Cigarette Smoke Extract-Exposed Methicillin-Resistant Staphylococcus aureus Regulates Leukocyte Function for...

Area of Science:

• Microbiology
• Immunology
• Toxicology

Background:

• Cigarette smoke (CS) impairs immune responses and increases susceptibility to bacterial infections.
• Methicillin-resistant Staphylococcus aureus (MRSA) USA300 virulence is influenced by environmental factors.
• Quorum sensing regulates virulence in Staphylococcus aureus.

Purpose of the Study:

• To investigate the impact of CS exposure on Staphylococcus aureus gene expression and virulence.
• To determine how CS affects MRSA USA300's interaction with host immune cells.

Main Methods:

• RNA sequencing (RNAseq) was used to analyze gene expression changes in MRSA USA300 exposed to CS extract (CSE).
• Functional assays assessed the ability of CSE-exposed MRSA to evade phagocytosis and neutrophil extracellular trap (NET)-mediated killing.
• Bacterial burden was quantified in mouse lungs following infection with CSE-exposed MRSA.

Main Results:

• CS exposure up-regulated key MRSA virulence genes, including those for adhesins and immune evasion proteins (staphylococcal protein A, nuclease).
• CSE-exposed MRSA exhibited enhanced resistance to phagocytosis by macrophages and neutrophils.
• CSE-exposed MRSA showed increased survival against NETs due to CS-induced nuclease production.
• Infection with CSE-exposed MRSA resulted in significantly higher pulmonary bacterial burden in mice.

Conclusions:

• Bioactive compounds in CS induce hypervirulence in MRSA USA300.
• CS enhances MRSA's ability to evade critical host immune defenses, including phagocytosis and NET killing.
• CS exposure poses a significant risk for more severe Staphylococcus aureus pulmonary infections.