Adaptation of Staphylococcus aureus to Airway Environments in Patients With Cystic Fibrosis by Upregulation of Superoxide Dismutase M and Iron-Scavenging Proteins

Abstract

Adaptation of S. aureus to the hostile environment of CF airways resulted in changed abundance of proteins involved in energy metabolism, cellular processes, transport and binding, but most importantly in an iron-scavenging phenotype and increased activity of superoxide dismutase M.

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

“…Recently, we identified SodM as a protein that was higher abundant in a late S. aureus isolate, which persisted 13 years in the airways of an individual CF patient, in comparison with the clonal first isolate (Treffon et al, 2018). Such results were confirmed by high expression of sodM in long-persisting S. aureus isolates of several CF patients compared with first isolates (Treffon et al, 2018).…”

“…In our former study, we investigated the expression of sodM in several first and late S. aureus isolates cultured from CF airways and laboratory strains after 6 hr of growth in ASM (Treffon et al, 2018). To extend the knowledge about sod expression during S. aureus persistence in CF airways, we used the same S. aureus CF isolates and laboratory strains (Treffon et al, 2018; Tables S1 and S2) and determined transcription of the second staphylococcal SOD, sodA, by quantitative reverse transcription polymerase chain reaction (RT-qPCR) under the same growth conditions as before. Interestingly, by comparing sodA expression of the S. aureus isolates from each of the six CF patients, only for one patient (P12) we detected a significantly reduced expression of sodA in the late isolate compared with the respective first isolate ( Figure 1).…”

“… Figure S1 Expression analysis of sodA (A) and sodM (B) by quantitative reverse transcription PCR (RT‐qPCR) in the first and late clinical S. aureus isolates of six CF patients (P3, P8, P12, P13, P20, P27) and three S. aureus laboratory strains after cultivation of bacteria for 6 h in artificial sputum medium (ASM). The normalised data of the sodM expression were generated in our earlier study (Treffon et al, ) and are presented for better comparison. Data were normalised against expression levels of the housekeeping genes aroE and gyrB in the respective sample, which were set to 1, and grouped according to the origin of the S. aureus strain (clinical isolate or laboratory strain).…”

“…Importantly, while SodA is present in all staphylococci (Valderas, Gatson, Wreyford, & Hart, 2002) and seems to be exclusively dependent on its cofactor manganese (Clements et al, 1999), SodM is unique to S. aureus (Valderas et al, 2002) and was found to be cambialistic being active with either manganese or iron (Garcia et al, 2017). Additionally, although SodA is the main SOD in S. aureus with higher protein abundance (Treffon et al, 2018), under special conditions, for example S. aureus presence in inflamed tissues with S100A8/A9 availability, SodM seems to have a unique role for maintaining SOD activity (Garcia et al, 2017).…”

“…In this study, we analysed survival and gene expression of the same S. aureus CF isolates and laboratory strains (Treffon et al, 2018) in different in vitro infection models and during growth in artificial sputum medium (ASM; Sriramulu, Lunsdorf, Lam, & Romling, 2005), thereby further exploring the role of SodM and SodA during chronic S. aureus infection within CF airways. Additionally, to compare our results with in vivo conditions, we characterised the CF habitat of S. aureus and its influence on the bacterial gene expression by measuring the levels of inflammatory (S100A8/A9) and oxidative stress (8-isoprostane) markers as well as transcription levels of sodA, sodM, and other genes involved in bacterial oxidative stress defence within CF sputum samples by RNA sequencing (RNA-Seq) analysis.…”