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Pharmaceuticals (Basel, Switzerland) Apr 2024Several biologically active compounds involved in the green synthesis of silver and gold nanoparticles have been isolated from snail mucus and characterized. This paper...
Several biologically active compounds involved in the green synthesis of silver and gold nanoparticles have been isolated from snail mucus and characterized. This paper presents a successful method for the application of snail mucus from as a bioreducing agent of copper sulfate and as a biostabilizer of the copper oxide nanoparticles (CuONPs-Muc) obtained. The synthesis at room temperature and neutral pH yielded nanoparticles with a spherical shape and an average diameter of 150 nm. The structure and properties of CuONPs-Muc were characterized using various methods and techniques, such as ultraviolet-visible spectroscopy (UV-vis), high-performance liquid chromatography (HPLC), one-dimensional polyacrylamide gel electrophoresis (1D-PAGE), up-conversion infrared spectroscopy Fourier transform (FTIR), scanning electron microscopy combined with energy dispersive spectroscopy (SEM/EDS), Raman spectroscopy and imaging, thermogravimetric analysis (TG-DSC), etc. Mucus proteins with molecular weights of 30.691 kDa and 26.549 kDa were identified, which are involved in the biogenic production of CuONPs-Muc. The macromolecular shell of proteins formed around the copper ions contributes to a higher efficiency of the synthesized CuONPs-Muc in inhibiting the bacterial growth of several Gram-positive (Bacillus subtilis NBIMCC2353, ATCC 6633, ATCC 6538, NBIMCC8755) and Gram-negative ( ATCC8739, NBIMCC8691, ATCC 14028, ATCC 17666) bacteria compared to baseline mucus. The bioorganic synthesis of snail mucus presented here provides CuONPs-Muc with a highly pronounced antimicrobial effect. These results will expand knowledge in the field of natural nanomaterials and their role in emerging dosage forms.
PubMed: 38675466
DOI: 10.3390/ph17040506 -
Journal of Clinical Medicine Apr 2024: The clinical outcomes of usual doses of Trimethoprim-sulfamethoxazole (TMP/SMZ) for treating in critically ill patients on renal replacement therapies (RRT) have not...
: The clinical outcomes of usual doses of Trimethoprim-sulfamethoxazole (TMP/SMZ) for treating in critically ill patients on renal replacement therapies (RRT) have not been established. We sought to assess the clinical outcomes of TMP/SMZ in patients with sepsis utilizing RRT. : A retrospective study was performed on all critically ill adult patients with infections who received RRT between May 2015 and January 2022. The primary endpoint was clinical cure while the secondary endpoints were microbiologic cure, 30-day infection recurrence, and mortality. : Forty-five subjects met the inclusion criteria. The median age was 70.0 [interquartile range (IQR): 63.5-77] years, 57.8% were males, and the median body mass index was 25.7 [IQR: 22-30.2] kg/m. Clinical success and failure were reported in 18 (40%) and 27 (60%) cases, respectively. There was no significant difference between the 30-day reinfection rates of both groups; however, mortality was significantly higher in the clinical failure group, involving 12 patients (44.4%), versus none in the clinical success group ( = 0.001). The median daily dose of TMP/SMZ upon continuous veno-venous hemofiltration was 1064 [IQR: 776-1380] mg in the clinical cure group vs. 768 [IQR:540-1200] mg in the clinical failure group ( = 0.035). Meanwhile, the median dose for those who received intermittent hemodialysis was 500 [IQR: 320-928] mg in the clinical success group compared to 640 [IQR: 360-1005] mg in the clinical failure group ( = 0.372). A total of 55% experienced thrombocytopenia, 42% hyperkalemia, and 2.2% neutropenia. The multivariable logistic regression analysis showed that the total daily dose at therapy initiation was the only independent factor associated with clinical success after adjusting for different variables including the body mass index [Odds ratio 1.004; 95% confidence interval: (1-1.007), = 0.044]. : Although the isolates were reported as susceptible, TMP/SMZ with conventional doses to treat bacteremia and pneumonia in critically ill patients utilizing RRT was associated with high rates of clinical and microbiologic failure as well as with mortality. Larger outcomes and pharmacokinetics studies are needed to confirm our findings.
PubMed: 38673547
DOI: 10.3390/jcm13082275 -
Foods (Basel, Switzerland) Apr 2024is a major threat to the food industry and human health owing to its strong protease production and biofilm formation abilities. However, information regarding...
is a major threat to the food industry and human health owing to its strong protease production and biofilm formation abilities. However, information regarding regulatory factors or potential mechanisms is limited. Herein, we observed that temperature differentially regulates biofilm formation and protease production, and a cAMP receptor-like protein (Clp) negatively regulates thermosensor biofilm formation, in contrast to protease synthesis. Among four c-di-GMP-related two-component systems (TCSs), promoter fusion analysis revealed that transcription levels were predominantly controlled by LotS/LotR, partially controlled by both RpfC/RpfG and a novel TCS Sm0738/Sm0737, with no obvious effect caused by Sm1912/Sm1911. Biofilm formation in Δ and ΔTCSs strains suggested that LotS/LotR controlled biofilm formation in a Clp-mediated manner, whereas both RpfC/RpfG and Sm0738/Sm0737 may occur in a distinct pathway. Furthermore, enzymatic activity analysis combined with c-di-GMP level indicated that the enzymatic activity of c-di-GMP-related metabolism proteins may not be a vital contributor to changes in c-di-GMP level, thus influencing physiological functions. Our findings elucidate that the regulatory pathway of c-di-GMP-related TCSs and Clp in controlling spoilage or the formation of potentially pathogenic factors in expand the understanding of c-di-GMP metabolism and provide clues to control risk factors of in food safety.
PubMed: 38672874
DOI: 10.3390/foods13081201 -
Antibiotics (Basel, Switzerland) Apr 2024is an opportunistic pathogen that produces respiratory infections in immunosuppressed and cystic fibrosis patients. The therapeutic options to treat infections are...
is an opportunistic pathogen that produces respiratory infections in immunosuppressed and cystic fibrosis patients. The therapeutic options to treat infections are limited since it exhibits resistance to a wide variety of antibiotics such as β-lactams, aminoglycosides, tetracyclines, cephalosporins, macrolides, fluoroquinolones, or carbapenems. The antibiotic combination trimethoprim/sulfamethoxazole (SXT) is the treatment of choice to combat infections caused by , while ceftazidime, ciprofloxacin, or tobramycin are used in most SXT-resistant infections. In the current study, experimental evolution and whole-genome sequencing (WGS) were used to examine the evolutionary trajectories of towards resistance against tobramycin, ciprofloxacin, and SXT. The genetic changes underlying antibiotic resistance, as well as the evolutionary trajectories toward that resistance, were determined. Our results determine that genomic changes in the efflux pump regulatory genes and are essential to confer resistance to ciprofloxacin, and the mutation in the gene is significant in the resistance to tobramycin. We identified mutations in and the efflux pump regulator as the basis of SXT resistance. Detailed and reliable knowledge of ciprofloxacin, tobramycin, and SXT resistance is essential for safe and effective use in clinical settings. Herein, we were able to prove once again the extraordinary ability that has to acquire resistance and the importance of looking for alternatives to combat this resistance.
PubMed: 38667006
DOI: 10.3390/antibiotics13040330 -
Bioresources and Bioprocessing Nov 2023Enzymatic degradation of synthetic dyes holds an immense promise for addressing the environmental concerns associated with the textile and dye industries. This study...
Optimization of laccase from Stenotrophomonas maltophilia E1 by submerge fermentation using coconut husk with its detoxification and biodecolorization ability of synthetic dyes.
Enzymatic degradation of synthetic dyes holds an immense promise for addressing the environmental concerns associated with the textile and dye industries. This study aimed to isolate bacteria capable of producing laccase enzymes from an anthropogenic environment. Subsequently, viability of utilizing cost-effective agricultural residues as substrates for laccase production was assessed. Response Surface Methodology (RSM) and the One Variable at a Time (OVAT) approach was pursued for the optimization of laccase production, followed by pH and temperature stability, dye degradation and decolorization experiments, toxicological studies on the degraded dye metabolites. In results, laccase-producing bacterial strain was identified as Stenotrophomonas maltophilia strain E1 (S. maltophilia). Among variety of substrates, coconut husk exhibited optimal efficacy. In a statistical optimization study, it was found that S. maltophilia was capable of producing laccase 51.38 IU/mL, i.e., three times higher than the amount of laccase produced by unoptimized medium (16.7 IU/mL), and the enzyme activity was found to be steady at an acidic pH, and a mesophilic temperature range. The laccase obtained from S. maltophilia E1 demonstrated proficient dye decolorization capabilities, achieving a notable 92.1% reduction in Malachite green dye coloration at a concentration of 500 ppm. Gas chromatography-mass spectrometry (GC-MS) analysis of the decolorized derivatives of Malachite green revealed a conversion into a distinct compounds. Moreover, after undergoing laccase treatment, Malachite green exhibited decreased phytotoxic effects on Oryza sativa, pointing to enzymatic detoxification. Collectively, insights gained from the present study will contribute to the development of efficient enzymatic approaches for addressing the environmental pollution caused by synthetic dyes.
PubMed: 38647840
DOI: 10.1186/s40643-023-00703-x -
IDCases 2024Carbapenem resistance due to metallo-beta-lactamases (MBLs) is a global phenomenon and an important challenge for antibiotic therapy (Boyd et al., 2020 [1]). While...
Novel case of combination antibiotic therapy for treatment of a complicated polymicrobial urinary tract infection with one organism harboring a metallo-β-lactamase (MBL) in a pregnant patient.
Carbapenem resistance due to metallo-beta-lactamases (MBLs) is a global phenomenon and an important challenge for antibiotic therapy (Boyd et al., 2020 [1]). While previous reports have demonstrated both and synergy using the combination of ceftazidime-avibactam and aztreonam against , an MBL-harboring organism, this treatment strategy has not been reported during pregnancy (Mojic et al., 2017 [2], [3], Mojica et al., 2016 [4], Alexander et al., 2020 [5]). We describe a 33-year-old pregnant female with polymicrobial, bilateral pyelonephritis caused by and other gram-negative bacteria. The organisms were eradicated with the combination of ceftazidime-avibactam and aztreonam followed by successful delivery with no observed adverse effects in either mother or child post-partum.
PubMed: 38646598
DOI: 10.1016/j.idcr.2024.e01946 -
PloS One 2024Infections caused by Stenotrophomonas maltophilia and related species are increasing worldwide. Unfortunately, treatment options are limited, whereas the antimicrobial...
In vitro activity of ceftazidime/avibactam, cefiderocol, meropenem/vaborbactam and imipenem/relebactam against clinical strains of the Stenotrophomonas maltophilia complex.
BACKGROUND
Infections caused by Stenotrophomonas maltophilia and related species are increasing worldwide. Unfortunately, treatment options are limited, whereas the antimicrobial resistance is increasing.
METHODS
We included clinical isolates identified as S. maltophilia by VITEK 2 Compact. Ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, cefiderocol, quinolones, and tetracycline family members were evaluated by broth microdilution method and compared with first-line treatment drugs. Minimum inhibitory concentrations (MICs) were reported for all antibiotics. We sequenced the Whole Genome of cefiderocol resistant strains (CRSs) and annotated their genes associated with cefiderocol resistance (GACR). Presumptive phylogenetic identification employing the 16S marker was performed.
RESULTS
One hundred and one clinical strains were evaluated, sulfamethoxazole and trimethoprim, levofloxacin and minocycline showed susceptibilities of 99.01%, 95.04% and 100% respectively. Ceftazidime was the antibiotic with the highest percentage of resistance in all samples (77.22%). Five strains were resistant to cefiderocol exhibiting MIC values ≥ 2 μg/mL (4.95%). The β-lactamase inhibitors meropenem/vaborbactam and imipenem/relebactam, failed to inhibit S. maltophilia, preserving both MIC50 and MIC90 ≥64 μg/mL. Ceftazidime/avibactam restored the activity of ceftazidime decreasing the MIC range. Tigecycline had the lowest MIC range, MIC50 and MIC90. Phylogeny based on 16S rRNA allowed to identify to cefiderocol resistant strains as putative species clustered into Stenotrophomonas maltophilia complex (Smc). In these strains, we detected GARCs such as Mutiple Drug Resistance (MDR) efflux pumps, L1-type β-lactamases, iron transporters and type-1 fimbriae.
CONCLUSION
Antimicrobial resistance to first-line treatment is low. The in vitro activity of new β-lactamase inhibitors against S. maltophilia is poor, but avibactam may be a potential option. Cefiderocol could be considered as a potential new option for multidrug resistant infections. Tetracyclines had the best in vitro activity of all antibiotics evaluated.
Topics: Ceftazidime; Cefiderocol; Meropenem; Stenotrophomonas maltophilia; beta-Lactamase Inhibitors; Stenotrophomonas; Phylogeny; RNA, Ribosomal, 16S; Anti-Bacterial Agents; Azabicyclo Compounds; Drug Combinations; Imipenem; Microbial Sensitivity Tests; beta-Lactamases; Boronic Acids
PubMed: 38635685
DOI: 10.1371/journal.pone.0298577 -
PloS One 2024Regular monitoring of bacterial susceptibility to antibiotics in clinical settings is key for ascertaining the current trends as well as re-establish empirical therapy....
Regular monitoring of bacterial susceptibility to antibiotics in clinical settings is key for ascertaining the current trends as well as re-establish empirical therapy. This study aimed to determine bacterial contaminants and their antimicrobial susceptibility patterns from medical equipment, inanimate surfaces and clinical samples obtained from Thika Level V Hospital (TLVH), Thika, in Central Kenya. Three hundred and five samples were collected between the period of March 2021 to November 2021 and comprised urine, pus swabs, catheter swabs, stool, and environmental samples. Bacterial identification and antimicrobial susceptibility were performed using VITEK 2 and disc diffusion respectively. We observed that Coagulase-negative Staphylococci (28 /160, 17.5%) were the most commonly isolated species from clinical samples followed by E. coli (22 /160 13.8%) and S. aureus (22/160, 13.8%). The bed rails were the mostly contaminated surface with S. aureus accounting for 14.2% (6/42). Among the clinical samples, pus swabs yielded the highest number of pathogens was pus (92/160). Trauma patients had the highest proportion of isolates (67/160, 41.8%). High level of antimicrobial resistance to key antimicrobials, particularly among Enterobacterales was observed. Extended Spectrum Beta Lactamase (ESBL) phenotype was noted in 65.9% (29/44) of enteric isolates. While further ESBL genetic confirmatory studies are needed, this study highlights the urgent need for actions that mitigate the spread of antibiotic-resistant bacteria.
Topics: Humans; Stenotrophomonas maltophilia; Burkholderia cepacia; Escherichia coli; Drug Resistance, Multiple, Bacterial; Staphylococcus aureus; Kenya; Microbial Sensitivity Tests; Anti-Bacterial Agents; Hospitals; Bacteria; Referral and Consultation; Suppuration; beta-Lactamases
PubMed: 38626173
DOI: 10.1371/journal.pone.0298873 -
Respiratory Research Apr 2024Little is known about the relationships between human genetics and the airway microbiome. Deeply sequenced airway metagenomics, by simultaneously characterizing the...
Little is known about the relationships between human genetics and the airway microbiome. Deeply sequenced airway metagenomics, by simultaneously characterizing the microbiome and host genetics, provide a unique opportunity to assess the microbiome-host genetic associations. Here we performed a co-profiling of microbiome and host genetics with the identification of over 5 million single nucleotide polymorphisms (SNPs) through deep metagenomic sequencing in sputum of 99 chronic obstructive pulmonary disease (COPD) and 36 healthy individuals. Host genetic variation was the most significant factor associated with the microbiome except for geography and disease status, with its top 5 principal components accounting for 12.11% of the microbiome variability. Within COPD individuals, 113 SNPs mapped to candidate genes reported as genetically associated with COPD exhibited associations with 29 microbial species and 48 functional modules (P < 1 × 10), where Streptococcus salivarius exhibits the strongest association to SNP rs6917641 in TBC1D32 (P = 9.54 × 10). Integration of concurrent host transcriptomic data identified correlations between the expression of host genes and their genetically-linked microbiome features, including NUDT1, MAD1L1 and Veillonella parvula, TTLL9 and Stenotrophomonas maltophilia, and LTA4H and Haemophilus influenzae. Mendelian randomization analyses revealed a potential causal link between PARK7 expression and microbial type III secretion system, and a genetically-mediated association between COPD and increased relative abundance of airway Streptococcus intermedius. These results suggest a previously underappreciated role of host genetics in shaping the airway microbiome and provide fresh hypotheses for genetic-based host-microbiome interactions in COPD.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Microbiota; Sputum; Transcriptome; Human Genetics; Adaptor Proteins, Signal Transducing
PubMed: 38622589
DOI: 10.1186/s12931-024-02805-2 -
International Journal of Molecular... Mar 2024Cystic fibrosis (CF) is an inherited genetic disorder which manifests primarily in airway disease. Recent advances in molecular technologies have unearthed the diverse...
Cystic fibrosis (CF) is an inherited genetic disorder which manifests primarily in airway disease. Recent advances in molecular technologies have unearthed the diverse polymicrobial nature of the CF airway. Numerous studies have characterised the genus-level composition of this airway community using targeted 16S rDNA sequencing. Here, we employed whole-genome shotgun metagenomics to provide a more comprehensive understanding of the early CF airway microbiome. We collected 48 sputum samples from 11 adolescents and children with CF over a 12-month period and performed shotgun metagenomics on the Illumina NextSeq platform. We carried out functional and taxonomic analysis of the lung microbiome at the species and strain levels. Correlations between microbial diversity measures and independent demographic and clinical variables were performed. Shotgun metagenomics detected a greater diversity of bacteria than culture-based methods. A large proportion of the top 25 most-dominant species were anaerobes. Samples dominated by and had significantly higher microbiome diversity, while no CF pathogen was associated with reduced microbial diversity. There was a diverse resistome present in all samples in this study, with 57.8% agreement between shotgun metagenomics and culture-based methods for detection of resistance. Pathogenic sequence types (STs) of , , and were observed to persist in young CF patients, while STs of were both persistent and shared between patients. This study provides new insight into the temporal changes in strain level composition of the microbiome and the landscape of the resistome in young people with CF. Shotgun metagenomics could provide a very useful one-stop assay for detecting pathogens, emergence of resistance and conversion to persistent colonisation in early CF disease.
Topics: Child; Humans; Adolescent; Cystic Fibrosis; Staphylococcus aureus; Biological Assay; DNA, Ribosomal; Microbiota
PubMed: 38612702
DOI: 10.3390/ijms25073893