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

Abstract

Staphylococcus aureus and cystic fibrosis (CF) are closely interlinked. To date, however, the impact of S. aureus culture in CF airways on lung function and disease progression has only been elucidated to a limited degree. This analysis aims to identify bacterial factors associated to clinical deterioration. Data were collected during an observational prospective multi-center study following 195 patients from 17 centers. The average follow-up time was 80 weeks. S. aureus isolates (n = 3180) were scanned for the presence of 25 virulence genes and agr-types using single and multiplex PCR. The presence of specific virulence genes was not associated to clinical deterioration. For the agr-types 1 and 4, however, a link to the subjects’ clinical status became evident. Furthermore, a significant longitudinal decrease in the virulence gene quantity was observed. Analyses of the plasticity of the virulence genes revealed significantly increased plasticity rates in the presence of environmental stress. The results suggest that the phylogenetic background defines S. aureus pathogenicity rather than specific virulence genes. The longitudinal loss of virulence genes most likely reflects the adaptation process directed towards a persistent and colonizing rather than infecting lifestyle.

Correlations of Host and Bacterial Characteristics with Clinical Parameters and Survival in Staphylococcus aureus Bacteremia

“…Despite the small sample size of only three isolates, this result was statistically significant. We recently reported a link between agr 4 and increased rates of disease exacerbation in S. aureus infections in cystic fibrosis [ 94 ], another hint toward agr 4 aggressiveness in invasive infection. Considering the low prevalence of agr type 4, a large-scale prospective study would be necessary to confirm this finding.…”

Allergic Reactions to Serine Protease-Like Proteins of Staphylococcus aureus

“…We analyzed 76 CF patients from two cohorts, a multi-center study (n = 62) ( 5 , 15 ) and a two-center study (n = 14), as well as 46 healthy adults. All patients were persistently colonized and recurrently infected with S. aureus in their airways.…”

“…However, the knowledge about the Spls’ pathophysiological substrates is very limited ( 20 , 21 ). The extensive and long-term exposure of the CF patients’ airways to S. aureus drives a strong antibody response to many S. aureus antigens, documented by high specific IgG titers ( 5 , 15 ). However, this pronounced humoral immune reaction to the bacteria cannot be the only reason for the sensitization to the Spls in CF, which is very selective.…”

“…Serum samples from CF patients (n = 76) were obtained at the Institute of Medical Microbiology, University Hospital Münster, Germany. They comprise two cohorts, a multicenter study (n = 62) ( 5 , 15 ) as well as a two center study that was conducted in Münster (n = 14). Samples from healthy individuals were obtained from in-house volunteers (n = 46).…”

“…Persistent colonization with S. aureus occurs early in the disease course in up to 70% of CF patients, a much higher percentage than in the general population ( 2 , 4 ). In the long term, the pathogen adapts to the host, gradually reducing its virulence during airway infection ( 5 ). Nevertheless, recurrent pulmonary exacerbations gradually worsen the lung function and clinical condition of CF patients ( 6 ).…”