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Molecular Signaling and Nanobiotechnology: Prospects for Future Antimicrobial Therapy

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

Deadline for manuscript submissions: closed (28 February 2018) | Viewed by 69963

Special Issue Editors

Department of Science and Engineereing of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, Politehnica University of Bucharest, RO-011061 Bucharest, Romania
Interests: synthesis and characterization of nanobiomaterials; polymers; pharmaceutical nanotechnology; drug delivery; anti-biofilm surfaces; nanomodified surfaces; natural products
Special Issues, Collections and Topics in MDPI journals
1. Department of Microbiology and Immunology, Faculty of Biology, University of Bucharest, 060101 Bucharest, Romania
2. The Research Institute of the University of Bucharest, ICUB, 060023 Bucharest, Romania
Interests: microbiology; immunology; new antimicrobial agents; host-pathogen signaling; infection control; antimicrobial nanomaterials; bacterial pathogenesis; virulence factors; quorum sensing; biofilms; antibacterial activity; antibiotic resistance; Staphylococcus aureus; Escherichia coli; Pseudomonas aeruginosa; microbial molecular biology; bioactive materials; nanotechnology; nanoengineering
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Since current antimicrobial approaches are becoming less efficient and the antibiotic resistance phenomenon is emerging, alternative therapies are highly investigated for infection control. Recent progress made in order to limit the development of severe infections show that the modulation of certain bacterial behaviors by using signaling molecules or nanosized structures may reduce pathogenicity and virulence, resulting in mild infections. These small molecules proved their efficiency both in vitro and in vivo studies and are currently considered for the development of alternative and ecological anti-infectious therapies, being mostly represented by natural factors obtained from microbial, plant and even animal cells. Nanotechnology, the science of nanometer sized materials, plays a very important role in the implementation of novel antimicrobial therapies by stabilizing, improving the delivery and efficiency and by reducing side effects of many antimicrobial compounds. Moreover, many nanosized materials proved their antimicrobial efficiency in severe and difficult to treat infections, such as those caused by highly resistant pathogens and biofilm associated infectious diseases. The purpose of this special issue is to reveal the most recent and applicative progress developed on the field of novel antimicrobial approaches by highlighting the impact of signaling molecules and nanostructured biomaterials in the design of future anti-infectious therapies.

Dr. Alexandru Mihai Grumezescu
Dr. Alina Maria Holban
Guest Editors

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Keywords

  • signaling molecules
  • antimicrobial nanoparticles
  • anti-biofilm nanocoatings
  • molecular communication
  • virulence modulation
  • natural antibiotics
  • drug-delivery

Published Papers (8 papers)

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Research

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14 pages, 4622 KiB  
Article
Preparation of Fish Skin Gelatin-Based Nanofibers Incorporating Cinnamaldehyde by Solution Blow Spinning
by Fei Liu, Furkan Türker Saricaoglu, Roberto J. Avena-Bustillos, David F. Bridges, Gary R. Takeoka, Vivian C. H. Wu, Bor-Sen Chiou, Delilah F. Wood, Tara H. McHugh and Fang Zhong
Int. J. Mol. Sci. 2018, 19(2), 618; https://doi.org/10.3390/ijms19020618 - 22 Feb 2018
Cited by 29 | Viewed by 5768
Abstract
Cinnamaldehyde, a natural preservative that can non-specifically deactivate foodborne pathogens, was successfully incorporated into fish skin gelatin (FSG) solutions and blow spun into uniform nanofibers. The effects of cinnamaldehyde ratios (5–30%, w/w FSG) on physicochemical properties of fiber-forming emulsions (FFEs) and [...] Read more.
Cinnamaldehyde, a natural preservative that can non-specifically deactivate foodborne pathogens, was successfully incorporated into fish skin gelatin (FSG) solutions and blow spun into uniform nanofibers. The effects of cinnamaldehyde ratios (5–30%, w/w FSG) on physicochemical properties of fiber-forming emulsions (FFEs) and their nanofibers were investigated. Higher ratios resulted in higher values in particle size and viscosity of FFEs, as well as higher values in diameter of nanofibers. Loss of cinnamaldehyde was observed during solution blow spinning (SBS) process and cinnamaldehyde was mainly located on the surface of resultant nanofibers. Nanofibers all showed antibacterial activity by direct diffusion and vapor release against Escherichia coli O157:H7, Salmonella typhimurium, and Listeria monocytogenes. Inhibition zones increased as cinnamaldehyde ratio increased. Nanofibers showed larger inhibition effects than films prepared by casting method when S. typhimurium was exposed to the released cinnamaldehyde vapor, although films had higher remaining cinnamaldehyde than nanofibers after preparation. Lower temperature was favorable for cinnamaldehyde retention, and nanofibers added with 10% cinnamaldehyde ratio showed the highest retention over eight-weeks of storage. Results suggest that FSG nanofibers can be prepared by SBS as carriers for antimicrobials. Full article
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1915 KiB  
Article
Azithromycin and Chloramphenicol Diminish Neutrophil Extracellular Traps (NETs) Release
by Weronika Bystrzycka, Aneta Manda-Handzlik, Sandra Sieczkowska, Aneta Moskalik, Urszula Demkow and Olga Ciepiela
Int. J. Mol. Sci. 2017, 18(12), 2666; https://doi.org/10.3390/ijms18122666 - 08 Dec 2017
Cited by 60 | Viewed by 5950
Abstract
Neutrophils are one of the first cells to arrive at the site of infection, where they apply several strategies to kill pathogens: degranulation, respiratory burst, phagocytosis, and release of neutrophil extracellular traps (NETs). Antibiotics have an immunomodulating effect, and they can influence the [...] Read more.
Neutrophils are one of the first cells to arrive at the site of infection, where they apply several strategies to kill pathogens: degranulation, respiratory burst, phagocytosis, and release of neutrophil extracellular traps (NETs). Antibiotics have an immunomodulating effect, and they can influence the properties of numerous immune cells, including neutrophils. The aim of this study was to investigate the effects of azithromycin and chloramphenicol on degranulation, apoptosis, respiratory burst, and the release of NETs by neutrophils. Neutrophils were isolated from healthy donors by density-gradient centrifugation method and incubated for 1 h with the studied antibiotics at different concentrations (0.5, 10 and 50 μg/mL—azithromycin and 10 and 50 μg/mL—chloramphenicol). Next, NET release was induced by a 3 h incubation with 100 nM phorbol 12-myristate 13-acetate (PMA). Amount of extracellular DNA was quantified by fluorometry, and NETs were visualized by immunofluorescent microscopy. Degranulation, apoptosis and respiratory burst were assessed by flow cytometry. We found that pretreatment of neutrophils with azithromycin and chloramphenicol decreases the release of NETs. Moreover, azithromycin showed a concentration-dependent effect on respiratory burst in neutrophils. Chloramphenicol did not affect degranulation, apoptosis nor respiratory burst. It can be concluded that antibiotics modulate the ability of neutrophils to release NETs influencing human innate immunity. Full article
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3616 KiB  
Article
pH-Dependent Antimicrobial Properties of Copper Oxide Nanoparticles in Staphylococcus aureus
by Yi-Huang Hsueh, Ping-Han Tsai and Kuen-Song Lin
Int. J. Mol. Sci. 2017, 18(4), 793; https://doi.org/10.3390/ijms18040793 - 08 Apr 2017
Cited by 57 | Viewed by 6176
Abstract
The antimicrobial properties of CuO nanoparticles have been investigated, but the underlying mechanisms of toxicity remain the subject of debate. Here, we show that CuO nanoparticles exhibit significant toxicity at pH 5 against four different Staphylococcus aureus (S. aureus) strains, including Newman, SA113, [...] Read more.
The antimicrobial properties of CuO nanoparticles have been investigated, but the underlying mechanisms of toxicity remain the subject of debate. Here, we show that CuO nanoparticles exhibit significant toxicity at pH 5 against four different Staphylococcus aureus (S. aureus) strains, including Newman, SA113, USA300, and ATCC6538. At this pH, but not at pH 6 and 7, 5 mM CuO nanoparticles effectively caused reduction of SA113 and Newman cells and caused at least 2 log reduction, whereas 20 mM killed most strains but not USA300. At 5 mM, the nanoparticles were also found to dramatically decrease reductase activity in SA113, Newman, and ATCC6538 cells, but not USA300 cells. In addition, analysis of X-ray absorption near-edge structure and extended X-ray absorption fine structure confirmed that S. aureus cells exposed to CuO nanoparticles contain CuO, indicating that Cu2+ ions released from nanoparticles penetrate bacterial cells and are subsequently oxidized intracellularly to CuO at mildly acidic pH. The CuO nanoparticles were more soluble at pH 5 than at pH 6 and 7. Taken together, the data conclusively show that the toxicity of CuO nanoparticles in mildly acidic pH is caused by Cu2+ release, and that USA300 is more resistant to CuO nanoparticles (NPs) than the other three strains. Full article
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7668 KiB  
Article
Interaction of New-Developed TiO2-Based Photocatalytic Nanoparticles with Pathogenic Microorganisms and Human Dermal and Pulmonary Fibroblasts
by Ionela Cristina Nica, Miruna Silvia Stan, Marcela Popa, Mariana Carmen Chifiriuc, Veronica Lazar, Gratiela G. Pircalabioru, Iuliana Dumitrescu, Madalina Ignat, Marcel Feder, Liviu Cristian Tanase, Ionel Mercioniu, Lucian Diamandescu and Anca Dinischiotu
Int. J. Mol. Sci. 2017, 18(2), 249; https://doi.org/10.3390/ijms18020249 - 25 Jan 2017
Cited by 25 | Viewed by 4989
Abstract
TiO2-based photocatalysts were obtained during previous years in order to limit pollution and to ease human daily living conditions due to their special properties. However, obtaining biocompatible photocatalysts is still a key problem, and the mechanism of their toxicity recently received [...] Read more.
TiO2-based photocatalysts were obtained during previous years in order to limit pollution and to ease human daily living conditions due to their special properties. However, obtaining biocompatible photocatalysts is still a key problem, and the mechanism of their toxicity recently received increased attention. Two types of TiO2 nanoparticles co-doped with 1% of iron and nitrogen (TiO2-1% Fe–N) atoms were synthesized in hydrothermal conditions at pH of 8.5 (HT1) and 5.5 (HT2), and their antimicrobial activity and cytotoxic effects exerted on human pulmonary and dermal fibroblasts were assessed. These particles exhibited significant microbicidal and anti-biofilm activity, suggesting their potential application for microbial decontamination of different environments. In addition, our results demonstrated the biocompatibility of TiO2-1% Fe–N nanoparticles at low doses on lung and dermal cells, which may initiate oxidative stress through dose accumulation. Although no significant changes were observed between the two tested photocatalysts, the biological response was cell type specific and time- and dose-dependent; the lung cells proved to be more sensitive to nanoparticle exposure. Taken together, these experimental data provide useful information for future photocatalytic applications in the industrial, food, pharmaceutical, and medical fields. Full article
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Review

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28 pages, 1720 KiB  
Review
Nanoparticles for Signaling in Biodiagnosis and Treatment of Infectious Diseases
by Clara I. Colino, Carmen Gutiérrez Millán and José M. Lanao
Int. J. Mol. Sci. 2018, 19(6), 1627; https://doi.org/10.3390/ijms19061627 - 31 May 2018
Cited by 43 | Viewed by 6410
Abstract
Advances in nanoparticle-based systems constitute a promising research area with important implications for the treatment of bacterial infections, especially against multidrug resistant strains and bacterial biofilms. Nanosystems may be useful for the diagnosis and treatment of viral and fungal infections. Commercial diagnostic tests [...] Read more.
Advances in nanoparticle-based systems constitute a promising research area with important implications for the treatment of bacterial infections, especially against multidrug resistant strains and bacterial biofilms. Nanosystems may be useful for the diagnosis and treatment of viral and fungal infections. Commercial diagnostic tests based on nanosystems are currently available. Different methodologies based on nanoparticles (NPs) have been developed to detect specific agents or to distinguish between Gram-positive and Gram-negative microorganisms. Also, biosensors based on nanoparticles have been applied in viral detection to improve available analytical techniques. Several point-of-care (POC) assays have been proposed that can offer results faster, easier and at lower cost than conventional techniques and can even be used in remote regions for viral diagnosis. Nanoparticles functionalized with specific molecules may modulate pharmacokinetic targeting recognition and increase anti-infective efficacy. Quorum sensing is a stimuli-response chemical communication process correlated with population density that bacteria use to regulate biofilm formation. Disabling it is an emerging approach for combating its pathogenicity. Natural or synthetic inhibitors may act as antibiofilm agents and be useful for treating multi-drug resistant bacteria. Nanostructured materials that interfere with signal molecules involved in biofilm growth have been developed for the control of infections associated with biofilm-associated infections. Full article
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20 pages, 10295 KiB  
Review
Nanocoatings for Chronic Wound Repair—Modulation of Microbial Colonization and Biofilm Formation
by Mara Mădălina Mihai, Mădălina Preda, Iulia Lungu, Monica Cartelle Gestal, Mircea Ioan Popa and Alina Maria Holban
Int. J. Mol. Sci. 2018, 19(4), 1179; https://doi.org/10.3390/ijms19041179 - 12 Apr 2018
Cited by 82 | Viewed by 8502
Abstract
Wound healing involves a complex interaction between immunity and other natural host processes, and to succeed it requires a well-defined cascade of events. Chronic wound infections can be mono- or polymicrobial but their major characteristic is their ability to develop a biofilm. A [...] Read more.
Wound healing involves a complex interaction between immunity and other natural host processes, and to succeed it requires a well-defined cascade of events. Chronic wound infections can be mono- or polymicrobial but their major characteristic is their ability to develop a biofilm. A biofilm reduces the effectiveness of treatment and increases resistance. A biofilm is an ecosystem on its own, enabling the bacteria and the host to establish different social interactions, such as competition or cooperation. With an increasing incidence of chronic wounds and, implicitly, of chronic biofilm infections, there is a need for alternative therapeutic agents. Nanotechnology shows promising openings, either by the intrinsic antimicrobial properties of nanoparticles or their function as drug carriers. Nanoparticles and nanostructured coatings can be active at low concentrations toward a large variety of infectious agents; thus, they are unlikely to elicit emergence of resistance. Nanoparticles might contribute to the modulation of microbial colonization and biofilm formation in wounds. This comprehensive review comprises the pathogenesis of chronic wounds, the role of chronic wound colonization and infection in the healing process, the conventional and alternative topical therapeutic approaches designed to combat infection and stimulate healing, as well as revolutionizing therapies such as nanotechnology-based wound healing approaches. Full article
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40 pages, 28288 KiB  
Review
Antibacterial Free Fatty Acids and Monoglycerides: Biological Activities, Experimental Testing, and Therapeutic Applications
by Bo Kyeong Yoon, Joshua A. Jackman, Elba R. Valle-González and Nam-Joon Cho
Int. J. Mol. Sci. 2018, 19(4), 1114; https://doi.org/10.3390/ijms19041114 - 08 Apr 2018
Cited by 322 | Viewed by 19410
Abstract
Antimicrobial lipids such as fatty acids and monoglycerides are promising antibacterial agents that destabilize bacterial cell membranes, causing a wide range of direct and indirect inhibitory effects. The goal of this review is to introduce the latest experimental approaches for characterizing how antimicrobial [...] Read more.
Antimicrobial lipids such as fatty acids and monoglycerides are promising antibacterial agents that destabilize bacterial cell membranes, causing a wide range of direct and indirect inhibitory effects. The goal of this review is to introduce the latest experimental approaches for characterizing how antimicrobial lipids destabilize phospholipid membranes within the broader scope of introducing current knowledge about the biological activities of antimicrobial lipids, testing strategies, and applications for treating bacterial infections. To this end, a general background on antimicrobial lipids, including structural classification, is provided along with a detailed description of their targeting spectrum and currently understood antibacterial mechanisms. Building on this knowledge, different experimental approaches to characterize antimicrobial lipids are presented, including cell-based biological and model membrane-based biophysical measurement techniques. Particular emphasis is placed on drawing out how biological and biophysical approaches complement one another and can yield mechanistic insights into how the physicochemical properties of antimicrobial lipids influence molecular self-assembly and concentration-dependent interactions with model phospholipid and bacterial cell membranes. Examples of possible therapeutic applications are briefly introduced to highlight the potential significance of antimicrobial lipids for human health and medicine, and to motivate the importance of employing orthogonal measurement strategies to characterize the activity profile of antimicrobial lipids. Full article
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17 pages, 3729 KiB  
Review
Similarities and Differences between Silver Ions and Silver in Nanoforms as Antibacterial Agents
by Anna Kędziora, Mateusz Speruda, Eva Krzyżewska, Jacek Rybka, Anna Łukowiak and Gabriela Bugla-Płoskońska
Int. J. Mol. Sci. 2018, 19(2), 444; https://doi.org/10.3390/ijms19020444 - 02 Feb 2018
Cited by 319 | Viewed by 11641
Abstract
Silver is considered as antibacterial agent with well-known mode of action and bacterial resistance against it is well described. The development of nanotechnology provided different methods for the modification of the chemical and physical structure of silver, which may increase its antibacterial potential. [...] Read more.
Silver is considered as antibacterial agent with well-known mode of action and bacterial resistance against it is well described. The development of nanotechnology provided different methods for the modification of the chemical and physical structure of silver, which may increase its antibacterial potential. The physico-chemical properties of silver nanoparticles and their interaction with living cells differs substantially from those of silver ions. Moreover, the variety of the forms and characteristics of various silver nanoparticles are also responsible for differences in their antibacterial mode of action and probably bacterial mechanism of resistance. The paper discusses in details the aforementioned aspects of silver activity. Full article
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