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1.
Eur Rev Med Pharmacol Sci ; 28(10): 3548-3555, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38856130

RESUMEN

OBJECTIVE: Extended-spectrum beta-lactamases (ESBLs) targeting beta-lactam antibiotics pose a major healthcare challenge. Carbapenems are known to be less impacted. However, the emergence of carbapenem-resistant strains can add further complexity to this existing challenge. With slow drug discovery and rapid resistance, repurposing existing drugs is crucial. This research study aims to provide insight into the antimicrobial effectiveness of 3-hydrazinoquinoxaline-2-thiol against diverse clinical ESBL-producing isolates. MATERIALS AND METHODS: The broth microdilution assay was conducted on a total of sixty-nine clinical ESBL-producing isolates to assess the minimum inhibitory concentrations (MICs) of 3-hydrazinoquinoxaline-2-thiol. The assay was conducted in triplicate, and the average MIC values were calculated. RESULTS: The most repeatedly observed MIC was 64 µg/ml (37.7%), followed by 256 µg/ml (23.2%) and 128 µg/ml (17.4%). Other MICs: 32 µg/ml (11.6%), 16 µg/ml (7.2%), 4-8 µg/ml (1.4%). CONCLUSIONS: This study demonstrated an effect of 3-hydrazinoquinoxaline-2-thiol on various ESBL-producing strains in vitro, indicating its promising therapeutic potential. To comprehensively understand the drug, rigorous testing, including pharmacokinetics, resistance assays, safety assessments, and exploration of potential synergies with other antibiotics against ESBL-producing organisms, is crucial.


Asunto(s)
Antibacterianos , Pruebas de Sensibilidad Microbiana , Quinoxalinas , beta-Lactamasas , Quinoxalinas/farmacología , beta-Lactamasas/metabolismo , Antibacterianos/farmacología , Humanos
2.
J Vis Exp ; (207)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38856199

RESUMEN

Gram-negative (GN) sepsis is a medical emergency where management in resource-limited settings relies on conventional microbiological culture techniques providing results in 3-4 days. Recognizing this delay in turnaround time (TAT), both EUCAST and CLSI have developed protocols for determining AST results directly from positively flagged automated blood culture bottles (+aBCs). EUCAST rapid AST (RAST) protocol was first introduced in 2018, where zone diameter breakpoints for four common etiological agents of GN sepsis, i.e., Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii complex can be reported. However, those clinical laboratories that have implemented this method in their routine workflow rely on mass spectrometry-based microbial identification, which is not easily available, thus precluding its implementation in resource-limited settings. To circumvent it, we evaluated a direct inoculum protocol (DIP) using a commercial automated microbial identification and antimicrobial susceptibility testing system (aMIAST) to enable early microbial identification within 8 h of positive flagging of aBC. We evaluated this protocol from January to October 2023 to identify the four RAST reportable GN (RR-GN) in the positively flagged aBC. The microbial identification results in DIP were compared with the standard inoculum preparation protocol (SIP) in aMIAST. Of 204 +aBCs with monomorphic GN (+naBC), one of the 4 RR-GN was identified in 105 +naBCs by SIP (E. coli: 50, K. pneumoniae: 20, P. aeruginosa: 9 and A. baumannii complex: 26). Of these, 94% (98/105) were correctly identified by DIP whereas major error and very major error rates were 6% (7/105) and 1.7% (4/240), respectively. When DIP for microbial identification is done using the EUCAST RAST method, provisional clinical reports can be provided within 24 h of receiving the sample. This approach has the potential to significantly reduce the TAT, enabling early institution of appropriate antimicrobial therapy.


Asunto(s)
Pruebas de Sensibilidad Microbiana , Humanos , Pruebas de Sensibilidad Microbiana/métodos , Sepsis/microbiología , Sepsis/diagnóstico , Técnicas Bacteriológicas/métodos
3.
Clin Lab ; 70(6)2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38868882

RESUMEN

BACKGROUND: The objective of this study is to understand the characteristics of the common spectrum of pathogen and the resistance of Mycoplasma in Sialidase-positive bacterial vaginosis. METHODS: The vaginal secretion specimens collected from August 2018 to October 2018 for the analysis of bacterial vaginosis (BV) were subjected to various techniques. These included routine leukorrhea examination, bacterial vaginosis sialidase testing, routine culture for common pathogens, mass spectrometry identification, and Mycoplasma resistance testing. RESULTS: A total of 238 patients with BV were identified. The cleanliness grading was mostly clean (+) and clean (2+), accounting for 38.24% and 30.67%, respectively. The bacterial vaginosis test for vaginal secretions showed leukocyte esterase positivity in 220 cases, resulting in a positivity rate of 92.44%. The spectrum of routine culture was analyzed and divided into four groups: A, B, C, and D. Group A consisted of Candidal vaginitis (13.45%); group B consisted of Gardnerella vaginalis vaginitis (32.77%); group C consisted of gram-negative bacillus vaginitis (46.22%); and group D consisted of Streptococcus agalactiae vaginitis (7.56%). The identification and antimicrobial susceptibility testing results for Mycoplasma showed a high detection rate of BV, with a positivity rate of 86.13%. There was a high sensitivity to tetracyclines for Ureaplasma urealyticum and Mycoplasma hominis, but a high resistance to macrolides and quinolones. CONCLUSIONS: Bacterial vaginosis existed in various complex forms, including Candida, Gardnerella vaginalis, Gram-negative bacillus, and Streptococcus agalactiae types. Moreover, there was an increasing trend of multi-drug resistance in Mycoplasma hominis. Therefore, it is crucial to pay attention to this condition and make accurate judgments based on the etiological characteristics and common antimicrobial susceptibility tests. This will enable the implementation of effective therapeutic interventions.


Asunto(s)
Farmacorresistencia Bacteriana , Mycoplasma , Neuraminidasa , Vaginosis Bacteriana , Humanos , Femenino , Vaginosis Bacteriana/microbiología , Vaginosis Bacteriana/diagnóstico , Neuraminidasa/metabolismo , Mycoplasma/aislamiento & purificación , Adulto , Vagina/microbiología , Adulto Joven , Antibacterianos/farmacología , Infecciones por Mycoplasma/microbiología , Infecciones por Mycoplasma/diagnóstico , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Adolescente
4.
Clin Lab ; 70(6)2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38868883

RESUMEN

BACKGROUND: Antibiotic resistance is a major problem threatening human beings. The genetic determinants that carry resistance genes can be transmitted in several ways in clinical and food environments. Hence, this research study aimed to investigate the presence of New Delhi metallo-beta-lactamase-1 (blaNDM-1) produced by enterotoxigenic Enterobacter cloacae in both clinical and food samples. METHODS AND RESULTS: Twenty-four isolates of Enterobacter spp. were isolated, seven isolates from food samples and 17 isolates from blood taken from neonates and children (1 day - 10 years old) resident in a children's hospital. Antibiotic susceptibility test to 14 antibiotics was performed for all isolates. Enterotoxigenicity of the clinical and foodborne isolates was detected phenotypically using Suckling mouse bioassay. Genomic deoxyribonucleic acid (DNA) was extracted from the isolated Enterobacter spp. that were detected resistant to imipenem. Polymerase chain reaction (PCR) was used to amplify blaNDM-1 gene followed by sequencing. The results of the bioassay revealed that 64.28% of E. cloacae ssp. cloacae isolates were enterotoxigenic. Two E. cloacae ssp. cloacae were imipenem resistant. CONCLUSIONS: This study showed that one isolate from a male child 1 < year was bla NDM-1 positive that was con-firmed by sequencing. This is the first report that revealed blaNDM-1 producing Enterobacter cloacae in Iraq.


Asunto(s)
Antibacterianos , Enterobacter cloacae , Infecciones por Enterobacteriaceae , Pruebas de Sensibilidad Microbiana , beta-Lactamasas , beta-Lactamasas/genética , Enterobacter cloacae/genética , Enterobacter cloacae/aislamiento & purificación , Enterobacter cloacae/efectos de los fármacos , Enterobacter cloacae/enzimología , Humanos , Lactante , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/diagnóstico , Niño , Preescolar , Antibacterianos/farmacología , Animales , Recién Nacido , Irak , Microbiología de Alimentos , Ratones
5.
World J Microbiol Biotechnol ; 40(8): 243, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38869625

RESUMEN

It was known that UVc irradiation increases the reactive oxygen species' (ROS) levels in bacteria hence the intervention of antioxidant enzymes and causes also changes in fatty acids (FAs) composition enabling bacteria to face antibiotics. Here, we intended to elucidate an interrelationship between SOD and susceptibility to antibiotics by studying FA membrane composition of UVc-treated P. aeruginosa PAO1 and its isogenic mutants (sodM, sodB and sod MB) membrane, after treatment with antibiotics. Swarmer mutants defective in genes encoding superoxide dismutase were pre-exposed to UVc radiations and then tested by disk diffusion method for their contribution to antibiotic tolerance in comparison with the P. aeruginosa wild type (WT). Moreover, fatty acid composition of untreated and UVc-treated WT and sod mutants was examined by Gaz chromatography and correlated to antibiotic resistance. Firstly, it has been demonstrated that after UVc exposure, swarmer WT strain, sodM and sodB mutants remain resistant to polymixin B, a membrane target antibiotic, through membrane unsaturation supported by the intervention of Mn-SOD after short UVc exposure and cyclopropanation of unsaturated FAs supported by the action of Fe-SOD after longer UVc exposure. However, resistance for ciprofloxacin is correlated with increase in saturated FAs. This correlation has been confirmed by a molecular docking approach showing that biotin carboxylase, involved in the initial stage of FA biosynthesis, exhibits a high affinity for ciprofloxacin. This investigation has explored the correlation of antibiotic resistance with FA content of swarmer P.aeruginosa pre-exposed to UVc radiations, confirmed to be antibiotic target dependant.


Asunto(s)
Antibacterianos , Mutación , Pseudomonas aeruginosa , Superóxido Dismutasa , Rayos Ultravioleta , Antibacterianos/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/genética , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Ciclopropanos/farmacología , Farmacorresistencia Bacteriana/genética , Ácidos Grasos/metabolismo , Ciprofloxacina/farmacología , Pruebas de Sensibilidad Microbiana , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Simulación por Computador , Polimixina B/farmacología
6.
Arch Microbiol ; 206(7): 304, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38878097

RESUMEN

The extension of multidrug-resistant strains of Staphylococcus aureus (S. aureus) is one of the main health challenges in the world, which requires serious solutions to deal with it. Combination therapies using conventional antibiotics and new antibacterial compounds that target different bacterial pathways are effective methods against resistant bacterial infections. Gallium is an iron-like metal that competes with iron for uptake into bacteria and has the potential to disrupt iron-dependent vital processes in bacteria. In this study, we explored the antibacterial effects of gallium nitrate (Ga(NO3)3) and vancomycin alone and in combination with each other on methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) using microdilution assay and checkerboard test, respectively. Then, their effect on the formation and destruction of biofilms was investigated. Finally, the amount of ROS production in the presence of these two compounds in bacteria was evaluated. The results indicated that the vancomycin/ Ga(NO3)3 combination reduced the MIC of vancomycin in the MRSA strain and had an additive effect on it. Vancomycin plus Ga(NO3)3 reduced the formation of biofilms and increased the destruction of biofilms formed in both strains, especially in the MRSA strain. ROS production was also higher in the combination of vancomycin with Ga(NO3)3 compared to vancomycin alone, especially in MRSA. Therefore, our results showed that Ga(NO3)3 enhances the antibacterial activity of vancomycin and this combination therapy can be considered as a new strategy for the treatment of MRSA infections.


Asunto(s)
Antibacterianos , Biopelículas , Galio , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus , Vancomicina , Galio/farmacología , Vancomicina/farmacología , Antibacterianos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Biopelículas/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Sinergismo Farmacológico , Especies Reactivas de Oxígeno/metabolismo , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Humanos
7.
Arch Microbiol ; 206(7): 305, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38878211

RESUMEN

Aspergillus fumigatus is a ubiquitous filamentous fungus commonly found in the environment. It is also an opportunistic human pathogen known to cause a range of respiratory infections, such as invasive aspergillosis, particularly in immunocompromised individuals. Azole antifungal agents are widely used for the treatment and prophylaxis of Aspergillus infections due to their efficacy and tolerability. However, the emergence of azole resistance in A. fumigatus has become a major concern in recent years due to their association with increased treatment failures and mortality rates. The development of azole resistance in A. fumigatus can occur through both acquired and intrinsic mechanisms. Acquired resistance typically arises from mutations in the target enzyme, lanosterol 14-α-demethylase (Cyp51A), reduces the affinity of azole antifungal agents for the enzyme, rendering them less effective, while intrinsic resistance refers to a natural resistance of certain A. fumigatus isolates to azole antifungals due to inherent genetic characteristics. The current review aims to provide a comprehensive overview of azole antifungal resistance in A. fumigatus, discusses underlying resistance mechanisms, including alterations in the target enzyme, Cyp51A, and the involvement of efflux pumps in drug efflux. Impact of azole fungicide uses in the environment and the spread of resistant strains is also explored.


Asunto(s)
Antifúngicos , Aspergilosis , Aspergillus fumigatus , Azoles , Farmacorresistencia Fúngica , Proteínas Fúngicas , Aspergillus fumigatus/efectos de los fármacos , Aspergillus fumigatus/genética , Azoles/farmacología , Farmacorresistencia Fúngica/genética , Antifúngicos/farmacología , Humanos , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Aspergilosis/microbiología , Aspergilosis/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Mutación
8.
Pestic Biochem Physiol ; 202: 105967, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38879344

RESUMEN

Coumarin is a natural product known for its diverse biological activities. While its antifungal properties in agricultural chemistry have been extensively studied, there is limited research on its antibacterial potential. In this study, we developed several novel coumarin derivatives by combining coumarin with pyridinium salt through molecular hybridization and chemical synthesis. Our findings reveal that most of these derivatives exhibit promising antibacterial activity. Among them, derivative A25 has been identified as the most effective compound based on three-dimensional quantitative structure-activity relationships. It demonstrates significant in vitro and in vivo activity against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas oryzae pv. oryzicola (Xoc), and Xanthomonas campestris pv. citri (Xac), outperforming the commercially available thiediazole copper. Initial investigations into its mechanism of action suggest that A25 disrupts the cell membranes of Xoc and Xoo, thereby inhibiting bacterial growth. Additionally, A25 enhances the activity of defense enzymes in rice and modulates the expression of proteins related to the pyruvate metabolism pathway. This dual action contributes to rice's resistance against bacterial infestation. We anticipate that this study will serve as a foundation for the development of coumarin-based bactericides.


Asunto(s)
Antibacterianos , Cumarinas , Pruebas de Sensibilidad Microbiana , Oryza , Xanthomonas , Cumarinas/farmacología , Cumarinas/síntesis química , Cumarinas/química , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Xanthomonas/efectos de los fármacos , Oryza/microbiología , Compuestos de Piridinio/farmacología , Compuestos de Piridinio/química , Compuestos de Piridinio/síntesis química , Xanthomonas campestris/efectos de los fármacos , Diseño de Fármacos , Sales (Química)/farmacología , Sales (Química)/química , Relación Estructura-Actividad
9.
Nat Commun ; 15(1): 5074, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38871710

RESUMEN

Antimicrobial resistance (AMR) is a growing public health crisis that requires innovative solutions. Current susceptibility testing approaches limit our ability to rapidly distinguish between antimicrobial-susceptible and -resistant organisms. Salmonella Typhimurium (S. Typhimurium) is an enteric pathogen responsible for severe gastrointestinal illness and invasive disease. Despite widespread resistance, ciprofloxacin remains a common treatment for Salmonella infections, particularly in lower-resource settings, where the drug is given empirically. Here, we exploit high-content imaging to generate deep phenotyping of S. Typhimurium isolates longitudinally exposed to increasing concentrations of ciprofloxacin. We apply machine learning algorithms to the imaging data and demonstrate that individual isolates display distinct growth and morphological characteristics that cluster by time point and susceptibility to ciprofloxacin, which occur independently of ciprofloxacin exposure. Using a further set of S. Typhimurium clinical isolates, we find that machine learning classifiers can accurately predict ciprofloxacin susceptibility without exposure to it or any prior knowledge of resistance phenotype. These results demonstrate the principle of using high-content imaging with machine learning algorithms to predict drug susceptibility of clinical bacterial isolates. This technique may be an important tool in understanding the morphological impact of antimicrobials on the bacterial cell to identify drugs with new modes of action.


Asunto(s)
Antibacterianos , Ciprofloxacina , Farmacorresistencia Bacteriana , Aprendizaje Automático , Pruebas de Sensibilidad Microbiana , Salmonella typhimurium , Ciprofloxacina/farmacología , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/aislamiento & purificación , Antibacterianos/farmacología , Humanos , Infecciones por Salmonella/microbiología , Infecciones por Salmonella/tratamiento farmacológico , Algoritmos
10.
J Microorg Control ; 29(2): 81-89, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38880620

RESUMEN

Although recent propagation of carbapenemase-producing Enterobacterales (CPE) has become a problem worldwide, the picture of CPE infection in Japan has not fully been elucidated. In this study, we examined clinical and microbiological characteristics of invasive CPE infection occurring at 8 hospitals in Minami Ibaraki Area between July 2001 to June 2017. Of 7294 Enterobacterales strains isolated from independent cases of bacteremia and/or meningitis, 10 (0.14%) were CPE (8 Enterobacter cloacae-complex, 1 Escherichia coli, and 1 Edwardsiella tarda), all of which had the blaIMP-1 gene and susceptible to gentamicin and trimethoprim/sulfamethoxazole. These strains were isolated from 7 adult and 2 infant bacteremia (1 infant patient developed CPE bacteremia twice) after 2007. The most common portal of entry was intravenous catheters. All of the adult patients were recovered, while the infant patients eventually died. Genomic analyses showed that the 8 E. cloacae-complex strains were classified into 5 groups, each of which was exclusively detected in specific facilities at intervals of up to 3 years, suggesting persistent colonization in the facilities. This study showed that invasive CPE infection in the area was rare, caused by IMP-1-type CPE having susceptibility to various antibiotics, and nonfatal among adult patients.


Asunto(s)
Antibacterianos , Bacteriemia , Proteínas Bacterianas , Infecciones por Enterobacteriaceae , Pruebas de Sensibilidad Microbiana , beta-Lactamasas , Humanos , Japón/epidemiología , Bacteriemia/microbiología , Bacteriemia/tratamiento farmacológico , Bacteriemia/epidemiología , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/epidemiología , Infecciones por Enterobacteriaceae/tratamiento farmacológico , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Masculino , Femenino , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Lactante , Persona de Mediana Edad , Adulto , Anciano , Enterobacter cloacae/genética , Enterobacter cloacae/efectos de los fármacos , Enterobacter cloacae/aislamiento & purificación , Gentamicinas/farmacología , Gentamicinas/uso terapéutico , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Combinación Trimetoprim y Sulfametoxazol/farmacología , Anciano de 80 o más Años , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Enterobacteriaceae Resistentes a los Carbapenémicos/aislamiento & purificación
11.
Mycoses ; 67(6): e13752, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38880933

RESUMEN

BACKGROUND: Candida auris is an emerging multidrug-resistant yeast, frequently causing outbreaks in health care facilities. The pathogen persistently colonises human skin and inanimate surfaces such as catheters, aiding to its spread. Moreover, colonisation is a risk factor to develop invasive infection. OBJECTIVES: We investigated 61 C. auris strains isolated from non-sterile human body sites (n = 53) and the hospital environment (n = 8), originating from four different centres in a single Brazilian state. MATERIALS AND METHODS: Antifungal susceptibility testing (AFST) against common antifungals was performed, and resistance-associated genes were evaluated. Genetic relatedness was investigated with short tandem repeat (STR) genotyping and validated with whole-genome sequencing (WGS) single nucleotide polymorphism (SNP) analysis. RESULTS: Antifungal susceptibility testing demonstrated that all isolates were susceptible to azoles, echinocandins and amphotericin B. No mutations were detected in ERG11 and FKS1 genes. With STR typing, isolates were allocated to clade IV and appeared closely related. This was confirmed by WGS SNP analysis of 6 isolates, which demonstrated a maximal difference of only 41 SNPs between these strains. Furthermore, the Brazilian isolates formed a distinct autochthonous branch within clade IV, excluding recent introductions from outside the country. A molecular clock analysis of clade IV isolates from various countries suggests that early in the previous century there was a unique event causing environmental spread of a C. auris ancestor throughout the Latin-American continent, followed by human introduction during the last decades. CONCLUSION: We report the emergence of C. auris patient colonisation in multiple centres by fluconazole-susceptible clade IV close-related strains in Pernambuco State, Brazil.


Asunto(s)
Antifúngicos , Azoles , Candida auris , Candidiasis , Brotes de Enfermedades , Pruebas de Sensibilidad Microbiana , Polimorfismo de Nucleótido Simple , Humanos , Brasil/epidemiología , Antifúngicos/farmacología , Candidiasis/microbiología , Candidiasis/epidemiología , Azoles/farmacología , Candida auris/genética , Candida auris/efectos de los fármacos , Secuenciación Completa del Genoma , Genotipo , Femenino , Masculino , Farmacorresistencia Fúngica/genética , Adulto , Persona de Mediana Edad , Candidiasis Invasiva
12.
Am J Case Rep ; 25: e943920, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38881048

RESUMEN

BACKGROUND Flavonifractor plautii belongs to the clostridium family, which can lead to local infections as well as the bloodstream infections. Flavonifractor plautii caused infection is rarely few in the clinic. To understand better Flavonifractor plautii, we investigated the drug sensitivity and perform genome sequencing of Flavonifractor plautii isolated from blood samples in China and explored the drug resistance and pathogenic mechanism of the bacteria. CASE REPORT The Epsilometer test method was used to detect the sensitivity of flavonoid bacteria to antimicrobial agents. PacBio sequencing technology was employed to sequence the whole genome of Flavonifractor plautii, and gene prediction and functional annotation were also analyzed. Flavonifractor plautii displayed sensitivity to most drugs but resistance to fluoroquinolones and tetracycline, potentially mediated by tet (W/N/W). The total genome size of Flavonifractor plautii was 4,573,303 bp, and the GC content was 59.78%. Genome prediction identified 4,506 open reading frames, including 9 ribosomal RNAs and 66 transfer RNAs. It was detected that the main virulence factor-coding genes of the bacteria were the capsule, polar flagella and FbpABC, which may be associated with bacterial movement, adhesion, and biofilm formation. CONCLUSIONS The results of whole-genome sequencing could provide relevant information about the drug resistance mechanism and pathogenic mechanism of bacteria and offer a basis for clinical diagnosis and treatment.


Asunto(s)
Bacteriemia , Humanos , Bacteriemia/microbiología , Bacteriemia/tratamiento farmacológico , Genoma Bacteriano , Secuenciación Completa del Genoma , Antibacterianos/uso terapéutico , Masculino , Pruebas de Sensibilidad Microbiana , Flavobacteriaceae/genética , Flavobacteriaceae/aislamiento & purificación
13.
J Assoc Physicians India ; 72(6): 69-73, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38881138

RESUMEN

OBJECTIVES: Antimicrobial resistance (AMR) is a major health issue. To determine trends in bacterial organisms in respiratory tract infections (RTIs) and their antibiotic sensitivity at a tertiary care center in India, we performed this study. METHODS: Successive samples received from January 2017 to December 2021 from the respiratory tract (sputum, endotracheal secretion, and bronchoalveolar lavage) from intensive care units and medical inpatients were processed for bacterial growth. The identification of isolates and antibiotic sensitivity patterns was performed using an automated VITEK-2 system. Descriptive statistics are reported. RESULTS: We received 7,204 respiratory samples. Significant bacterial growth was in 3,000 (41.6%), and 2,992 (41.5%) were gram-negative. Klebsiella pneumoniae was the most prevalent, followed by Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, and Enterobacter aerogenes. Increasing secular trends were observed for Klebsiella and Pseudomonas and declining trends for Acinetobacter and Escherichia (p < 0.05). Antimicrobial sensitivity patterns showed that Klebsiella, Pseudomonas, Acinetobacter, E. coli, and Enterobacter had a high sensitivity with colistin and polymyxin (99-100%). Moderate sensitivity was observed with carbapenems (Acinetobacter: 47.5%, Enterobacter: 62.0%, Escherichia: 76.5%, Klebsiella: 72.3%, Pseudomonas: 66.7%) and tigecycline (Acinetobacter: 50.4%, Enterobacter: 68.0%, Escherichia: 81.1%, Klebsiella: 66.6%, Pseudomonas: 0%). Aminoglycosides had <50% sensitivity for various organisms, and <25% sensitivity was observed with third-generation cephalosporins and quinolones. Trend analysis showed persistent sensitivity of various pathogenic bacteria to colistin and polymyxin and declining pharmacological sensitivity in Acinetobacter (carbapenems and tigecycline), Escherichia (carbapenems, quinolones, and tigecycline), Klebsiella (carbapenems, quinolones, aminoglycosides, and tigecycline), and Pseudomonas (carbapenems and aminoglycosides) species (p < 0.05). CONCLUSION: Common respiratory tract gram-negative bacterial pathogens at a tertiary care hospital are K. pneumoniae, P. aeruginosa, A. baumannii, and E. coli. All these bacteria demonstrate high sensitivity only with colistin and polymyxin. Significant AMR is observed to carbapenems, tigecycline, aminoglycosides, and third-generation cephalosporins. Secular trends show declining antimicrobial sensitivity among various bacterial pathogens.


Asunto(s)
Antibacterianos , Pruebas de Sensibilidad Microbiana , Infecciones del Sistema Respiratorio , Centros de Atención Terciaria , Humanos , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Antibacterianos/farmacología , India/epidemiología , Farmacorresistencia Bacteriana , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/aislamiento & purificación
14.
J Agric Food Chem ; 72(23): 13360-13370, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38830379

RESUMEN

This study reports a peptide design model for engineering fusion-expressed antimicrobial peptides (AMPs) with the AflR dinuclear zinc finger motif to improve the defense against aflatoxins and Aspergillus flavus. The study identified AflR, a Zn2Cys6-type sequence-specific DNA-binding protein, as a key player in the regulation of aflatoxin biosynthesis. By integrating the AflR motif into AMPs, we demonstrate that these novel fusion peptides significantly lower the minimum inhibitory concentrations (MICs) and reduce aflatoxin B1 and B2 levels, outperforming traditional AMPs. Comprehensive analysis, including bioinformatics and structural determination, elucidates the enhanced structure-function relationship underlying their efficacy. Furthermore, the study reveals the possibility that the fusion peptides have the potential to bind to the DNA binding sites of transcriptional regulators, binding DNA sites of key transcriptional regulators, thereby inhibiting genes critical for aflatoxin production. This research not only deepens our understanding of aflatoxin inhibition mechanisms but also presents a promising avenue for developing advanced antifungal agents, which are essential for global food safety and crop protection.


Asunto(s)
Aspergillus flavus , Dedos de Zinc , Aspergillus flavus/efectos de los fármacos , Aspergillus flavus/genética , Aspergillus flavus/metabolismo , Aspergillus flavus/química , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/farmacología , Péptidos Antimicrobianos/genética , Péptidos Antimicrobianos/metabolismo , Aflatoxinas/biosíntesis , Aflatoxinas/química , Aflatoxinas/genética , Ingeniería de Proteínas , Pruebas de Sensibilidad Microbiana , Antifúngicos/farmacología , Antifúngicos/química , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Recombinantes de Fusión/farmacología
15.
BMC Biotechnol ; 24(1): 38, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38831403

RESUMEN

BACKGROUND: Antibiotic-containing carrier systems are one option that offers the advantage of releasing active ingredients over a longer period of time. In vitro sustained drug release from a carrier system consisting of microporous ß-TCP ceramic and alginate has been reported in previous works. Alginate dialdehyde (ADA) gelatin gel showed both better mechanical properties when loaded into a ß-TCP ceramic and higher biodegradability than pure alginate. METHODS: Dual release of daptomycin and BMP-2 was measured on days 1, 2, 3, 6, 9, 14, 21, and 28 by HPLC and ELISA. After release, the microbial efficacy of the daptomycin was verified and the biocompatibility of the composite was tested in cell culture. RESULTS: Daptomycin and the model compound FITC protein A (n = 30) were released from the composite over 28 days. A Daptomycin release above the minimum inhibitory concentration (MIC) by day 9 and a burst release of 71.7 ± 5.9% were observed in the loaded ceramics. Low concentrations of BMP-2 were released from the loaded ceramics over 28 days.


Asunto(s)
Antibacterianos , Proteína Morfogenética Ósea 2 , Fosfatos de Calcio , Cerámica , Daptomicina , Gelatina , Proteína Morfogenética Ósea 2/química , Proteína Morfogenética Ósea 2/metabolismo , Daptomicina/química , Daptomicina/farmacología , Gelatina/química , Cerámica/química , Antibacterianos/química , Antibacterianos/farmacología , Fosfatos de Calcio/química , Animales , Pruebas de Sensibilidad Microbiana , Ratones , Portadores de Fármacos/química , Liberación de Fármacos
16.
J Enzyme Inhib Med Chem ; 39(1): 2351861, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38847308

RESUMEN

In this study, a library of phthalimide Schiff base linked to 1,4-disubstituted-1,2,3-triazoles was designed, synthesised, and characterised by different spectral analyses. All analogues have been introduced for in vitro assay of their antiviral activity against COVID-19 virus using Vero cell as incubator with different concentrations. The data revealed most of these derivatives showed potent cellular anti-COVID-19 activity and prevent viral growth by more than 90% at two different concentrations with no or weak cytotoxic effect on Vero cells. Furthermore, in vitro assay was done against this enzyme for all analogues and the results showed two of them have IC50 data by 90 µM inhibitory activity. An extensive molecular docking simulation was run to analyse their antiviral mechanism that found the proper non-covalent interaction within the Mpro protease enzyme. Finally, we profiled two reversible inhibitors, COOH and F substituted analogues that might be promising drug candidates for further development have been discovered.


Asunto(s)
Antivirales , Simulación del Acoplamiento Molecular , Ftalimidas , SARS-CoV-2 , Triazoles , Triazoles/química , Triazoles/farmacología , Triazoles/síntesis química , Ftalimidas/química , Ftalimidas/farmacología , Ftalimidas/síntesis química , Antivirales/farmacología , Antivirales/química , Antivirales/síntesis química , Células Vero , Chlorocebus aethiops , SARS-CoV-2/efectos de los fármacos , Animales , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad , Estructura Molecular , Humanos , Relación Dosis-Respuesta a Droga , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Proteasas 3C de Coronavirus/metabolismo , Modelos Moleculares
17.
Sci Rep ; 14(1): 13235, 2024 06 09.
Artículo en Inglés | MEDLINE | ID: mdl-38853154

RESUMEN

The study investigated the economic concerns associated with livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) in livestock (cow), examining its connection to severe infections, antimicrobial resistance (AMR), and virulence factors. The research, conducted in Edo State, Nigeria, analyzed 400 samples (200 rectal and 200 nasal swabs) collected between March 2018 and February 2019. MRSA prevalence was identified using conventional culture-based methods and polymerase chain reaction (PCR) techniques, revealing 63.5% (n = 254) for Staphylococcus aureus and 55% (n = 220) for MRSA. Of the 76 mecA-positive MRSA isolates, 64.5% (n = 49) exhibited multidrug resistance (MDR) while the remaining were sensitive to specific antimicrobials. Key virulence genes, such as PVL (81.6%; n = 62) and tsst-1 (44.7%; n = 34), were prevalent, along with AMR genes like mecC, tetM, ermA, ermC, vanA, and vanC. Staphylococcal chromosomal cassette mec (SCCmec) typing identified different types, notably II, IVa, and IVb. Biofilm formation, a crucial virulence factor varied in strength, is associated with icaA and icaB genes (p < 0.01). The findings highlighted substantial AMR and biofilm-forming capacity within LA-MRSA isolates, emphasizing the importance of ongoing surveillance for informed treatment strategies, AMR policies, and control measures against MDR staphylococcal infections.


Asunto(s)
Biopelículas , Ganado , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Factores de Virulencia , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Animales , Factores de Virulencia/genética , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/veterinaria , Ganado/microbiología , Bovinos , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Nigeria/epidemiología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo
18.
Proc Natl Acad Sci U S A ; 121(25): e2315670121, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38861604

RESUMEN

Tuberculosis (TB) is the world's deadliest infectious disease, with over 1.5 million deaths and 10 million new cases reported anually. The causative organism Mycobacterium tuberculosis (Mtb) can take nearly 40 d to culture, a required step to determine the pathogen's antibiotic susceptibility. Both rapid identification and rapid antibiotic susceptibility testing of Mtb are essential for effective patient treatment and combating antimicrobial resistance. Here, we demonstrate a rapid, culture-free, and antibiotic incubation-free drug susceptibility test for TB using Raman spectroscopy and machine learning. We collect few-to-single-cell Raman spectra from over 25,000 cells of the Mtb complex strain Bacillus Calmette-Guérin (BCG) resistant to one of the four mainstay anti-TB drugs, isoniazid, rifampicin, moxifloxacin, and amikacin, as well as a pan-susceptible wildtype strain. By training a neural network on this data, we classify the antibiotic resistance profile of each strain, both on dried samples and on patient sputum samples. On dried samples, we achieve >98% resistant versus susceptible classification accuracy across all five BCG strains. In patient sputum samples, we achieve ~79% average classification accuracy. We develop a feature recognition algorithm in order to verify that our machine learning model is using biologically relevant spectral features to assess the resistance profiles of our mycobacterial strains. Finally, we demonstrate how this approach can be deployed in resource-limited settings by developing a low-cost, portable Raman microscope that costs <$5,000. We show how this instrument and our machine learning model enable combined microscopy and spectroscopy for accurate few-to-single-cell drug susceptibility testing of BCG.


Asunto(s)
Antituberculosos , Aprendizaje Automático , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis , Espectrometría Raman , Espectrometría Raman/métodos , Mycobacterium tuberculosis/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana/métodos , Antituberculosos/farmacología , Farmacorresistencia Bacteriana , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis/tratamiento farmacológico , Tuberculosis/microbiología , Isoniazida/farmacología
19.
Mycopathologia ; 189(4): 50, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38864903

RESUMEN

Aspergillus fumigatus is a saprophytic fungal pathogen that causes opportunistic infections in animals and humans. Azole resistance has been reported globally in human A. fumigatus isolates, but the prevalence of resistance in isolates from animals is largely unknown. A retrospective resistance surveillance study was performed using a collection of clinical A. fumigatus isolates from various animal species collected between 2015 and 2020. Agar-based azole resistance screening of all isolates was followed by in vitro antifungal susceptibility testing and cyp51A gene sequencing of the azole-resistant isolates. Over the 5 year period 16 (11.3%) of 142 A. fumigatus culture-positive animals harbored an azole-resistant isolate. Resistant isolates were found in birds (15%; 2/13), cats (21%; 6/28), dogs (8%; 6/75) and free-ranging harbor porpoise (33%; 2/6). Azole-resistance was cyp51A mediated in all isolates: 81.3% (T-67G/)TR34/L98H, 12.5% TR46/Y121F/T289A. In one azole-resistant A. fumigatus isolate a combination of C(-70)T/F46Y/C(intron7)T/C(intron66)T/M172V/E427K single-nucleotide polymorphisms in the cyp51A gene was found. Of the animals with an azole-resistant isolate and known azole exposure status 71.4% (10/14) were azole naive. Azole resistance in A. fumigatus isolates from animals in the Netherlands is present and predominantly cyp51A TR-mediated, supporting an environmental route of resistance selection. Our data supports the need to include veterinary isolates in resistance surveillance programs. Veterinarians should consider azole resistance as a reason for therapy failure when treating aspergillosis and consider resistance testing of relevant isolates.


Asunto(s)
Antifúngicos , Aspergilosis , Aspergillus fumigatus , Azoles , Farmacorresistencia Fúngica , Pruebas de Sensibilidad Microbiana , Aspergillus fumigatus/efectos de los fármacos , Aspergillus fumigatus/genética , Aspergillus fumigatus/aislamiento & purificación , Animales , Azoles/farmacología , Farmacorresistencia Fúngica/genética , Aspergilosis/microbiología , Aspergilosis/veterinaria , Antifúngicos/farmacología , Países Bajos/epidemiología , Estudios Retrospectivos , Proteínas Fúngicas/genética , Aves/microbiología , Gatos , Perros , Sistema Enzimático del Citocromo P-450
20.
Sci Rep ; 14(1): 13500, 2024 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-38867066

RESUMEN

The continuous search for natural product-based biopesticides from fungi isolated from untapped sources is an effective tool. In this study, we studied a pre-selected fungal endophyte, isolate Aa22, from the medicinal plant Artemisia absinthium, along with the antifungal, insect antifeedant and nematicidal compounds present in the extract. The endophyte Aa22 was identified as Stemphylium solani by molecular analysis. The antifungal activity was tested by broth microdilution against Fusarium solani, F. oxysporum, F. moniliforme and Botrytis cinerea, the insect antifeedant by choice bioassays against Spodoptera littoralis, Myzus persicae and Rhopalosiphum padi and the in vitro mortality against the root-knot nematode Meloiydogyne javanica. The structures of bioactive compounds were determined on the basis of 1D and 2D NMR spectroscopy and mass spectrometry. The ethyl acetate extract obtained from the solid rice fermentation showed mycelial growth inhibition of fungal pathogens (EC50 0.08-0.31 mg/mL), was antifeedant to M. persicae (99%) and nematicidal (68% mortality). A bioguided fractionation led to the isolation of the new compound stempholone A (1), and the known stempholone B (2) and stemphol (3). These compounds exhibited antifeedant (EC50 0.50 mg/mL), antifungal (EC50 0.02-0.43 mg/L) and nematicidal (MLD 0.5 mg/mL) activities. The extract activities can be explained by 3 (antifungal), 1-3 (antifeedant) and 1 (nematicidal). Phytotoxicity tests on Lolium perenne and Lactuca sativa showed that the extract and 1 increased L. sativa root growth (121-130%) and 1 reduced L. perenne growth (48-49%). These results highlight the potential of the endophytic fungi Aa22 as biotechnological source of natural product-based biopesticides.


Asunto(s)
Antifúngicos , Antinematodos , Endófitos , Animales , Endófitos/química , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Antinematodos/farmacología , Antinematodos/aislamiento & purificación , Antinematodos/química , Fusarium/efectos de los fármacos , Spodoptera/efectos de los fármacos , Spodoptera/crecimiento & desarrollo , Ascomicetos/efectos de los fármacos , Botrytis/efectos de los fármacos , Botrytis/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Tylenchoidea/efectos de los fármacos
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