Colonization of medical devices by staphylococci

Abstract

The use of medical devices in modern medicine is constantly increasing. Despite the multiple precautionary strategies that are being employed in hospitals, which include increased hygiene and sterilization measures, bacterial infections on these devices still happen frequently. Staphylococci are among the major causes of medical device infection. This is mostly due to the strong capacity of those bacteria to form device-associated biofilms, which provide resistance to chemical and physical treatments as well as attacks by the host's immune system. Biofilm development is a multistep process with specific factors participating in each step. It is tightly regulated to provide a balance between biofilm expansion and detachment. Detachment from a biofilm on a medical device can lead to severe systemic infection, such as bacteremia and sepsis. While our understanding of staphylococcal biofilm formation has increased significantly and staphylococcal biofilm formation on medical devices is among the best understood biofilm-associated infections, the extensive effort put in preclinical studies with the goal to find novel therapies against staphylococcal device-associated infections has not yet resulted in efficient, applicable therapeutic options for that difficult-to-treat type of disease.

Figure 1. Biofilm development and regulation

Biofilm development includes three stages: initial attachment, accumulation/maturation and dispersal. Firstly, attachment is accomplished via hydrophobic interaction (directly to the device) or surface proteins (after human matrix proteins have covered the device). During the accumulation and maturation process, bacterial cells proliferate and produce biofilm matrix, which is composed of protein, eDNA and polysaccharides (e.g., PIA). Beta-toxin creates a covalently linked eDNA network. Structuring factors (e.g., PSMs) create channels. Finally, PSMs and other dispersal factors release cells, which may lead to dissemination of the infection. The biofilm “lifecycle” is tightly regulated by a complicated signaling network, which includes multiple regulation systems such as the Agr quorum-sensing system, Sar paralogues including SarA, and the alternative sigma factor, σ^B. Agr is cell density-controlled, linking biofilm development to the bacterial growth phase. σ^B expression is increased during environmental stress, linking biofilm development to external conditions.