic foot wounds (CECT 976, Xu212, SA 1199B, RN4220, MJMC102, MJMC109, MJMC110 and MJMC111), their potentiation effects on the antibiotics fusidic acid, mupirocin, gentamicin, oxacillin and methicillin were evaluated through the disc diffusion method. Farnesol at sub-MIC was able to restore the activity of methicillin and oxacillin on the MJMC102 and MJMC111 strains, as well as two MRSA clinical isolates, and potentiated the effect of the remaining antibiotics. The results obtained demonstrate the great potential for the topical application of phytochemicals and derivatives as antibiotic resistance modifier agents to combat multidrug resistance in bacterial wound infections. Full article
(This article belongs to the Special Issue Nature Inspired Antibiotic Adjuvants to Face the Problem of Multidrug Resistance and Biofilm Infections)
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14 pages, 1064 KiB  
Article
Self-Disinfecting Paints with the Natural Antimicrobial Substances: Colophony and Curcumin
by Micaela Machado Querido, Ivo Paulo, Sriram Hariharakrishnan, Daniel Rocha, Nuno Barbosa, Rui Galhano dos Santos, João Moura Bordado, João Paulo Teixeira and Cristiana Costa Pereira
Antibiotics 2021, 10(11), 1351; https://doi.org/10.3390/antibiotics10111351 - 5 Nov 2021
Cited by 8 | Viewed by 2985
Abstract
The risk of infection arising from indirect sources—namely, contaminated surfaces—has been proved, particularly in healthcare facilities. In the attempt to minimize this problem, innumerable research projects involving the development of surfaces with self-disinfecting properties are being conducted. In this work, wall-paints with self-disinfecting [...] Read more.
The risk of infection arising from indirect sources—namely, contaminated surfaces—has been proved, particularly in healthcare facilities. In the attempt to minimize this problem, innumerable research projects involving the development of surfaces with self-disinfecting properties are being conducted. In this work, wall-paints with self-disinfecting properties were developed with the scope of being applied in environments prone to contamination, such as those at healthcare settings. Our approach was to develop new paint formulations containing two natural plant-based products with known antimicrobial activity—colophony (CLF) and curcumin (CUR). The natural substances were separately incorporated on a commercial paint and their antibacterial activity was evaluated with several bacterial species following ISO 22196. To assess the paints’ safety, cytotoxicity tests were performed on HaCaT and A549 cell lines, using tests on extracts and direct contact tests, as suggested by the standardized protocol ISO 10993. In general, both paints containing CLF and CUR were able to reduce the bacterial growth after 24 h, compared with the control, the commercial unmodified paint. Colophony was even able to reduce the number of culturable bacteria by over 2 log for Staphylococcus aureus, Escherichia coli, and Bacillus cereus. Regarding the cytotoxicity tests performed (WST-1, NRU, and LDH), both formulations revealed promising results regardless of the methodology used. Full article
(This article belongs to the Special Issue Nature Inspired Antibiotic Adjuvants to Face the Problem of Multidrug Resistance and Biofilm Infections)
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12 pages, 1537 KiB  
Article
Insulin Regulation of Escherichia coli Abiotic Biofilm Formation: Effect of Nutrients and Growth Conditions
by Nina Patel, Jeremy C. Curtis and Balbina J. Plotkin
Antibiotics 2021, 10(11), 1349; https://doi.org/10.3390/antibiotics10111349 - 5 Nov 2021
Cited by 4 | Viewed by 2632
Abstract
Escherichia coli plays an important role in biofilm formation across a wide array of disease and ecological settings. Insulin can function as an adjuvant in the regulation of biofilm levels. The modulation of insulin-regulated biofilm formation by environmental conditions has not been previously [...] Read more.
Escherichia coli plays an important role in biofilm formation across a wide array of disease and ecological settings. Insulin can function as an adjuvant in the regulation of biofilm levels. The modulation of insulin-regulated biofilm formation by environmental conditions has not been previously described. In the present study, the effects that various environmental growth conditions and nutrients have on insulin-modulated levels of biofilm production were measured. Micropipette tips were incubated with E. coli ATCC® 25922™ in a Mueller Hinton broth (MH), or a yeast nitrogen base with 1% peptone (YNBP), which was supplemented with glucose, lactose, galactose and/or insulin (Humulin®-R). The incubation conditions included a shaking or static culture, at 23 °C or 37 °C. After incubation, the biofilm production was calculated per CFU. At 23 °C, the presence of insulin increased biofilm formation. The amount of biofilm formation was highest in glucose > galactose >> lactose, while the biofilm levels decreased in shaking cultures, except for galactose (3-fold increase; 0.1% galactose and 20 μU insulin). At 37 °C, regardless of condition, there was more biofilm formation/CFU under static conditions in YNBP than in MH, except for the MH containing galactose. E. coli biofilm formation is influenced by aeration, temperature, and insulin concentration in combination with the available sugars. Full article
(This article belongs to the Special Issue Nature Inspired Antibiotic Adjuvants to Face the Problem of Multidrug Resistance and Biofilm Infections)
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24 pages, 6805 KiB  
Article
Prevalence and Impact of Biofilms on Bloodstream and Urinary Tract Infections: A Systematic Review and Meta-Analysis
by Henrique Pinto, Manuel Simões and Anabela Borges
Antibiotics 2021, 10(7), 825; https://doi.org/10.3390/antibiotics10070825 - 8 Jul 2021
Cited by 30 | Viewed by 5292
Abstract
This study sought to assess the prevalence and impact of biofilms on two commonly biofilm-related infections, bloodstream and urinary tract infections (BSI and UTI). Separated systematic reviews and meta-analyses of observational studies were carried out in PubMed and Web of Sciences databases from [...] Read more.
This study sought to assess the prevalence and impact of biofilms on two commonly biofilm-related infections, bloodstream and urinary tract infections (BSI and UTI). Separated systematic reviews and meta-analyses of observational studies were carried out in PubMed and Web of Sciences databases from January 2005 to May 2020, following PRISMA protocols. Studies were selected according to specific and defined inclusion/exclusion criteria. The obtained outcomes were grouped into biofilm production (BFP) prevalence, BFP in resistant vs. susceptible strains, persistent vs. non-persistent BSI, survivor vs. non-survivor patients with BSI, and catheter-associated UTI (CAUTI) vs. non-CAUTI. Single-arm and two-arm analyses were conducted for data analysis. In vitro BFP in BSI was highly related to resistant strains (odds ratio-OR: 2.68; 95% confidence intervals-CI: 1.60–4.47; p < 0.01), especially for methicillin-resistant Staphylococci. BFP was also highly linked to BSI persistence (OR: 2.65; 95% CI: 1.28–5.48; p < 0.01) and even to mortality (OR: 2.05; 95% CI: 1.53–2.74; p < 0.01). Candida spp. was the microorganism group where the highest associations were observed. Biofilms seem to impact Candida BSI independently from clinical differences, including treatment interventions. Regarding UTI, multi-drug resistant and extended-spectrum β-lactamase-producing strains of Escherichia coli, were linked to a great BFP prevalence (OR: 2.92; 95% CI: 1.30–6.54; p < 0.01 and OR: 2.80; 95% CI: 1.33–5.86; p < 0.01). More in vitro BFP was shown in CAUTI compared to non-CAUTI, but with less statistical confidence (OR: 2.61; 95% CI: 0.67–10.17; p < 0.17). This study highlights that biofilms must be recognized as a BSI and UTI resistance factor as well as a BSI virulence factor. Full article
(This article belongs to the Special Issue Nature Inspired Antibiotic Adjuvants to Face the Problem of Multidrug Resistance and Biofilm Infections)
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Review

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24 pages, 2260 KiB  
Review
Biofilms in Surgical Site Infections: Recent Advances and Novel Prevention and Eradication Strategies
by Andriy Hrynyshyn, Manuel Simões and Anabela Borges
Antibiotics 2022, 11(1), 69; https://doi.org/10.3390/antibiotics11010069 - 7 Jan 2022
Cited by 50 | Viewed by 7731
Abstract
Surgical site infections (SSIs) are common postoperative occurrences due to contamination of the surgical wound or implanted medical devices with community or hospital-acquired microorganisms, as well as other endogenous opportunistic microbes. Despite numerous rules and guidelines applied to prevent these infections, SSI rates [...] Read more.
Surgical site infections (SSIs) are common postoperative occurrences due to contamination of the surgical wound or implanted medical devices with community or hospital-acquired microorganisms, as well as other endogenous opportunistic microbes. Despite numerous rules and guidelines applied to prevent these infections, SSI rates are considerably high, constituting a threat to the healthcare system in terms of morbidity, prolonged hospitalization, and death. Approximately 80% of human SSIs, including chronic wound infections, are related to biofilm-forming bacteria. Biofilm-associated SSIs are extremely difficult to treat with conventional antibiotics due to several tolerance mechanisms provided by the multidrug-resistant bacteria, usually arranged as polymicrobial communities. In this review, novel strategies to control, i.e., prevent and eradicate, biofilms in SSIs are presented and discussed, focusing mainly on two attractive approaches: the use of nanotechnology-based composites and natural plant-based products. An overview of new therapeutic agents and strategic approaches to control epidemic multidrug-resistant pathogenic microorganisms, particularly when biofilms are present, is provided alongside other combinatorial approaches as attempts to obtain synergistic effects with conventional antibiotics and restore their efficacy to treat biofilm-mediated SSIs. Some detection and real-time monitoring systems to improve biofilm control strategies and diagnosis of human infections are also discussed. Full article
(This article belongs to the Special Issue Nature Inspired Antibiotic Adjuvants to Face the Problem of Multidrug Resistance and Biofilm Infections)
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