Streptococcus adherence and colonization

Abstract

Streptococci readily colonize mucosal tissues in the nasopharynx; the respiratory, gastrointestinal, and genitourinary tracts; and the skin. Each ecological niche presents a series of challenges to successful colonization with which streptococci have to contend. Some species exist in equilibrium with their host, neither stimulating nor submitting to immune defenses mounted against them. Most are either opportunistic or true pathogens responsible for diseases such as pharyngitis, tooth decay, necrotizing fasciitis, infective endocarditis, and meningitis. Part of the success of streptococci as colonizers is attributable to the spectrum of proteins expressed on their surfaces. Adhesins enable interactions with salivary, serum, and extracellular matrix components; host cells; and other microbes. This is the essential first step to colonization, the development of complex communities, and possible invasion of host tissues. The majority of streptococcal adhesins are anchored to the cell wall via a C-terminal LPxTz motif. Other proteins may be surface anchored through N-terminal lipid modifications, while the mechanism of cell wall associations for others remains unclear. Collectively, these surface-bound proteins provide Streptococcus species with a "coat of many colors," enabling multiple intimate contacts and interplays between the bacterial cell and the host. In vitro and in vivo studies have demonstrated direct roles for many streptococcal adhesins as colonization or virulence factors, making them attractive targets for therapeutic and preventive strategies against streptococcal infections. There is, therefore, much focus on applying increasingly advanced molecular techniques to determine the precise structures and functions of these proteins, and their regulatory pathways, so that more targeted approaches can be developed.

FIG. 1.

Taxonomic relationship tree for Streptococcus based on 16S rRNA gene sequence comparisons showing positions of selected species. A number of species are not included to simplify the figure, and a full description may be found in a review by Kilian (295). (Courtesy of Mogens Kilian, Aarhus University, Denmark, reproduced with permission.)

FIG. 2.

Temporal sequence of adherence and colonization by streptococci. (A) Pioneer streptococcal species associate with a conditioned surface (green), utilizing longer-range interactions, e.g., pili, which can penetrate mucus, or shorter-range interactions. (B) Some of the pioneers form stronger bonds with the surface molecules (blue) engaging multiple adhesins (red). (C) Nutritional adaptation, intermicrobial signaling (stars), and extracellular polymeric substance (EPS) production result in the formation of societies. (D) Incorporation of other microorganisms, including intergeneric coaggregation and cell-cell signaling, leads to the development of complex communities. These communities contain specific microbial associations within metabolic networks, ensuring more efficient utilization of nutrients and reduced susceptibility to antibiotics and immune surveillance.

FIG. 3.

Streptococcus colonization depends upon adherence, signaling, nutritional adaptation, and host modulation. Adhesins include cell wall-anchored polypeptides, e.g., SfbI, and anchorless proteins, e.g., Eno, which mediate attachment and possibly also host cell modulation. Secreted polypeptides may be synthetic, e.g., GtfBC producing polysaccharides, or degrade host proteins, e.g., SpeB, and supply additional nutrients. Extracellular polymeric substance (EPS) (blue shading) and capsular material (purple shading) contribute to a developing ECM. Secreted peptides, and possibly other signaling molecules, e.g., AI-2 (stars), and environmental stimuli, e.g., pH, may be sensed by TCSS, with an ensuing modulation of transcription. ABC transporters, e.g., ScaABCD, ensure nutritional homeostasis as well as a possible involvement in regulating adherence, directly or indirectly. The quadrants are labeled to indicate the processes of adherence, environmental sensing, biofilm formation, and virulence that may be orchestrated by the expression of surface-bound or secreted proteins. These processes are not, however, exclusive to those molecules in each quadrant. For example, cell wall-linked proteins (southeast quadrant) may also contribute to virulence, while transporters (northwest quadrant) may contribute to adherence.

FIG. 4.

Streptococcus-host interactions. (A) Pili (arrows) of GBS immunogold labeled with antibody generated to the backbone subunit of PI-2a. Bar, 0.5 μm. (B) Internalization of GAS by cultured epithelial cells showing formation of caveolae (arrow) containing a streptococcal cell being engulfed. Bar, 1 μm. (Image courtesy of Manfred Rohde, GBF-German Research Centre for Biotechnology, Braunschweig, Germany, reproduced with permission.) (C) Aggregation of human platelets (red) (phalloidin stained) by S. sanguinis (green) (fluorescein isothiocyanate stained). Bar, 20 μm. (Image courtesy of Steve Kerrigan, Royal College of Surgeons in Ireland, reproduced with permission.) (D) Flow cell biofilm (24 h) showing xy perspective and three-dimensional projection by confocal imaging of S. gordonii (green) and Veillonella atypica (red) growing in human saliva. Under salivary flow conditions, V. atypica is unable to form monospecies biofilms, but it is able to form mixed-species biofilms with S. gordonii. (Image courtesy of Rob Palmer, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, reproduced with permission.)

FIG. 5.

Structural features of seven streptococcal cell surface proteins that function in adherence and colonization. Emm6, S. pyogenes; SpaP, S. mutans; Spg, S. dysgalactiae; SfbI, S. pyogenes; Hsa, S. gordonii; SclA, S. pyogenes; ScpB, S. agalactiae. Precursor polypeptides are drawn N terminal (left) to C terminal (right), and all of the proteins are thought to be held at the cell surface through covalent cell wall anchorage (CWA) via a specialized C-terminal motif (see text). Leader (signal) peptides (SP) are cleaved at conventional sites by signal peptidase I. Specific structural features and amino acid residue repeat block regions are indicated (see descriptions in the text). Like-shaded regions across the different proteins indicate only similarities in amino acid composition or predicted secondary structure, e.g., α-helical coiled coil, and not sequence homologies. Conversely, amino acid residue repeat blocks within a polypeptide, e.g., SpaP, are highly conserved. Some of the substrates bound by the polypeptides, and the approximate locations of the binding sites, are indicated below each structure. fH, factor H; gp340, cysteine-rich scavenger protein (salivary agglutinin).

FIG. 6.

Integration of adhesins, receptors, signals, adaptation, and nutrition in Streptococcus biofilm formation. The colonization process depends upon the expression of genes encoding adhesins (gbpA and srpA, etc.), transporters (scaABC, etc.), transcriptional regulators (codY, etc.), posttranslational processing (htrA, etc.), TCSS (vikRK, etc.), and cell-cell communication (pheromones and AI-2, etc.), with only a few selected examples shown.