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New Types of Antibacterial Biocides

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: closed (30 November 2022) | Viewed by 27801

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N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, 119991 Moscow, Russia
Interests: application of electrochemical methods in organic chemistry and synthesis; elaboration of selective synthetic methods in electroorganic and organic chemistry; domino and multicomponent reactions with C-H acids, carbonyls and olefins; development of synthetic approaches to new classes of antiseptics and disinfectants
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Special Issue Information

Dear Colleagues,

Today, the development of new highly effective antiseptics, disinfectants, and materials that bestow antimicrobial activity, environmental safety, and relatively low toxicity is of exceptional importance for significant areas of chemistry and materials science. The SARS-CoV-2 (COVID-19) pandemic, which began in 2020, has contributed to a sharp increase in the use of disinfectants, which multiply the risk of developing bacterial resistance and could lead to a sharp decrease in the effectiveness of biocidal in the future. A separate challenge for the scientific community is the ability of microorganisms to organize themselves into biofilms, i.e., a structured community in a self-produced polymeric matrix. The formation of biofilms is a global problem affecting various spheres of life. Thus, biofilms cause up to 80% of chronic human bacterial infections, and contribute to the development of microbial tolerance to traditional drugs and multidrug resistance. The ever-increasing number of resistant bacterial strains is of great concern, because if this problem is left unaddressed, by 2050, antimicrobial resistance (AMR) could claim more lives than cancer.

In general, there are two main strategies for combating biofilms: preventing their formation or destroying/removing already formed biofilm. Amino acids and antimicrobial peptides, metal chelators, quorum sensing inhibitors, surfactants, and other antibiofilm agents can be effectively used at different stages of biofilm formation.

The aim of the Special Issue is to review recent research on the synthesis and application of new antibacterial biocides. Full articles, short communications, and reviews are accepted for publication in the Special Issue. 

Prof. Dr. Anatoly N. Vereshchagin
Guest Editor

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Keywords

  • tantimicrobial biocides
  • pathogens
  • bacterial resistance
  • microbial biofilms
  • quaternary ammonium compounds
  • antiseptics

Published Papers (14 papers)

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14 pages, 1941 KiB  
Article
Antibacterial and Antibiofilm Properties of Self-Assembled Dipeptide Nanotubes
by Iris Soares, Inês Rodrigues, Paulo Martins da Costa and Luís Gales
Int. J. Mol. Sci. 2023, 24(1), 328; https://doi.org/10.3390/ijms24010328 - 25 Dec 2022
Cited by 3 | Viewed by 1441
Abstract
Over recent decades, multidrug-resistant pathogens have become a global concern, with WHO even considering it one of the biggest threats to global health, food security, and development today, which led to the search for alternative antibacterial agents. A special class is formed by [...] Read more.
Over recent decades, multidrug-resistant pathogens have become a global concern, with WHO even considering it one of the biggest threats to global health, food security, and development today, which led to the search for alternative antibacterial agents. A special class is formed by peptides composed by the diphenylalanine motif whose antibacterial properties result from their supramolecular arrangement into nanotubes. However, several other dipeptides that also form nanotubes have been largely overlooked. Here, we present the antibacterial activity of four dipeptide nanotubes. The results point to diverse mechanisms through which dipeptide nanotubes exert their effect against bacteria. Antibacterial activity was similar for dipeptide nanotubes sufficiently wide to allow water flux while dipeptides displaying smaller channels were inactive. This suggests that two of the tested dipeptides, L-Phe-L-Phe (FF, diphenylalanine) and L-Leu-L-Ser (LS), are pore forming structures able to induce membrane permeation and affect cellular hydration and integrity. Of these two dipeptides, only FF demonstrated potential to inhibit biofilm formation. The amyloid-like nature and hydrophobicity of diphenylalanine assemblies are probably responsible for their adhesion to cell surfaces preventing biofilm formation and bacteria attachment. Full article
(This article belongs to the Special Issue New Types of Antibacterial Biocides)
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12 pages, 2047 KiB  
Article
Evolution of Ceftriaxone Resistance of Penicillin-Binding Proteins 2 Revealed by Molecular Modeling
by Alexandra V. Krivitskaya and Maria G. Khrenova
Int. J. Mol. Sci. 2023, 24(1), 176; https://doi.org/10.3390/ijms24010176 - 22 Dec 2022
Viewed by 1890
Abstract
Penicillin-binding proteins 2 (PBP2) are critically important enzymes in the formation of the bacterial cell wall. Inhibition of PBP2 is utilized in the treatment of various diseases, including gonorrhea. Ceftriaxone is the only drug used to treat gonorrhea currently, and recent growth in [...] Read more.
Penicillin-binding proteins 2 (PBP2) are critically important enzymes in the formation of the bacterial cell wall. Inhibition of PBP2 is utilized in the treatment of various diseases, including gonorrhea. Ceftriaxone is the only drug used to treat gonorrhea currently, and recent growth in PBP2 resistance to this antibiotic is a serious threat to human health. Our study reveals mechanistic aspects of the inhibition reaction of PBP2 from the wild-type FA19 strain and mutant 35/02 and H041 strains of Neisseria Gonorrhoeae by ceftriaxone. QM(PBE0-D3/6-31G**)/MM MD simulations show that the reaction mechanism for the wild-type PBP2 consists of three elementary steps including nucleophilic attack, C–N bond cleavage in the β-lactam ring and elimination of the leaving group in ceftriaxone. In PBP2 from the mutant strains, the second and third steps occur simultaneously. For all considered systems, the acylation rate is determined by the energy barrier of the first step that increases in the order of PBP2 from FA19, 35/02 and H041 strains. Dynamic behavior of ES complexes is analyzed using geometry and electron density features including Fukui electrophilicity index and Laplacian of electron density maps. It reveals that more efficient activation of the carbonyl group of the antibiotic leads to the lower energy barrier of nucleophilic attack and larger stabilization of the first reaction intermediate. Dynamical network analysis of MD trajectories explains the differences in ceftriaxone binding affinity: in PBP2 from the wild-type strain, the β34 loop conformation facilitates substrate binding, whereas in PBP2 from the mutant strains, it exists in the conformation that is unfavorable for complex formation. Thus, we clarify that the experimentally observed decrease in the second-order rate constant of acylation (k2/KS) in PBP2 from the mutant strains is due to both a decrease in the acylation rate constant k2 and an increase in the dissociation constant KS. Full article
(This article belongs to the Special Issue New Types of Antibacterial Biocides)
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16 pages, 2622 KiB  
Article
Succinyl Chitosan-Colistin Conjugates as Promising Drug Delivery Systems
by Natallia V. Dubashynskaya, Anton N. Bokatyi, Anatoliy V. Dobrodumov, Igor V. Kudryavtsev, Andrey S. Trulioff, Artem A. Rubinstein, Arthur D. Aquino, Yaroslav A. Dubrovskii, Elena S. Knyazeva, Elena V. Demyanova, Yuliya A. Nashchekina and Yury A. Skorik
Int. J. Mol. Sci. 2023, 24(1), 166; https://doi.org/10.3390/ijms24010166 - 22 Dec 2022
Cited by 3 | Viewed by 2351
Abstract
The growth of microbial multidrug resistance is a problem in modern clinical medicine. Chemical modification of active pharmaceutical ingredients is an attractive strategy to improve their biopharmaceutical properties by increasing bioavailability and reducing drug toxicity. Conjugation of antimicrobial drugs with natural polysaccharides provides [...] Read more.
The growth of microbial multidrug resistance is a problem in modern clinical medicine. Chemical modification of active pharmaceutical ingredients is an attractive strategy to improve their biopharmaceutical properties by increasing bioavailability and reducing drug toxicity. Conjugation of antimicrobial drugs with natural polysaccharides provides high efficiency of these systems due to targeted delivery, controlled drug release and reduced toxicity. This paper reports a two-step synthesis of colistin conjugates (CT) with succinyl chitosan (SucCS); first, we modified chitosan with succinyl anhydride to introduce a carboxyl function into the polymer molecule, which was then used for chemical grafting with amino groups of the peptide antibiotic CT using carbodiimide chemistry. The resulting polymeric delivery systems had a degree of substitution (DS) by CT of 3–8%, with conjugation efficiencies ranging from 54 to 100% and CT contents ranging from 130–318 μg/mg. The size of the obtained particles was 100–200 nm, and the ζ-potential varied from −22 to −28 mV. In vitro release studies at pH 7.4 demonstrated ultra-slow hydrolysis of amide bonds, with a CT release of 0.1–0.5% after 12 h; at pH 5.2, the hydrolysis rate slightly increased; however, it remained extremely low (1.5% of CT was released after 12 h). The antimicrobial activity of the conjugates depended on the DS. At DS 8%, the minimum inhibitory concentration (MIC) of the conjugate was equal to the MIC of native CT (1 µg/mL); at DS of 3 and 5%, the MIC increased 8-fold. In addition, the developed systems reduced CT nephrotoxicity by 20–60%; they also demonstrated the ability to reduce bacterial lipopolysaccharide-induced inflammation in vitro. Thus, these promising CT-SucCS conjugates are prospective for developing safe and effective nanoantibiotics. Full article
(This article belongs to the Special Issue New Types of Antibacterial Biocides)
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14 pages, 609 KiB  
Article
Efficacy of Vaporized Hydrogen Peroxide Combined with Silver Ions against Multidrug-Resistant Gram-Negative and Gram-Positive Clinical Isolates
by Sandra Patricia Rivera-Sánchez, José María Rojas-Abadía, John Jairo Ríos-Acevedo, Ana Fernanda Mejía-Hurtado, Luz Natalia Espinosa-Moya and Iván Darío Ocampo-Ibáñez
Int. J. Mol. Sci. 2022, 23(24), 15826; https://doi.org/10.3390/ijms232415826 - 13 Dec 2022
Cited by 2 | Viewed by 1743
Abstract
Antimicrobial resistance (AMR) is a serious public health problem that results in high morbidity and mortality rates. In particular, multidrug-resistant (MDR) strains circulating in hospital settings pose a major threat as they are associated with serious nosocomial infections. Therefore, regular cleaning and disinfection [...] Read more.
Antimicrobial resistance (AMR) is a serious public health problem that results in high morbidity and mortality rates. In particular, multidrug-resistant (MDR) strains circulating in hospital settings pose a major threat as they are associated with serious nosocomial infections. Therefore, regular cleaning and disinfection procedures, usually using chemical disinfectants, must be implemented in these facilities. Hydrogen peroxide (HP)-based disinfectants have proven high microbicidal activity and several comparative advantages over conventional disinfectants. We assessed the in vitro biocidal activity of an 8% HP solution combined with 30 mg/L silver ions (HP + Ag) against MDR clinical isolates of Klebsiella pneumoniae (MDRKp) and Pseudomonas aeruginosa (MDRPa), and methicillin-resistant Staphylococcus aureus (MRSA). Accordingly, the in vitro antibacterial activity was determined using the macrodilution method, and the efficacy was determined for 30 min in terms of (1) activity on bacteria in suspension and (2) activity on surfaces using vaporized HP + Ag on a 20 cm2 stainless steel surface. A strong bactericidal effect of HP + Ag was observed against MDRKp, MDRPa, and MRSA strains, with minimum inhibitory concentrations and minimum bactericidal concentrations between 362.5 and 5800 mg/L. A strong effect was observed during the 30 min of HP + Ag exposure to the resistant clinical isolates, with over 4-Log10 reduction in CFUs. Regarding the efficacy of the disinfectant on surfaces, bacterial load reductions of >99% were observed. These results suggest that HP + Ag is potentially useful as an effective disinfectant for decontaminating surfaces in hospital settings suspected of contamination with MDR bacteria. Full article
(This article belongs to the Special Issue New Types of Antibacterial Biocides)
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15 pages, 1804 KiB  
Article
Derivatives of Trimethoxybenzoic Acid and Gallic Acid as Potential Efflux Pump Inhibitors: In Silico and In Vitro Studies
by Ana Rita Neves, Fernando Durães, Joana Freitas-Silva, Nikoletta Szemerédi, Paulo Martins-da-Costa, Eugénia Pinto, Marta Correia-da-Silva, Gabriella Spengler and Emília Sousa
Int. J. Mol. Sci. 2022, 23(22), 14468; https://doi.org/10.3390/ijms232214468 - 21 Nov 2022
Viewed by 1536
Abstract
The overexpression of efflux pumps is one of the strategies used by bacteria to resist antibiotics and could be targeted to circumvent the antibiotic crisis. In this work, a series of trimethoxybenzoic acid derivatives previously described as antifouling compounds was explored for potential [...] Read more.
The overexpression of efflux pumps is one of the strategies used by bacteria to resist antibiotics and could be targeted to circumvent the antibiotic crisis. In this work, a series of trimethoxybenzoic acid derivatives previously described as antifouling compounds was explored for potential antimicrobial activity and efflux pump (EP) inhibition. First, docking studies on the acridine resistance proteins A and B coupled to the outer membrane channel TolC (AcrAB-TolC) efflux system and a homology model of the quinolone resistance protein NorA EP were performed on 11 potential bioactive trimethoxybenzoic acid and gallic acid derivatives. The synthesis of one new trimethoxybenzoic acid derivative (derivative 13) was accomplished. To investigate the potential of this series of 11 derivatives as antimicrobial agents, and in reverting drug resistance, the minimum inhibitory concentration was determined on several strains (bacteria and fungi), and synergy with antibiotics and EP inhibition were investigated. Derivative 10 showed antibacterial activity against the studied strains, derivatives 5 and 6 showed the ability to inhibit EPs in the acrA gene inactivated mutant Salmonella enterica serovar Typhimurium SL1344, and 6 also inhibited EPs in Staphylococcus aureus 272123. Structure-activity relationships highlighted trimethoxybenzoic acid as important for EP inhibitory activity. Although further studies are necessary, these results show the potential of simple trimethoxybenzoic acid derivatives as a source of feasible EP inhibitors. Full article
(This article belongs to the Special Issue New Types of Antibacterial Biocides)
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19 pages, 1766 KiB  
Article
Expanding the Landscape of Amino Acid-Rich Antimicrobial Peptides: Definition, Deployment in Nature, Implications for Peptide Design and Therapeutic Potential
by Aaron P. Decker, Abraham F. Mechesso and Guangshun Wang
Int. J. Mol. Sci. 2022, 23(21), 12874; https://doi.org/10.3390/ijms232112874 - 25 Oct 2022
Cited by 9 | Viewed by 2533
Abstract
Unlike the α-helical and β-sheet antimicrobial peptides (AMPs), our knowledge on amino acid-rich AMPs is limited. This article conducts a systematic study of rich AMPs (>25%) from different life kingdoms based on the Antimicrobial Peptide Database (APD) using the program R. Of 3425 [...] Read more.
Unlike the α-helical and β-sheet antimicrobial peptides (AMPs), our knowledge on amino acid-rich AMPs is limited. This article conducts a systematic study of rich AMPs (>25%) from different life kingdoms based on the Antimicrobial Peptide Database (APD) using the program R. Of 3425 peptides, 724 rich AMPs were identified. Rich AMPs are more common in animals and bacteria than in plants. In different animal classes, a unique set of rich AMPs is deployed. While histidine, proline, and arginine-rich AMPs are abundant in mammals, alanine, glycine, and leucine-rich AMPs are common in amphibians. Ten amino acids (Ala, Cys, Gly, His, Ile, Lys, Leu, Pro, Arg, and Val) are frequently observed in rich AMPs, seven (Asp, Glu, Phe, Ser, Thr, Trp, and Tyr) are occasionally observed, and three (Met, Asn, and Gln) were not yet found. Leucine is much more frequent in forming rich AMPs than either valine or isoleucine. To date, no natural AMPs are simultaneously rich in leucine and lysine, while proline, tryptophan, and cysteine-rich peptides can simultaneously be rich in arginine. These findings can be utilized to guide peptide design. Since multiple candidates are potent against antibiotic-resistant bacteria, rich AMPs stand out as promising future antibiotics. Full article
(This article belongs to the Special Issue New Types of Antibacterial Biocides)
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13 pages, 3782 KiB  
Article
Respiratory Depression as Antibacterial Mechanism of Linalool against Pseudomonas fragi Based on Metabolomics
by Yuansong Li, Rongrong He, Haiming Chen, Da Chen and Wenxue Chen
Int. J. Mol. Sci. 2022, 23(19), 11586; https://doi.org/10.3390/ijms231911586 - 30 Sep 2022
Cited by 3 | Viewed by 1726
Abstract
Linalool showed a broad-spectrum antibacterial effect, but few studies have elucidated the antibacterial mechanism of linalool on Pseudomonas fragi (P. fragi) to date. The present study aimed to uncover the antimicrobial activity and potential mechanism of linalool against P. fragi by [...] Read more.
Linalool showed a broad-spectrum antibacterial effect, but few studies have elucidated the antibacterial mechanism of linalool on Pseudomonas fragi (P. fragi) to date. The present study aimed to uncover the antimicrobial activity and potential mechanism of linalool against P. fragi by determining key enzyme activities and metabolites combined with a high-throughput method and metabolomic pathway analysis. As a result, linalool had excellent inhibitory activity against P. fragi with MIC of 1.5 mL/L. In addition, the presence of linalool significantly altered the intracellular metabolic profile and a total of 346 differential metabolites were identified, of which 201 were up-regulated and 145 were down-regulated. The highlight pathways included beta-alanine metabolism, pantothenic acid and CoA metabolism, alanine, aspartate and glutamate metabolism, nicotinate and nicotinamide metabolism. Overall, linalool could cause metabolic disorders in cells, and the main metabolic pathways involved energy metabolism, amino acid metabolism and nucleic acid metabolism. In particular, the results of intracellular ATP content and related enzymatic activities (ATPase, SDH, and GOT) also highlighted that energy limitation and amino acid disturbance occurred intracellularly. Together, these findings provided new insights into the mechanism by which linalool inhibited P. fragi and theoretical guidance for its development as a natural preservative. Full article
(This article belongs to the Special Issue New Types of Antibacterial Biocides)
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24 pages, 1897 KiB  
Article
Eco-Friendly Solution Based on Rosmarinus officinalis Hydro-Alcoholic Extract to Prevent Biodeterioration of Cultural Heritage Objects and Buildings
by Viorica Maria Corbu, Irina Gheorghe-Barbu, Ioana Cristina Marinas, Sorin Marius Avramescu, Ionut Pecete, Elisabeta Irina Geanǎ and Mariana Carmen Chifiriuc
Int. J. Mol. Sci. 2022, 23(19), 11463; https://doi.org/10.3390/ijms231911463 - 28 Sep 2022
Cited by 4 | Viewed by 1663
Abstract
Biodeterioration of cultural heritage is caused by different organisms capable of inducing complex alteration processes. The present study aimed to evaluate the efficiency of Rosmarinus officinalis hydro-alcoholic extract to inhibit the growth of deteriogenic microbial strains. For this, the physico-chemical characterization of the [...] Read more.
Biodeterioration of cultural heritage is caused by different organisms capable of inducing complex alteration processes. The present study aimed to evaluate the efficiency of Rosmarinus officinalis hydro-alcoholic extract to inhibit the growth of deteriogenic microbial strains. For this, the physico-chemical characterization of the vegetal extract by UHPLC–MS/MS, its antimicrobial and antibiofilm activity on a representative number of biodeteriogenic microbial strains, as well as the antioxidant activity determined by DPPH, CUPRAC, FRAP, TEAC methods, were performed. The extract had a total phenol content of 15.62 ± 0.97 mg GAE/mL of which approximately 8.53% were flavonoids. The polyphenolic profile included carnosic acid, carnosol, rosmarinic acid and hesperidin as major components. The extract exhibited good and wide spectrum antimicrobial activity, with low MIC (minimal inhibitory concentration) values against fungal strains such as Aspergillus clavatus (MIC = 1.2 mg/mL) and bacterial strains such as Arthrobacter globiformis (MIC = 0.78 mg/mL) or Bacillus cereus (MIC = 1.56 mg/mL). The rosemary extract inhibited the adherence capacity to the inert substrate of Penicillium chrysogenum strains isolated from wooden objects or textiles and B. thuringiensis strains. A potential mechanism of R. officinalis antimicrobial activity could be represented by the release of nitric oxide (NO), a universal signalling molecule for stress management. Moreover, the treatment of microbial cultures with subinhibitory concentrations has modulated the production of microbial enzymes and organic acids involved in biodeterioration, with the effect depending on the studied microbial strain, isolation source and the tested soluble factor. This paper reports for the first time the potential of R. officinalis hydro-alcoholic extract for the development of eco-friendly solutions dedicated to the conservation/safeguarding of tangible cultural heritage. Full article
(This article belongs to the Special Issue New Types of Antibacterial Biocides)
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16 pages, 2564 KiB  
Article
“Universal” Antimicrobial Combination of Bacitracin and His6-OPH with Lactonase Activity, Acting against Various Bacterial and Yeast Cells
by Aysel Aslanli, Maksim Domnin, Nikolay Stepanov and Elena Efremenko
Int. J. Mol. Sci. 2022, 23(16), 9400; https://doi.org/10.3390/ijms23169400 - 20 Aug 2022
Cited by 10 | Viewed by 1619
Abstract
The effect of Bacitracin as an antibiotic acting against Gram-positive bacterial cells was evaluated in combination with hexahistidine-containing organophosphate hydrolase (His6-OPH), possessing lactonase activity against various N-acylhomoserine lactones produced by most Gram-negative bacteria as quorum-sensing molecules. The molecular docking technique [...] Read more.
The effect of Bacitracin as an antibiotic acting against Gram-positive bacterial cells was evaluated in combination with hexahistidine-containing organophosphate hydrolase (His6-OPH), possessing lactonase activity against various N-acylhomoserine lactones produced by most Gram-negative bacteria as quorum-sensing molecules. The molecular docking technique was used to obtain in silico confirmation of possible interactions between molecules of His6-OPH and Bacitracin as well as the absence of a significant influence of such interactions on the enzymatic catalysis. The in vitro experiments showed a sufficient catalytic efficiency of action of the His6-OPH/Bacitracin combination as compared to the native enzyme. The notable improvement (up to 3.3 times) of antibacterial efficiency of Bacitracin was revealed in relation to Gram-negative bacteria when it was used in combination with His6-OPH. For the first time, the action of the Bacitracin with and without His6-OPH was shown to be effective against various yeast strains, and the presence of the enzyme increased the antibiotic effect up to 8.5 times. To estimate the role of the enzyme in the success of His6-OPH/Bacitracin with yeast, in silico experiments (molecular docking) with various fungous lactone-containing molecules were undertaken, and the opportunity of their enzymatic hydrolysis by His6-OPH was revealed in the presence and absence of Bacitracin. Full article
(This article belongs to the Special Issue New Types of Antibacterial Biocides)
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19 pages, 3720 KiB  
Article
In Vitro Bioactivity and Antibacterial Effects of a Silver-Containing Mesoporous Bioactive Glass Film on the Surface of Titanium Implants
by Yueh-Ching Wang, Sheng-Hui Lin, Chi-Sheng Chien, Jung-Chang Kung and Chi-Jen Shih
Int. J. Mol. Sci. 2022, 23(16), 9291; https://doi.org/10.3390/ijms23169291 - 18 Aug 2022
Cited by 14 | Viewed by 1895
Abstract
Peri-implantitis is defined as a bacterial infection-induced inflammation and suppuration of soft and hard tissues surrounding a dental implant. If bacteria further invade the alveolar bone, they can easily cause bone loss and even lead to the early failure of a dental implant [...] Read more.
Peri-implantitis is defined as a bacterial infection-induced inflammation and suppuration of soft and hard tissues surrounding a dental implant. If bacteria further invade the alveolar bone, they can easily cause bone loss and even lead to the early failure of a dental implant surgery. In the present study, an 80SiO2–15CaO–5P2O5 mesoporous bioactive glass film system containing 1, 5, and 10 mol% of silver was prepared on titanium implant discs (MBG–Ag–coated Ti) using sol-gel and spin coating methods. The wettability and adhesion strength of the films were evaluated using contact angle measurements and adhesion strength tests, respectively. The phase composition, chemical bonding, morphology, and oxidation states of the films were analyzed via X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS). In vitro bioactivity analysis of the films was performed by immersion in a simulated body fluid (SBF) for 24 h. Disk diffusion tests were performed on the early colonizing bacteria Aggregatibacter actinomycetemcomitans and Streptococcus mutans to evaluate the antibacterial ability of the films. A silver-containing mesoporous bioactive glass film with excellent biocompatibility and antibacterial properties was successfully prepared. Full article
(This article belongs to the Special Issue New Types of Antibacterial Biocides)
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18 pages, 3725 KiB  
Article
Promiscuous Lipase-Catalyzed Knoevenagel–Phospha–Michael Reaction for the Synthesis of Antimicrobial β-Phosphono Malonates
by Jan Samsonowicz-Górski, Dominik Koszelewski, Paweł Kowalczyk, Paweł Śmigielski, Anastasiia Hrunyk, Karol Kramkowski, Aleksandra Wypych, Mateusz Szymczak, Rafał Lizut and Ryszard Ostaszewski
Int. J. Mol. Sci. 2022, 23(15), 8819; https://doi.org/10.3390/ijms23158819 - 8 Aug 2022
Cited by 6 | Viewed by 1911
Abstract
An enzymatic route for phosphorous–carbon bond formation was developed by discovering new promiscuous activity of lipase. We reported a new metal-free biocatalytic method for the synthesis of pharmacologically relevant β-phosphonomalononitriles via a lipase-catalyzed one-pot Knoevenagel–phospha–Michael reaction. We carefully analyzed the best conditions for [...] Read more.
An enzymatic route for phosphorous–carbon bond formation was developed by discovering new promiscuous activity of lipase. We reported a new metal-free biocatalytic method for the synthesis of pharmacologically relevant β-phosphonomalononitriles via a lipase-catalyzed one-pot Knoevenagel–phospha–Michael reaction. We carefully analyzed the best conditions for the given reaction: the type of enzyme, temperature, and type of solvent. A series of target compounds was synthesized, with yields ranging from 43% to 93% by enzymatic reaction with Candida cylindracea (CcL) lipase as recyclable and, a few times, reusable catalyst. The advantages of this protocol are excellent yields, mild reaction conditions, low costs, and sustainability. The applicability of the same catalyst in the synthesis of β-phosphononitriles is also described. Further, the obtained compounds were validated as new potential antimicrobial agents with characteristic E. coli bacterial strains. The pivotal role of such a group of phosphonate derivatives on inhibitory activity against selected pathogenic E. coli strains was revealed. The observed results are especially important in the case of the increasing resistance of bacteria to various drugs and antibiotics. The impact of the β-phosphono malonate chemical structure on antimicrobial activity was demonstrated. The crucial role of the substituents attached to the aromatic ring on the inhibitory action against selected pathogenic E. coli strains was revealed. Among tested compounds, four β-phosphonate derivatives showed an antimicrobial activity profile similar to that obtained with currently used antibiotics such as ciprofloxacin, bleomycin, and cloxacillin. In addition, the obtained compounds constitute a convenient platform for further chemical functionalization, allowing for a convenient change in their biological activity profile. It should also be noted that the cost of the compounds obtained is low, which may be an attractive alternative to the currently used antimicrobial agents. The observed results are especially important because of the increasing resistance of bacteria to various drugs and antibiotics. Full article
(This article belongs to the Special Issue New Types of Antibacterial Biocides)
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13 pages, 8228 KiB  
Article
Antibiofilm Activities of Cinnamaldehyde Analogs against Uropathogenic Escherichia coli and Staphylococcus aureus
by Yeseul Kim, Sanghun Kim, Kiu-Hyung Cho, Jin-Hyung Lee and Jintae Lee
Int. J. Mol. Sci. 2022, 23(13), 7225; https://doi.org/10.3390/ijms23137225 - 29 Jun 2022
Cited by 13 | Viewed by 2261
Abstract
Bacterial biofilm formation is a major cause of drug resistance and bacterial persistence; thus, controlling pathogenic biofilms is an important component of strategies targeting infectious bacterial diseases. Cinnamaldehyde (CNMA) has broad-spectrum antimicrobial and antibiofilm activities. In this study, we investigated the antibiofilm effects [...] Read more.
Bacterial biofilm formation is a major cause of drug resistance and bacterial persistence; thus, controlling pathogenic biofilms is an important component of strategies targeting infectious bacterial diseases. Cinnamaldehyde (CNMA) has broad-spectrum antimicrobial and antibiofilm activities. In this study, we investigated the antibiofilm effects of ten CNMA derivatives and trans-CNMA against Gram-negative uropathogenic Escherichia coli (UPEC) and Gram-positive Staphylococcus aureus. Among the CNMA analogs tested, 4-nitrocinnamaldehyde (4-nitroCNMA) showed antibacterial and antibiofilm activities against UPEC and S. aureus with minimum inhibitory concentrations (MICs) for cell growth of 100 µg/mL, which were much more active than those of trans-CNMA. 4-NitroCNMA inhibited UPEC swimming motility, and both trans-CNMA and 4-nitroCNMA reduced extracellular polymeric substance production by UPEC. Furthermore, 4-nitroCNMA inhibited the formation of mixed UPEC/S. aureus biofilms. Collectively, our observations indicate that trans-CNMA and 4-nitroCNMA potently inhibit biofilm formation by UPEC and S. aureus. We suggest efforts be made to determine the therapeutic scope of CNMA analogs, as our results suggest CNMA derivatives have potential therapeutic use for biofilm-associated diseases. Full article
(This article belongs to the Special Issue New Types of Antibacterial Biocides)
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Review

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14 pages, 1650 KiB  
Review
Added Value of Biophysics to Study Lipid-Driven Biological Processes: The Case of Surfactins, a Class of Natural Amphiphile Molecules
by Guillaume Gilliard, Aurélien L. Furlan, Willy Smeralda, Jelena Pršić and Magali Deleu
Int. J. Mol. Sci. 2022, 23(22), 13831; https://doi.org/10.3390/ijms232213831 - 10 Nov 2022
Cited by 3 | Viewed by 1278
Abstract
The role of membrane lipids is increasingly claimed to explain biological activities of natural amphiphile molecules. To decipher this role, biophysical studies with biomimetic membrane models are often helpful to obtain insights at the molecular and atomic levels. In this review, the added [...] Read more.
The role of membrane lipids is increasingly claimed to explain biological activities of natural amphiphile molecules. To decipher this role, biophysical studies with biomimetic membrane models are often helpful to obtain insights at the molecular and atomic levels. In this review, the added value of biophysics to study lipid-driven biological processes is illustrated using the case of surfactins, a class of natural lipopeptides produced by Bacillus sp. showing a broad range of biological activities. The mechanism of interaction of surfactins with biomimetic models showed to be dependent on the surfactins-to-lipid ratio with action as membrane disturber without membrane lysis at low and intermediate ratios and a membrane permeabilizing effect at higher ratios. These two mechanisms are relevant to explain surfactins’ biological activities occurring without membrane lysis, such as their antiviral and plant immunity-eliciting activities, and the one involving cell lysis, such as their antibacterial and hemolytic activities. In both biological and biophysical studies, influence of surfactin structure and membrane lipids on the mechanisms was observed with a similar trend. Hence, biomimetic models represent interesting tools to elucidate the biological mechanisms targeting membrane lipids and can contribute to the development of new molecules for pharmaceutical or agronomic applications. Full article
(This article belongs to the Special Issue New Types of Antibacterial Biocides)
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33 pages, 1553 KiB  
Review
“Omic” Approaches to Bacteria and Antibiotic Resistance Identification
by Daria Janiszewska, Małgorzata Szultka-Młyńska, Paweł Pomastowski and Bogusław Buszewski
Int. J. Mol. Sci. 2022, 23(17), 9601; https://doi.org/10.3390/ijms23179601 - 24 Aug 2022
Cited by 5 | Viewed by 2841
Abstract
The quick and accurate identification of microorganisms and the study of resistance to antibiotics is crucial in the economic and industrial fields along with medicine. One of the fastest-growing identification methods is the spectrometric approach consisting in the matrix-assisted laser ionization/desorption using a [...] Read more.
The quick and accurate identification of microorganisms and the study of resistance to antibiotics is crucial in the economic and industrial fields along with medicine. One of the fastest-growing identification methods is the spectrometric approach consisting in the matrix-assisted laser ionization/desorption using a time-of-flight analyzer (MALDI-TOF MS), which has many advantages over conventional methods for the determination of microorganisms presented. Thanks to the use of a multiomic approach in the MALDI-TOF MS analysis, it is possible to obtain a broad spectrum of data allowing the identification of microorganisms, understanding their interactions and the analysis of antibiotic resistance mechanisms. In addition, the literature data indicate the possibility of a significant reduction in the time of the sample preparation and analysis time, which will enable a faster initiation of the treatment of patients. However, it is still necessary to improve the process of identifying and supplementing the existing databases along with creating new ones. This review summarizes the use of “-omics” approaches in the MALDI TOF MS analysis, including in bacterial identification and antibiotic resistance mechanisms analysis. Full article
(This article belongs to the Special Issue New Types of Antibacterial Biocides)
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