Staphylococcus aureus Pneumonia: Preceding Influenza Infection Paves the Way for Low-Virulent Strains

Abstract

Staphylococcus aureus is a facultative pathogenic bacterium that colonizes the nasopharyngeal area of healthy individuals, but can also induce severe infection, such as pneumonia. Pneumonia caused by mono- or superinfected S.aureus leads to high mortality rates. To establish an infection, S. aureus disposes of a wide variety of virulence factors, which can vary between clinical isolates. Our study aimed to characterize pneumonia isolates for their virulent capacity. For this, we analyzed isolates from colonization, pneumonia due to S. aureus, and pneumonia due to S. aureus/influenza virus co-infection. A total of 70 strains were analyzed for their virulence genes and the host-pathogen interaction was analyzed through functional assays in cell culture systems. Strains from pneumonia due to S. aureus mono-infection showed enhanced invasion and cytotoxicity against professional phagocytes than colonizing and co-infecting strains. This corresponded to the high presence of cytotoxic components in pneumonia strains. By contrast, strains obtained from co-infection did not exhibit these virulence characteristics and resembled strains from colonization, although they caused the highest mortality rate in patients. Taken together, our results underline the requirement of invasion and toxins to cause pneumonia due to S. aureus mono-infection, whereas in co-infection even low-virulent strains can severely aggravate pneumonia.

Keywords: Staphylococcus aureus; influenza virus; pneumonia.

Figure 1

Clonal complexes (CC) of Staphylococcus aureus strains isolated from (A) colonization, (B) co-infection with influenza virus, (C) CAP—community-acquired pneumonia, and (D) HAP—hospital-acquired pneumonia determined with the PanStaph Genotyping Kit (Alere Technologies GmbH, Jena, Germany).

Figure 1

Clonal complexes (CC) of Staphylococcus aureus strains isolated from (A) colonization, (B) co-infection with influenza virus, (C) CAP—community-acquired pneumonia, and (D) HAP—hospital-acquired pneumonia determined with the PanStaph Genotyping Kit (Alere Technologies GmbH, Jena, Germany).

Figure 2

(A) Internalization ability (in %) and (B) biofilm formation of each of 10 S. aureus strains isolated from nasopharyngeal swabs (colonization), CAP, HAP, and from co-infection with IV. Two-way ANOVA with Tukey’s multiple comparisons test ** p < 0.01, **** p < 0.000.

Figure 3

(A) Cell death (in %) carried out on endothelial cells and (B) on neutrophil granulocytes induced with 10 S. aureus strains each isolated from nasopharyngeal swabs (colonization), CAP, HAP, and from co-infection with IV. Two-way ANOVA with Tukey’s multiple comparisons test: ns = non-significant, ** p < 0.01, **** p < 0.0001.