Week 2

• Bacterial pathogens use various strategies to evade and subvert essential host immune defence processes, including resistance to humoral factors, anti-microbial peptides, antibodies, subversion of complement, and evasion of phagocytosis.
• Cholera and ETEC coli are resistant to secretory IgA.
• IgA proteases are produced by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis.
• Cholera and ETEC coli are caused by bacteria.
• IgA proteases are serine-endopeptidase or zinc metalloprotease.
• IgA proteases cleave specific peptide bonds in the IgA proline-rich hinge region.
• Certain gram-positive organisms produce and secrete IgA proteases dedicated to cleave and disable the IgA.
• Anti-microbial peptides (AMPs) are essential components of host defences against infections and are produced by humans in the form of small proteins (10 to 100+ amino acids) by epithelial cells (Paneth cells) and immune cells (neutrophils, macrophages), with broad spectrum microbicidal activity from viruses to parasites.
• Most AMPs act by binding to microbial membrane and creating pore-like structure leading to microbes killing.
• Bacterial resistance to AMPs can involve modification of AMP target, production of molecules preventing binding of AMP, production of proteolytic factors degrading AMP, and removal of AMP from membrane or cytoplasm (efflux pumps).
• Gram-positive bacteria such as Staphylococcus aureus resist AMPs via teichoic acid modification and modification of phospholipids, increasing positive charge.
• Bacterial proteases (peptidases) targeting AMPs include GAS streptococcal pyrogenic exotoxin B (SpeB) protease, S. aureus aureolysin, V8 protease S. epidermidis SepA, S. Typhimurium PgtE, P. aeruginosa elastase, and E. faecalis gelatinase.
• Bacterial resistance to AMPs can involve enhancing membrane rigidity and resistance, modification of AMP target, production of molecules preventing membrane binding of AMP, production of proteolytic factors degrading AMPs, removal of AMP from membrane or cytoplasm (efflux pumps), and bacterial proteases (peptidases) targeting AMPs.
• Secretory IgA neutralizes microbes and toxins, prevents them to reach epithelium, and facilitates their clearance via peristalsis.
• Bacteria can produce polysaccharide capsules and some pilus shielding/preventing the access to the membrane for AMP (LL-37).
• Secretory IgA immunoglobulins are one of the first innate immune defence at mucosal surfaces with a key role in immune homeostasis.
• Gram-negative bacteria like Salmonella resist AMPs by modifying LPS molecules with aminoarabinose, increasing positive charge or acylation of Lipid A unit of LPS molecules.
• Type 3 secretion systems (T3SS) are present in a large variety of Gram-negative bacteria, including human, animal pathogens, plant pathogens, and symbiotic bacteria.
• Common features of T3SS include molecular syringe used to inject proteins called effectors into host cells, and the ability to inject proteins called Effectors directly from the bacteria cytoplasm into the host cells cytoplasm where they manipulate host cell functions to the benefit of the pathogen.
• T3SS genes are generally clustered on the genome on specific loci, such as pathogenicity islands and plasmids.
• T3SS effectors display a large repertoire of biochemical activities that are common to eukaryotic proteins and modulate the functions of crucial host regulatory molecules such as small GTP-binding proteins (cytoskeleton), mitogen-activated protein kinases (MAPKs), nuclear factor NF-kB (inflammation-immunity), Ubiquitin system, caspases (apoptosis).
• T3SS effectors show sequence, structural or functional resemblance to proteins found in higher organisms.
• T3SS effectors are sophisticated proteins borrowed from the eukaryotic world.
• Functions of the T3SS effectors include virulence factors, a broad range of functions such as adhesion, invasion, colonization, intracellular survival and subversion of cellular trafficking processes, reprogramming cell death (cytotoxicity, induction/prevention of apoptosis, necrosis or disruption of tissue barriers like epithelial Tight Junctions (TJs), and interference with host immunity.
• EPEC and EHEC cause acute gastroenteritis and Haemolytic Uremic Syndrome (HUS).
• EPEC and EHEC are the major cause of infantile diarrhoea in the developing world.
• The most common strain of EHEC is EHEC O157:H7.
• The pathogenicity island of EPEC and EHEC is the Locus of Enterocyte Effacement (LEE).
• EPEC and EHEC cause attaching and effacing lesions (A/E) in vivo.
• Production of Shigatoxin by EPEC and EHEC can lead to kidney failure (HUS).
• Resistance to phagocytosis in EPEC and EHEC is modulated by the NF-κB pathway.
• Enteropathogenic Escherichia coli (EPEC) and Enterohemorrhagic Escherichia coli (EHEC) are emerging zoonotic pathogens that cause severe illness.
• T3SS and associated effectors are important for Enteropathogenic and Enterohaemorragic Escherichia coli (EPEC and EHEC) pathogenesis, contributing to A/E lesions formation (actin polymerisation), innate immunity/inflammation, and interference with host immunity.
• EPEC WT, EPEC Δ tir, and EPEC Δ eae show different growth and mortality rates in rabbits.
• K12 chromosome is found in EPEC.
• espA, espD, and espB are intimin (eae)-translocated receptor (Tir) in EPEC.
• EPEC mutated for Intimin (eae) or for Tir are unable to induce the actin pedestal in vitro.
• EPEC cellule hôte (Host cell contact) and translocation of effector proteins via EspA filaments.
• escF and escL are chaperones in EPEC.
• Tir is necessary for the formation of A/E lesions and virulence in vivo.