International Journal of Molecular Sciences

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19 pages, 2101 KiB

Open AccessArticle

Design and Synthesis of Menthol and Thymol Derived Ciprofloxacin: Influence of Structural Modifications on the Antibacterial Activity and Anticancer Properties

by Tomasz Szostek, Daniel Szulczyk, Jolanta Szymańska-Majchrzak, Michał Koliński, Sebastian Kmiecik, Dagmara Otto-Ślusarczyk, Aleksandra Zawodnik, Eliza Rajkowska, Kinga Chaniewicz, Marta Struga and Piotr Roszkowski

Int. J. Mol. Sci. 2022, 23(12), 6600; https://doi.org/10.3390/ijms23126600 - 13 Jun 2022

Cited by 5 | Viewed by 2852

Abstract

Sixteen new Ciprofloxacin derivatives were designed and successfully synthesized. In an in silico experiment, lipophilicity was established for obtained compounds. All compounds were screened for antimicrobial activity using standard and clinical strains. As for Gram-positive hospital microorganisms, all tested derivatives were active. Measured [...] Read more.

Sixteen new Ciprofloxacin derivatives were designed and successfully synthesized. In an in silico experiment, lipophilicity was established for obtained compounds. All compounds were screened for antimicrobial activity using standard and clinical strains. As for Gram-positive hospital microorganisms, all tested derivatives were active. Measured MICs were in the range 1–16 µg/mL, confirming high antimicrobial potency. Derivative 12 demonstrated activity against all standard Gram-positive Staphylococci, within the range of 0.8–1.6 µg/mL and was confirmed as the leading structure with MICs 1 µg/mL for S. pasteuri KR 4358 and S. aureus T 5591 (clinical strains). All compounds were screened for their in vitro cytotoxic properties via the MTT method. Three of the examined compounds (3, 11 and 16) showed good activity against cancer cells, and in parallel were found not to be cytotoxic toward normal cells. Doxorubicin SI ranged 0.14–1.11 while the mentioned three ranged 1.9–3.4. Selected Ciprofloxacin derivatives were docked into the crystal structure of topoisomerase II (DNA gyrase) in complex with DNA (PDB ID: 5BTC). In summary, leading structures were established (3, 11, 12 and 16). We have observed poor results in preformed studies for disubstituted derivatives, suggesting that 3-oxo-4-carboxylic acid core is the active DNA-gyrase binding site, and when structural changes were made in this fragment, there was an observed decrease in antibacterial potency. Full article

(This article belongs to the Special Issue New Antibacterial Agents)

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14 pages, 5261 KiB

Open AccessArticle

A Type Ib Crustin from Deep-Sea Shrimp Possesses Antimicrobial and Immunomodulatory Activity

by Yu-Jian Wang and Li Sun

Int. J. Mol. Sci. 2022, 23(12), 6444; https://doi.org/10.3390/ijms23126444 - 9 Jun 2022

Viewed by 1887

Abstract

Crustins are small antimicrobial proteins produced by crustaceans. Of the many reported crustins, very few are from deep sea environments. Crustins are categorized into several types. Recently, the Type I crustin has been further classified into three subtypes, one of which is Type [...] Read more.

Crustins are small antimicrobial proteins produced by crustaceans. Of the many reported crustins, very few are from deep sea environments. Crustins are categorized into several types. Recently, the Type I crustin has been further classified into three subtypes, one of which is Type Ib, whose function is unknown. Here, we studied the function of a Type Ib crustin (designated Crus2) identified from a deep-sea crustacean. Crus2 has a whey acidic protein (WAP) domain and a long C-terminal region (named P58). Recombinant Crus2 bound to peptidoglycan (PGN), lipoteichoic acid (LTA), and lipopolysaccharide (LPS), and killed Gram-positive and Gram-negative bacteria by permeabilizing the bacterial cytomembrane. Consistently, Crus2 dramatically attenuated the inflammatory response induced by LPS and LTA. Disruption of the disulfide bonds in the WAP domain abolished the bactericidal ability of Crus2, but had no effect on the bacterial binding ability of Crus2. Deletion of the C-terminal P58 region moderately affected the antimicrobial activity of Crus2 against some bacteria. P58 as a synthesized peptide could bind bacteria and inhibit the bactericidal activity of Crus2. Taken together, these results revealed different roles played by the WAP domain and the P58 region in Type Ib crustin, and provided new insights into the antimicrobial and immunomodulatory functions of crustins. Full article

(This article belongs to the Special Issue New Antibacterial Agents)

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28 pages, 4637 KiB

Open AccessArticle

The Effect of Conjugation of Ciprofloxacin and Moxifloxacin with Fatty Acids on Their Antibacterial and Anticancer Activity

by Alicja Chrzanowska, Marta Struga, Piotr Roszkowski, Michał Koliński, Sebastian Kmiecik, Karolina Jałbrzykowska, Anna Zabost, Joanna Stefańska, Ewa Augustynowicz-Kopeć, Małgorzata Wrzosek and Anna Bielenica

Int. J. Mol. Sci. 2022, 23(11), 6261; https://doi.org/10.3390/ijms23116261 - 2 Jun 2022

Cited by 11 | Viewed by 3284

Abstract

Novel conjugates (CP) of moxifloxacin (MXF) with fatty acids (1m–16m) were synthesized with good yields utilizing amides chemistry. They exhibit a more pronounced cytotoxic potential than the parent drug. They were the most effective for prostate cancer cells with [...] Read more.

Novel conjugates (CP) of moxifloxacin (MXF) with fatty acids (1m–16m) were synthesized with good yields utilizing amides chemistry. They exhibit a more pronounced cytotoxic potential than the parent drug. They were the most effective for prostate cancer cells with an IC₅₀ below 5 µM for respective conjugates with sorbic (2m), oleic (4m), 6-heptenoic (10m), linoleic (11m), caprylic (15m), and stearic (16m) acids. All derivatives were evaluated against a panel of standard and clinical bacterial strains, as well as towards mycobacteria. The highest activity towards standard isolates was observed for the acetic acid derivative 14m, followed by conjugates of unsaturated crotonic (1m) and sorbic (2m) acids. The activity of conjugates tested against an expanded panel of clinical coagulase-negative staphylococci showed that the compound (14m) was recognized as a leading structure with an MIC of 0.5 μg/mL denoted for all quinolone-susceptible isolates. In the group of CP derivatives, sorbic (2) and geranic (3) acid amides exhibited the highest bactericidal potential against clinical strains. The M. tuberculosis Spec. 210 strain was the most sensitive to sorbic (2m) conjugate and to conjugates with medium- and long-chain polyunsaturated acids. To establish the mechanism of antibacterial action, selected CP and MXF conjugates were examined in both topoisomerase IV decatenation assay and the DNA gyrase supercoiling assay, followed by suitable molecular docking studies. Full article

(This article belongs to the Special Issue New Antibacterial Agents)

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13 pages, 3116 KiB

Open AccessArticle

In Vitro Antimicrobial Potential of CAPE and Caffeamide Derivatives against Oral Microbes

by Yin-Hwa Shih, Shih-Min Hsia, Kuo-Chou Chiu, Tong-Hong Wang, Chi-Ying Chien, Po-Jung Li, Yueh-Hsiung Kuo and Tzong-Ming Shieh

Int. J. Mol. Sci. 2022, 23(8), 4099; https://doi.org/10.3390/ijms23084099 - 7 Apr 2022

Cited by 4 | Viewed by 2203

Abstract

Caffeic acid phenethyl ester (CAPE) is a natural component isolated from propolis and used in traditional medicine. We aimed to investigate the antimicrobial properties and action mechanism of CAPE and caffeamide derivatives (26G and 36M) against oral disease microbes. We resolved the minimum [...] Read more.

Caffeic acid phenethyl ester (CAPE) is a natural component isolated from propolis and used in traditional medicine. We aimed to investigate the antimicrobial properties and action mechanism of CAPE and caffeamide derivatives (26G and 36M) against oral disease microbes. We resolved the minimum inhibitory and bactericidal concentrations of 26G and 36M and their stability at different temperatures and pH. We also evaluated their effect on biofilm formation and antibiotic resistance gene expression in methicillin-resistant Staphylococcus aureus (MRSA). Our results revealed that 26G and 36M showed the best anticancer and antimicrobial activities, respectively, compared with the other four caffeamide derivatives. Both 26G and 36M showed heat-dependent decreases in antimicrobial activity. The 36M derivative was stable irrespective of pH, whereas 26G was not stable under high pH conditions. Biofilm formation and antibiotic resistance-related gene expression were consistent with their respective phenotypes. This study provides evidence for the potential application of CAPE and caffeamide derivatives in dental medicine to cure or prevent oral diseases. Full article

(This article belongs to the Special Issue New Antibacterial Agents)

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18 pages, 4428 KiB

Open AccessArticle

The Antibacterial Effect of PEGylated Carbosilane Dendrimers on P. aeruginosa Alone and in Combination with Phage-Derived Endolysin

by Sara Quintana-Sanchez, Natalia Gómez-Casanova, Javier Sánchez-Nieves, Rafael Gómez, Jarosław Rachuna, Sławomir Wąsik, Jacek Semaniak, Barbara Maciejewska, Zuzanna Drulis-Kawa, Karol Ciepluch, F. Javier de la Mata and Michał Arabski

Int. J. Mol. Sci. 2022, 23(3), 1873; https://doi.org/10.3390/ijms23031873 - 7 Feb 2022

Cited by 19 | Viewed by 3284

Abstract

The search for new microbicide compounds is of an urgent need, especially against difficult-to-eradicate biofilm-forming bacteria. One attractive option is the application of cationic multivalent dendrimers as antibacterials and also as carriers of active molecules. These compounds require an adequate hydrophilic/hydrophobic structural balance [...] Read more.

The search for new microbicide compounds is of an urgent need, especially against difficult-to-eradicate biofilm-forming bacteria. One attractive option is the application of cationic multivalent dendrimers as antibacterials and also as carriers of active molecules. These compounds require an adequate hydrophilic/hydrophobic structural balance to maximize the effect. Herein, we evaluated the antimicrobial activity of cationic carbosilane (CBS) dendrimers unmodified or modified with polyethylene glycol (PEG) units, against planktonic and biofilm-forming P. aeruginosa culture. Our study revealed that the presence of PEG destabilized the hydrophilic/hydrophobic balance but reduced the antibacterial activity measured by microbiological cultivation methods, laser interferometry and fluorescence microscopy. On the other hand, the activity can be improved by the combination of the CBS dendrimers with endolysin, a bacteriophage-encoded peptidoglycan hydrolase. This enzyme applied in the absence of the cationic CBS dendrimers is ineffective against Gram-negative bacteria because of the protective outer membrane shield. However, the endolysin—CBS dendrimer mixture enables the penetration through the membrane and then deterioration of the peptidoglycan layer, providing a synergic antimicrobial effect. Full article

(This article belongs to the Special Issue New Antibacterial Agents)

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14 pages, 1830 KiB

Open AccessArticle

Novel Tetrazole-Based Antimicrobial Agents Targeting Clinical Bacteria Strains: Exploring the Inhibition of Staphylococcus aureus DNA Topoisomerase IV and Gyrase

by Piotr Roszkowski, Jolanta Szymańska-Majchrzak, Michał Koliński, Sebastian Kmiecik, Małgorzata Wrzosek, Marta Struga and Daniel Szulczyk

Int. J. Mol. Sci. 2022, 23(1), 378; https://doi.org/10.3390/ijms23010378 - 29 Dec 2021

Cited by 10 | Viewed by 2096

Abstract

Eleven novel imide-tetrazoles were synthesized. In the initial stage of research, in silico structure-based pharmacological prediction was conducted. All compounds were screened for antimicrobial activity using standard and clinical strains. Within the studied group, compounds 1–3 were recognized as leading structures [...] Read more.

Eleven novel imide-tetrazoles were synthesized. In the initial stage of research, in silico structure-based pharmacological prediction was conducted. All compounds were screened for antimicrobial activity using standard and clinical strains. Within the studied group, compounds 1–3 were recognized as leading structures with the most promising results in antimicrobial studies. Minimal inhibitory concentration values for compounds 1, 2, 3 were within the range of 0.8–3.2 μg/mL for standard and clinical Gram-positive and Gram-negative bacterial strains, showing in some cases higher activity than the reference Ciprofloxacin. Additionally, all three inhibited the growth of all clinical Staphylococci panels: Staphylococcus aureus (T5592; T5591) and Staphylococcus epidermidis (5253; 4243) with MIC values of 0.8 μg/mL. Selected compounds were examined in topoisomerase IV decatenation assay and DNA gyrase supercoiling assay, followed by suitable molecular docking studies to explore the possible binding modes. In summary, the presented transition from substrate imide-thioureas to imide-tetrazole derivatives resulted in significant increase of antimicrobial properties. The compounds 1–3 proposed here provide a promising basis for further exploration towards novel antimicrobial drug candidates. Full article

(This article belongs to the Special Issue New Antibacterial Agents)

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17 pages, 4094 KiB

Open AccessArticle

Specific Inhibition of VanZ-Mediated Resistance to Lipoglycopeptide Antibiotics

by Vishma Pratap Sur, Aninda Mazumdar, Vladimir Vimberg, Tommaso Stefani, Ladislav Androvic, Lucie Kracikova, Richard Laga, Zdenek Kamenik and Katerina Komrskova

Int. J. Mol. Sci. 2022, 23(1), 97; https://doi.org/10.3390/ijms23010097 - 22 Dec 2021

Cited by 4 | Viewed by 4075

Abstract

Teicoplanin is a natural lipoglycopeptide antibiotic with a similar activity spectrum as vancomycin; however, it has with the added benefit to the patient of low cytotoxicity. Both teicoplanin and vancomycin antibiotics are actively used in medical practice in the prophylaxis and treatment of [...] Read more.

Teicoplanin is a natural lipoglycopeptide antibiotic with a similar activity spectrum as vancomycin; however, it has with the added benefit to the patient of low cytotoxicity. Both teicoplanin and vancomycin antibiotics are actively used in medical practice in the prophylaxis and treatment of severe life-threatening infections caused by gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, Enterococcus faecium and Clostridium difficile. The expression of vancomycin Z (vanZ), encoded either in the vancomycin A (vanA) glycopeptide antibiotic resistance gene cluster or in the genomes of E. faecium, as well as Streptococcus pneumoniae and C. difficile, was shown to specifically compromise the antibiotic efficiency through the inhibition of teicoplanin binding to the bacterial surface. However, the exact mechanisms of this action and protein structure remain unknown. In this study, the three-dimensional structure of VanZ from E. faecium EnGen0191 was predicted by using the I-TASSER web server. Based on the VanZ structure, a benzimidazole based ligand was predicted to bind to the VanZ by molecular docking. Importantly, this new ligand, named G3K, was further confirmed to specifically inhibit VanZ-mediated resistance to teicoplanin in vivo. Full article

(This article belongs to the Special Issue New Antibacterial Agents)

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15 pages, 1458 KiB

Open AccessArticle

Sterically Hindered Quaternary Phosphonium Salts (QPSs): Antimicrobial Activity and Hemolytic and Cytotoxic Properties

by Vadim V. Ermolaev, Daria M. Arkhipova, Vasili A. Miluykov, Anna P. Lyubina, Syumbelya K. Amerhanova, Natalia V. Kulik, Alexandra D. Voloshina and Valentine P. Ananikov

Int. J. Mol. Sci. 2022, 23(1), 86; https://doi.org/10.3390/ijms23010086 - 22 Dec 2021

Cited by 26 | Viewed by 3355

Abstract

Structure–activity relationships are important for the design of biocides and sanitizers. During the spread of resistant strains of pathogenic microbes, insights into the correlation between structure and activity become especially significant. The most commonly used biocides are nitrogen-containing compounds; the phosphorus-containing ones have [...] Read more.

Structure–activity relationships are important for the design of biocides and sanitizers. During the spread of resistant strains of pathogenic microbes, insights into the correlation between structure and activity become especially significant. The most commonly used biocides are nitrogen-containing compounds; the phosphorus-containing ones have been studied to a lesser extent. In the present study, a broad range of sterically hindered quaternary phosphonium salts (QPSs) based on tri-tert-butylphosphine was tested for their activity against Gram-positive (Staphylococcus aureus, Bacillus cereus, Enterococcus faecalis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria and fungi (Candida albicans, Trichophyton mentagrophytes var. gypseum). The cation structure was confirmed to determine their biological activity. A number of QPSs not only exhibit high activity against both Gram-positive and -negative bacteria but also possess antifungal properties. Additionally, the hemolytic and cytotoxic properties of QPSs were determined using blood and a normal liver cell line, respectively. The results show that tri-tert-butyl(n-dodecyl)phosphonium and tri-tert-butyl(n-tridecyl)phosphonium bromides exhibit both low cytotoxicity against normal human cells and high antimicrobial activity against bacteria, including methicillin-resistant strains S. aureus (MRSA). The mechanism of QPS action on microbes is discussed. Due to their high selectivity for pathogens, sterically hindered QPSs could serve as effective tunable biocides. Full article

(This article belongs to the Special Issue New Antibacterial Agents)

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11 pages, 1642 KiB

Open AccessArticle

Uptake of Ozenoxacin and Other Quinolones in Gram-Positive Bacteria

by Yuly López, Laura Muñoz, Domingo Gargallo-Viola, Rafael Cantón, Jordi Vila and Ilonka Zsolt

Int. J. Mol. Sci. 2021, 22(24), 13363; https://doi.org/10.3390/ijms222413363 - 12 Dec 2021

Cited by 4 | Viewed by 2842

Abstract

The big problem of antimicrobial resistance is that it requires great efforts in the design of improved drugs which can quickly reach their target of action. Studies of antibiotic uptake and interaction with their target it is a key factor in this important [...] Read more.

The big problem of antimicrobial resistance is that it requires great efforts in the design of improved drugs which can quickly reach their target of action. Studies of antibiotic uptake and interaction with their target it is a key factor in this important challenge. We investigated the accumulation of ozenoxacin (OZN), moxifloxacin (MOX), levofloxacin (LVX), and ciprofloxacin (CIP) into the bacterial cells of 5 species, including Staphylococcus aureus (SA4-149), Staphylococcus epidermidis (SEP7602), Streptococcus pyogenes (SPY165), Streptococcus agalactiae (SAG146), and Enterococcus faecium (EF897) previously characterized.The concentration of quinolone uptake was estimated by agar disc-diffusion bioassay. Furthermore, we determined the inhibitory concentrations 50 (IC₅₀) of OZN, MOX, LVX, and CIP against type II topoisomerases from S. aureus.The accumulation of OZN inside the bacterial cell was superior in comparison to MOX, LVX, and CIP in all tested species. The accumulation of OZN inside the bacterial cell was superior in comparison to MOX, LVX, and CIP in all tested species. The rapid penetration of OZN into the cell was reflected during the first minute of exposure with antibiotic values between 190 and 447 ng/mg (dry weight) of bacteria in all strains. Moreover, OZN showed the greatest inhibitory activity among the quinolones tested for both DNA gyrase and topoisomerase IV isolated from S. aureus with IC50 values of 10 and 0.5 mg/L, respectively. OZN intracellular concentration was significantly higher than that of MOX, LVX and CIP. All of these features may explain the higher in vitro activity of OZN compared to the other tested quinolones. Full article

(This article belongs to the Special Issue New Antibacterial Agents)

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13 pages, 1876 KiB

Open AccessArticle

Therapeutic Effects of Inhibitor of ompA Expression against Carbapenem-Resistant Acinetobacter baumannii Strains

by Seok-Hyeon Na, Hyejin Jeon, Man-Hwan Oh, Yoo-Jeong Kim, Mingi Chu, Ill-Young Lee and Je-Chul Lee

Int. J. Mol. Sci. 2021, 22(22), 12257; https://doi.org/10.3390/ijms222212257 - 12 Nov 2021

Cited by 10 | Viewed by 2176

Abstract

The widespread of carbapenem-resistant Acinetobacter baumannii (CRAB) is of great concern in clinical settings worldwide. It is urgent to develop new therapeutic agents against this pathogen. This study aimed to evaluate the therapeutic potentials of compound 62520, which has been previously identified as [...] Read more.

The widespread of carbapenem-resistant Acinetobacter baumannii (CRAB) is of great concern in clinical settings worldwide. It is urgent to develop new therapeutic agents against this pathogen. This study aimed to evaluate the therapeutic potentials of compound 62520, which has been previously identified as an inhibitor of the ompA promoter activity of A. baumannii, against CRAB isolates, both in vitro and in vivo. Compound 62520 was found to inhibit the ompA expression and biofilm formation in A. baumannii ATCC 17978 at sub-inhibitory concentrations in a dose-dependent manner. These inhibitory properties were also observed in clinical CRAB isolates belonging to sequence type (ST) 191. Additionally, compound 62520 exhibited a bacteriostatic activity against clinical clonal complex (CC) 208 CRAB isolates, including ST191, and ESKAPE pathogens. This bacteriostatic activity was not different between STs of CRAB isolates. Bacterial clearance was observed in mice infected with bioimaging A. baumannii strain 24 h after treatment with compound 62520. Compound 62520 was shown to significantly increase the survival rates of both immunocompetent and neutropenic mice infected with A. baumannii ATCC 17978. This compound also increased the survival rates of mice infected with clinical CRAB isolate. These results suggest that compound 62520 is a promising scaffold to develop a novel therapeutic agent against CRAB infections. Full article

(This article belongs to the Special Issue New Antibacterial Agents)

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21 pages, 3195 KiB

Open AccessArticle

Selective Inhibition of Helicobacter pylori Carbonic Anhydrases by Carvacrol and Thymol Could Impair Biofilm Production and the Release of Outer Membrane Vesicles

by Rossella Grande, Simone Carradori, Valentina Puca, Irene Vitale, Andrea Angeli, Alessio Nocentini, Alessandro Bonardi, Paola Gratteri, Paola Lanuti, Giuseppina Bologna, Pasquale Simeone, Clemente Capasso, Viviana De Luca and Claudiu T. Supuran

Int. J. Mol. Sci. 2021, 22(21), 11583; https://doi.org/10.3390/ijms222111583 - 27 Oct 2021

Cited by 43 | Viewed by 4278

Abstract

Helicobacter pylori, a Gram-negative neutrophilic pathogen, is the cause of chronic gastritis, peptic ulcers, and gastric cancer in humans. Current therapeutic regimens suffer from an emerging bacterial resistance rate and poor patience compliance. To improve the discovery of compounds targeting bacterial alternative [...] Read more.

Helicobacter pylori, a Gram-negative neutrophilic pathogen, is the cause of chronic gastritis, peptic ulcers, and gastric cancer in humans. Current therapeutic regimens suffer from an emerging bacterial resistance rate and poor patience compliance. To improve the discovery of compounds targeting bacterial alternative enzymes or essential pathways such as carbonic anhydrases (CAs), we assessed the anti-H. pylori activity of thymol and carvacrol in terms of CA inhibition, isoform selectivity, growth impairment, biofilm production, and release of associated outer membrane vesicles-eDNA. The microbiological results were correlated by the evaluation in vitro of H. pylori CA inhibition, in silico analysis of the structural requirements to display such isoform selectivity, and the assessment of their limited toxicity against three probiotic species with respect to amoxicillin. Carvacrol and thymol could thus be considered as new lead compounds as alternative H. pylori CA inhibitors or to be used in association with current drugs for the management of H. pylori infection and limiting the spread of antibiotic resistance. Full article

(This article belongs to the Special Issue New Antibacterial Agents)

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15 pages, 10517 KiB

Open AccessArticle

The Mutation in wbaP cps Gene Cluster Selected by Phage-Borne Depolymerase Abolishes Capsule Production and Diminishes the Virulence of Klebsiella pneumoniae

by Marta Kaszowska, Grazyna Majkowska-Skrobek, Pawel Markwitz, Cédric Lood, Wojciech Jachymek, Anna Maciejewska, Jolanta Lukasiewicz and Zuzanna Drulis-Kawa

Int. J. Mol. Sci. 2021, 22(21), 11562; https://doi.org/10.3390/ijms222111562 - 26 Oct 2021

Cited by 16 | Viewed by 4052

Abstract

Klebsiella pneumoniae is considered one of the most critical multidrug-resistant pathogens and urgently requires new therapeutic strategies. Capsular polysaccharides (CPS), lipopolysaccharides (LPS), and exopolysaccharides (EPS) are the major virulence factors protecting K. pneumoniae against the immune response and thus may be targeted by [...] Read more.

Klebsiella pneumoniae is considered one of the most critical multidrug-resistant pathogens and urgently requires new therapeutic strategies. Capsular polysaccharides (CPS), lipopolysaccharides (LPS), and exopolysaccharides (EPS) are the major virulence factors protecting K. pneumoniae against the immune response and thus may be targeted by phage-based therapeutics such as polysaccharides-degrading enzymes. Since the emergence of resistance to antibacterials is generally considered undesirable, in this study, the genetic and phenotypic characteristics of resistance to the phage-borne CPS-degrading depolymerase and its effect on K. pneumoniae virulence were investigated. The K63 serotype targeting depolymerase (KP36gp50) derived from Klebsiella siphovirus KP36 was used as the selective agent during the treatment of K. pneumoniae 486 biofilm. Genome-driven examination combined with the surface polysaccharide structural analysis of resistant mutant showed the point mutation and frameshift in the wbaP gene located within the cps gene cluster, resulting in the loss of the capsule. The sharp decline in the yield of CPS was accompanied by the production of a larger amount of smooth LPS. The modification of the surface polysaccharide layers did not affect bacterial fitness nor the insensitivity to serum complement; however, it made bacteria more prone to phagocytosis combined with the higher adherence and internalization to human lung epithelial cells. In that context, it was showed that the emerging resistance to the antivirulence agent (phage-borne capsule depolymerase) results in beneficial consequences, i.e., the sensitization to the innate immune response. Full article

(This article belongs to the Special Issue New Antibacterial Agents)

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26 pages, 82283 KiB

Open AccessArticle

The Effect of Rotating Magnetic Field on Susceptibility Profile of Methicillin-Resistant Staphylococcus aureus Strains Exposed to Activity of Different Groups of Antibiotics

by Marta Woroszyło, Daria Ciecholewska-Juśko, Adam Junka, Marcin Wardach, Grzegorz Chodaczek, Bartłomiej Dudek and Karol Fijałkowski

Int. J. Mol. Sci. 2021, 22(21), 11551; https://doi.org/10.3390/ijms222111551 - 26 Oct 2021

Cited by 8 | Viewed by 3294

Abstract

Methicillin-resistant strains of Staphylococcus aureus (MRSA) have become a global issue for healthcare systems due to their resistance to most β-lactam antibiotics, frequently accompanied by resistance to other classes of antibiotics. In this work, we analyzed the impact of combined use of rotating [...] Read more.

Methicillin-resistant strains of Staphylococcus aureus (MRSA) have become a global issue for healthcare systems due to their resistance to most β-lactam antibiotics, frequently accompanied by resistance to other classes of antibiotics. In this work, we analyzed the impact of combined use of rotating magnetic field (RMF) with various classes of antibiotics (β-lactams, glycopeptides, macrolides, lincosamides, aminoglycosides, tetracyclines, and fluoroquinolones) against nine S. aureus strains (eight methicillin-resistant and one methicillin-sensitive). The results indicated that the application of RMF combined with antibiotics interfering with cell walls (particularly with the β-lactam antibiotics) translate into favorable changes in staphylococcal growth inhibition zones or in minimal inhibitory concentration values compared to the control settings, which were unexposed to RMF. As an example, the MIC value of cefoxitin was reduced in all MRSA strains by up to 42 times. Apart from the β-lactams, the reduced MIC values were also found for erythromycin, clindamycin, and tetracycline (three strains), ciprofloxacin (one strain), gentamicin (six strains), and teicoplanin (seven strains). The results obtained with the use of in vitro biofilm model confirm that the disturbances caused by RMF in the bacterial cell walls increase the effectiveness of the antibiotics towards MRSA. Because the clinical demand for new therapeutic options effective against MRSA is undisputable, the outcomes and conclusions drawn from the present study may be considered an important road into the application of magnetic fields to fight infections caused by methicillin-resistant staphylococci. Full article

(This article belongs to the Special Issue New Antibacterial Agents)

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19 pages, 14058 KiB

Open AccessArticle

Antimicrobial and Antioxidative Activity of Newly Synthesized Peptides Absorbed into Bacterial Cellulose Carrier against Acne vulgaris

by Iwona Golonka, Katarzyna E. Greber, Monika Oleksy-Wawrzyniak, Justyna Paleczny, Andrzej Dryś, Adam Junka, Wiesław Sawicki and Witold Musiał

Int. J. Mol. Sci. 2021, 22(14), 7466; https://doi.org/10.3390/ijms22147466 - 12 Jul 2021

Cited by 9 | Viewed by 3136

Abstract

The ongoing search for effective treatment of Acne vulgaris is concentrated, i.a., on natural peptides with antimicrobial properties. The aim of this work was the development of new amino acid derivatives with potential activity on dermal infections against selected microorganisms, including the facultative [...] Read more.

The ongoing search for effective treatment of Acne vulgaris is concentrated, i.a., on natural peptides with antimicrobial properties. The aim of this work was the development of new amino acid derivatives with potential activity on dermal infections against selected microorganisms, including the facultative anaerobe C. acne. The peptides P1–P6 were synthesized via Fmoc solid phase peptide synthesis using Rink amide AM resin, analyzed by RP-HPLC-MS, FTIR, DPPH radical scavenging activity, and evaluated against C. acne and S. aureus, both deposited and non-deposited in BC. Peptides P1–P6 presented a lack of cytotoxicity, antimicrobial activity, or antioxidative properties correlated with selected structural properties. P2 and P4–P6 sorption in BC resulted in variable data, i.a., confirming the prospective topical application of these peptides in a BC carrier. Full article

(This article belongs to the Special Issue New Antibacterial Agents)

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