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 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.

scholarly journals Erianin against Staphylococcus aureus Infection via Inhibiting Sortase A

Toxins ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 385 ◽  
Author(s):  
Ping Ouyang ◽  
Xuewen He ◽  
Zhong-Wei Yuan ◽  
Zhong-Qiong Yin ◽  
Hualin Fu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Hydrophobic Interactions ◽  
Multidrug Resistant ◽  
Vital Role ◽  
Surface Proteins ◽  
Dynamics Simulation ◽  
Sortase A

With continuous emergence and widespread of multidrug-resistant Staphylococcus aureus infections, common antibiotics have become ineffective in treating these infections in the clinical setting. Anti-virulence strategies could be novel, effective therapeutic strategies against drug-resistant bacterial infections. Sortase A (srtA), a transpeptidase in gram-positive bacteria, can anchor surface proteins that play a vital role in pathogenesis of these bacteria. SrtA is known as a potential antivirulent drug target to treat bacterial infections. In this study, we found that erianin, a natural bibenzyl compound, could inhibit the activity of srtA in vitro (half maximal inhibitory concentration—IC50 = 20.91 ± 2.31 μg/mL, 65.7 ± 7.2 μM) at subminimum inhibitory concentrations (minimum inhibitory concentrations—MIC = 512 μg/mL against S. aureus). The molecular mechanism underlying the inhibition of srtA by erianin was identified using molecular dynamics simulation: erianin binds to srtA residues Ile182, Val193, Trp194, Arg197, and Ile199, forming a stable bond via hydrophobic interactions. In addition, the activities of S. aureus binding to fibronectin and biofilm formation were inhibited by erianin, when co-culture with S. aureus. In vivo, erianin could improve the survival in mice that infected with S. aureus by tail vein injection. Experimental results showed that erianin is a potential novel therapeutic compound against S. aureus infections via affecting srtA.

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