scholarly journals Photodynamic antimicrobial chemotherapy for Staphylococcus aureus and multidrug-resistant bacterial burn infection in vitro and in vivo

2017 ◽  
Vol Volume 12 ◽  
pp. 5915-5931 ◽  
Author(s):  
Bingjie Mai ◽  
Yiru Gao ◽  
Min Li ◽  
Xiaobing Wang ◽  
Kun Zhang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Chemotherapy ◽  
Multidrug Resistant ◽  
Photodynamic Antimicrobial Chemotherapy

scholarly journals Rapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258592
Author(s):  
Christopher R. Miller ◽  
Jonathan M. Monk ◽  
Richard Szubin ◽  
Andrew D. Berti
Keyword(s):  
Staphylococcus Aureus ◽  
Subsequent Development ◽  
Multidrug Resistant ◽  
Blood Cultures ◽  
Therapeutic Interventions ◽  
Prevention Measures ◽  
Beta Lactam ◽  
Resistance Development

Understating how antibiotic tolerance impacts subsequent resistance development in the clinical setting is important to identifying effective therapeutic interventions and prevention measures. This study describes a patient case of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia which rapidly developed resistance to three primary MRSA therapies and identifies genetic and metabolic changes selected in vivo that are associated with rapid resistance evolution. Index blood cultures displayed susceptibility to all (non-beta-lactam) antibiotics with the exception of trimethoprim/ sulfamethoxazole. One month after initial presentation, during the same encounter, blood cultures were again positive for MRSA, now displaying intermediate resistance to vancomycin and ceftaroline and resistance to daptomycin. Two weeks later, blood cultures were positive for a third time, still intermediate resistant to vancomycin and ceftaroline and resistant to daptomycin. Mutations in mprF and vraT were common to all multidrug resistant isolates whereas mutations in tagH, agrB and saeR and secondary mprF mutation emerged sequentially and transiently resulting in distinct in vitro phenotypes. The baseline mutation rate of the patient isolates was unremarkable ruling out the hypermutator phenotype as a contributor to the rapid emergence of resistance. However, the index isolate demonstrated pronounced tolerance to the antibiotic daptomycin, a phenotype that facilitates the subsequent development of resistance during antibiotic exposure. This study exemplifies the capacity of antibiotic-tolerant pathogens to rapidly develop both stable and transient genetic and phenotypic changes, over the course of a single patient encounter.

scholarly journals Development of a Conserved Chimeric Vaccine for Induction of Strong Immune Response against Staphylococcus aureus Using Immunoinformatics Approaches

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1038
Author(s):  
Rahul Chatterjee ◽  
Panchanan Sahoo ◽  
Soumya Ranjan Mahapatra ◽  
Jyotirmayee Dey ◽  
Mrinmoy Ghosh ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
Multidrug Resistant ◽  
Host Cells ◽  
Dynamics Simulation ◽  
Population Coverage ◽  
Strong Immune Response ◽  
Chimeric Vaccine

Staphylococcus aureus is one of the most notorious Gram-positive bacteria with a very high mortality rate. The WHO has listed S. aureus as one of the ESKAPE pathogens requiring urgent research and development efforts to fight against it. Yet there is a major layback in the advancement of effective vaccines against this multidrug-resistant pathogen. SdrD and SdrE proteins are attractive immunogen candidates as they are conserved among all the strains and contribute specifically to bacterial adherence to the host cells. Furthermore, these proteins are predicted to be highly antigenic and essential for pathogen survival. Therefore, in this study, using the immunoinformatics approach, a novel vaccine candidate was constructed using highly immunogenic conserved T-cell and B-cell epitopes along with specific linkers, adjuvants, and consequently modeled for docking with human Toll-like receptor 2. Additionally, physicochemical properties, secondary structure, disulphide engineering, and population coverage analysis were also analyzed for the vaccine. The constructed vaccine showed good results of worldwide population coverage and a promising immune response. For evaluation of the stability of the vaccine-TLR-2 docked complex, a molecular dynamics simulation was performed. The constructed vaccine was subjected to in silico immune simulations by C-ImmSim and Immune simulation significantly provided high levels of immunoglobulins, T-helper cells, T-cytotoxic cells, and INF-γ. Lastly, upon cloning, the vaccine protein was reverse transcribed into a DNA sequence and cloned into a pET28a (+) vector to ensure translational potency and microbial expression. The overall results of the study showed that the designed novel chimeric vaccine can simultaneously elicit humoral and cell-mediated immune responses and is a reliable construct for subsequent in vivo and in vitro studies against the pathogen.

Rationally designed curcumin based ruthenium(ii) antimicrobials effective against drug-resistant Staphylococcus aureus

2019 ◽  
Vol 48 (31) ◽  
pp. 11822-11828 ◽  
Author(s):  
Payal Srivastava ◽  
Manjulika Shukla ◽  
Grace Kaul ◽  
Sidharth Chopra ◽  
Ashis K. Patra
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Polypyridyl Complexes

Two curcumin conjugated ruthenium(ii) polypyridyl complexes, [Ru(NN)2(cur)](PF6) (1, 2), were systematically exploited for their antimicrobial activity in vitro and in vivo and potential selectivity against multidrug resistant S. aureus strains.

Susceptibility of Staphylococcus aureus to porphyrin-mediated photodynamic antimicrobial chemotherapy: an in vitro study

2009 ◽  
Vol 25 (3) ◽  
pp. 391-395 ◽  
Author(s):  
Mariana M. Gois ◽  
Christina Kurachi ◽  
E. J. B. Santana ◽  
E. G. O. Mima ◽  
D. M. P. Spolidório ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Chemotherapy ◽  
In Vitro Study ◽  
Vitro Study ◽  
Photodynamic Antimicrobial Chemotherapy

scholarly journals In silicoidentification of novel peptides with antibacterial activity against multidrug resistantStaphylococcus aureus

2019 ◽  
Author(s):  
Linda B Oyama ◽  
Hamza Olleik ◽  
Ana Carolina Nery Teixeira ◽  
Matheus M Guidini ◽  
James A Pickup ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Peptides ◽  
In Silico ◽  
Multidrug Resistant ◽  
Biofilm Inhibition ◽  
Methicillin Resistant ◽  
Drug Candidates ◽  
Wide Range

AbstractHerein we report the identification and characterisation of two linear antimicrobial peptides (AMPs), HG2 and HG4, with activity against a wide range of multidrug resistant (MDR) bacteria, especially methicillin resistantStaphylococcus aureus(MRSA) strains, a highly problematic group of Gram-positive bacteria in the hospital and community environment. To identify the novel AMPs presented here, we employed the classifier model design, a feature extraction method using molecular descriptors for amino acids for the analysis, visualization, and interpretation of AMP activities from a rumen metagenomic dataset. This allowed for thein silicodiscrimination of active and inactive peptides in order to define a small number of promising novel lead AMP test candidates for chemical synthesis and experimental evaluation.In vitrodata suggest that the chosen AMPs are fast acting, show strong biofilm inhibition and dispersal activity and are efficacious in anin vivomodel of MRSA USA300 infection, whilst showing little toxicity to human erythrocytes and human primary cell linesex vivo. Observations from biophysical AMP-lipid-interactions and electron microscopy suggest that the newly identified peptides interact with the cell membrane and may be involved in the inhibition of other cellular processes. Amphiphilic conformations associated with membrane disruption are also observed in 3D molecular modelling of the peptides. HG2 and HG4 both preferentially bind to MRSA total lipids rather than with human cell lipids indicating that HG4 may form superior templates for safer therapeutic candidates for MDR bacterial infections.Author SummaryWe are losing our ability to treat multidrug resistant (MDR) bacteria, otherwise known as superbugs. This poses a serious global threat to human health as bacteria are increasingly acquiring resistance to antibiotics. There is therefore urgent need to intensify our efforts to develop new safer alternative drug candidates. We emphasise the usefulness of complementing wet-lab andin silicotechniques for the rapid identification of new drug candidates from environmental samples, especially antimicrobial peptides (AMPs). HG2 and HG4, the AMPs identified in our study show promise as effective therapies for the treatment of methicillin resistantStaphylococcus aureusinfections bothin vitroandin vivowhilst having little cytotoxicity against human primary cells, a step forward in the fight against MDR infections.

scholarly journals Photodynamic antimicrobial chemotherapy with the novel amino acid-porphyrin conjugate 4I: In vitro and in vivo studies

PLoS ONE ◽  
2017 ◽  
Vol 12 (5) ◽  
pp. e0176529 ◽  
Author(s):  
Yao Yuan ◽  
Zi-Quan Liu ◽  
Heng Jin ◽  
Shi Sun ◽  
Tian-Jun Liu ◽  
...  
Keyword(s):  
Amino Acid ◽  
Antimicrobial Chemotherapy ◽  
In Vivo Studies ◽  
The Novel ◽  
Photodynamic Antimicrobial Chemotherapy

scholarly journals In Vitro and In Vivo Antibacterial Activity of Gliotoxin Alone and in Combination with Antibiotics against Staphylococcus aureus

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 85
Author(s):  
Patricia Esteban ◽  
Sergio Redrado ◽  
Laura Comas ◽  
M. Pilar Domingo ◽  
M. Isabel Millán-Lou ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Resistant Bacteria ◽  
Infection Model ◽  
Antimicrobial Drugs ◽  
Hospital Acquired ◽  
Antibiotic Efficacy

Multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) is one of the major causes of hospital-acquired and community infections and pose a challenge to the human health care system. Therefore, it is important to find new drugs that show activity against these bacteria, both in monotherapy and in combination with other antimicrobial drugs. Gliotoxin (GT) is a mycotoxin produced by Aspergillus fumigatus and other fungi of the Aspergillus genus. Some evidence suggests that GT shows antimicrobial activity against S. aureus in vitro, albeit its efficacy against multidrug-resistant strains such as MRSA or vancomycin-intermediate S. aureus (VISA) strainsis not known. This work aimed to evaluate the antibiotic efficacy of GT as monotherapy or in combination with other therapeutics against MRSA in vitro and in vivo using a Caenorhabditis elegans infection model.

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