Molecular Docking and Validation of Methicillin Resistant Staphylococcus aureus Targets against Geninthiocin

Antibiotic resistance has been a serious public health concern in recent years. Methicillin resistant “Staphylococcus aureus” (MRSA) is a superbug that causes life threatening infections of Humanity which is difficult to treat. Geninthiocin is a macrocyclic thiopeptide with a 35-membered core moiety, which was isolated from marine streptomyces sp. ICN19, which has proven potent activity against MRSA. Five target proteins PDB ID: 4YMX, 3ZDS, 3QLB, 4IEN and 1DXL were identified from MRSA for their presumptive action for Geninthiocin. In this study, we used molecular docking and molecular dynamic simulation, in order to validate Geninthiocin’s potential target protein. Target proteins were subjected to ligand-protein docking studies. Based on their docking scores and Hydrogen bonding interactions, two possible proteins 4YMX and 3ZDS were further subjected to simulation strategies to validate the protein-drug interaction. Out of which, homogentisate1,2 dioxygenase turned out to be a possible drug target for Geninthiocin. The compound Geninthiocin could be developed as a potential inhibitor against the target protein homogentisate1,2-dioxygenase for exhibiting an effective antimicrobial activity.

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Novel T-C@AgNPs mediated biocidal mechanism against biofilm associated methicillin-resistant Staphylococcus aureus (Bap-MRSA) 090, cytotoxicity and its molecular docking studies

MedChemComm ◽

10.1039/c7md00486a ◽

2017 ◽

Vol 8 (12) ◽

pp. 2181-2194 ◽

Cited By ~ 21

Author(s):

H. M. Manukumar ◽

B. Chandrasekhar ◽

K. P. Rakesh ◽

A. P. Ananda ◽

M. Nandhini ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Molecular Docking ◽

Methicillin Resistant Staphylococcus Aureus ◽

Docking Studies ◽

Methicillin Resistant ◽

Molecular Docking Studies ◽

Life Threatening

Staphylococcus aureus is a commonly found pathogen cause life threatening infections and can be controlled by nanoparticles as antibiofilm candidates.

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Anti-methicillin resistant Staphylococcus aureus activity, synergism with oxacillin and molecular docking studies of metronidazole-triazole hybrids

European Journal of Medicinal Chemistry ◽

10.1016/j.ejmech.2016.03.041 ◽

2016 ◽

Vol 115 ◽

pp. 426-437 ◽

Cited By ~ 27

Author(s):

Beena Negi ◽

Deepak Kumar ◽

Widuranga Kumbukgolla ◽

Sampath Jayaweera ◽

Prija Ponnan ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Molecular Docking ◽

Methicillin Resistant Staphylococcus Aureus ◽

Docking Studies ◽

Methicillin Resistant ◽

Molecular Docking Studies

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Anti-methicillin resistant Staphylococcus aureus (MRSA) activity of an acetone extract from the leaves of Canarium odontophyllum (Miq.)

The Journal of Phytopharmacology ◽

10.31254/phyto.2018.7301 ◽

2018 ◽

Vol 7 (3) ◽

pp. 225-229

Author(s):

Nur Amira Mohd Shamsuddin ◽

◽

Dayang Fredalina Basri ◽

Keyword(s):

Staphylococcus Aureus ◽

Methicillin Resistant Staphylococcus Aureus ◽

Acetone Extract ◽

Health Concern ◽

Antimicrobial Drugs ◽

Methicillin Resistant ◽

Bacteriostatic Action ◽

Broth Microdilution Method ◽

Canarium Odontophyllum ◽

Time Kill

Methicillin-resistant Staphylococcus aureus (MRSA) is a global health concern that has caused nosocomial and community infections over the past decade. The emergence of multi-drug resistant strains and limitations of present antimicrobial drugs have led to continuous search for natural products as curative agents for MRSA infections. Canarium odontophyllum Miq., locally known as dabai, has been considered an alternative phytotherapeutic treatment for MRSA. The aim of this study was to evaluate the bacteriostatic activity of an acetone extract from C. odontophyllum leaves against MRSA. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the extract against the ATCC 33591 and Mu50 strains were determined using the broth microdilution method, and a time-kill assay was employed to assess the type of bacteriostatic action of the extract against the Mu50 strain only. The MIC and MBC values of the extract against Mu50 were 312.5 µg/ml and 625 µg/ml, respectively, whereas the MIC and MBC values for ATCC 33591 were 625 µg/ml and 1,250 µg/ml, respectively, confirming the bacteriostatic effect against both MRSA strains. A time-kill assay showed that the acetone extract of C. odontophyllum leaves exhibited concentrationdependent bacteriostatic action against the Mu50 strain at 1/2× MIC, 1× MIC and 2× MIC. However, the extract was bactericidal only at the highest concentration (4× MIC) with a reduction in cell viability of more than 3 log10 within 24 hours. These findings confirm that an acetone extract from C. odontophyllum leaves inhibited growth of MRSA at low concentration and could be utilised as an alternative anti-MRSA agent in immune uncompromised hosts

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Methicillin-Resistant Staphylococcus aureus: An Emerging Pathogen in Small Animals

Journal of the American Animal Hospital Association ◽

10.5326/0410150 ◽

2005 ◽

Vol 41 (3) ◽

pp. 150-157 ◽

Cited By ~ 36

Author(s):

J. Scott Weese

Keyword(s):

Staphylococcus Aureus ◽

Disease Surveillance ◽

Methicillin Resistant Staphylococcus Aureus ◽

Diagnostic Testing ◽

Small Animals ◽

Emerging Pathogen ◽

Methicillin Resistant ◽

Mild Disease ◽

Life Threatening ◽

The Impact

Methicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial pathogen in humans and is increasingly implicated in community-associated infections in people. In household pets, MRSA infections are uncommon but are on the rise, possibly because of the increased prevalence of human MRSA in the community. Clinical MRSA infections in some animals can be life threatening and difficult to treat; however, other animals may develop mild disease or only become colonized. Veterinarians should be aware of the concerns regarding MRSA and should develop an understanding of appropriate disease surveillance, diagnostic testing, and infection control in order to lessen the impact of MRSA on small animals.

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Methicillin Resistant Staphylococcus aureus (MRSA): An Emerging Veterinary and Zoonotic Pathogen of Public Health Concern and Some Studies in Malaysia

Journal of Animal and Veterinary Advances ◽

10.3923/javaa.2010.1094.1098 ◽

2010 ◽

Vol 9 (7) ◽

pp. 1094-1098 ◽

Cited By ~ 3

Author(s):

A.A. Saleha ◽

Z. Zunita

Keyword(s):

Public Health ◽

Staphylococcus Aureus ◽

Methicillin Resistant Staphylococcus Aureus ◽

Health Concern ◽

Public Health Concern ◽

Methicillin Resistant ◽

Zoonotic Pathogen

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Phenotypic and Genotypic Characteristics of Methicillin-Resistant Staphylococcus aureus (MRSA) Related to Persistent Endovascular Infection

Antibiotics ◽

10.3390/antibiotics8020071 ◽

2019 ◽

Vol 8 (2) ◽

pp. 71 ◽

Cited By ~ 3

Author(s):

Liang Li ◽

Michael R. Yeaman ◽

Arnold S. Bayer ◽

Yan Q. Xiong

Keyword(s):

Staphylococcus Aureus ◽

Methicillin Resistant Staphylococcus Aureus ◽

Specific Mechanism ◽

Host Defense Peptides ◽

Methicillin Resistant ◽

Preventative Measures ◽

Life Threatening ◽

Genotypic Characteristics

Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (PB) represents an important subset of S. aureus infection and correlates with poor clinical outcomes. MRSA isolates from patients with PB differ significantly from those of resolving bacteremia (RB) with regard to several in vitro phenotypic and genotypic profiles. For instance, PB strains exhibit less susceptibility to cationic host defense peptides and vancomycin (VAN) killing under in vivo-like conditions, greater damage to endothelial cells, thicker biofilm formation, altered growth rates, early activation of many global virulence regulons (e.g., sigB, sarA, sae and agr) and higher expression of purine biosynthesis genes (e.g., purF) than RB strains. Importantly, PB strains are significantly more resistant to VAN treatment in experimental infective endocarditis as compared to RB strains, despite similar VAN minimum inhibitory concentrations (MICs) in vitro. Here, we review relevant phenotypic and genotypic characteristics related to the PB outcome. These and future insights may improve our understanding of the specific mechanism(s) contributing to the PB outcome, and aid in the development of novel therapeutic and preventative measures against this life-threatening infection.

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Methicillin-resistant Staphylococcus aureus bacteraemia associated with Lemierre's syndrome: case report and literature review

The Journal of Laryngology & Otology ◽

10.1017/s0022215113001035 ◽

2013 ◽

Vol 127 (7) ◽

pp. 721-723 ◽

Cited By ~ 10

Author(s):

V Kizhner ◽

G Samara ◽

R Panesar ◽

Y P Krespi

Keyword(s):

Staphylococcus Aureus ◽

Literature Review ◽

Methicillin Resistant Staphylococcus Aureus ◽

Blood Cultures ◽

Health Concern ◽

Lemierre’S Syndrome ◽

Intravenous Antibiotic ◽

Methicillin Resistant ◽

The Past ◽

Lemierre's Syndrome

AbstractBackground:Community-acquired methicillin-resistant Staphylococcus aureus is a growing health concern. Lemierre's syndrome is a septic jugular thrombophlebitis that primarily affects young adults. This paper aimed to identify a possible sub-group of Lemierre's syndrome cases associated with community-acquired methicillin-resistant Staphylococcus aureus.Method:This paper reports the case of a 16-year-old male who was admitted for increasing fever, tachycardia, tachypnoea and neck pain. The patient was diagnosed with methicillin-resistant Staphylococcus aureus bacteraemia associated with Lemierre's syndrome. A literature review was subsequently conducted.Results:Following intravenous antibiotic treatment and the sterilisation of blood cultures, the patient improved. The literature review indicated a rise in the past 2 years of Lemierre's syndrome associated with methicillin-resistant Staphylococcus aureus among patients less than 18 years of age.Conclusion:Community-acquired methicillin-resistant Staphylococcus aureus bacteraemia can lead to pulmonary sequelae. When it is associated with pharyngitis, nasopharyngitis or parapharyngeal lymphadenitis, the affected patient may be predisposed to Lemierre's syndrome. As bacterial carriage is predominantly nasal, pharyngitis may not be present. Methicillin-resistant Staphylococcus aureus should be included as an offending bacterium where there is suspicion of Lemierre's syndrome. It is unclear whether anticoagulation alters the course of the bacterium, and surgery is probably contraindicated.

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The effects of NX-AS-401 on methicillin resistant Staphylococcus aureus

10.23889/suthesis.59037 ◽

2021 ◽

Author(s):

◽

Phillip Butterick

Keyword(s):

Staphylococcus Aureus ◽

Biofilm Formation ◽

Methicillin Resistant Staphylococcus Aureus ◽

Galleria Mellonella ◽

Standard Of Care ◽

Health Concern ◽

Current Standard ◽

Methicillin Resistant ◽

Biofilm Development ◽

Strain Dependent

Antimicrobial resistance is a global health concern, with once treatable infections becoming resistant to current standard of care antimicrobials. The search for new antimicrobials has led Neem Biotech Ltd. to manufacture NX-AS-401 an ajoene containing compound derived from Allium sativuum, commonly known as garlic. The research contained within this thesis aimed to identify the effects of NX-AS-401 on Methicillin Resistant Staphylococcus aureus (MRSA), one of the most well documented and commonly isolated antimicrobial resistant bacterial pathogens. A multi-stage approach was utilised, identifying how NX-AS-401 affects planktonic growth, biofilm development and virulence factor production. In Chapters 3 and 4 initial comparison between different NX-AS-401 formulations was performed in determined that ajoene content did not alter the antimicrobial effect of NX-AS-401. EUCAST broth microdilution compared NX-AS-401 to current standard of care antibiotic and determined effective inhibitory and bactericidal concentrations as 128 µg/ml and 2048 µg/ml respectively. When NX-AS-401 was used in combination with various antibiotic classes a synergistic effect was identified and the inhibitory concentrations of both agents were reduced. The primary focus on Chapter 5 was how NX-AS-401 affected S. aureus biofilm formation. NX-AS-401 concentrations of 32 µg/ml inhibited biofilm formation and a concentration of 512 µg/ml caused disruption of pre-established biofilms. These effects were confirmed using scanning electron microscopy and confocal microscopy with live/dead staining. In gene expression studies it was determined that the effects of NX-AS-401 on S. aureus biofilms were strain dependent and a target gene was not identified. Chapter 6 demonstrated that NX-AS-401 did not alter the production of Staphylococcus aureus exo-enzyme production in vitro during phenotypic studies. In Galleria mellonella low NX-AS-401 concentrations assisted in the recovery from S. aureus in a strain dependent manner, however, high concentrations caused increased Galleria mellonella fatality. NX-AS-401 altered the ability of S. aureus cells to invade human epithelial cells but did not prevent adhesion of S. aureus to the cells. NX-AS-401 has multiple effects on S. aureus with the ability to affect both planktonic cells and biofilm structure showing promise as an antimicrobial. Its main effects are growth inhibition and biofilm disruption rather than causing bacterial cell death. These attributes and the synergistic effects between NX-AS-401 and multiple antibiotic classes, indicate NX-AS-401 has potential as a strong antimicrobial adjuvant.

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