Synthesis of Mixed Ligand Ruthenium (II/III) Complexes and Their Antibacterial Evaluation on Drug-Resistant Bacterial Organisms

The potential antimicrobial properties of a tridentate polypyridyl ligand 4-butoxy-N,N-bis(pyridin-2-ylmethyl)aniline (BUT) 1 and its corresponding mixed ligand ruthenium complexes were investigated on drug-resistant and non-drug-resistant bacterial species. The ligand and its complexes were synthesized and successfully characterized by 1H NMR, UV/Vis, and FTIR spectra; ESI-MS; and magnetic susceptibility. Electronic spectra and magnetic susceptibility of these Ru(II)/(III) complexes suggest that they are of a low spin crystal field split, where the Ru(III) is a d5 and Ru(II) d6 low spin. These compounds were tested for antibacterial activity on two bacterial species: Staphylococcus aureus (S. aureus) and Klebsiella pneumoniae (K. pneumoniae), as well as their drug-resistant strains methicillin-resistant Staphylococcus aureus (MRSA) and multidrug resistant Klebsiella pneumoniae (MDR K. pneumoniae). All the compounds inhibited growth of the two non-drug-resistant bacteria and only one drug-resistant strain MRSA. However, only the ligands BUT and 2,2-dipyridylamine showed activity against MRSA, while all complexes did not show any antibacterial activity on MRSA. We observed large zones of inhibition for the Gram-positive S. aureus and MRSA bacteria, compared to the Gram-negative K. pneumoniae bacteria. DNA cleavage studies with gel electrophoresis showed denatured bacterial DNA on the gel from all the complexes, with the exception of the ligand, suggesting DNA nuclease activity of the complexes in the bacterial DNA.

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Antimicrobial Mechanism of pBD2 against Staphylococcus aureus

Molecules ◽

10.3390/molecules25153513 ◽

2020 ◽

Vol 25 (15) ◽

pp. 3513 ◽

Cited By ~ 1

Author(s):

Kun Zhang ◽

Heng Zhang ◽

Chunyu Gao ◽

Ruibo Chen ◽

Chunli Li

Keyword(s):

Staphylococcus Aureus ◽

Antibacterial Activity ◽

Morphological Changes ◽

Bacterial Species ◽

Resistant Bacteria ◽

Quantitative Real Time Pcr ◽

Bacterial Membranes ◽

Qrt Pcr ◽

High Antibacterial Activity ◽

Therapeutic Substance

Antimicrobial peptides (AMPs) show high antibacterial activity against pathogens, which makes them potential new therapeutics to prevent and cure diseases. Porcine beta defensin 2 (pBD2) is a newly discovered AMP and has shown antibacterial activity against different bacterial species including multi-resistant bacteria. In this study, the functional mechanism of pBD2 antibacterial activity against Staphylococcus aureus was investigated. After S. aureus cells were incubated with different concentrations of pBD2, the morphological changes in S. aureus and locations of pBD2 were detected by electron microscopy. The differentially expressed genes (DEGs) were also analyzed. The results showed that the bacterial membranes were broken, bulging, and perforated after treatment with pBD2; pBD2 was mainly located on the membranes, and some entered the cytoplasm. Furthermore, 31 DEGs were detected and confirmed by quantitative real-time PCR (qRT-PCR). The known functional DEGs were associated with transmembrane transport, transport of inheritable information, and other metabolic processes. Our data suggest that pBD2 might have multiple modes of action, and the main mechanism by which pBD2 kills S. aureus is the destruction of the membrane and interaction with DNA. The results imply that pBD2 is an effective bactericide for S. aureus, and deserves further study as a new therapeutic substance against S. aureus.

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Isolation of Four Lytic Phages Infecting Klebsiella pneumoniae K22 Clinical Isolates from Spain

International Journal of Molecular Sciences ◽

10.3390/ijms21020425 ◽

2020 ◽

Vol 21 (2) ◽

pp. 425 ◽

Cited By ~ 1

Author(s):

Pilar Domingo-Calap ◽

Beatriz Beamud ◽

Justine Vienne ◽

Fernando González-Candelas ◽

Rafael Sanjuán

Keyword(s):

Klebsiella Pneumoniae ◽

Host Specificity ◽

Bacterial Species ◽

Clinical Isolates ◽

Resistant Bacteria ◽

Drug Resistant ◽

Capsular Type ◽

Full Genome Sequencing ◽

Promising Alternative ◽

Drug Resistant Bacteria

The emergence of multi-drug-resistant bacteria represents a major public-health threat. Phages constitute a promising alternative to chemical antibiotics due to their high host specificity, abundance in nature, and evolvability. However, phage host specificity means that highly diverse bacterial species are particularly difficult to target for phage therapy. This is the case of Klebsiella pneumoniae, which presents a hypervariable extracellular matrix capsule exhibiting dozens of variants. Here, we report four novel phages infecting K. pneumoniae capsular type K22 which were isolated from environmental samples in Valencia, Spain. Full genome sequencing showed that these phages belong to the Podoviridae family and encode putative depolymerases that allow digestion of specific K22 K. pneumoniae capsules. Our results confirm the capsular type-specificity of K. pneumoniae phages, as indicated by their narrow infectivity in a panel of K. pneumoniae clinical isolates. Nonetheless, this work represents a step forward in the characterization of phage diversity, which may culminate in the future use of large panels of phages for typing and/or for combating multi-drug-resistant K. pneumoniae.

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Synthesis Ruthenium complexes Functionalized with Benzothiophene and their Antibacterial activity against Staphylococcus aureus

Dalton Transactions ◽

10.1039/d0dt04258g ◽

2021 ◽

Author(s):

Xiangwen Liao ◽

lianghong liu ◽

yanhui Tan ◽

guijuan jiang ◽

haihong fang ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antibacterial Activity ◽

Mode Of Action ◽

Antimicrobial Agents ◽

Ruthenium Complexes ◽

Resistant Bacteria ◽

Drug Resistant ◽

Drug Resistant Bacteria

New effective antimicrobial agents with novel mode of action are urgently need due to the continued emergence of drug-resistant bacteria. Here, three ruthenium complexes functionalized with benzothiophene: [Ru(phen)2(BTPIP)](ClO4)2 (Ru(II)-1), [Ru(dmp)2(BTPIP)](ClO4)2...

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Detection of Drug Susceptible and Resistant Viridans Streptococci spp., Staphylococcus Aureus, Klebsiella Pneumoniae and E.coli in Complete Denture Patients and Visualisation using Scanning Electron Microscopy

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2020/45074.14033 ◽

2020 ◽

Author(s):

Leoney Andonissamy ◽

Suma Karthigeyan ◽

Seyed Asharaf Ali

Keyword(s):

Staphylococcus Aureus ◽

Drug Resistance ◽

Klebsiella Pneumoniae ◽

Oral Cavity ◽

Antibiotic Sensitivity ◽

Complete Denture ◽

Resistant Bacteria ◽

Drug Resistant ◽

Drug Resistant Bacteria ◽

Sensitivity Tests

Introduction: The bacteria colonising the oral cavity and the dentures acquire drug resistance due to frequent usage of antibiotics systemically and application of mouth rinses and denture disinfectants locally. These multidrug resistant bacteria pose potential threat to the health of the patient as infections caused by them do not respond to conventional antibiotics. Aim: The present study aims at detecting the drug resistant bacteria in patients who wear complete dentures. Materials and Methods: The study is a descriptive study and follows laboratory invitro study design involving 30 complete denture patients. Swabs were collected from their oral cavity as well as complete denture surfaces. Antibiotic sensitivity tests were performed for the following bacteriae namely Viridans streptococci species, Staphylococcus aureus, Klebsiella pneumoniae and E.coli. Isolation of the bacteria were done by means of selective media and subjected to biochemical tests. The 16S rRNA sequencing was done to ascertain the microorganisms by which 20 isolates of each of the selective bacteria were obtained. The bacteria were classified as sensitive, intermediate sensitive and resistant based on antibiotic sensitivity tests. Those isolates which exhibited Multi-Drug Resistance (MDR) were visualised using SEM. Results:Viridans streptococci spp. (40%) and Staphylococcus aureus (25%) isolates were resistant to Amoxiclavulinic acid and Methicilin, whereas Klebsiella pneumoniae (30%) and (30%) E.coli isolates were most resistant to Cefotaxime and Doxicilin. Conclusion: Drug resistant bacteria have been identified from complete dentures and oral cavity in the present study. Antibiotic sensitivity tests, 16S rRNA sequencing and SEM are vital investigative tools to detect and to visualise drug resistant bacteria. Cell density, Extracellular Polymeric Substances (EPS) and capsule could be important factors for providing drug resistance.

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Synergistic antibacterial effects of colistin in combination with aminoglycoside, carbapenems, cephalosporins, fluoroquinolones, tetracyclines, fosfomycin, and piperacillin on multidrug resistant Klebsiella pneumoniae isolates

PLoS ONE ◽

10.1371/journal.pone.0244673 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0244673

Author(s):

Julalak C. Ontong ◽

Nwabor F. Ozioma ◽

Supayang P. Voravuthikunchai ◽

Sarunyou Chusri

Keyword(s):

Antibacterial Activity ◽

Klebsiella Pneumoniae ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Drug Resistant ◽

Antibacterial Effects ◽

Drug Resistant Bacteria ◽

Multidrug Resistant Pathogens ◽

Conventional Antibiotics ◽

Global Health Problem

Multidrug resistant Enterobacterales have become a serious global health problem, with extended hospital stay and increased mortality. Antibiotic monotherapy has been reported ineffective against most drug resistant bacteria including Klebsiella pneumoniae, thus encouraging the use of multidrug therapies as an alternative antibacterial strategy. The present works assessed the antibacterial activity of colistin against K. pneumoniae isolates. Resistant isolates were tested against 16 conventional antibiotics alone and in combination with colistin. The results revealed that all colistin resistant isolates demonstrated multidrug resistance against the tested antibiotics except amikacin. At sub-inhibitory concentrations, combinations of colistin with amikacin, or fosfomycin showed synergism against 72.72% (8 of 11 isolates). Colistin with either of gentamicin, meropenem, cefoperazone, cefotaxime, ceftazidime, moxifloxacin, minocycline, or piperacillin exhibited synergism against 81.82% (9 of 11 isolates). Combinations of colistin with either of tobramycin or ciprofloxacin showed synergism against 45.45% (5 in 11 isolates), while combinations of colistin with imipenem or ceftolozane and tazobactam displayed 36.36% (4 of 11 isolates) and 63.64% (7 of 11 isolates) synergism. In addition, combinations of colistin with levofloxacin was synergistic against 90.91% (10 of 11 isolates). The results revealed that combinations of colistin with other antibiotics could effectively inhibit colistin resistant isolates of K. pneumoniae, and thus could be further explore for the treatment of multidrug resistant pathogens.

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Synthesis and Study of New Quinolineaminoethanols as Anti-Bacterial Drugs

Pharmaceuticals ◽

10.3390/ph12020091 ◽

2019 ◽

Vol 12 (2) ◽

pp. 91

Author(s):

Laumaillé ◽

Dassonville-Klimpt ◽

Peltier ◽

Mullié ◽

Andréjak ◽

...

Keyword(s):

Escherichia Coli ◽

Staphylococcus Aureus ◽

Pseudomonas Aeruginosa ◽

Klebsiella Pneumoniae ◽

Resistant Bacteria ◽

Drug Resistant ◽

E Coli ◽

Gram Positive Bacteria ◽

Drug Resistant Bacteria ◽

Escherichia Coli Bacteria

The lack of antibiotics with a novel mode of action associated with the spread of drug resistant bacteria make the fight against infectious diseases particularly challenging. A quinoline core is found in several anti-infectious drugs, such as mefloquine and bedaquiline. Two main objectives were set in this work. Firstly, we evaluated the anti-mycobacterial properties of the previous quinolines 3, which have been identified as good candidates against ESKAPEE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli) bacteria. Secondly, a new series 4 was designed and assessed against the same bacteria strains, taking the pair of enantiomers 3m/3n as the lead. More than twenty compounds 4 were prepared through a five-step asymmetric synthesis with good enantiomeric excesses (>90%). Interestingly, all compounds of series 3 were efficient on M. avium with MIC = 2–16 µg/mL, while series 4 was less active. Both series 3 and 4 were generally more active than mefloquine against the ESKAPEE bacteria. The quinolines 4 were either active against Gram-positive bacteria (MIC ≤ 4 µg/mL for 4c–4h and 4k/4l) or E. coli (MIC = 32–64 µg/mL for 4q–4v) according to the global lipophilicity of these compounds.

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In Vitro Antibacterial Activity of Different Honey Samples Against Clinical Isolates

10.21203/rs.3.rs-411631/v1 ◽

2021 ◽

Author(s):

Mahasin Ahmed Wadi

Keyword(s):

Staphylococcus Aureus ◽

Antibacterial Activity ◽

Bacterial Species ◽

Antibacterial Properties ◽

Salmonella Typhi ◽

Clinical Isolates ◽

Base Line ◽

Drug Resistant ◽

Low Sensitivity

Abstract BackgroundThe emergence of multi–drug resistant organisms has created a lot of clinicalproblems. Hence there is a need to find natural alternative treatment to counter the multi–drug resistant organisms. Honey has a well-established usage as wound dressing in ancient and traditional medicine. The aim of this work is to establish a base-line of the antibacterial activity of 32 natural and commercial various honey samples against 8 clinical isolates.MethodsThirty two honey samples (raw and commercial honey) collected from different countries with different floral origin were tested in vitro for antibacterial activity against 8 clinical isolates collected from patients, at private Hospital from Sudan, using disk diffusion technique. The following 6 Epsilometer test (E Test), Amoxicillin, Augamentin, Ceftaxime, Chloramphenicol, Gentamicin and tetracycline were used against 8 clinical isolates for Minimum Inhibitory Concentration.ResultsThe following 8 clinical isolates were identified by conventional bacteriological methods; Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aerouginosa, Proteus.vulgaris, Salmonella typhi, Shigella sonnei and Methicillin Resistant Staphylococcus aureus (MRSA). Honey has been shown to have antibacterial properties against both Gram-positive and Gram-negative bacteria. The tested organisms showed low sensitivity to antibiotics E test.ConclusionMost of the bacterial species studied were uniformly receptive to all the tested honey. In contrast The tested organisms showed low sensitivity to antibiotics with low MIC.

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Antibacterial activity of methanol extracts of the leaves of three medicinal plants against selected bacteria isolated from wounds of lymphoedema patients

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-020-03183-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Dereje Nigussie ◽

Gail Davey ◽

Belete Adefris Legesse ◽

Abebaw Fekadu ◽

Eyasu Makonnen

Keyword(s):

Escherichia Coli ◽

Staphylococcus Aureus ◽

Pseudomonas Aeruginosa ◽

Antibacterial Activity ◽

Medicinal Plants ◽

Klebsiella Pneumoniae ◽

Streptococcus Pyogenes ◽

Bacterial Species ◽

Wound Infections ◽

Methanol Extracts

Abstract Background Patients with lymphoedema are at high risk of getting bacterial and fungal wound infections leading to acute inflammatory episodes associated with cellulitis and erysipelas. In Ethiopia, wound infections are traditionally treated with medicinal plants. Methods Agar well diffusion and colorimetric microdilution methods were used to determine the antibacterial activity of methanol extracts of the three medicinal plants against Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Shewanella alage, methicillin-resistant S. aureus ATCC®43300TM, Staphylococcus aureus ATCC25923, Escherichia coli ATCC25922, Klebsiella pneumoniae ATCC700603, and Pseudomonas aeruginosa ATCC37853. Results The methanol extract of L. inermis leaves showed high activity against all tested bacterial species, which was comparable to the standard drugs. Similarly, the extracts of A. indica showed activity against all tested species though at higher concentrations, and higher activity was recorded against Streptococcus pyogenes isolates at all concentrations. However, the extract of A. aspera showed the lowest activity against all tested species except Streptococcus pyogenes isolates. The lowest minimum inhibitory concentration (MIC) was recorded with the extract of L. inermis against E. coli isolate and S. aureus ATCC 25923. Conclusion Methanol extracts of L. inermis, A. indica, and A. aspera leaves exhibited antimicrobial activity against selected bacterial isolates involved in wound infections, of which the methanol extracts of L. inermis exhibited the highest activity. The results of the present study support the traditional use of plants against microbial infections, which could potentially be exploited for the treatment of wound infections associated with lymphoedema.

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1,2,4-Oxadiazole/2-Imidazoline Hybrids: Multi-target-directed Compounds for the Treatment of Infectious Diseases and Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20071699 ◽

2019 ◽

Vol 20 (7) ◽

pp. 1699 ◽

Cited By ~ 7

Author(s):

Anton Shetnev ◽

Sergey Baykov ◽

Stanislav Kalinin ◽

Alexandra Belova ◽

Vladimir Sharoyko ◽

...

Keyword(s):

Escherichia Coli ◽

Staphylococcus Aureus ◽

Antibacterial Activity ◽

Efflux Pump ◽

Ductal Adenocarcinoma ◽

Resistant Bacteria ◽

Drug Resistant ◽

Gram Negative ◽

Drug Resistant Bacteria ◽

Efflux Pump Inhibitors

Replacement of amide moiety with the 1,2,4-oxadiazole core in the scaffold of recently reported efflux pump inhibitors afforded a novel series of oxadiazole/2-imidazoline hybrids. The latter compounds exhibited promising antibacterial activity on both Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gram-negative (Escherichia coli, Pseudomonas fluorescens) strains. Furthermore, selected compounds markedly inhibited the growth of certain drug-resistant bacteria. Additionally, the study revealed the antiproliferative activity of several antibacterial frontrunners against pancreas ductal adenocarcinoma (PANC-1) cell line, as well as their type-selective monoamine oxidase (MAO) inhibitory profile.

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New Antimicrobials Based on the Adarotene Scaffold with Activity against Multi-Drug Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococcus

Antibiotics ◽

10.3390/antibiotics10020126 ◽

2021 ◽

Vol 10 (2) ◽

pp. 126

Author(s):

Salvatore Princiotto ◽

Stefania Mazzini ◽

Loana Musso ◽

Fabio Arena ◽

Sabrina Dallavalle ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antibacterial Activity ◽

Anticancer Activity ◽

Bactericidal Effect ◽

Biological Assessment ◽

Drug Resistant ◽

Vancomycin Resistant Enterococcus ◽

Vancomycin Resistant ◽

Global Increase ◽

Common Infections

The global increase in infections by multi-drug resistant (MDR) pathogens is severely impacting our ability to successfully treat common infections. Herein, we report the antibacterial activity against S. aureus and E. faecalis (including some MDR strains) of a panel of adarotene-related synthetic retinoids. In many cases, these compounds showed, together with favorable MICs, a detectable bactericidal effect. We found that the pattern of substitution on adarotene could be modulated to obtain selectivity for antibacterial over the known anticancer activity of these compounds. NMR experiments allowed us to define the interaction between adarotene and a model of microorganism membrane. Biological assessment confirmed that the scaffold of adarotene is promising for further developments of non-toxic antimicrobials active on MDR strains.

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