scholarly journals In Silico Characterization of the Interaction between the PBP2a “Decoy” Protein of Resistant Staphylococcus aureus and the Monomeric Units of Eudragit E-100 and Poly(Maleic Acid-alt-Octadecene) Polymers

Polymers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 2320
Author(s):  
Yamil Liscano ◽  
Ana Amú ◽  
Astrid González ◽  
Jose Oñate-Garzón ◽  
Constain H. Salamanca
Keyword(s):  
Staphylococcus Aureus ◽  
Active Site ◽  
Maleic Acid ◽  
In Silico ◽  
Binding Free Energy ◽  
Meca Gene ◽  
Polymeric Materials ◽  
Antimicrobial Treatment ◽  
Receptor Protein ◽  
Eudragit E

Antimicrobial treatment alternatives for methicillin-resistant Staphylococcus aureus (MRSA) are increasingly limited. MRSA strains are resistant to methicillin due to the formation of β-lactamase enzymes, as well as the acquisition of the mecA gene, which encodes the penicillin-binding protein (PBP2a) that reduces the affinity for β-lactam drugs. Previous studies have shown that the use of ampicillin-loaded nanoparticles can improve antimicrobial activity on resistant S. aureus strains. However, the biological mechanism of this effect has not yet been properly elucidated. Therefore, this short communication focused on characterizing the in silico interactions of the PBP2a membrane receptor protein from S. aureus against the monomeric units of two polymeric materials previously used in the development of different nanoparticles loaded with ampicillin. Such polymers correspond to Eudragit E-100 chloride (EuCl) and the sodium salt of poly(maleic acid-alt-octadecene) (PAM-18Na). For this, molecular coupling studies were carried out in the active site of the PBP2a protein with the monomeric units of both polymers in neutral and ionized form, as well as with ampicillin antibiotic (model β-lactam drug). The results showed that ampicillin, as well as the monomeric units of EuCl and PAM18Na, described a slight binding free energy to the PBPa2 protein. In addition, it was found that the amino acids of the active site of the PBPa2 protein have interactions of different types and intensities, suggesting, in turn, different forms of protein–substrate coupling.

scholarly journals Mutation-Based Antibiotic Resistance Mechanism in Methicillin-Resistant Staphylococcus aureus Clinical Isolates

2021 ◽  
Vol 14 (5) ◽  
pp. 420
Author(s):  
Tanveer Ali ◽  
Abdul Basit ◽  
Asad Mustafa Karim ◽  
Jung-Hun Lee ◽  
Jeong-Ho Jeon ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Active Site ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Meca Gene ◽  
Resistance Mechanism ◽  
Ligand Docking ◽  
Clinical Samples ◽  
Allosteric Site ◽  
Methicillin Resistant

β-Lactam antibiotics target penicillin-binding proteins and inhibit the synthesis of peptidoglycan, a crucial step in cell wall biosynthesis. Staphylococcus aureus acquires resistance against β-lactam antibiotics by producing a penicillin-binding protein 2a (PBP2a), encoded by the mecA gene. PBP2a participates in peptidoglycan biosynthesis and exhibits a poor affinity towards β-lactam antibiotics. The current study was performed to determine the diversity and the role of missense mutations of PBP2a in the antibiotic resistance mechanism. The methicillin-resistant Staphylococcus aureus (MRSA) isolates from clinical samples were identified using phenotypic and genotypic techniques. The highest frequency (60%, 18 out of 30) of MRSA was observed in wound specimens. Sequence variation analysis of the mecA gene showed four amino acid substitutions (i.e., E239K, E239R, G246E, and E447K). The E239R mutation was found to be novel. The protein-ligand docking results showed that the E239R mutation in the allosteric site of PBP2a induces conformational changes in the active site and, thus, hinders its interaction with cefoxitin. Therefore, the present report indicates that mutation in the allosteric site of PBP2a provides a more closed active site conformation than wide-type PBP2a and then causes the high-level resistance to cefoxitin.

scholarly journals Three Alkaloids from an Apocynaceae Species, Aspidosperma spruceanum as Antileishmaniasis Agents by In Silico Demo-case Studies

Plants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 983 ◽  
Author(s):  
Diana Morales-Jadán ◽  
José Blanco-Salas ◽  
Trinidad Ruiz-Téllez ◽  
Francisco Centeno
Keyword(s):  
Free Energy ◽  
Active Site ◽  
In Silico ◽  
Binding Free Energy ◽  
New Drugs ◽  
Neglected Tropical Disease ◽  
Physiological Importance ◽  
Promising Tool ◽  
Binding Pockets ◽  
Simulation Results

This paper is focused on demonstrating with a real case that Ethnobotany added to Bioinformatics is a promising tool for new drugs search. It encourages the in silico investigation of “challua kaspi”, a medicinal kichwa Amazonian plant (Aspidosperma spruceanum) against a Neglected Tropical Disease, leishmaniasis. The illness affects over 150 million people especially in subtropical regions, there is no vaccination and conventional treatments are unsatisfactory. In attempts to find potent and safe inhibitors of its etiological agent, Leishmania, we recovered the published traditional knowledge on kichwa antimalarials and selected three A. spruceanum alkaloids, (aspidoalbine, aspidocarpine and tubotaiwine), to evaluate by molecular docking their activity upon five Leishmania targets: DHFR-TS, PTR1, PK, HGPRT and SQS enzymes. Our simulation results suggest that aspidoalbine interacts competitively with the five targets, with a greater affinity for the active site of PTR1 than some physiological ligands. Our virtual data also point to the demonstration of few side effects. The predicted binding free energy has a greater affinity to Leishmania proteins than to their homologous in humans (TS, DHR, PKLR, HGPRT and SQS), and there is no match with binding pockets of physiological importance. Keys for the in silico protocols applied are included in order to offer a standardized method replicable in other cases. Apocynaceae having ethnobotanical use can be virtually tested as molecular antileishmaniasis new drugs.

Assessment of the Multifactorial Effect on Antimicrobial Sensitivity in Positive Staphylococcus Aureus Clinical Isolates from Assir Region, Saudi Arabia

2012 ◽  
Vol 13 (2) ◽  
pp. 152-159 ◽  
Author(s):  
Nazar M Abdalla ◽  
Waleed O Haimour ◽  
Amani A Osman ◽  
Hassan Abdul Aziz
Keyword(s):  
Staphylococcus Aureus ◽  
Saudi Arabia ◽  
Culture Media ◽  
Meca Gene ◽  
Laboratory Data ◽  
Age Groups ◽  
Clinical Isolates ◽  
Diabetic Patients ◽  
Staph Aureus ◽  
Antimicrobial Sensitivity

General objectives: This study aimed at assessment of factors affecting antimicrobial sensitivity in Staphylococcus aureus clinical isolates from Assir region, Saudi Arabia. Materials and Methods: In this study, eighty one patients presented with Staph. aureus infections either nosocomial or community acquired infections were involved by collecting nasal swabs from them at Aseer Central Hospital General Lab. These patients were from all age groups and from males and females during the period of Jan 2011- Jun 2011. These samples were undergone variable laboratory procedures mainly; bactech, culture media, antibiotics sensitivity test using diffusion disc test (MIC) and molecular (PCR) for detection of mec A gene. Clinical and laboratory data were recorded in special formats and analyzed by statistical computer program (SPSS). Results: Showed that; Descriptive and analytical statistical analysis were performed and final results were plotted in tables. In Staph aureus MecA gene positive cases (50) showed: Oxacillin/ Mithicillin, Ciprofloxacin and Fusidin resistant in diabetic patients were 13, 26.0%, 9, 18% and 7, 14% respectively and in non diabetic patients were 37, 74.0%, 22, 44% and 20, 40% respectively. While no sensitivity in diabetic and non diabetic patients using Oxacillin/ Mithicillin. In Staph aureus MecA gene negative cases (31) showed: Oxacillin/ Mithicillin, sensitivity in diabetic patients (5, 16.1%) and in non diabetic were (26, 83.9%). While no resistant in diabetic and non diabetic patients. In Ciprofloxacin and Fusidin resistant in diabetic patients were 1, 3.2% and 1, 3.2% respectively and in non diabetic patients were 12, 38.7% and 7, 22.6%respectively. Erythromycin in Staph aureus ( MecA gene) positive cases (50) showed: resistant in age (0-15) years were (5, 10%), (16-50) years were (16, 32%) and ( ›50 years) were (12, 24%). Erythromycin in Staph aureus (MecA gene) negative cases (31) showed: resistant in age (0-15) years were (6, 19.3%), (16-50) years were (5, 16.1%) and ( ›50 years) were (3, 9.7%). Conclusion: Drugs resistance is a major progressive multifactorial problem facing the treatment of Staph aureus infections. DOI: http://dx.doi.org/10.3329/jom.v13i2.12750 J Medicine 2012; 13 : 152-159

Synthesis and In-silico Studies of C-4 Substituted Coumarin Analogues as Anticancer Agents

2020 ◽  
Vol 16 ◽  
Author(s):  
Jyoti Dandriyal ◽  
Kamalpreet Kaur ◽  
Vikas Jaitak
Keyword(s):  
Anticancer Agents ◽  
Active Site ◽  
In Silico ◽  
Oral Absorption ◽  
In Vivo Studies ◽  
Conventional Heating ◽  
Microwave Assisted Synthesis ◽  
Standard Drug ◽  
In Silico Studies ◽  
Adme Properties

Background: Coumarin is a fused ring system and possesses enormous capability of targeting various receptors participating in cancer pathway. Coumarin and its derivatives were found to exhibit very rare toxicity and other side effects. It has been found its immense anticancer potential depends on the nature of group present and its pattern of substitution on the basic nucleus. Objectives: Synthesis of C-4 substituted coumarin derivatives and to study their molecular interactions with ERα for anticancer activity for Breast Cancer. Method: C-4 substituted coumarins analogues (1-10) have been synthesized using conventional heating and microwave irradiation. Using Schrodinger software molecular modeling studies were carried out and ADME properties of the compounds were predicted. Results: All the synthesized compounds have shown better G-Score (-6.87 to -8.43 kcal/mol) as compared to the standard drug tamoxifen (-5.28kcal/mol) and auraptene (-3.89kcal/mol). Molecular docking suggests that all compounds fit in the active site of protein as they have the same hydrophobic pocket as standard drug tamoxifen, and have an acceptable range of ADME properties. Conclusion: Microwave-assisted synthesis showed better results as compared to conventional heating. In-silico studies revealed that all the compounds befit in the active site of protein. ADME properties showed that all compounds are in allowable limits for human oral absorption. In future, there is a possibility of in-vitro and in-vivo studies of the synthesized compounds.

scholarly journals In Silico Molecular Docking and Interaction Analysis of Traditional Chinese Medicines Against SARS-CoV-2 Receptor

2021 ◽  
Vol 16 (5) ◽  
pp. 1934578X2110150
Author(s):  
Gang Li ◽  
Wei Zhou ◽  
Xiurong Zhao ◽  
Ying Xie
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Interaction Analysis ◽  
Herbal Remedies ◽  
Receptor Protein ◽  
Stable Complex ◽  
Traditional Chinese Medicines ◽  
Ligand Interaction ◽  
Chinese Medicines ◽  
In Silico Molecular Docking

The novel coronavirus, 2019-nCoV, has led to a major pandemic in 2020 and is responsible for more than 2.9 million officially recorded deaths worldwide. As well as synthetic anti-viral drugs, there is also a need to explore natural herbal remedies. The Traditional Chinese Medicines (TCMs) system has been used for thousands of years for the prevention, diagnosis, and treatment of several chronic diseases. In this paper, we performed an in silico molecular docking and interaction analysis of TCMs against SARS-CoV-2 receptor RNA-dependent RNA polymerase (RdRp). We obtained the 5 most effective plant compounds which had a better binding affinity towards the target receptor protein. These compounds areforsythoside A, rutin, ginkgolide C, icariside II, and nolinospiroside E. The top-ranked compound, based on docking score, was nolinospiroside, a glycoside found in Ophiopogon japonicas that has antioxidant properties. Protein-ligand interaction analysis discerned that nolinospiroside formed a strong bond between ARG 349 of the protein receptor and the carboxylate group of the ligand, forming a stable complex. Hence, nolinospiroside could be deployed as a lead compound against SARS-CoV-2 infection that can be further investigated for its potential benefits in curbing the viral infection.

scholarly journals Whole Genome Sequencing and Antimicrobial Resistance of Staphylococcus aureus from Surgical Site Infections in Ghana

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 196
Author(s):  
Beverly Egyir ◽  
Jeannette Bentum ◽  
Naiki Attram ◽  
Anne Fox ◽  
Noah Obeng-Nkrumah ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Meca Gene ◽  
Surgical Site Infections ◽  
Illumina Miseq ◽  
Multi Drug Resistance ◽  
Toxin Gene ◽  
Whole Genome ◽  
Flight Mass Spectrometry

Staphylococcus aureus (S. aureus) is a common cause of surgical site infections (SSIs) globally. Data on the occurrence of methicillin-susceptible S. aureus (MSSA) as well as methicillin-resistant S. aureus (MRSA) among patients with surgical site infections (SSIs) in sub-Saharan African are scarce. We characterized S. aureus from SSIs in Ghana using molecular methods and antimicrobial susceptibility testing (AST). Wound swabs or aspirate samples were collected from subjects with SSIs. S. aureus was identified by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF-MS); AST was performed by Kirby-Bauer disk diffusion, and results were interpreted according to the Clinical and Laboratory Standards Institute (CLSI) guideline. Detection of spa, mecA, and pvl genes was performed by polymerase chain reaction (PCR). Whole-genome sequencing (WGS) was done using the Illumina MiSeq platform. Samples were collected from 112 subjects, with 13 S. aureus isolates recovered. Of these, 92% were sensitive to co-trimoxazole, 77% to clindamycin, and 54% to erythromycin. Multi-drug resistance was detected in 5 (38%) isolates. The four mecA gene-positive MRSA isolates detected belonged to ST152 (n = 3) and ST5 (n = 1). In total, 62% of the isolates were positive for the Panton-Valentine leukocidin (pvl) toxin gene. This study reports, for the first time, a pvl-positive ST152-t355 MRSA clone from SSIs in Ghana. The occurrence of multi-drug-resistant S. aureus epidemic clones suggests that continuous surveillance is required to monitor the spread and resistance trends of S. aureus in hospital settings in the country.

Comparable Outcomes of Short-Course and Prolonged-Course Therapy in Selected Cases of Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Pooled Cohort Study

2021 ◽  
Author(s):  
Louise Thorlacius-Ussing ◽  
Håkon Sandholdt ◽  
Jette Nissen ◽  
Jon Rasmussen ◽  
Robert Skov ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Clinical Outcomes ◽  
Treatment Duration ◽  
Cohort Analysis ◽  
Antimicrobial Treatment ◽  
Low Risk ◽  
Logistic Regression Models ◽  
Staphylococcus Aureus Bacteremia ◽  
Short Course ◽  
The Individual

Abstract Background The recommended duration of antimicrobial treatment for Staphylococcus aureus bacteremia (SAB) is a minimum of 14 days. We compared the clinical outcomes of patients receiving short-course (SC; 6–10 days), or prolonged-course (PC; 11–16 days) antibiotic therapy for low-risk methicillin-susceptible SAB (MS-SAB). Methods Adults with MS-SAB in 1995–2018 were included from 3 independent retrospective cohorts. Logistic regression models fitted with inverse probability of treatment weighting were used to assess the association between the primary outcome of 90-day mortality and treatment duration for the individual cohorts as well as a pooled cohort analysis. Results A total of 645, 219, and 141 patients with low-risk MS-SAB were included from cohorts I, II, and III. Median treatment duration in the 3 SC groups was 8 days (interquartile range [IQR], 7–10), 9 days (IQR, 8–10), and 8 days (IQR, 7–10). In the PC groups, patients received a median therapy of 14 days (IQR, 13–15), 14 days (IQR, 13–15), and 13 days (IQR, 12–15). No significant differences in 90-day mortality were observed between the SC and PC group in cohort I (odds ratio [OR], 0.85 [95% confidence interval {CI}, .49–1.41]), cohort II (OR, 1.24 [95% CI, .60–2.62]), or cohort III (OR, 1.15 [95% CI, .24–4.01]). This result was consistent in the pooled cohort analysis (OR, 1.05 [95% CI, .71–1.51]). Furthermore, duration of therapy was not associated with the risk of relapse. Conclusions In patients with low-risk MS-SAB, shorter courses of antimicrobial therapy yielded similar clinical outcomes as longer courses of therapy.

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