One of the body's innate immune defenses is the ability to physically remove bacteria from the body via constant shedding of surface epithelial cells from the skin and mucous membranes. Give examples for removal of bacteria in the body.
Removal of bacteria by such means as coughing, sneezing, vomiting, and diarrhea
Bacterial removal by bodily fluids such as saliva, blood, mucous, and urine
What are Adhesins?
Adhesins are binding proteins, usually on tips of long fibrillary organelles called fimbriae or pili, that are anchored to the cell wall
Adhesins are critical to biofilm formation
Biofilms are multicellular communities that are 1000-fold more resistant to antibiotics and immune defense than are planktonic (swimming or drifting) bacteria
How do bacteria adhere?
Pili enable some organisms to adhere to receptors on target host cells and thus colonize and resist flushing by the body
Pilus has a shaft composed of the protein pilin
Shaft end has an adhesive tip structure
shape corresponds to specific glycoprotein or glycolipid receptors on host cells
Once attached to host cells, pili can depolymerize and enable adhesions in the bacterial cell wall to make more intimate contact
Also evidence that binding of pili to host cell receptors can serve as a trigger for activating the synthesis of additional cell wall adhesins
Pili are thin protein tubes originating from the cytoplasmic membrane and are found in virtually all
Name examples for pathogenic bacteria that use pili to adhere to host cells include
Escherichia coli & Salmonella
Can bacteria switch types of adhesive tips of the pili?
Yes, in order to adhere to different cell types and evade immune defenses
e.g., E. coli is able to make over 30 different types of pili
Enteropathogenic E. coli (EPEC) use pili to adhere to
In UPEC, the fim operon encodes
What are the components of phili?
Both types of pili are heteropolymeric
→ Major pilus protein subunit provides pilus stalk
→ Several minor subunit proteins at distal end
→ PapG and FimH represent the actual adhesins
→ Chaperone-usher (CU) pathway assembles pili
P pilus is composed of 6 different subunits arranged into two distinct subassemblies (tip fibrillum and pilus rod)
At distal end, tip fibrillum is composed of 1x PapG adhesin followed by PapF and PapE subunits
Pilus rod is made by >1,000 copies of PapA subunit
Adaptor subunit PapK connects above subunits to the PapA rod (superhelical structure at base of the pilum)
What is special about type 4 phili?
attachment to cells, food and fibers and enables twitching motility
Located at poles of cell and allows for a gliding motility along a solid surface such as a host cell
Extension and retraction of these pili allows the bacterium to drag itself along the solid surface
Other functions include biofilm formation and molecule exchange (e.g. DNA)
Structure of type 4 phili
These pili are strong, flexible rod -like filaments of 5 –8 nm in diameter and 1 –2 μm in length -
Pilin subunits are assembled through interactions between their conserved N - terminal α-helices
→ forms a hydrophobic core in the filament that is believed to provide extreme mechanical strength
Type IV pili bind to the glycolipids asialo - GM1 and asialo-GM2 on epithelial cell surfaces -
In Pseudomonas and Neisseria, type IV pili are believed to be a major virulence- associated adhesin
Adhesins are surface proteins found in the cell wall of various bacteria that bind to specific receptor molecules on the surface of host cells → enable bacterium to adhere intimately to that cell in order to colonize and resist physical removal
What does MSCRAMMS stand for?
microbial surface components recognising adhesive matrix proteins
What are MSCRAMMS – microbial surface components recognising adhesive matrix proteins?
bind host proteins
may aid adherence to host tissues, and serum-coated plastic
provides a critical step to establish infection
important in Gram+ve’s
What are molecular mechanisms by which MSCRAMMs binds their ligands?
‘dock lock latch ’
‘collagen hug’
tandem β-zipper
How is a biofilm formed on a host tissue?
Many bacteria produce a capsular polysaccharide matrix or glycocalyx
Flagella have also been reported to function as adhesins, what are their other functions?
movement and chemotaxis
H7 flagellum in E. coli
H7 flagellum in Pseudomonas aeruginosa
H7 flagellum in Clostridioides difficile
E. coli O157 (an EPEC strain) utilizes a type 3 secretion system (T3SS) to inject effector proteins into intestinal epithelial cells. How does it work?
Some of these effector proteins cause polymerization of actin at the cell surface
→ pushes host cell cytoplasmic membrane up to form a pedestal
Another effector protein inserts into the membrane of the pedestal to serve as a receptor molecule for E. coli adhesins
How do you call this?
attaching and effacing (A/E) lesions in the intestinal epithelium
Hallmark of EPEC (Pathogenic E. coli) infection
Formation of A/E lesions is mediated by genes located on the pathogenicity island locus of enterocyte effacement (LEE)
encodes the adhesin intimin
T3SS • six effectors
including essential translocated intimin receptor (Tir)
→ interaction between Tir and intimin anchors the bacterium to host membrane
How does Helicobacter pylori adhese?
H. pylori use a type 4 secretion system (T4SS) to inject effector proteins into stomach epithelial cells → induces host cells to display more receptors on their surface for H. pylori adhesins
CagA
H. pylori causes chronic gastritis, peptic ulcers, and gastric cancer in humans
How does Bordetella pertussis adhese?
Filamentous hemagglutinin is an adhesin that allows the bacterium to adhere to galactose residues of glycolipids on respiratory tract ciliated epithelial cells
Pertussis toxin also functions as an adhesion
One subunit of pertussis toxin remains bound to the bacterial cell wall while another subunit binds to glycolipids on membrane of ciliated epithelial cells of respiratory tract
Pertussis also produces an adhesin called pertactin that further enables the bacterium to adhere to cells
B. pertussis causes whooping cough
How does Neisseria gonorrhoeae adhese?
Neisseria gonorrhoeae produces an adhesin called Opa (protein II) that enables the bacterium to make a more intimate contact with host cell after it first adheres with its pili
Like with adhesive tips of pili, N. gonorrhoeae has multiple alleles for Opa protein adhesins enabling the bacterium to adhere to a variety of host cell types
N. gonorrhoeae is a bacterial pathogen responsible for gonorrhoea
Borrelia burgdorferi
Treponema pallidum (also spirochete)
Streptococcus pyogenes (group A beta streptococci)
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