scholarly journals A Murine Skin Infection Model Capable of Differentiating the Dermatopathology of Community-Associated MRSA Strain USA300 from Other MRSA Strains

2021 ◽  
Vol 9 (2) ◽  
pp. 287
Author(s):  
Jack Zhang ◽  
John Conly ◽  
JoAnn McClure ◽  
Kaiyu Wu ◽  
Bjӧrn Petri ◽  
...  

USA300 is a predominant and highly virulent community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain that is a leading cause of skin and soft tissue infections. We established a murine intradermal infection model capable of demonstrating dermatopathological differences between USA300 and other MRSA strains. In this model, USA300 induced dermonecrosis, uniformly presenting as extensive open lesions with a histologically documented profound inflammatory cell infiltrate extending below the subcutis. In contrast, USA400 and a colonizing control strain M92 caused only localized non-ulcerated skin infections associated with a mild focal inflammatory infiltrate. It was also determined that the dermonecrosis induced by USA300 was associated with significantly increased neutrophil recruitment, inhibition of an antibacterial response, and increased production of cytokines/chemokines associated with disease severity. These results suggest that induction of severe skin lesions by USA300 is related to over-activation of neutrophils, inhibition of host antibacterial responses, and selective alteration of host cytokine/chemokine profiles.

2021 ◽  
Vol 7 (7) ◽  
pp. 533
Author(s):  
Ailish Williams ◽  
Helen Rogers ◽  
David Williams ◽  
Xiao-Qing Wei ◽  
Damian Farnell ◽  
...  

Previous research into the inflammatory cell infiltrate of chronic hyperplastic candidosis (CHC) determined that the immune response is primarily composed of T cells, the majority of which are T helper (CD4+) cells. This present investigation used immunohistochemistry to further delineate the inflammatory cell infiltrate in CHC. Cells profiled were those expressing IL-17A cytokine, EBI3 and IL-12A subunits of the IL-35 cytokine, and FoxP3+ cells. Squamous cell papilloma (with Candida infection) and oral lichen planus tissues served as comparative controls to understand the local immune responses to Candida infection. The results demonstrated that Candida-induced inflammation and immune regulation co-exist in the oral mucosa of CHC and that high prevalence of cells expressing the EBI3 cytokine subunit may play an important role in this regulation. This balance between inflammation and immune tolerance toward invading Candida in the oral mucosa may be critical in determining progress of infection.


PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e108069 ◽  
Author(s):  
Tom-Ole Løvås ◽  
Jo C. Bruusgaard ◽  
Inger Øynebråten ◽  
Kristian Gundersen ◽  
Bjarne Bogen

1987 ◽  
Vol 18 (5) ◽  
pp. 511-520 ◽  
Author(s):  
Debra A. Bell ◽  
Thomas J. Flotie ◽  
Atul K. Bhan

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S120-S121
Author(s):  
Sungim Choi ◽  
Taeeun Kim ◽  
Seongman Bae ◽  
Eunmi Yang ◽  
Su-Jin Park ◽  
...  

Abstract Background There is a concern that the vancomycin MIC of methicillin-resistant Staphylococcus aureus (MRSA) could be increased by concomitant colistin administered against multidrug-resistant gram-negative pathogen. Methods We confirmed the molecular genotypes of MRSA blood isolates collected in a tertiary hospital in Seoul, South Korea, and selected representative strains from the community-associated MRSA strains (CA-MRSA, ST72-SCCmec IV) and hospital-acquired MRSA strains (HA-MRSA, ST5-SCCmec II). USA CA-MRSA (USA300, ST8-SCCmec IV) and MRSA standard strain (ATCC 43300, ST39-SCCmec II) were also used for comparison with representative. We identified changes of the vancomycin MIC in MRSA by colistin exposure in a checkerboard assay and performed a time-kill assay to evaluate the combined effect of vancomycin and colistin on MRSA. In addition, we administered vancomycin, colistin, and combination of two antibiotics, respectively, to a neutropenic murine thigh infection model to evaluate the in vivo antagonistic effect of colistin on vancomycin treatment. Results In the checkerboard assay, all 4 MRSA strains showed a tendency for the vancomycin MIC to increase along with increasing concentrations of colistin. However, the time-kill assay showed the antagonism of vancomycin and colistin only against ST5-MRSA, when vancomycin concentration was 2 times the vancomycin MIC (Figure 1). No antagonism was observed in other strains. In the murine thigh infection model of ST5-MRSA, vancomycin monotherapy showed a significant log CFU reduction compared with a combination of vancomycin and colistin at 24 hours, demonstrating the antagonistic effect of vancomycin and colistin combination (Figure 2). Conclusion This study showed that exposure of colistin to certain MRSA strains may reduce the susceptibility to vancomycin. Combination therapy with vancomycin and colistin for MDR pathogens infections might result in treatment failure for concurrent MRSA infection. Disclosures All authors: No reported disclosures.


Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 606 ◽  
Author(s):  
Maria Mir ◽  
Naveed Ahmed ◽  
Andi Dian Permana ◽  
Aoife Maria Rodgers ◽  
Ryan F. Donnelly ◽  
...  

Methicillin resistant Staphylococcus aureus (MRSA) induced skin infections have become a challenging problem due to the escalating antibiotic resistance. Carvacrol (CAR) has been reported to be effective against MRSA. However, due to its characteristics, CAR exhibits low skin retention. In this study, CAR was formulated into site-specific nanoparticle (NPs) delivery system using poly(ε-caprolactone) (PCL), following incorporation into a hydrogel matrix to facilitate dermal delivery. The release study exhibited significantly higher release of CAR from PCL NPs in the presence of bacterial lipase, highlighting its potential for differential delivery. Moreover, encapsulation of CAR in PCL NPs resulted in a two-fold increase in its anti-MRSA activity. Dermatokinetic studies revealed that the NPs loaded hydrogel was able to enhance skin retention of CAR after 24 h (83.29 ± 3.15%), compared to free CAR-loaded hydrogel (0.85 ± 0.14%). Importantly, this novel approach exhibited effective antimicrobial activity in an ex-vivo skin infection model. Hence, these findings have proven the concept that the loading of CAR into a responsive NPs system can lead to sustained antimicrobial effect at the desired site, and may provide a novel effective approach for treatment of MRSA induced skin infections. However, further studies must be conducted to investigate in-vivo efficacy of the developed system in an appropriate infection model.


1997 ◽  
Vol 26 (2) ◽  
pp. 83-89 ◽  
Author(s):  
D. W. Williams ◽  
A. J. C. Potts ◽  
M. J. Wilson ◽  
J. B. Matthews ◽  
M. A. O. Lewis

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