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Antibiofilm and antimicrobial activity of curcumin-chitosan nanocomplexes and trimethoprim-sulfamethoxazole on , and isolates. Expert review of anti-infective therapy BACKGROUND:Non-fermenting Gram-negative complex, and species cause healthcare-associated infections, often showing resistance to first-line drugs such as trimethoprim-sulfamethoxazole (TMP-SXT). The aim of this study was to determine the effect of curcumin-chitosan nanocomplexes on biofilm-producing clinical isolates of non-fermenting Gram-negative bacilli. METHODS: complex, and clinical isolates were identified by MALDI-TOF mass spectrometry. Antimicrobial susceptibility was determined by broth microdilution. Curcumin (Cur), chitosan (Chi), and sodium tripolyphosphate (TPP) were encapsulated by ionotropic gelation in magnetic nanoparticles (MNP) and were assessed by scanning electron microscopy (SEM) and Fourier-transform infrared (FTIR). Biofilm inhibition and eradication by Cur-Chi-TPP-MNP with TMP-SXT was assessed. RESULTS:Cur-Chi-TPP-MNP in combination with TMP-SXT showed biofilm inhibition activity in (37.5 µg/mL), (18.75 µg/mL), and (4.69-18.75 µg/mL) and low biofilm eradication activity in all three strains (150 - 300 µg/mL). CONCLUSIONS:Cur-Chi-TPP-MNP in combination with TMP-SXT was able to inhibit biofilm and in lower effect to eradicate established biofilms of clinical isolates of complex, and species. Our results highlight the need to assess these potential treatment options to be used clinically in biofilm-associated infections. 10.1080/14787210.2023.2166933
Quorum-quenching enzymes: Promising bioresources and their opportunities and challenges as alternative bacteriostatic agents in food industry. Comprehensive reviews in food science and food safety The problems of spoilage, disease, and biofilm caused by bacterial quorum-sensing (QS) systems have posed a significant challenge to the development of the food industry. Quorum-quenching (QQ) enzymes can block QS by hydrolyzing or modifying the signal molecule, making these enzymes promising new candidates for use as antimicrobials. With many recent studies of QQ enzymes and their potential to target foodborne bacteria, an updated and systematic review is necessary. Thus, the goals of this review were to summarize what is known about the effects of bacterial QS on the food industry; discuss the current understanding of the catalytic mechanisms of QQ enzymes, including lactonase, acylase, and oxidoreductase; and describe strategies for the engineering and evolution of QQ enzymes for practical use. In particular, this review focuses on the latest progress in the application of QQ enzymes in the field of food. Finally, the current challenges limiting the systematic application of QQ enzymes in the food industry are discussed to help guide the future development of these important enzymes. 10.1111/1541-4337.13104
Antimicrobial and Antibiofilm Effects of Combinatorial Treatment Formulations of Anti-Inflammatory Drugs-Common Antibiotics against Pathogenic Bacteria. Pharmaceutics With the spread of multi-drug-resistant (MDR) bacteria and the lack of effective antibiotics to treat them, developing new therapeutic methods and strategies is essential. In this study, we evaluated the antibacterial and antibiofilm activity of different formulations composed of ibuprofen (IBP), acetylsalicylic acid (ASA), and dexamethasone sodium phosphate (DXP) in combination with ciprofloxacin (CIP), gentamicin (GEN), cefepime (FEP), imipenem (IPM), and meropenem (MEM) on clinical isolates of () and () as well as the transcription levels of biofilm-associated genes in the presence of sub-MICs of IBP, ASA, and DXP. The minimal inhibitory concentrations (MICs), minimal biofilm inhibitory concentrations (MBICs), and minimum biofilm eradication concentrations (MBECs) of CIP, GEN, FEP, IPM, and MEM with/without sub-MICs of IBP (200 µg/mL), ASA (200 µg/mL), and DXP (500 µg/mL) for the clinical isolates were determined by the microbroth dilution method. Quantitative real-time-PCR (qPCR) was used to determine the expression levels of biofilm-related genes, including in and in at sub-MICs of IBP, ASA, and DXP. All isolates were methicillin-resistant (MRSA), and all were resistant to carbapenems. IBP decreased the levels of MIC, MBIC, and MBEC for all antibiotic agents in both clinical isolates, except for FEP among isolates. In MRSA isolates, ASA decreased the MICs of GEN, FEP, and IPM and the MBICs of IPM and MEM. In , ASA decreased the MICs of FEP, IPM, and MEM, the MBICs of FEP and MEM, and the MBEC of FEP. DXP increased the MICs of CIP, GEN, and FEP, and the MBICs of CIP, GEN, and FEP among both clinical isolates. The MBECs of CIP and FEP for MRSA isolates and the MBECs of CIP, GEN, and MEM among isolates increased in the presence of DXP. IBP and ASA at 200 µg/mL significantly decreased the transcription level of in , and IBP significantly decreased the transcription level of in . DXP at 500 µg/mL significantly increased the expression levels of and genes in and isolates, respectively. Our findings showed that the formulations containing ASA and IBP have significant effects on decreasing the MIC, MBIC, and MBEC levels of some antibiotics and can down-regulate the expression of biofilm-related genes such as and . Therefore, NSAIDs represent appropriate candidates for the design of new antibacterial and antibiofilm therapeutic formulations. 10.3390/pharmaceutics15010004
Development and Characterization of Pharmaceutical Systems Containing Rifampicin. Pharmaceutics Rifampicin is a potent antimicrobial drug with some suboptimal properties, such as poor stability, low solubility, and variable bioavailability. Therefore, in the current study, a multicomponent complex between rifampicin, γ-cyclodextrin, and arginine was prepared with the aim of improving drug properties. Solubility was evaluated by phase-solubility studies. The mechanism of interaction was established through proton nuclear magnetic resonance spectroscopy and molecular modeling. Physicochemical characterization was investigated using Fourier transform-infrared spectroscopy, powder X-ray diffraction, and scanning electron microscopy. The dissolution properties, antimicrobial activity (antibacterial, antibiofilm, and antileishmanial), and stability of the different samples were studied. The results obtained in this investigation demonstrate that multicomponent complexes can improve the water solubility and dissolution rate of rifampicin, as well as its antibacterial and antileishmanial action, and present suitable stability. In conclusion, rifampicin complexed with γ-cyclodextrin and arginine is an attractive approach for developing pharmaceutical dosage forms of rifampicin with increased antimicrobial activities. 10.3390/pharmaceutics15010198
Combined Use of Antimicrobial Peptides with Antiseptics against Multidrug-Resistant Bacteria: Pros and Cons. Pharmaceutics Antimicrobial peptides (AMPs) are acknowledged as a promising template for designing new antimicrobials. At the same time, existing toxicity issues and limitations in their pharmacokinetics make topical application one of the less complicated routes to put AMPs-based therapeutics into actual medical practice. Antiseptics are one of the common components for topical treatment potent against antibiotic-resistant pathogens but often with toxicity limitations of their own. Thus, the interaction of AMPs and antiseptics is an interesting topic that is also less explored than combined action of AMPs and antibiotics. Herein, we analyzed antibacterial, antibiofilm, and cytotoxic activity of combinations of both membranolytic and non-membranolytic AMPs with a number of antiseptic agents. Fractional concentration indices were used as a measure of possible effective concentration reduction achievable due to combined application. Cases of both synergistic and antagonistic interaction with certain antiseptics and surfactants were identified, and trends in the occurrence of these types of interaction were discussed. The data may be of use for AMP-based drug development and suggest that the topic requires further attention for successfully integrating AMPs-based products in the context of complex treatment. AMP/antiseptic combinations show promise for creating topical formulations with improved activity, lowered toxicity, and, presumably, decreased chances of inducing bacterial resistance. However, careful assessment is required to avoid AMP neutralization by certain antiseptic classes in either complex drug design or AMP application alongside other therapeutics/care products. 10.3390/pharmaceutics15010291
Effect of chemical modifications of tannins on their antimicrobial and antibiofilm effect against Gram-negative and Gram-positive bacteria. Frontiers in microbiology Background:Tannins have demonstrated antibacterial and antibiofilm activity, but there are still unknown aspects on how the chemical properties of tannins affect their biological properties. We are interested in understanding how to modulate the antibiofilm activity of tannins and in delineating the relationship between chemical determinants and antibiofilm activity. Materials and methods:The effect of five different naturally acquired tannins and their chemical derivatives on biofilm formation and planktonic growth of Typhimurium, , and was determined in the Calgary biofilm device. Results:Most of the unmodified tannins exhibited specific antibiofilm activity against the assayed bacteria. The chemical modifications were found to alter the antibiofilm activity level and spectrum of the tannins. A positive charge introduced by derivatization with higher amounts of ammonium groups shifted the anti-biofilm spectrum toward Gram-negative bacteria, and derivatization with lower amounts of ammonium groups and acidifying derivatization shifted the spectrum toward Gram-positive bacteria. Furthermore, the quantity of phenolic OH-groups per molecule was found to have a weak impact on the anti-biofilm activity of the tannins. Conclusion:We were able to modulate the antibiofilm activity of several tannins by specific chemical modifications, providing a first approach for fine tuning of their activity and antibacterial spectrum. 10.3389/fmicb.2022.987164
Inhibition of planktonic growth and biofilm formation of by entrectinib through disrupting the cell membrane. Frontiers in microbiology Over the last few decades, infection remain a major medical challenge and health concern worldwide. Biofilm formation and antibiotic resistance caused by make it difficult to be eradicated from bacterial infections in clinics. In this study, our data demonstrated the antibacterial and excellent anti-biofilm activity of entrectinib against . Entrectinib also exhibited the good safety, suggesting no toxicity with antibacterial concentration of entrectinib toward the erythrocytes and mammalian 239 T cells. Moreover, entrectinib significantly reduced the bacterial burden of septic tissue in a murine model of MRSA infection. Global proteomic analysis of treated with entrectinib showed significant changes in the expression levels of ribosomal structure-related (rpmC, rpmD, rplX, and rpsT) and oxidative stress-related proteins (Thioredoxin system), suggesting the possible inhibition of bacterial protein biosynthesis with entrectinib exposure. The increased production of reactive oxygen species (ROS) was demonstrated in the entrectinib-treated , supported the impact of entrectinib on the expression changes of ROS-correlated proteins involved in oxidative stress. Furthermore, entrectinib-induced resistant clone was selected by induction under entrectinib exposure and 3 amino acid mutations in the entrectinib-induced resistant strain, 2 of which were located in the gene encoding Type II NADH: quinoneoxidoreductase and one were found in GTP pyrophosphokinase family protein. Finally, the bactericidal action of entrectinib on were confirmed by disrupting the bacterial cell membrane. Conclusively, entrectinib exhibit the antibacterial and anti-biofilm activity by destroying cell membrane against . 10.3389/fmicb.2022.1106319
Evaluation of bactericidal effects of silver hydrosol nanotherapeutics against 1449 drug resistant biofilms. Frontiers in cellular and infection microbiology Introduction:Silver (Ag) nanoparticles (NPs) are well documented for their broad-spectrum bactericidal effects. This study aimed to test the effect of bioactive Ag-hydrosol NPs on drug-resistant 1449 strain and explore the use of artificial intelligence (AI) for automated detection of the bacteria. Methods:The formation of 1449 biofilms in the absence and presence of Ag-hydrosol NPs at different concentrations ranging from 12.4 mg/L to 123 mg/L was evaluated using a 3-dimentional culture system. The biofilm reduction was evaluated using the confocal microscopy in addition to the Transmission Electronic Microscopy (TEM) visualization and spectrofluorimetric quantification using a Biotek Synergy Neo2 microplate reader. The cytotoxicity of the NPs was evaluated in human nasal epithelial cells using the MTT assay. The AI technique based on Fast Regional Convolutional Neural Network architecture was used for the automated detection of the bacteria. Results:Treatment with Ag-hydrosol NPs at concentrations ranging from 12.4 mg/L to 123 mg/L resulted in 78.09% to 95.20% of biofilm reduction. No statistically significant difference in biofilm reduction was found among different batches of Ag-hydrosol NPs. Quantitative concentration-response relationship analysis indicated that Ag-hydrosol NPs exhibited a relative high anti-biofilm activity and low cytotoxicity with an average EC50 and TC50 values of 0.0333 and 6.55 mg/L, respectively, yielding an average therapeutic index value of 197. The AI-assisted TEM image analysis allowed automated detection of 1449 with 97% ~ 99% accuracy. Discussion:Conclusively, the bioactive Ag-hydrosol NP is a promising nanotherapeutic agent against drug-resistant pathogens. The AI-assisted TEM image analysis was developed with the potential to assess its treatment effect. 10.3389/fcimb.2022.1095156