Enhanced bacterial virulence through exploitation of host glycosaminoglycans

Abstract

SummaryPresent in the extracellular matrix and membranes of virtually all animal cells, proteoglycans (PGs) are among the first host macromolecules encountered by infectious agents. Because of their wide distribution and direct accessibility, it is not surprising that pathogenic bacteria have evolved mechanisms to exploit PGs for their own purposes, including mediating attachment to target cells. This is achieved through the expression of adhesins that recognize glycosaminoglycans (GAGs) linked to the core protein of PGs. Some pathogens, such as Bordetella pertussis and Chlamydia trachomatis, may express more than one GAG-binding adhesin. Bacterial interactions with PGs may also facilitate cell invasion or systemic dissemination, as observed for Neisseria gonorrhoeae and Mycobacterium tuberculosis respectively. Moreover, pathogenic bacteria can use PGs to enhance their virulence via a shedding of PGs that leads to the release of effectors that weaken the host defences. The exploitation of PGs by pathogenic bacteria is thus a multifaceted mechanistic process directly related to the potential virulence of a number of microorganisms. Bacteria and host proteoglycans: a multifaceted interactionCell-to-cell interactions are essential for many physiologi-

Chlamydial Intracellular Survival Strategies

“…These include glycosaminoglycan (Menozzi et al 2002), the major outer membrane protein (MOMP) (Su et al 1996), OmcB (Fadel and Eley 2007), and PmpD (Mölleken et al 2010). OmcB from Chlamydia pneumoniae but not from C. trachomatis has an identifiable heparan sulfate-binding domain that, when expressed on the surface of yeast, is necessary for OmcB binding to HSPGs (Moelleken and Hegemann 2008).…”

P159 is a proteolytically processed, surface adhesin ofMycoplasma hyopneumoniae: defined domains of P159 bind heparin and promote adherence to eukaryote cells

“…Heparin, dextran sulphate, chondroitin sulphate, laminin, mucin and fucoidan also inhibit the ability of M. hyopneumoniae to bind respiratory cilia (Zhang et al ., 1994). The ability to bind glycosaminoglycans is likely to arm M. hyopneumoniae with the capability to bind a variety of important host molecules (Patti et al ., 1994;Duensing et al ., 1999;Wadstrom and Ljungh, 1999;Menozzi et al ., 2002) that also possess glycosaminoglycan binding capabilities, and thus circumvents the need to evolve specific receptors that target these molecules (Jenkins et al ., 2006). Although these experiments indicate that heparinbinding surface proteins are likely to be important in pathogenesis, knowledge of heparin-binding surface proteins (apart from P97) of M. hyopneumoniae is lacking.…”

Sequence TTKF↓QE Defines the Site of Proteolytic Cleavage in Mhp683 Protein, a Novel Glycosaminoglycan and Cilium Adhesin of Mycoplasma hyopneumoniae

“…Epithelial surfaces are awash with mucins, antimicrobial peptides, and mucopolysaccharides that act as decoys for microbial adhesins (60). Glycosaminoglycans are present in the extracellular matrix and include regions of proteoglycans that are exposed on the surface of almost all eukaryotic cells (61). Heparan sulfate, an important component of proteoglycans, has been identified on the cilial surface in the swine upper respiratory tract (21).…”