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Inoculation Pneumonia Caused by Coagulase Negative Staphylococcus
Meng-Meng Shi1,2, Antoine Monsel3,4,5, Jean-Jacques Rouby3
1Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Rationale:
Although frequently retrieved in tracheal secretions of critically ill patients on mechanical ventilation, the existence of pneumonia caused by coagulase-negative staphylococci (CoNS) remains controversial.
Objective:
To assess whether Staphylococcus haemolyticus (S. haemolyticus) inoculated in mice's trachea can infect normal lung parenchyma, increasing concentrations of S. haemolyticus were intratracheally administered in 221 immunocompetent mice.
Methods:
Each animal received intratracheally phosphate-buffered saline (PBS) (n = 43) or live (n = 141) or inactivated (n = 37) S. haemolyticus at increasing load: 1.0 × 106, 1.0 × 107, and 1.0 × 108 colony forming units (CFU). Forty-three animals were sacrificed at 12 h and 178 were sacrificed at 36 h; 64 served for post-mortem lung histology, 157 served for pre-mortem bronchoalveolar lavage (BAL) analysis, and 42 served for post-mortem quantitative bacteriology of lung tissue. The distribution of biofilm-associated genes was investigated in the S. haemolyticus strain used in our in vivo experiment as well as among 19 other clinical S. haemolyticus strains collected from hospitals or nursing houses.
Measurements And Main Results:
Intratracheal inoculation of 1.0 × 108 CFU live S. haemolyticus caused macroscopic and histological confluent pneumonia with significant increase in BAL white cell count, tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein (MIP)-2. At 12 h, high concentrations of S. haemolyticus were identified in BAL. At 36 h, lung injury and BAL inflammation were less severe than at 12 h and moderate concentrations of species belonging to the oropharyngeal flora were identified in lung tissue. The inoculation of 1.0 × 106 and 1.0 × 107 CFU live S. haemolyticus caused histologic interstitial pneumonia and moderate BAL inflammation. Similar results were observed after inoculation of inactivated S. haemolyticus. Moreover, biofilm formation was a common phenotype in S. haemolyticus isolates. The low prevalence of the ica operon in our clinical S. haemolyticus strain collection indicated icaA and icaD independent-biofilm formation.
Conclusion:
In immunocompetent spontaneously breathing mice, inoculation of S. haemolyticus causes concentration-dependent lung infection that spontaneously recovers over time. icaA and icaD independent biofilm formation is a common phenotype in S. haemolyticus isolates.
Insights
Coagulase-negative staphylococci (CoNS) pneumonia is controversial. In mice, Staphylococcus haemolyticus caused lung infection that resolved over time, independent of biofilm formation.
Area of Science:
- Microbiology
- Infectious Diseases
- Pulmonary Medicine
Background:
- The role of coagulase-negative staphylococci (CoNS) in causing pneumonia, particularly in mechanically ventilated patients, remains debated.
- Staphylococcus haemolyticus is frequently found in respiratory secretions, but its pathogenic potential in the lungs is not well-established.
Purpose of the Study:
- To investigate the capacity of Staphylococcus haemolyticus to infect lung parenchyma in a mouse model.
- To determine the dose-dependent effects and resolution of Staphylococcus haemolyticus-induced lung infection.
Main Methods:
- Immunocompetent mice were intratracheally inoculated with varying concentrations of live or inactivated Staphylococcus haemolyticus or phosphate-buffered saline (PBS).
- Animals were analyzed at 12 and 36 hours post-inoculation, with assessments including bronchoalveolar lavage (BAL) analysis, lung histology, and quantitative bacteriology.
- Biofilm-associated gene distribution was examined in the experimental strain and other clinical isolates.
Main Results:
- High-dose (1.0 × 10^8 CFU) live Staphylococcus haemolyticus induced macroscopic and histological pneumonia with increased inflammatory markers in BAL fluid.
- Lung injury and inflammation decreased by 36 hours, with the emergence of oropharyngeal flora in lung tissue, suggesting resolution.
- Lower doses and inactivated bacteria also caused interstitial pneumonia and BAL inflammation, while biofilm formation was common and independent of the ica operon.
Conclusions:
- Staphylococcus haemolyticus can cause a concentration-dependent lung infection in immunocompetent mice that resolves spontaneously.
- Biofilm formation in Staphylococcus haemolyticus is a common phenotype, often independent of the icaA and icaD genes.
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