scholarly journals Evaluating the antibacterial activity of muramyl dipeptide derivatives, retro-tuftsin derivatives, and anthraquinone oligopeptides against a range of pathogenic bacteria

Author(s):  
Magdalena Wysocka ◽  
Krystyna Dzierzbicka ◽  
Beata Krawczyk

Search for new and efficient antibiotic is crucial because of microbial drug resistance and problems with side effects of the administered medication. In this study, we evaluate the in vitro microbiological activity of muramyl dipeptide derivatives, retro-tuftsin derivatives (i.e., tuftsin with reversed amino acid sequences), and combinations of retro-tuftsin derivatives with substituted anthraquinones. The potency of the investigated derivatives towards methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae ESBL (extended-spectrum β-lactamases) was compared based on the spectroscopically-measured minimal inhibitory concentrations (MIC values). The bacterial growth have also been studied with different concentrations of compounds. Statistical analysis of the results revealed that certain modifications lead to promising activity against S. aureus (anthraquinone analogue – 3c and retro-tuftsin derivative – 2b), while other derivatives exhibit activity against P. aeruginosa (muramyl dipeptide derivative – 1d and retro-tuftsin derivative – 2b). The obtained results of microbiological activity indicate that the structure of the tested compounds may be the basis for further modifications.

2021 ◽  
Vol 11 (Suppl_1) ◽  
pp. S23-S23
Author(s):  
Evelina Klochkova ◽  
Aydar Bikmullin ◽  
Shamil Validov ◽  
Natalia Garaeva ◽  
Marat Yusupov ◽  
...  

Background: An essential in bacteria GTPase Era is a multifunctional protein that is involved in cell cycle regulation and appears to play a significant role in ribosome biogenesis. It is required for the maturation of the 30S ribosomal subunit. Era consists of two domains: the GTPase N-terminal domain, conserved in the GTPase family, and a C-terminal RNA-binding KH domain. Era specifically binds to the 16S rRNA and stimulates processing of the small ribosomal subunit to its mature form. Precise determination of nucleotide and amino acid sequences in the active site of binding will help in finding specific ways to prevent this interaction. In this way, it will be possible to disrupt the biogenesis of the ribosome and, thereby, stop or slow down protein synthesis in the bacterial cell. It is very important in the fight against pathogenic bacteria, such as Staphylococcus aureus (S. aureus). Methods: The His-tagged Era (His–Era) protein from S. aureus was expressed in E. coli BL21 strain and purified by Ni-NTA and SEC. The 30S ribosomal subunits were collected after dissociation of the S. aureus 70S ribosomes in sucrose gradient (0 – 30%). Complex 30S-Era was obtained by mixing in vitro 30S subunits and His–Era, incubated for 15 min at 37°C and followed by Ni-NTA purification to remove unbound 30S subunits. The presence of a stable 30S-Era complex has been confirmed by SDS-PAGE and agarose gel electrophoresis. The final sample quality was analyzed by negative staining EM. Results: For the first time in vitro 30S-Era complex from S. aureus was assembled and a sample was prepared for further structural studies by cryo-electron microscopy.


2005 ◽  
Vol 187 (2) ◽  
pp. 554-566 ◽  
Author(s):  
Lauren M. Mashburn ◽  
Amy M. Jett ◽  
Darrin R. Akins ◽  
Marvin Whiteley

ABSTRACT Pseudomonas aeruginosa is a gram-negative opportunistic human pathogen often infecting the lungs of individuals with the heritable disease cystic fibrosis and the peritoneum of individuals undergoing continuous ambulatory peritoneal dialysis. Often these infections are not caused by colonization with P. aeruginosa alone but instead by a consortium of pathogenic bacteria. Little is known about growth and persistence of P. aeruginosa in vivo, and less is known about the impact of coinfecting bacteria on P. aeruginosa pathogenesis and physiology. In this study, a rat dialysis membrane peritoneal model was used to evaluate the in vivo transcriptome of P. aeruginosa in monoculture and in coculture with Staphylococcus aureus. Monoculture results indicate that approximately 5% of all P. aeruginosa genes are differentially regulated during growth in vivo compared to in vitro controls. Included in this analysis are genes important for iron acquisition and growth in low-oxygen environments. The presence of S. aureus caused decreased transcription of P. aeruginosa iron-regulated genes during in vivo coculture, indicating that the presence of S. aureus increases usable iron for P. aeruginosa in this environment. We propose a model where P. aeruginosa lyses S. aureus and uses released iron for growth in low-iron environments.


1992 ◽  
Vol 114 (6) ◽  
pp. 1838-1841
Author(s):  
A. �. Medvedev ◽  
B. B. Fuks ◽  
N. V. Bovin ◽  
A. E. Zemlyakov

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Jang-Gi Choi ◽  
Ok-Hwa Kang ◽  
Young-Seob Lee ◽  
Hee-Sung Chae ◽  
You-Chang Oh ◽  
...  

Punica granatumis commonly used in Korea as a traditional medicine for the treatment of pathogenic bacteria. In this study, we investigated thein vitroandin vivoantimicrobial activity ofP. granatumpeel EtOH extract (PGPE) against 16 strains ofSalmonella. The minimal inhibitory concentrations of PGPE were in the range of 62.5–1000 x03BCg mL-1. In addition, thein vivoantibacterial activity of the PGPE extract was examined in aS. typhimuriuminfection mouse model. Mice were initially infected withS. typhimuriumand then with PGPE. The extract was found to have significant effects on mortality and the numbers of viableS. typhimuriumrecovered from feces. Although clinical signs and histological damage were rarely observed in the treated mice, the untreated controls showed signs of lethargy and histological damage in the liver and spleen. Taken together, the results of this study indicate that PGPE has the potential to provide an effective treatment for salmonellosis.


Author(s):  
Shanjun Gao ◽  
Guangzhi Liu ◽  
Jianguo Li ◽  
Jing Chen ◽  
Lina Li ◽  
...  

Compared to mono-species biofilm, biofilms formed by cross-kingdom pathogens are more refractory to conventional antibiotics, thus complicating clinical treatment and causing significant morbidity. Lemongrass essential oil and its bioactive component citral were previously demonstrated to possess strong antimicrobial efficacy against pathogenic bacteria and fungi. However, their effects on polymicrobial biofilms remain to be determined. In this study, the efficacy of lemongrass (Cymbopogon flexuosus) essential oil and its bioactive part citral against dual-species biofilms formed by Staphylococcus aureus and Candida species was evaluated in vitro. Biofilm staining and viability test showed both lemongrass essential oil and citral were able to reduce biofilm biomass and cell viability of each species in the biofilm. Microscopic examinations showed these agents interfered with adhesive characteristics of each species and disrupted biofilm matrix through counteracting nucleic acids, proteins and carbohydrates in the biofilm. Moreover, transcriptional analyses indicated citral downregulated hyphal adhesins and virulent factors of Candida albicans, while also reducing expression of genes involved in quorum sensing, peptidoglycan and fatty acids biosynthesis of S. aureus. Taken together, our results demonstrate the potential of lemongrass essential oil and citral as promising agents against polymicrobial biofilms as well as the underlying mechanisms of their activity in this setting.


Planta Medica ◽  
2020 ◽  
Vol 86 (12) ◽  
pp. 858-866
Author(s):  
Patricia Homobono Brito de Moura ◽  
Amaryllis Almeida de Sousa ◽  
Andrea Porzel ◽  
Ludger A. Wessjohann ◽  
Ivana Correa Ramos Leal ◽  
...  

Abstract Dalbergia monetaria is an Amazonian plant whose bark is widely used to treat urinary tract infections. This paper describes a bio-guided study of ethanolic extracts from the bark and leaves of D. monetaria, in a search for metabolites active against human pathogenic bacteria. In vitro assays were performed against 10 bacterial strains, highlighting methicillin-sensitive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Fractioning of the extracts was performed using instrumental and classical techniques, and samples were characterized by UHPLC-HRMS/MS. Ethyl acetate fractions from bark and leaves showed similar antibacterial activities. EAFB is enriched in isoflavone C-glucosides and EAFL enriched in proanthocyanidins. Subfractions from EAFL presented higher activity and showed a complex profile of proanthocyanidins constructed by (epi)-cassiaflavan and (epi)-catechin units, including dimers, trimers and tetramers. The fragmentation pattern emphasized the neutral loss of cassiaflavan units by quinone-methide fission. Fraction SL7-6, constituted by (ent)-cassiaflavan-(ent)-cassiaflavan-(epi)-catechin isomers, showed the lowest MIC against the S. aureus and P. aeruginosa with values corresponding to 64 and 32 µg/mL, respectively. Cassiaflavan-proanthocyanidins have not been found previously in another botanical genus, except in Cassia, and the traditional medicinal use of D. monetaria might be related to the antibacterial activity of proanthocyanidins characterized in the species.


1973 ◽  
Vol 19 (8) ◽  
pp. 973-981 ◽  
Author(s):  
T. Gadbois ◽  
J. De Repentigny ◽  
L. G. Mathieu

We have studied aspects of interbacterial ecology with nutritionally dependent Staphylococcus aureus strains; they were grown in association with Pseudomonas aeruginosa in systems of mixed cultures and infections in vitro in a semisynthetic medium and in vivo in mouse peritoneal cavity and rabbit skin. In mixed cultures and in P. aeruginosa culture filtrates, thymine and tryptophan deficiencies in staphylococci were partly overcome. This is probably because P. aeruginosa supplied the essential metabolites required to ensure growth; however, other metabolic activities could also be involved. Other experiments showed that the sensitivity of thymineless staphylococci to nucleoside inhibitions was alleviated. In mixed infections with P. aeruginosa, the S. aureus thymineless strain has shown a greater ability to survive in the peritoneal cavity of mice than when injected alone, even when one species was injected after the other with different doses of bacteria. The examination of the liquid from the peritoneal cavity of infected mice by fluorescence microscopy after fluorochroming with acridine orange or auramine O has revealed that Pseudomonas endotoxin seems to damage leucocytes and consequently reduces the phagocytosis of Staphylococcus cells.Necrosis in rabbit skin was mainly due to S. aureus when both species were injected together intradermally; the thymineless strain was less harmful than the parent strain.It seems that survival and even growth of nutritionally dependent strains of a bacterial species can be favored by the metabolic activities of another species in mixed cultures and infections, in this instance S. aureus by P. aeruginosa. This phenomenon among others could be a determinant of bacterial pathogenicity for nutritionally dependent pathogenic bacteria; thus associated organisms could determine the effective pathogenicity of nutritionally dependent bacteria by contributing essential nutrilites at the site where infection is initiated.


2019 ◽  
Author(s):  
Clémentine Laffont ◽  
Catherine Brutesco ◽  
Christine Hajjar ◽  
Gregorio Cullia ◽  
Roberto Fanelli ◽  
...  

ABSTRACTIn metal-scarce environments, some pathogenic bacteria produce opine-type metallophores mainly to face the host’s nutritional immunity. This is the case of staphylopine, pseudopaline and yersinopine, identified inStaphylococcus aureus,Pseudomonas aeruginosaandYersinia pestisrespectively. These metallophores are synthesized by two (CntLM) or three enzymes (CntKLM), CntM catalyzing the last step of biosynthesis using diverse substrates (pyruvate or α-ketoglutarate), pathway intermediates (xNA or yNA) and cofactors (NADH or NADPH), depending on the species. Here, we explored substrate specificity of CntM by combining bioinformatics and structural analysis with chemical synthesis and enzymatic studies. We found that NAD(P)H selectivity was mainly due to the amino acid at position 33 (S. aureusnumbering) which ensures a preferential binding to NADPH when it is an arginine. Moreover, whereas CntM fromP. aeruginosapreferentially uses yNA over xNA, the staphylococcal enzyme is not stereospecific. Most importantly, selectivity towards α-ketoacids is largely governed by a single residue at position 150 of CntM (S. aureusnumbering): an aspartate at this position ensures selectivity towards pyruvate whereas an alanine leads to the consumption of both pyruvate and α-ketoglutarate. Modifying this residue inP. aeruginosaled to a complete reversal of selectivity. Thus, opine-type metallophore diversity is mainly mediated by the absence/presence of acntKgene encoding a histidine racemase, and the presence of an aspartate/alanine at position 150 of CntM. These two simple rules predict the production of a fourth metallophore byPaenibacillus mucilaginosus, which was confirmedin vitroand called bacillopaline.


10.5219/1544 ◽  
2021 ◽  
Vol 15 ◽  
pp. 460-466
Author(s):  
Yetti Marlida ◽  
Nurul Huda ◽  
Harnentis ◽  
Yuliaty Shafan Nur ◽  
Nuri Mekar Lestari ◽  
...  

Budu is a fermented food resulting from the activities of microorganisms like lactic acid bacteria and yeast. Budu, therefore, serves as a source of probiotics that can have beneficial effects on livestock and humans. Nonetheless, their selection has to be done with caution. The current study purposed to find out whether budu has desirable probiotic properties. This was done by determining its pH, bile acid tolerance, hydrophobicity, and inhibition of pathogens such as Staphylococcus aureus, Salmonella enteritidis, and Escherichia coli. An in vitro experiment was conducted using three Saccharomyces cerevisiae (coded as SC 11, SC 12, and SC 21) in the preparation of budu. The whole experiment was repeated four times. The budus were tested for their probiotic properties (low pH, bile salts, hydrophobicity, and inhibition of pathogenic bacteria). The results showed that the three Saccharomyces cerevisiae survived in gastric juice and bile acid, exhibited good hydrophobicity, and could inhibit pathogenic bacteria, both gram-positive and negative pathogens. They were able to survive at pH 2 for 3 h (40.70 to 55.1%), at pH 2 for 5 h (35.25 to 46.88%), in 0.3% bile acid incubated for 3 h (69.69 to 86.56%), in 0.3% bile acid incubated for 5 h (82.22 to 88.18%) and hydrophobicity ability of 97.0 to 98.1%. The inhibition activity against pathogenic bacteria, that is, Escherichia coli was 2.50 to 3.81 mm, Staphylococcus aureus was 1.66 to 3.71 mm, and Salmonella enteritidis was 1.20 to 2.64 mm.


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