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Scientific Reports Jul 2024Chalcones are intermediate products in the biosynthesis of flavonoids, which possess a wide range of biological properties, including antimicrobial and anticancer...
Chalcones are intermediate products in the biosynthesis of flavonoids, which possess a wide range of biological properties, including antimicrobial and anticancer activities. The introduction of a chlorine atom and the glucosyl moiety into their structure may increase their bioavailability, bioactivity, and pharmacological use. The combined chemical and biotechnological methods can be applied to obtain such compounds. Therefore, 2-chloro-2'-hydroxychalcone and 3-chloro-2'-hydroxychalcone were synthesized and biotransformed in cultures of two strains of filamentous fungi, i.e. Isaria fumosorosea KCH J2 and Beauveria bassiana KCH J1.5 to obtain their novel glycosylated derivatives. Pharmacokinetics, drug-likeness, and biological activity of them were predicted using cheminformatics tools. 2-Chloro-2'-hydroxychalcone, 3-chloro-2'-hydroxychalcone, their main glycosylation products, and 2'-hydrochychalcone were screened for antimicrobial activity against several microbial strains. The growth of Escherichia coli 10,536 was completely inhibited by chalcones with a chlorine atom and 3-chlorodihydrochalcone 2'-O-β-D-(4″-O-methyl)-glucopyranoside. The strain Pseudomonas aeruginosa DSM 939 was the most resistant to the action of the tested compounds. However, chalcone aglycones and glycosides with a chlorine atom almost completely inhibited the growth of bacteria Staphylococcus aureus DSM 799 and yeast Candida albicans DSM 1386. The tested compounds had different effects on lactic acid bacteria depending on the tested species. In general, chlorinated chalcones were more effective in the inhibition of the tested microbial strains than their unchlorinated counterparts and aglycones were a little more effective than their glycosides.
Topics: Chalcones; Chlorine; Anti-Infective Agents; Biotransformation; Microbial Sensitivity Tests; Beauveria; Fungi; Escherichia coli
PubMed: 38951205
DOI: 10.1038/s41598-024-65054-9 -
Biochemistry Jul 2024Many bacteria have hemerythrin (Hr) proteins that bind O, including , in which microoxia-induced Hr (Mhr) provide fitness advantages under microoxic conditions. Mhr has...
Many bacteria have hemerythrin (Hr) proteins that bind O, including , in which microoxia-induced Hr (Mhr) provide fitness advantages under microoxic conditions. Mhr has a 23 amino-acid extension at its -terminus relative to a well-characterized Hr from , and similar extensions are also found in Hrs from other bacteria. The last 11 amino acids of this extended, -terminal tail are highly conserved in gammaproteobacteria and predicted to form a helix with positively charged and hydrophobic faces. In cellular fractionation assays, wild-type (WT) Mhr was found in both membrane and cytosolic fractions, while a Mhr variant lacking the last 11 residues was largely in the cytosol and did not complement Mhr function in competition assays. Mhr, a variant that has a much longer-lived O-bound form, was fully functional and had a similar localization pattern to that of WT Mhr. Both Mhr and Mhr had secondary structures, stabilities, and O-binding kinetics similar to those of WT Mhr. Fluorescence studies revealed that the -terminal tail, and particularly the fragment corresponding to its last 11 residues, was sufficient and necessary for association with lipid vesicles. Molecular dynamics simulations and subsequent cellular analysis of Mhr variants have demonstrated that conserved, positively charged residues in the tail are important for Mhr interactions with negatively charged membranes and the contribution of this protein to competitive fitness. Together, these data suggest that peripheral interactions of Mhr with membranes are guided by the C-terminal tail and are independent of O-binding.
PubMed: 38951132
DOI: 10.1021/acs.biochem.4c00174 -
ACS Applied Materials & Interfaces Jul 2024Better infection control will accelerate wound healing and alleviate associated healthcare burdens. Traditional antibacterial dressings often inadequately control...
Better infection control will accelerate wound healing and alleviate associated healthcare burdens. Traditional antibacterial dressings often inadequately control infections, inadvertently promoting antibacterial resistance. Our research unveils a novel, dual-functional living dressing that autonomously generates antibacterial agents and delivers electrical stimulation, harnessing the power of spore-forming . This dressing is built on an innovative wearable microbial fuel cell (MFC) framework, using endospores as a powerful, dormant biocatalyst. The endospores are resilient, reactivating in nutrient-rich wound exudate to produce electricity and antibacterial compounds. The combination allows to outcompete pathogens for food and other resources, thus fighting infections. The strategy is enhanced by the extracellular synthesis of tin oxide and copper oxide nanoparticles on the endospore surface, boosting antibacterial action, and electrical stimulation. Moreover, the MFC framework introduces a pioneering dressing design featuring a conductive hydrogel embedded within a paper-based substrate. The arrangement ensures cell stability and sustains a healing-friendly moist environment. Our approach has proven very effective against three key pathogens in biofilms: , , and demonstrating exceptional capabilities in both in vitro and ex vivo models. Our innovation marks a significant leap forward in wearable MFC-based wound care, offering a potent solution for treating infected wounds.
PubMed: 38950522
DOI: 10.1021/acsami.4c06303 -
Journal of Colloid and Interface Science Jun 2024The study shows for the first time a fivefold difference in the survivability of the bacterium Pseudomonas Aeruginosa (PA) in a realistic respiratory fluid droplet on...
HYPOTHESIS
The study shows for the first time a fivefold difference in the survivability of the bacterium Pseudomonas Aeruginosa (PA) in a realistic respiratory fluid droplet on fomites undergoing drying at different environmental conditions. For instance, in 2023, the annual average outdoor relative humidity (RH) and temperature in London (UK) is 71 % and 11 °C, whereas in New Delhi (India), it is 45 % and 26 °C, showing that disease spread from fomites could have a demographic dependence. Respiratory fluid droplet ejections containing pathogens on inanimate surfaces are crucial in disease spread, especially in nosocomial settings. However, the interplay between evaporation dynamics, internal fluid flow and precipitation and their collective influence on the distribution and survivability of pathogens at different environmental conditions are less known.
EXPERIMENTS
Shadowgraphy imaging is employed to study evaporation, and optical microscopy imaging is used for precipitation dynamics. Micro-particle image velocimetry (MicroPIV) measurements reveal the internal flow dynamics. Confocal imaging of fluorescently labelled PA elucidates the bacterial distribution within the deposits.
FINDINGS
The study finds that the evaporation rate is drastically impeded during drying at elevated solutal concentrations, particularly at high RH and low temperature conditions. MicroPIV shows reduced internal flow under high RH and low temperature (low evaporation rate) conditions. Evaporation rate influences crystal growth, with delayed efflorescence and extending crystallization times. PA forms denser peripheral arrangements under high evaporation rates and shows a fivefold increase in survivability under low evaporation rates. These findings highlight the critical impact of environmental conditions on pathogen persistence and disease spread from inanimate surfaces.
PubMed: 38950464
DOI: 10.1016/j.jcis.2024.06.218 -
AMB Express Jun 2024Pseudomonas aeruginosa is a commonly found Gram-negative bacterium in healthcare facilities and is renowned for its ability to form biofilms and its virulence factors...
Pseudomonas aeruginosa is a commonly found Gram-negative bacterium in healthcare facilities and is renowned for its ability to form biofilms and its virulence factors that are controlled by quorum sensing (QS) systems. The increasing prevalence of multidrug-resistant strains of this bacterium poses a significant challenge in the field of medicine. Consequently, the exploration of novel antimicrobial agents has become a top priority. This research aims to optimize chitosan derived from white shrimp (Metapenaeus affinis) using the Response Surface Methodology (RSM) computational approach. The objective is to investigate chitosan's potential as a solution for inhibiting QS activity and biofilm formation in P. aeruginosa ATCC 10,145. Under optimized conditions, chitin was treated with NaOH (1.41 M) for 15.75 h, HCl (7.49% vol) for 2.01 h, and at a deacetylation temperature of 81.15 °C. The resulting chitosan exhibited a degree of deacetylation (DD%) exceeding 93.98%, as confirmed by Fourier-transform infrared (FTIR) spectral analysis, indicating its high purity. The extracted chitosan demonstrated a significant synergistic antibiotic effect against P. aeruginosa when combined with ceftazidime, enhancing its bactericidal activity by up to 15-fold. In addition, sub-MIC (minimum inhibitory concentration) concentrations of extracted chitosan (10 and 100 µg/mL) successfully reduced the production of pyocyanin and rhamnolipid, as well as the swimming motility, protease activity and biofilm formation ability in comparison to the control group (P < 0.05). Moreover, chitosan treatment downregulated the RhlR and LasR genes in P. aeruginosa when compared to the control group (P < 0.05). The optimized chitosan extract shows significant potential as a coating agent for surgical equipment, effectively preventing nosocomial infections caused by P. aeruginosa pathogens.
PubMed: 38949677
DOI: 10.1186/s13568-024-01732-1 -
Pharmacotherapy Jul 2024Antibiotic resistance has become a global threat as it is continuously growing due to the evolution of β-lactamases diminishing the activity of classic β-lactam (BL)... (Review)
Review
Antibiotic resistance has become a global threat as it is continuously growing due to the evolution of β-lactamases diminishing the activity of classic β-lactam (BL) antibiotics. Recent antibiotic discovery and development efforts have led to the availability of β-lactamase inhibitors (BLIs) with activity against extended-spectrum β-lactamases as well as Klebsiella pneumoniae carbapenemase (KPC)-producing carbapenem-resistant organisms (CRO). Nevertheless, there is still a lack of drugs that target metallo-β-lactamases (MBL), which hydrolyze carbapenems efficiently, and oxacillinases (OXA) often present in carbapenem-resistant Acinetobacter baumannii. This review aims to provide a snapshot of microbiology, pharmacology, and clinical data for currently available BL/BLI treatment options as well as agents in late stage development for CRO harboring various β-lactamases including MBL and OXA-enzymes.
PubMed: 38949413
DOI: 10.1002/phar.2950 -
Microbiology Spectrum Jul 2024Bacteriophages (hereafter "phages") are ubiquitous predators of bacteria in the natural world, but interest is growing in their development into antibacterial therapy as...
UNLABELLED
Bacteriophages (hereafter "phages") are ubiquitous predators of bacteria in the natural world, but interest is growing in their development into antibacterial therapy as complement or replacement for antibiotics. However, bacteria have evolved a huge variety of antiphage defense systems allowing them to resist phage lysis to a greater or lesser extent. In addition to dedicated phage defense systems, some aspects of the general stress response also impact phage susceptibility, but the details of this are not well known. In order to elucidate these factors in the opportunistic pathogen , we used the laboratory-conditioned strain PAO1 as host for phage infection experiments as it is naturally poor in dedicated phage defense systems. Screening by transposon insertion sequencing indicated that the uncharacterized operon PA3040-PA3042 was potentially associated with resistance to lytic phages. However, we found that its primary role appeared to be in regulating biofilm formation, particularly in a clinical isolate of in which it also altered tobramycin resistance. Its expression was highly growth-phase dependent and responsive to phage infection and cell envelope stress. Our results suggest that this operon may be a cryptic but important locus for stress tolerance.
IMPORTANCE
An important category of bacterial stress response systems is bacteriophage defense, where systems are triggered by bacteriophage infection and activate a response which may either destroy the phage genome or destroy the infected cell so that the rest of the population survives. In some bacteria, the cell envelope stress response is activated by bacteriophage infection, but it is unknown whether this contributes to the survival of the infection. We have found that a conserved uncharacterized operon (PA3040-PA3042) of the cell envelope stress regulon in , which has very few dedicated phage defense systems, responds to phage infection and stationary phase as well as envelope stress and is important for growth and biofilm formation in a clinical isolate of , even in the absence of phages. As homologs of these genes are found in other bacteria, they may be a novel component of the general stress response.
PubMed: 38949386
DOI: 10.1128/spectrum.03875-23 -
International Wound Journal Jul 2024Patients with chronic limb-threatening ischaemia (CLTI) are at risk of foot infections, which is associated with an increase in amputation rates. The use of antibiotics...
Patients with chronic limb-threatening ischaemia (CLTI) are at risk of foot infections, which is associated with an increase in amputation rates. The use of antibiotics may lead to a higher incidence of antimicrobial resistance (AMR) in subsequent episodes of ischaemic foot infections (IFI). This retrospective single-centre cohort study included 130 patients with IFI undergoing endovascular revascularisation. Staphylococcus aureus and Pseudomonas aeruginosa were the two most common pathogens, accounting for 20.5% and 10.8% of cases, respectively. The prevalence of antimicrobial resistance (AMR) and multi-drug resistance did not significantly increase between episodes (10.2% vs. 13.4%, p = 0.42). In 59% of subsequent episodes, the identified pathogens were unrelated to the previous episode. However, the partial concordance of identified pathogens significantly increased to 66.7% when S. aureus was identified (p = 0.027). Subsequent episodes of IFI in the same patient are likely to differ in causative pathogens. However, in the case of S. aureus, the risk of reinfection, particularly with S. aureus, is increased. Multi-drug resistance does not appear to change between IFI episodes. Therefore, recommendations for empirical antimicrobial therapy should be based on local pathogen and resistance statistics without the need to broaden the spectrum of antibiotics in subsequent episodes.
Topics: Humans; Male; Retrospective Studies; Female; Aged; Middle Aged; Ischemia; Anti-Bacterial Agents; Aged, 80 and over; Cohort Studies; Staphylococcus aureus; Drug Resistance, Bacterial; Pseudomonas aeruginosa
PubMed: 38949168
DOI: 10.1111/iwj.14961 -
Biochemistry Research International 2024The plant has been utilized in folk medicine. Analyzing phytochemical composition of dichloromethane/methanol (1 : 1) root part of gave oleic acid (), caffeic...
The plant has been utilized in folk medicine. Analyzing phytochemical composition of dichloromethane/methanol (1 : 1) root part of gave oleic acid (), caffeic acid-2-hydroxynonylester (), catechin (), and a pregnane derivative (). NMR spectroscopy was used to characterize compounds , while compound was identified through GC-MS analysis and literature comparison. The cytotoxicity of extracts from roots of was conducted against MCF-7 cell lines (human breast cancer) by MTT assay. According to the cytotoxicity study, -hexane extract exhibited a high level of toxicity with 28.9 ± 5.6% cell viability. Antibacterial activity was tested against , , , and The highest bacterial growth mean inhibition zone was measured for catechin (3) (13.72 ± 0.05 mm)) against at 0.25 mg/mL and acceptable related to standard. Antioxidant activity was studied by the DPPH assay. Based on the data from the antioxidant study, DCM/MeOH extract (70.32%) and catechin () showed good antioxidant activity (65.61%) (IC 0.25 g/mL) relative to that of the positive control (78.21%, IC 0.014 g/mL) at 12.5 g/mL. In each docking pose, catechin () scored higher binding affinity of -7.9, -7.2, and -6.4 kcal/mol towards PqsA, DNA gyraseB, and PK, respectively, compared to amoxicillin (-8.1, -6.1, and -6.4 kcal/mol). All five Lipinski rules were obeyed by compounds , which showed an acceptable drug resemblance. The lipophilicity was computed as less than five (1.47-4.01) indicating a lipophilic property. Catechin () obeys Veber's rule implying its good oral bioavailability. Binding affinity scores of catechin ()-protein interactions are in line with those from tests, indicating its potential antibacterial effect. The obtained cytotoxicity and antibacterial activity results support the utilization of in folk medicine.
PubMed: 38948887
DOI: 10.1155/2024/3713620 -
World Journal of Transplantation Jun 2024Transplant recipients commonly harbor multidrug-resistant organisms (MDROs), as a result of frequent hospital admissions and increased exposure to antimicrobials and...
BACKGROUND
Transplant recipients commonly harbor multidrug-resistant organisms (MDROs), as a result of frequent hospital admissions and increased exposure to antimicrobials and invasive procedures.
AIM
To investigate the impact of patient demographic and clinical characteristics on MDRO acquisition, as well as the impact of MDRO acquisition on intensive care unit (ICU) and hospital length of stay, and on ICU mortality and 1-year mortality post heart transplantation.
METHODS
This retrospective cohort study analyzed 98 consecutive heart transplant patients over a ten-year period (2013-2022) in a single transplantation center. Data was collected regarding MDROs commonly encountered in critical care.
RESULTS
Among the 98 transplanted patients (70% male), about a third (32%) acquired or already harbored MDROs upon transplantation (MDRO group), while two thirds did not (MDRO-free group). The prevalent MDROs were (14%), (12%) and (11%). Compared to MDRO-free patients, the MDRO group was characterized by higher body mass index ( = 0.002), higher rates of renal failure ( = 0.017), primary graft dysfunction (10% 4.5%, = 0.001), surgical re-exploration (34% 14%, = 0.017), mechanical circulatory support (47% 26% = 0.037) and renal replacement therapy (28% 9%, = 0.014), as well as longer extracorporeal circulation time (median 210 161 min, = 0.003). The median length of stay was longer in the MDRO group, namely ICU stay was 16 9 d in the MDRO-free group ( = 0.001), and hospital stay was 38 28 d ( = 0.006), while 1-year mortality was higher (28% 7.6%, log-rank- : 7.34).
CONCLUSION
Following heart transplantation, a predominance of Gram-negative MDROs was noted. MDRO acquisition was associated with higher complication rates, prolonged ICU and total hospital stay, and higher post-transplantation mortality.
PubMed: 38947964
DOI: 10.5500/wjt.v14.i2.93567