Membrane-Targeting Mechanism of Host Defense Peptides Inspiring the Design of Polypeptide-Conjugated Gold Nanoparticles Exhibiting Effective Antibacterial Activity against Methicillin-Resistant Staphylococcus aureus

2021 ◽  
Author(s):  
Weiwei Zhang ◽  
Yueming Wu ◽  
Longqiang Liu ◽  
Ximian Xiao ◽  
Zihao Cong ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Gold Nanoparticles ◽  
Antibacterial Activity ◽  
Health System ◽  
Host Defense ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Multidrug Resistant ◽  
Grand Challenge ◽  
Host Defense Peptides ◽  
Bacteria Resistance

Multidrug-resistant bacterial infection is a grand challenge to global medical and health system. Therefore, it is urgent to develop versatile antibacterial strategies that can combat bacteria resistance without displaying toxicity....

scholarly journals Sensitizing Staphylococcus aureus to antibacterial host defense by decoding and blocking the lipid flippase MprF

2020 ◽  
Author(s):  
Christoph Josef Slavetinsky ◽  
Janna Nadine Hauser ◽  
Cordula Gekeler ◽  
Jessica Slavetinsky ◽  
André Geyer ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Monoclonal Antibodies ◽  
Host Defense ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Resistance Mechanisms ◽  
Proof Of Concept ◽  
Host Defense Peptides ◽  
Bacterial Lipid ◽  
Lipid Flippase ◽  
Antibacterial Host Defense

The pandemic of antibiotic resistance represents a major human health threat demanding new antimicrobial strategies. MprF is the synthase and flippase of the phospholipid lysyl-phosphatidylglycerol that increases virulence and resistance of methicillin-resistant Staphylococcus aureus (MRSA) and other pathogens to cationic host defense peptides and antibiotics. With the aim to design MprF inhibitors that could sensitize MRSA to both, human antimicrobials and antibiotics and support the clearance of staphylococcal infections with minimal selection pressure, we developed MprF-targeting monoclonal antibodies, which bound and blocked the MprF flippase subunit. Antibody M-C7.1 targeted a specific loop in the flippase domain that proved to be exposed at both sides of the bacterial membrane, thereby enhancing the mechanistic understanding into bacterial lipid translocation. M-C7.1 rendered MRSA susceptible to host antimicrobial peptides and antibiotics such as daptomycin. Moreover, it impaired MRSA survival in human phagocytes, which recommends MprF inhibitors for new anti-MRSA approaches. MprF-directed monoclonal antibodies provide a proof of concept for development of precisely targeted anti-virulence approaches, which block bacterial antimicrobial resistance mechanisms.

scholarly journals A New Nano-Platform of Erythromycin Combined with Ag Nano-Particle ZnO Nano-Structure against Methicillin-Resistant Staphylococcus aureus

Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 841 ◽  
Author(s):  
Atanu Naskar ◽  
Sohee Lee ◽  
Yunhee Lee ◽  
Semi Kim ◽  
Kwang-sun Kim
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Multidrug Resistant ◽  
Nano Particles ◽  
Nano Composite ◽  
Nano Structure ◽  
Methicillin Resistant ◽  
X Ray ◽  
Gram Positive Bacteria

Nano-particles have been combined with antibiotics in recent studies to overcome multidrug-resistant bacteria. Here, we synthesized a nano-material in which Ag nano-particles were assembled with a ZnO nano-structure to form an Ag-ZnO (AZO) nano-composite at low temperature. This material was combined with erythromycin (Ery), an antibiotic effective towards gram-positive bacteria, using three different approaches (AZO + Ery (AZE) [centrifuged (AZE1), used separately after 1-h gap (AZE2), without centrifugation (AZE3)]) to prepare a nano-antibiotic against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). X-ray diffraction analysis and transmission electron microscopy confirmed the presence of Ag nano-particles and ZnO nano-structure. The elemental and chemical state of the elements present in the AZO nano-composite were assessed by X-ray photoelectron spectroscopy. The antibacterial activity of AZE samples against both Escherichia coli and S. aureus strains including MRSA was evaluated in antibacterial and morphological analyses. The AZE3 sample showed greater antibacterial activity than the other samples and was comparable to erythromycin. AZE3 was ~20-fold less prone to developing bacterial resistance following multiple exposures to bacteria compared to erythromycin alone. The AZE3 nano-composite showed good biocompatibility with 293 human embryonic kidney cells. Our newly synthesized nano-platform antibiotics may be useful against multidrug-resistant gram-positive bacteria.

scholarly journals Antimicrobial activity of Rhipsalis baccifera and Drymoglossum piloselloides against Methicillin Resistant Staphylococcus Aureus and Drug Resistant Acinetobacter baumanii.

2021 ◽  
pp. 32-40
Author(s):  
S. D. Kugaperumal ◽  
R. D. De Silva ◽  
T. D. Karunarathne ◽  
C. P. Gunasekara ◽  
D. N. A. W. Samarakoon
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Antibacterial Activity ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Chronic Wounds ◽  
Multidrug Resistant ◽  
Antibiotic Activity ◽  
Diffusion Method ◽  
Acinetobacter Baumanii ◽  
Methicillin Resistant

Methicillin Resistant Staphylococcus aureus (MRSA) and multidrug-resistant Acinetobacter baumanii are known to cause delayed healing of infections in both acute and chronic wounds. Plants are a natural source of novel antimicrobials and many new drugs are derived from plants, as plants contain phytochemicals that have antimicrobial activity. Sri Lanka is a tropical country with a wide variety of plant species, many of which were identified as possessing medicinal qualities and have been used by traditional medicinal practitioners in the treatment of various diseases and ailments. Dressings made of Rhipsalis baccifera and Drymoglossum piloselloides have been used to treat wounds by Sri Lankan traditional medicine practitioners. This study determined the antibacterial activity of aqueous and methanol extracts of R. baccifera and D. piloselloides against MRSA and Multidrug-resistant A. baumanii. Aqueous and methanolic extractions of both plants were done by maceration. Their antibacterial properties were checked against MRSA and A. baumanii by the well diffusion method. The effectiveness of the extract was further tested against factors like temperature and storage time. R. baccifera (aqueous extract) exhibited antimicrobial properties against MRSA but no activity against A. baumanii. The antibiotic activity against MRSA was increased after two months of storage at 4°C. D. piloselloides exhibited no antibiotic activity against both MRSA and A. baumanii. The methanolic extracts did not demonstrate any antibacterial activity.

scholarly journals The Prevalence of Virulence Determinants and Antibiotic Resistance Patterns in Methicillin—Resistant Staphylococcus aureus in a Nursing Home in Poland

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 427
Author(s):  
Martyna Kasela ◽  
Agnieszka Grzegorczyk ◽  
Bożena Nowakowicz-Dębek ◽  
Anna Malm
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Variable Number Tandem Repeat ◽  
Multidrug Resistant ◽  
Variable Number ◽  
Pulse Field ◽  
Virulence Determinants ◽  
Gene Encoding ◽  
Methicillin Resistant ◽  
Pulse Field Gel Electrophoresis

Nursing homes (NH) contribute to the regional spread of methicillin-resistant Staphylococcus aureus (MRSA). Moreover, residents are vulnerable to the colonization and subsequent infection of MRSA etiology. We aimed at investigating the molecular and phenotypic characteristics of 21 MRSA collected from the residents and personnel in an NH (Lublin, Poland) during 2018. All MRSA were screened for 20 genes encoding virulence determinants (sea-see, eta, etb, tst, lukS-F-PV, eno, cna, ebpS, fib, bbp, fnbA, fnbB, icaADBC) and for resistance to 18 antimicrobials. To establish the relatedness and clonal complexes of MRSA in NH we applied multiple-locus variable-number tandem-repeat fingerprinting (MLVF), pulse field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCCmec) typing. We identified four sequence types (ST) among two clonal complexes (CC): ST (CC22) known as EMRSA-15 as well as three novel STs—ST6295 (CC8), ST6293 (CC8) and ST6294. All tested MRSA were negative for sec, eta, etb, lukS-F-PV, bbp and ebpS genes. The most prevalent gene encoding toxin was sed (52.4%; n = 11/21), and adhesins were eno and fnbA (100%). Only 9.5% (n = 2/21) of MRSA were classified as multidrug-resistant. The emergence of novel MRSA with a unique virulence and the presence of epidemic clone EMRSA-15 creates challenges for controlling the spread of MRSA in NH.

Antibacterial Activity of Ecklonia cava Against Methicillin-Resistant Staphylococcus aureus and Salmonella spp.

2010 ◽  
Vol 7 (4) ◽  
pp. 435-441 ◽  
Author(s):  
Jang-Gi Choi ◽  
Ok-Hwa Kang ◽  
Obiang-Obounou Brice ◽  
Young-Seob Lee ◽  
Hee-Sung Chae ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Ecklonia Cava ◽  
Salmonella Spp ◽  
Methicillin Resistant

Non-Multidrug-Resistant, Methicillin-Resistant Staphylococcus aureus in a Neonatal Unit

2014 ◽  
Vol 33 (10) ◽  
pp. e252-e259 ◽  
Author(s):  
Cilmara P. Garcia ◽  
Juliana F. Rosa ◽  
Maria A. Cursino ◽  
Renata D. Lobo ◽  
Carla H. Mollaco ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Multidrug Resistant ◽  
Neonatal Unit ◽  
Methicillin Resistant
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