Biofilm and Small Colony Variants-An Update on Staphylococcus aureus Strategies toward Drug Resistance

Abstract

Recently, the drawbacks arising from the overuse of antibiotics have drawn growing public attention. Among them, drug-resistance (DR) and even multidrug-resistance (MDR) pose significant challenges in clinical practice. As a representative of a DR or MDR pathogen, Staphylococcus aureus can cause diversity of infections related to different organs, and can survive or adapt to the diverse hostile environments by switching into other phenotypes, including biofilm and small colony variants (SCVs), with altered physiologic or metabolic characteristics. In this review, we briefly describe the development of the DR/MDR as well as the classical mechanisms (accumulation of the resistant genes). Moreover, we use multidimensional scaling analysis to evaluate the MDR relevant hotspots in the recent published reports. Furthermore, we mainly focus on the possible non-classical resistance mechanisms triggered by the two important alternative phenotypes of the S. aureus, biofilm and SCVs, which are fundamentally caused by the different global regulation of the S. aureus population, such as the main quorum-sensing (QS) and agr system and its coordinated regulated factors, such as the SarA family proteins and the alternative sigma factor σB (SigB). Both the biofilm and the SCVs are able to escape from the host immune response, and resist the therapeutic effects of antibiotics through the physical or the biological barriers, and become less sensitive to some antibiotics by the dormant state with the limited metabolisms.

Keywords: Staphylococcus aureus; biofilm; drug-resistance; global regulation; multidrug-resistance; resistant mechanisms; small colony variants.

Figure 1

Classical drug-resistant mechanisms of common antibiotics. This figure was modified based on the Figure 1 of Dunn, et al. [31]. Labels in different colors stand for various drug-resistant mechanisms.

Figure 2

Multidimensional scaling (MDS) of MDR-related reports in the Web of Science core collection.

Figure 3

Global regulation of S. aureus biofilm formation. This figure was modified based on Figure 2 of Schilcher et al. [54].

Figure 4

Formation and characteristics of S. aureus SCVs.

Figure 5

Effects of S. aureus ΔhemB SCV infection to mice. This figure was drawn according to the report of Lung et al. [153].