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Published on: June 15, 2019
Community-acquired methicillin-resistant Staphylococcus aureus provoked cytokine storm causing severe infection on
Feng Liao1, Wenpeng Gu2, Xiaoqing Fu2
1Department of Respiratory Medicine, The First People's Hospital of Yunnan Province, 650022, Kunming, PR China; Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650500, PR China; The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650500, PR China.
Abstract:
Methicillin-resistant Staphylococcus aureus (MRSA) has become the most important pathogen of hospital-acquired (HA) or community-acquired (CA) infections. However, it is unclear of the cytokines responsible for pathological hyper-inflammation in sepsis related cytokine storm for MRSA infection. In this study, we selected typical HA-MRSA strain (YNSA163: ST239-t030-SCCmecⅢ) and two CA-MRSA isolates (YNSA7: ST59-t439-SCCmecⅣa and YNSA53: ST59-t437-SCCmecⅤb) from our previous research, infected on BALB/c mice, and analyzed the cytokine storm patterns during infection process. The animal experiments revealed the most serious lethal effect on BALB/c mice caused by YNSA7 strain infection, followed by YNSA53, and no BALB/c mice died for YNSA163 infection. Histopathological analyses revealed that lung was the most seriously damaged organs, followed by spleen and kidney, especially for CA-MRSA infection. The severe inflammatory reactions, tissue destruction, and massive exudation of inflammatory mediators and cells could be identified in CA-MRSA strains infected mice. Interleukin-6 (IL-6) and IL-10 were both highly expressed in spleen and lung of YNSA7 and YNSA53 dead cases compared with YNSA53 survived and YNSA163 cases, which demonstrated cytokine storm pattern for CA-MRSA strains infection. The results of IL-6 intervention experiment verified that the enhanced IL-6 secretion was responsible for the host lethality of YNSA7 infection. RNA-sequencing results among three MRSA isolates indicated most of the differentially expressed genes referred to cellular process, metabolism and genetic information processing of bacteria. Specifically, clpP, chp chemotaxis inhibit, fnbB, pathogencity island protein and virulence associated protein E were highly expressed in YNSA7 strain. In general, CA-MRSA strains provoked cytokine storm on BALB/c mice led to severe infection and lethality, the up-regulated of some virulence genes might play important role in pathogenesis.
Insights
Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) strains cause severe infections and lethality in mice by inducing a cytokine storm. Interleukin-6 (IL-6) plays a key role in this host response.
Area of Science:
- Infectious Diseases
- Immunology
- Microbiology
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital and community infections.
- The specific cytokines driving hyper-inflammation and cytokine storms in MRSA infections remain unclear.
- Community-acquired MRSA (CA-MRSA) strains are increasingly recognized for their virulence.
Purpose of the Study:
- To investigate the cytokine storm patterns induced by different MRSA strains (HA-MRSA and CA-MRSA) in a mouse model.
- To identify the key cytokines and bacterial factors contributing to MRSA-induced lethality and severe pathology.
- To elucidate the role of Interleukin-6 (IL-6) in MRSA-related mortality.
Main Methods:
- Infection of BALB/c mice with one hospital-acquired MRSA (HA-MRSA) strain and two community-acquired MRSA (CA-MRSA) strains.
- Analysis of survival rates, histopathology of major organs (lung, spleen, kidney), and cytokine expression (IL-6, IL-10).
- Intervention study using IL-6 blockade and RNA-sequencing to identify bacterial virulence genes.
Main Results:
- CA-MRSA strains (YNSA7 and YNSA53) caused significantly higher mortality and severe lung, spleen, and kidney damage compared to the HA-MRSA strain (YNSA163).
- High expression of IL-6 and IL-10 was observed in dead mice infected with CA-MRSA strains, indicating a cytokine storm.
- IL-6 blockade reduced lethality in mice infected with the virulent CA-MRSA strain YNSA7, confirming IL-6's critical role.
- RNA-sequencing identified upregulated virulence genes in CA-MRSA, including clpP, chp, fnbB, and others, potentially contributing to pathogenesis.
Conclusions:
- CA-MRSA strains induce a severe cytokine storm, leading to increased host lethality and organ damage in mice.
- Elevated IL-6 levels are a critical factor in the mortality associated with CA-MRSA infections.
- Specific bacterial virulence factors upregulated in CA-MRSA strains likely play a significant role in the observed pathogenesis.
