Discussions for microbiologists, infectious disease researchers, and graduate students on bacterial adhesion proteins, adhesins, biofilm formation, and antimicrobial resistance.
Posted by UTIResearcher · 46 replies
Fimbrial adhesins are organized into long, hair-like surface appendages composed of repeated structural subunit proteins (pilins) with an adhesive tip adhesin. In uropathogenic E. coli (UPEC), type 1 fimbriae are tipped by FimH, which binds mannosylated uroplakins on bladder epithelium, while P fimbriae are tipped by PapG, which recognizes globoside receptors. Non-fimbrial adhesins like Dr adhesins, Afa adhesins, and intimin are monomeric proteins embedded directly in the outer membrane or displayed without a classical pilus structure. Non-fimbrial adhesins often mediate tighter, more intimate attachment than fimbrial adhesins and may be less susceptible to mechanical shear forces in urinary flow.
Posted by BiofilmBiologist · 53 replies
Biofilm formation is a multi-stage process that begins with reversible surface attachment mediated by flagella and type IV pili, followed by irreversible attachment involving adhesins like Bap (biofilm-associated protein) in Staphylococcus aureus or curli fimbriae in E. coli. Within established biofilms, bacteria express a distinct gene expression program and are embedded in an extracellular polymeric substance (EPS) matrix that dramatically increases antibiotic tolerance — often 100-1000 fold compared to planktonic cells. The EPS matrix functions as a diffusion barrier for antibiotics, and biofilm bacteria express efflux pumps and stress response genes. Disrupting adhesin-mediated initial attachment is therefore a promising strategy to prevent biofilm establishment before tolerance mechanisms are activated.
Posted by StructuralMicro · 38 replies
For structural characterization, X-ray crystallography and cryo-electron microscopy (cryo-EM) are the gold standards for resolving adhesin-receptor complexes at atomic resolution. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) is increasingly used to map binding interfaces on larger adhesin complexes without requiring crystals. For function, site-directed mutagenesis combined with competitive binding assays using glycan arrays (available through the Consortium for Functional Glycomics) identifies key contact residues. SPR (surface plasmon resonance) and ITC (isothermal titration calorimetry) quantify binding kinetics and thermodynamics. For in vivo relevance, mouse infection models with adhesin knockout strains and trans-complementation remain the standard for confirming virulence contribution.
Posted by AntiAdhesionDev · 41 replies
FimH is one of the most validated anti-adhesion drug targets in infectious disease. Mannoside compounds — small molecule FimH antagonists — have shown dramatic efficacy in mouse UTI models by blocking FimH-mediated attachment to bladder epithelium without bactericidal activity, reducing the selection pressure for resistance development. Compound ORN03 and the biphenyl mannoside series have reached advanced preclinical stages. The key advantage of anti-adhesion approaches is that they don't kill bacteria directly, making resistance evolution less likely since they don't impose the same lethal selection pressure. Phase I clinical trials for mannoside-based FimH antagonists have been initiated, representing a potentially first-in-class non-antibiotic approach to UTI prevention and treatment.
Posted by GramPositiveMicro · 29 replies
MSCRAMMs (Microbial Surface Components Recognizing Adhesive Matrix Molecules) are cell wall-anchored surface proteins in Gram-positive bacteria that bind host extracellular matrix proteins. They share a C-terminal LPXTG sorting signal that is recognized by sortase A for covalent cell wall anchoring. Staphylococcus aureus expresses multiple MSCRAMMs including ClfA and ClfB (clumping factors that bind fibrinogen), FnBPA and FnBPB (fibronectin-binding proteins), and Cna (collagen adhesin). Streptococcus pyogenes expresses M protein and protein F. S. epidermidis uses MSCRAMM AtlE for initial implant surface adhesion. MSCRAMM-mediated adhesion to fibronectin and fibrinogen is critical for S. aureus colonization of implanted medical devices, making these proteins attractive vaccine and therapeutic targets.
Posted by PiliProfessor · 34 replies
Type IV pili (T4P) are dynamic surface appendages found in many Gram-negative and some Gram-positive bacteria that perform dual roles in twitching motility and adhesion. They polymerize from a pool of inner membrane pilin subunits, extending through the outer membrane, then rapidly depolymerize, generating one of the strongest molecular motors known in biology with forces up to 100 piconewtons. In Neisseria gonorrhoeae, T4P enable colonization of urogenital epithelium and undergo phase variation and antigenic variation to evade host immunity. In Pseudomonas aeruginosa, T4P-mediated twitching motility is critical for initial surface exploration and microcolony formation during biofilm establishment. The T4P machinery is encoded by a conserved gene cluster and shares evolutionary ancestry with type II secretion systems and archaeal flagella.
Posted by EPECResearcher · 22 replies
Intimin is an outer membrane adhesin in EPEC and EHEC encoded by the eae gene within the locus of enterocyte effacement (LEE) pathogenicity island. It mediates intimate attachment to intestinal epithelial cells by binding its own translocated receptor, Tir, which EPEC injects into the host cell plasma membrane via a type III secretion system (T3SS). After Tir insertion, intimin-Tir interaction triggers actin polymerization beneath the attached bacterium, forming the characteristic "attaching and effacing" (A/E) lesion that destroys intestinal microvilli. Intimin itself is a member of the inverse autotransporter family with a beta-barrel outer membrane domain and a C-terminal extracellular lectin-like adhesin domain. Multiple intimin subtypes (alpha, beta, gamma, delta) show receptor-binding specificity differences that correlate with tissue tropism.
Posted by VaccineDevMicro · 47 replies
Adhesins are excellent vaccine targets because they are surface-exposed, often immunogenic, functionally essential for colonization, and relatively conserved among pathogenic strains of a given species. Blocking adhesin-receptor interactions with antibodies prevents the first step of infection. The FimH adhesin of UPEC is in clinical trials as a UTI vaccine antigen. In Streptococcus pneumoniae, adhesins like PspA (pneumococcal surface protein A), PsaA (pneumococcal surface adhesin A), and CbpA (choline-binding protein A) are included in next-generation pneumococcal vaccine formulations that aim to provide broader serotype coverage than current polysaccharide-based vaccines. MSCRAMM-based vaccines against S. aureus (targeting IsdB, ClfA) have shown protection in animal models, though clinical trial results have been mixed.
Posted by PiliBiogenesis · 31 replies
The chaperone-usher (CU) pathway is the most widespread fimbrial assembly system in Gram-negative bacteria, responsible for assembling type 1, P, and hundreds of other fimbriae. Pilin subunits are exported across the inner membrane via the Sec translocon and immediately bound by a periplasmic chaperone (FimC for type 1 fimbriae) which caps the incomplete immunoglobulin-fold of each subunit via "donor strand complementation." The chaperone-subunit complex delivers subunits to the usher (FimD), an outer membrane beta-barrel pore that coordinates subunit-subunit "donor strand exchange" reactions that build the fimbrial rod. This donor strand exchange mechanism drives thermodynamically irreversible fimbrial elongation. Crystal structures of FimD by the Waksman and Hultgren labs revealed the molecular basis of this remarkable assembly machine and are available in the PDB under accession codes 3OHN and 3RFZ.
Posted by GastroMicrobiology · 39 replies
H. pylori employs multiple outer membrane proteins (OMPs) as adhesins to anchor in the mucus layer and on gastric epithelial cells despite the turbulent and acidic environment. BabA (blood group antigen-binding adhesin) binds Lewis b blood group antigens on gastric epithelial glycoproteins — Lewis b expression correlates with H. pylori colonization density and gastric cancer risk. SabA (sialic acid-binding adhesin) binds sialylated Lewis x antigens that are upregulated in inflamed gastric tissue, potentially helping H. pylori colonize deeper into gastric glands. AlpA and AlpB bind laminin in the gastric basement membrane. H. pylori also uses its flagella for initial motility through mucus, followed by adhesin-mediated stable colonization. BabA has been investigated as a vaccine antigen and its expression is subject to phase variation through slip-strand mispairing in a homopolymeric tract.