scholarly journals Galleria mellonella larvae exhibit a weight-dependent lethal median dose when infected with methicillin-resistant Staphylococcus aureus

2021 ◽  
Vol 79 (2) ◽  
Author(s):  
Poppy J Hesketh-Best ◽  
Michelle V Mouritzen ◽  
Kayleigh Shandley-Edwards ◽  
Richard A Billington ◽  
Mathew Upton
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Galleria Mellonella ◽  
Lethal Dose ◽  
Stable Model ◽  
Methicillin Resistant ◽  
Larval Length ◽  
Lipid Weight ◽  
The Impact

ABSTRACT Galleria mellonella is a recognised model to study antimicrobial efficacy; however, standardisation across the scientific field and investigations of methodological components are needed. Here, we investigate the impact of weight on mortality following infection with Methicillin-resistant Staphylococcus aureus (MRSA). Larvae were separated into six weight groups (180–300 mg at 20 mg intervals) and infected with a range of doses of MRSA to determine the 50% lethal dose (LD50), and the ‘lipid weight’ of larvae post-infection was quantified. A model of LD50 values correlated with weight was developed. The LD50 values, as estimated by our model, were further tested in vivo to prove our model. We establish a weight-dependent LD50 in larvae against MRSA and demonstrate that G. mellonella is a stable model within 180–260 mg. We present multiple linear models correlating weight with: LD50, lipid weight, and larval length. We demonstrate that the lipid weight is reduced as a result of MRSA infection, identifying a potentially new measure in which to understand the immune response. Finally, we demonstrate that larval length can be a reasonable proxy for weight. Refining the methodologies in which to handle and design experiments involving G. mellonella, we can improve the reliability of this powerful model.

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.

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.

scholarly journals A Novel Dicationic Boron Dipyrromethene-based Photosensitizer for Antimicrobial Photodynamic Therapy against Methicillin-Resistant Staphylococcus aureus

2020 ◽  
Vol 28 ◽  
Author(s):  
Priyanga Dharmaratne ◽  
Ligang Yu ◽  
Roy Chi-Hang Wong ◽  
Ben Chun-Lap Chan ◽  
Kit-Man Lau ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Photodynamic Therapy ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Skin Irritation ◽  
Scientific Basis ◽  
Positive Control ◽  
Methicillin Resistant ◽  
Boron Dipyrromethene ◽  
Mrsa Strains

Background: We report herein the synthesis of a novel dicationic boron dipyrromethene derivative (compound 3) which is symmetrically substituted with two trimethylammonium styryl groups. Methods: The antibacterial photodynamic activity of compound 3 was determined against sixteen methicillin-resistant Staphylococcus aureus (MRSA) strains, including four ATCC type strains (ATCC 43300, ATCC BAA-42, ATCC BAA-43, and ATCC BAA-44), two mutant strains [AAC(6’)-APH(2”) and RN4220/pUL5054], and ten non-duplicate clinical strains of hospital- and communityassociated MRSA. Upon light irradiation, the minimum bactericidal concentrations of compound 3 were in the range of 1.56-50 µM against all the sixteen MRSA strains. Interestingly, compound 3 was not only more active than an analogue in which the ammonium groups are not directly connected to the pconjugated system (compound 4), but also showed significantly higher (p < 0.05) antibacterial potency than the clinically approved photosensitizer methylene blue. The skin irritation of compound 3 during topical application was tested on human 3-D skin constructs and proven to be non-irritant in vivo at concentrations below 1.250 mM. In the murine MRSA infected wound study, the colony forming unit reduction of compound 3 + PDT group showed significantly (p < 0.05) higher value (>2.5 log10) compared to other test groups except for the positive control. Conclusion: In conclusion, the present study provides a scientific basis for future development of compound 3 as a potent photosensitizer for photodynamic therapy for MRSA wound infection.

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