Synthesis, antibacterial, antibiofilm evaluation and molecular docking studies of 3-methyl- 2-propyl-2H-[1,2,4]triazolo[4,3b] [1,2,4,6]thiatriazine-1,1-dioxide

ABSTRACT. In the current study, a simple method for the synthesis of 3-methyl-2-propyl-2H-[1,2,4]triazolo[4,3b][1,2,4,6]thiatriazine-1,1-dioxide (2) was carried out. In the presence of pyridine, a reaction between amidine (1) and sulfuryl chloride occurs. FTIR spectroscopy, 1H and 13C NMR, mass spectra, and elemental analysis were utilized in order to verify the structure of a novel synthetic molecule. The antibacterial activities of compound (2) were tested against eight pathogenic bacteria and the minimum inhibitory concentration as well as minimum bactericidal concentration were determined. Moreover, the possible antibiofilm effect of compound (2) was evaluated. Molecular docking was investigated to determine the interaction between compound (2) and eight crystal structures of bacterial and yeast proteins associated with virulence activity and antimicrobial resistance. Our results showed that the new 3-methyl-2-propyl-2H-[1,2,4]triazolo[4,3b][1,2,4,6]thiatriazine-1,1-dioxide (2) compound has a moderate antibacterial activity toward the selected pathogenic bacteria. The obtained MICs varied from 32 to 512 µg/mL being the lowest values attributed to Staphylococcus epidermidis ATCC 14990 and Streptococcus mutans ATCC 25175 (MIC = 32 µg/mL).We noted also that heterocyclic compound (2) may inhibit bacterial biofilm formation at concentration depend manner with a lowest value obtained against S.mutans ATCC 25175 (BIC50 = 490 µg/mL). Molecular docking showed a promising inhibitory activity of compound (2) on TetM-mediated tetracycline resistance (3J25) and Staphylococcus aureus gyrase (3G7B) with lower binding energy compared to the other target proteins.                 KEY WORDS: Synthesis, Thiatriazine-1,1-dioxide, Antibacterial, Antibiofilm, Molecular docking Bull. Chem. Soc. Ethiop. 2022, 36(1), 109-117.                                                             DOI: https://dx.doi.org/10.4314/bcse.v36i1.10                                                      &nbsp

Antibiotic resistance and adhesion properties of oral Enterococci associated to dental caries

<p>Abstract</p> <p>Background</p> <p><it>Enterococci </it>are increasingly associated with opportunistic infections in Humans but the role of the oral cavity as a reservoir for this species is unclear. This study aimed to explore the carriage rate of Enterococci in the oral cavity of Tunisian children and their antimicrobial susceptibility to a broad range of antibiotics together with their adherence ability to abiotic and biotic surfaces.</p> <p>Results</p> <p>In this study, 17 <it>E. faecalis </it>(27.5%) and 4 <it>E. faecium </it>(6.5%) were detected. The identified strains showed resistance to commonly used antibiotics. Among the 17 isolated <it>E. faecalis</it>, 12 strains (71%) were slime producers and 5 strains were non-producers. Among the 4 <it>E. faecium</it>, 2 strains were slime producers. All the tested strains were able to adhere to at least one of the two tested cell lines. Our result showed that 11 <it>E. faecalis </it>and 2 <it>E. faecium </it>strains adhered strongly to Hep-2 as well as to A549 cells.</p> <p>Conclusions</p> <p>Drugs resistance and strong biofilm production abilities together with a high phenotypic adhesion to host cells are important equipment in <it>E. faecalis </it>and <it>E. faecium </it>which lead to their oral cavity colonization and focal infections.</p

Manuka-type honeys can eradicate biofilms produced by Staphylococcus aureus strains with different biofilm-forming abilities

Chronic wounds are a major global health problem. Their management is difficult and costly, and the development of antibiotic resistance by both planktonic and biofilm-associated bacteria necessitates the use of alternative wound treatments. Honey is now being revisited as an alternative treatment due to its broad-spectrum antibacterial activity and the inability of bacteria to develop resistance to it. Many previous antibacterial studies have used honeys that are not well characterized, even in terms of quantifying the levels of the major antibacterial components present, making it difficult to build an evidence base for the efficacy of honey as an antibiofilm agent in chronic wound treatment. Here we show that a range of well-characterized New Zealand manuka-type honeys, in which two principle antibacterial components, methylglyoxal and hydrogen peroxide, were quantified, can eradicate biofilms of a range of Staphylococcus aureus strains that differ widely in their biofilm-forming abilities. Using crystal violet and viability assays, along with confocal laser scanning imaging, we demonstrate that in all S. aureus strains, including methicillin-resistant strains, the manuka-type honeys showed significantly higher anti-biofilm activity than clover honey and an isotonic sugar solution.We observed higher anti-biofilm activity as the proportion of manuka-derived honey, and thus methylglyoxal, in a honey blend increased. However, methylglyoxal on its own, or with sugar, was not able to effectively eradicate S. aureus biofilms.We also demonstrate that honey was able to penetrate through the biofilm matrix and kill the embedded cells in some cases. As has been reported for antibiotics, sub-inhibitory concentrations of honey improved biofilm formation by some S. aureus strains, however, biofilm cell suspensions recovered after honey treatment did not develop resistance towards manukatype honeys. New Zealand manuka-type honeys, at the concentrations they can be applied in wound dressings are highly active in both preventing S. aureus biofilm formation and in their eradication, and do not result in bacteria becoming resistant. Methylglyoxal requires other components in manuka-type honeys for this antibiofilm activity. Our findings support the use of well-defined manuka-type honeys as a topical anti-biofilm treatment for the effective management of wound healing. © 2014 Lu et al

Antibacterial and resistance-modifying activities of thymoquinone against oral pathogens

<p>Abstract</p> <p>Background</p> <p>The presence of resistant bacteria in the oral cavity can be the major cause of dental antibiotic prophylaxis failure. Multidrug efflux has been described for many organisms, including bacteria and fungi as part of their drugs resistance strategy. The discovery of a new efflux pump inhibitor could extend the useful lifetime of some antibiotics.</p> <p>Methods</p> <p>In this study, the MICs of thymoquinone (TQ), tetracycline and benzalkonium chloride (BC) were determined in absence and in presence of a sub-MIC doses of thymoquinone (1/2 MIC). In addition the 4,6-diamidino-2-phenylindole (DAPI) efflux assay was carried out to determine the effect of TQ on DAPI cells accumulation.</p> <p>Results</p> <p>TQ induced a selective antimicrobial activity. Its synergic effect resulted in at least a 4-fold potentiation of the tested antibiotics and antiseptic. In addition, TQ inhibited the DAPI efflux activity in a concentration-dependent manner. The rate of DAPI accumulation in clinical isolates was enhanced with TQ (0 to 200 μg/ml). There is also a decrease in loss of DAPI from bacteria in the presence of TQ. The concentration causing 50% of DAPI efflux inhibition after 15 minutes was approximately 59 μg/ml for <it>Pseudomonas aeroginosa </it>and 100 μg/ml and <it>Staphylococcus aureus </it>respectively.</p> <p>Conclusions</p> <p>TQ possesses a selective antibacterial activity against oral bacteria. It is therefore suggested that TQ could be used as a source of natural products with resistance-modifying activity. Further investigation is needed to assess their clinical relevance.</p

Detection of macrolide and disinfectant resistance genes in clinical Staphylococcus aureus and coagulase-negative staphylococci

<p>Abstract</p> <p>Background</p> <p><it>Staphylococcus aureus </it>and Coagulase-negative staphylococci (CoNS) are a major source of infections associated with indwelling medical devices. Many antiseptic agents are used in hygienic handwash to prevent nosocomial infections by Staphylococci. Our aim was to determine the antibiotic susceptibility and resistance to quaternary ammonium compound of 46 <it>S. aureus </it>strains and 71 CoNS.</p> <p>Methods</p> <p><it>S. aureus </it>(n = 46) isolated from auricular infection and CoNS (n = 71), 22 of the strains isolated from dialysis fluids and 49 of the strains isolated from needles cultures were investigated. Erythromycin resistance genes (<it>erm</it>A, <it>erm</it>B, <it>erm</it>C, <it>msr</it>A and <it>mef</it>) were analysed by multiplex PCR and disinfectant-resistant genes (<it>qac</it>A, <it>qac</it>B, and <it>qac</it>C) were studied by PCR-RFLP.</p> <p>Results</p> <p>The frequency of erythromycin resistance genes in <it>S. aureus </it>was: <it>erm</it>A+ 7.7%, <it>erm</it>B+ 13.7%, <it>erm</it>C+ 6% and <it>msr</it>A+ 10.2%. In addition, the number of positive isolates in CoNS was respectively <it>erm</it>A+ (9.4%), <it>erm</it>B+ (11.1%), <it>erm</it>C+ (27.4%), and <it>msr</it>A+ (41%). The MIC analyses revealed that 88 isolates (74%) were resistant to quaternary ammonium compound-based disinfectant benzalkonium chloride (BC). 56% of the BC-resistant staphylococcus isolates have at least one of the three resistant disinfectants genes (<it>qac</it>A, <it>qac</it>B and <it>qac</it>C). Nine strains (7.7%) among the CoNS species and two <it>S. aureus </it>strains (2%) harboured the three-<it>qac </it>genes. In addition, the <it>qac</it>C were detected in 41 strains.</p> <p>Conclusions</p> <p>Multi-resistant strains towards macrolide and disinfectant were recorded. The investigation of antibiotics and antiseptic-resistant CoNS may provide crucial information on the control of nosocomial infections.</p