Deciphering Streptococcal Biofilms

Abstract

Streptococci are a diverse group of bacteria, which are mostly commensals but also cause a considerable proportion of life-threatening infections. They colonize many different host niches such as the oral cavity, the respiratory, gastrointestinal, and urogenital tract. While these host compartments impose different environmental conditions, many streptococci form biofilms on mucosal membranes facilitating their prolonged survival. In response to environmental conditions or stimuli, bacteria experience profound physiologic and metabolic changes during biofilm formation. While investigating bacterial cells under planktonic and biofilm conditions, various genes have been identified that are important for the initial step of biofilm formation. Expression patterns of these genes during the transition from planktonic to biofilm growth suggest a highly regulated and complex process. Biofilms as a bacterial survival strategy allow evasion of host immunity and protection against antibiotic therapy. However, the exact mechanisms by which biofilm-associated bacteria cause disease are poorly understood. Therefore, advanced molecular techniques are employed to identify gene(s) or protein(s) as targets for the development of antibiofilm therapeutic approaches. We review our current understanding of biofilm formation in different streptococci and how biofilm production may alter virulence-associated characteristics of these species. In addition, we have summarized the role of surface proteins especially pili proteins in biofilm formation. This review will provide an overview of strategies which may be exploited for developing novel approaches against biofilm-related streptococcal infections.

Keywords: antibiotic therapy; biofilm; opportunistic pathogen; planktonic; quorum sensing (QS); streptococci.

Figure 1

Schematic diagram representing the life cycle of biofilm formation in Streptococci. The diagram shows the transition of planktonic cells to sessile cells by undergoing different stages of biofilm formation and repeating the cycle by the conversion of sessile cells to the planktonic state again.

Figure 2

Schematic diagram of general pilus architecture in different streptococci. The blue spheres represent the different bacterial strains, and the green color boxes represent host epithelial cells. The long pili shown in the diagram are formed by three major subunits ancillary protein AP1 (tip protein at the distal end) that attaches to the bacterial surface, backbone protein BP, and ancillary protein AP2, which are assembled by sortases that facilitate adherence with host epithelial cells. AP2 anchors the pilus to the bacterial surface. In S. agalactiae, there are three pilus islands designated as PI-1, PI-2a, and PI-2b. Each pilus island has major protein referred as PI-1 (include GBS104 as AP1, GBS80 as BP, and GBS52 as AP2 with two sortases SAG0647 and SAG0648), in PI-2a (GBS67 as AP1, GBS59 as BP, and GBS150 as AP2 with two sortases SAG1408 and SAG1405), and PI-2b (SAN1519 as AP1, SAN1518 as BP, and SAN1516 as AP2 with two sortases SAN1517 and SAN1515). In S. pneumoniae, pilus subunits are AP1 (RrgA), BP (RrgB), and AP2 (RrgC) with sortases designated as SrtC-1, SrtC-2, and SrtC-3. Here, RrgC does not depend on pilus-specific sortases for adherence to the cell wall; instead, it binds the preformed pilus to the peptidoglycan by retaining the catalytic activity of SrtA (blue box). RrgB is composed of 4 domains D1 at N-terminus, D2 and D3-positioned laterally, D3 connected to D2 through a loop (dark blue color), and D4 at the C-terminus. In S. pyogenes, the three subunits of pilus include pilus BP (tee6), AP1 and AP2 (fctX), and sortases (srtB and srtA). The monosyl receptors are present on the surface of epithelial cells and respond to the infection (arrow in yellow color).

Figure 3

(A) Regulation of biofilm in different streptococcal species at the genetic level. The figure describes the gene regulation system in S. pyogenes, S, mutans, S. agalactiae, and S. pneumoniae for direct effect on biofilm inhibition (shown in purple), induction (shown in green), negative regulators (shown in red), and positive regulators (shown in brown and blue). (B) Involvement of virulence genes in the regulation of biofilm in different species of the Streptococcus mitis group and S. suis. The represented genes of S. gordonii, S. sanguinis, and S. suis are involved in the positive regulation of biofilm formation and thus directly involved in increasing the biomass of forccpamed biofilm.