scholarly journals Phage Endolysin LysP108 Showed Promising Antibacterial Potential Against Methicillin-resistant Staphylococcus aureus

2021 ◽  
Vol 11 ◽  
Author(s):  
Yifei Lu ◽  
Yingran Wang ◽  
Jing Wang ◽  
Yan Zhao ◽  
Qiu Zhong ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Animal Experiments ◽  
Mainland China ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Standard Plate ◽  
Live Bacteria ◽  
Antibacterial Potential

As a potential antibacterial agent, endolysin can directly lyse Gram-positive bacteria from the outside and does not lead to drug resistance. Considering that XN108 is the first reported methicillin-resistant Staphylococcus aureus (MRSA) strain in mainland China with a vancomycin MIC that exceeds 8 µg mL-1, we conducted a systematic study on its phage-encoded endolysin LysP108. Standard plate counting method revealed that LysP108 could lyse S. aureus and Pseudomonas aeruginosa with damaged outer membrane, resulting in a significant reduction in the number of live bacteria. Scanning electron microscopy results showed that S. aureus cells could be lysed directly from the outside by LysP108. Live/dead bacteria staining results indicated that LysP108 possessed strong bactericidal ability, with an anti-bacterial rate of approximately 90%. Crystal violet staining results implied that LysP108 could also inhibit and destroy bacterial biofilms. In vivo animal experiments suggested that the area of subcutaneous abscess of mice infected with MRSA was significantly reduced after the combined injection of LysP108 and vancomycin in comparison with monotherapy. The synergistic antibacterial effects of LysP108 and vancomycin were confirmed. Therefore, the present data strongly support the idea that endolysin LysP108 exhibits promising antibacterial potential to be used as a candidate for the treatment of infections caused by MRSA.

scholarly journals Antimicrobial activity of SM-17466, a novel carbapenem antibiotic with potent activity against methicillin-resistant Staphylococcus aureus.

1995 ◽  
Vol 39 (4) ◽  
pp. 910-916 ◽  
Author(s):  
Y Sumita ◽  
H Nouda ◽  
K Kanazawa ◽  
M Fukasawa
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Inhibitory Concentration ◽  
Antibacterial Activities ◽  
Infection Model ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Wide Range

The in vitro and in vivo antibacterial activities of SM-17466, a new 1 beta-methyl carbapenem, were evaluated against a wide range of clinical bacterial isoaltes and compared with the activities of meropenem, imipenem, vancomycin, and arbekacin. SM-17466 had a broad spectrum of action against gram-positive bacteria, showing especially potent activity against methicillin-resistant staphylococci. The MICs of SM-17466, meropenem, imipenem, vancomycin, and arbekacin at which 90% of clinical isolates of methicillin-resistant Staphylococcus aureus were inhibited were 3.13, 50, 100, 1.56, and 3.13 micrograms/ml, respectively. This activity of SM-17466 was almost equivalent to those of the antibiotics used for the treatment of infections caused by this organism. SM-17466 also showed bactericidal activity against methicillin-resistant S. aureus. In contrast, SM-17466 was less active against gram-negative bacteria, especially against Pseudomonas aeruginosa, compared with the other carbapenems; however, of the carbapenems, SM-17466 exhibited the highest activity against Haemophilus influenzae and Bacteriodes fragilis. SM-17466, at a 50% inhibitory concentration of less than 1 microgram/ml, bound to penicillin-binding proteins 1 to 4 in methicillin-susceptible S. aureus and also had good binding to penicillin-binding protein 2' in a methicillin-resistant strain (50% inhibitory concentration, 5.9 micrograms/ml). This high affinity, which was 10 and 20 times greater than those for meropenem and imipenem, respectively, was reflected in the potent activity of SM-17466 against methicillin-resistant S. aureus. SM-17466 demonstrated excellent in vivo efficacy against methicillin-susceptible and -resistant S. aureus strains in a mouse peritoneal infection model: the efficacy of SM-17466 against methicillin-resistant strains was equal to or one-third that of vancomycin. This activity was comparable to the in vitro activity of SM-17466. The subcutaneous injection of SM-17466 in mice revealed that the half-life of SM-17466 in serum was about 18 min, intermediate between those of vancomycin and arbekacin and 1.5-fold that of imipenem-cilastatin. SM-17466 was resistant to hydrolysis by swine renal dehydropeptidase I, to an extent comparable to the resistance shown by meropenem.

scholarly journals Group V Phospholipase A2 Mediates Endothelial Dysfunction and Acute Lung Injury Caused by Methicillin-Resistant Staphylococcus aureus

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1731
Author(s):  
Yu Maw Htwe ◽  
Huashan Wang ◽  
Patrick Belvitch ◽  
Lucille Meliton ◽  
Mounica Bandela ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Acute Lung Injury ◽  
Endothelial Dysfunction ◽  
Lung Injury ◽  
Phospholipase A2 ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Group V ◽  
Methicillin Resistant

Lung endothelial dysfunction is a key feature of acute lung injury (ALI) and clinical acute respiratory distress syndrome (ARDS). Previous studies have identified the lipid-generating enzyme, group V phospholipase A2 (gVPLA2), as a mediator of lung endothelial barrier disruption and inflammation. The current study aimed to determine the role of gVPLA2 in mediating lung endothelial responses to methicillin-resistant Staphylococcus aureus (MRSA, USA300 strain), a major cause of ALI/ARDS. In vitro studies assessed the effects of gVPLA2 inhibition on lung endothelial cell (EC) permeability after exposure to heat-killed (HK) MRSA. In vivo studies assessed the effects of intratracheal live or HK-MRSA on multiple indices of ALI in wild-type (WT) and gVPLA2-deficient (KO) mice. In vitro, HK-MRSA increased gVPLA2 expression and permeability in human lung EC. Inhibition of gVPLA2 with either the PLA2 inhibitor, LY311727, or with a specific monoclonal antibody, attenuated the barrier disruption caused by HK-MRSA. LY311727 also reduced HK-MRSA-induced permeability in mouse lung EC isolated from WT but not gVPLA2-KO mice. In vivo, live MRSA caused significantly less ALI in gVPLA2 KO mice compared to WT, findings confirmed by intravital microscopy assessment in HK-MRSA-treated mice. After targeted delivery of gVPLA2 plasmid to lung endothelium using ACE antibody-conjugated liposomes, MRSA-induced ALI was significantly increased in gVPLA2-KO mice, indicating that lung endothelial expression of gVPLA2 is critical in vivo. In summary, these results demonstrate an important role for gVPLA2 in mediating MRSA-induced lung EC permeability and ALI. Thus, gVPLA2 may represent a novel therapeutic target in ALI/ARDS caused by bacterial infection.

scholarly journals Rhodomyrtone Accumulates in Bacterial Cell Wall and Cell Membrane and Inhibits the Synthesis of Multiple Cellular Macromolecules in Epidemic Methicillin-Resistant Staphylococcus aureus

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 543
Author(s):  
Ozioma F. Nwabor ◽  
Sukanlaya Leejae ◽  
Supayang P. Voravuthikunchai
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Cell Membrane ◽  
Bacterial Cell ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Treatment Options ◽  
Bacterial Cell Wall ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Inhibitor Compounds

As the burden of antibacterial resistance worsens and treatment options become narrower, rhodomyrtone—a novel natural antibiotic agent with a new antibacterial mechanism—could replace existing antibiotics for the treatment of infections caused by multi-drug resistant Gram-positive bacteria. In this study, rhodomyrtone was detected within the cell by means of an easy an inexpensive method. The antibacterial effects of rhodomyrtone were investigated on epidemic methicillin-resistant Staphylococcus aureus. Thin-layer chromatography demonstrated the entrapment and accumulation of rhodomyrtone within the bacterial cell wall and cell membrane. The incorporation of radiolabelled precursors revealed that rhodomyrtone inhibited the synthesis of macromolecules including DNA, RNA, proteins, the cell wall, and lipids. Following the treatment with rhodomyrtone at MIC (0.5–1 µg/mL), the synthesis of all macromolecules was significantly inhibited (p ≤ 0.05) after 4 h. Inhibition of macromolecule synthesis was demonstrated after 30 min at a higher concentration of rhodomyrtone (4× MIC), comparable to standard inhibitor compounds. In contrast, rhodomyrtone did not affect lipase activity in staphylococci—both epidemic methicillin-resistant S. aureus and S. aureus ATCC 29213. Interfering with the synthesis of multiple macromolecules is thought to be one of the antibacterial mechanisms of rhodomyrtone.

scholarly journals In Vitro and In Vivo Activities of DA-7867, a New Oxazolidinone, against Aerobic Gram-Positive Bacteria

2005 ◽  
Vol 49 (6) ◽  
pp. 2498-2500 ◽  
Author(s):  
Eun Jeong Yoon ◽  
Yeong Woo Jo ◽  
Sung Hak Choi ◽  
Tae Ho Lee ◽  
Jae Keol Rhee ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Vancomycin Resistant Enterococci ◽  
Infection Models ◽  
Vancomycin Resistant

ABSTRACT In vitro and in vivo activities of DA-7867 were assessed against methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae. All isolates were inhibited by DA-7867 at ≤0.78 μg/ml, a four-times-lower concentration than that of inhibition by linezolid. For murine infection models, DA-7867 also exhibited greater efficacy than linezolid against all isolates tested.

Recurrent Methicillin-Resistant Staphylococcus Aureus Osteomyelitis: Combination Antibiotic Therapy with Evaluation by Serum Bactericidal Titers

1995 ◽  
Vol 29 (7-8) ◽  
pp. 694-697 ◽  
Author(s):  
Sherrie L Aspinall ◽  
David M Friedland ◽  
Victor L Yu ◽  
John D Rihs ◽  
Robert R Muder
Keyword(s):  
Staphylococcus Aureus ◽  
Back Pain ◽  
Antibiotic Therapy ◽  
Sedimentation Rate ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Blood Cultures ◽  
Low Back ◽  
Methicillin Resistant ◽  
Trough Concentrations

Objective: To report on a patient with recurrent methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis and bacteremia successfully treated with combination antibiotic therapy. Case Summary: Two sets of blood cultures from a 55-year-old man with fever, malaise, and low back pain grew MRSA. Radiologic studies of the spine showed bony changes consistent with osteomyelitis. Soon after completing 6 weeks of vancomycin, the patient experienced a recurrence of back pain. Laboratory values included an increase in the sedimentation rate to 53 mm/h and positive blood cultures for MRSA. Vancomycin, gentamicin, and rifampin were administered for 8 weeks. Serum inhibitory and bactericidal titers were more than 1:1024 for both the peak and trough concentrations. Radiologic studies of the spine showed healing osteomyelitis. Two years after completion of antibiotic therapy, the infection has not recurred. Discussion: Antibiotic therapy alone was attempted because the patient was considered a risky surgical candidate. Serum inhibitory and bactericidal titers documented the high in vivo activity of the vancomycin, gentamicin, and rifampin combination. Initiation of vancomycin therapy led to disappearance of the fever and back pain. Cure was documented by sustained normalization of the erythrocyte sedimentation rate and radiologic evidence of healing. Conclusions: Combination antibiotic therapy with vancomycin, rifampin, and low-dose gentamicin (1 mg/kg q12h) may be useful for deep-seated tissue infection caused by MRSA.

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