Importance of superoxide dismutases A and M for protection ofStaphylococcus aureusin the oxidative stressful environment of cystic fibrosis airways

Abstract

Staphylococcus aureus is one of the earliest pathogens that persists the airways of cystic fibrosis (CF) patients and contributes to increased inflammation and decreased lung function. In contrast to other staphylococci, S. aureus possesses two superoxide dismutases (SODs), SodA and SodM, with SodM being unique to S. aureus. Both SODs arm S. aureus for its fight against oxidative stress, a by‐product of inflammatory reactions. Despite complex investigations, it is still unclear if both enzymes are crucial for the special pathogenicity of S. aureus. To investigate the role of both SODs during staphylococcal persistence in CF airways, we analysed survival and gene expression of S. aureus CF isolates and laboratory strains in different CF‐related in vitro and ex vivo settings. Bacteria located in inflammatory and oxidised CF sputum transcribed high levels of sodA and sodM. Especially expression values of sodM were remarkably higher in CF sputum than in bacterial in vitro cultures. Interestingly, also S. aureus located in airway epithelial cells expressed elevated transcript numbers of both SODs, indicating that S. aureus is exposed to oxidative stress at various sites within CF airways. Both enzymes promoted survival of S. aureus during polymorphonuclear leukocyte killing and seem to act compensatory, thereby giving evidence that the interwoven interaction of SodA and SodM contributes to S. aureus virulence and facilitates S. aureus persistence within CF airways.

How Bacterial Adaptation to Cystic Fibrosis Environment Shapes Interactions Between Pseudomonas aeruginosa and Staphylococcus aureus

“…A 21-month longitudinal study performed on 183 CF patients depicted that the clonal diversity of S. aureus strains decreased as patient aged, pointing out that some isolates tended to adapt more efficiently and dominate the airway sphere during infection history (Westphal et al, 2020). Several studies indeed highlighted that S. aureus isolates evolve in the CF lung environment and acquire features leading to better-fitted isolates (Figure 2; Chatterjee et al, 2008;Treffon et al, 2018Treffon et al, , 2020Herzog et al, 2019;Lennartz et al, 2019;Tan et al, 2019;Westphal et al, 2020).…”

The Virulence Potential of Livestock-Associated Methicillin-Resistant Staphylococcus aureus Cultured from the Airways of Cystic Fibrosis Patients

“…To further study these effects, gene expression analysis will be helpful to determine if differences in transcription might cause the respective phenotype. In addition, the investigation of virulence regulators such as sigma factor B ( sigB ), staphylococcal accessory regulator A ( sarA ), and agr or genes of the bacterial stress response, like superoxide dismutases sodA and sodM , or the caseinolytic protease clpC , which were shown to be involved in intracellular survival and long-term persistence of S. aureus in non-professional phagocytes [ 39 , 40 , 41 , 42 ], could be helpful to explore the different invasion and cytotoxicity traits of the bacterial CF isolates.…”

“…Clinical S. aureus strains were isolated from the sputum samples or throat swabs of nine chronically S. aureus -infected CF patients from the CF centers of the University Hospital Münster, Germany, and the Clemenshospital, Münster, Germany, and were processed as described recently [ 40 ]. Per patient, two clonal S. aureus isolates, an early and a late isolate, which carried the same spa -type and MLST, were selected for analysis.…”

“…We performed infection assays using A549 airway epithelial cells (ATCC ® CCL-185™). The cells were cultivated and infected as described recently [ 40 ], with some modifications. Briefly, the cells were seeded in 75 cm 2 cell culture flasks (Greiner Bio-One, Frickenhausen, Germany) and cultivated in RPMI-1640 (R7388, Sigma-Aldrich [now Merck kGaA, Darmstadt, Germany]) medium, supplemented with 2 mg/mL NaHCO 3 (Sigma-Aldrich [now Merck kGaA, Darmstadt, Germany]) and 10% fetal bovine serum (FBS) (Biochrom GmbH [now Merck kGaA, Darmstadt, Germany]) at 37 °C and 5% CO 2 .…”

Staphylococcus aureus Pathogenicity in Cystic Fibrosis Patients—Results from an Observational Prospective Multicenter Study Concerning Virulence Genes, Phylogeny, and Gene Plasticity

“…The preponderance of colonizing clones results from the suppression of virulence genes for the sake of an intensified expression of protective factors [6]. Manifold strategies have been described to evade immune response and antibiotic treatment, including biofilm formation [13,14] emergence of small colony variants (SCVs) [15][16][17], intracellular persistence [18], and agr-dysfunction [19], among others [14,[20][21][22].…”