Bacteria spp in unit 1 (campylobacter, helicobacter, neisseria spp.)

Diarrheal diseases

leading cause of global morbidity and mortality unevenly distributed to LMICs

Campylobacter species

more then 25 different species when most can cause gastroenteritis in humans

C. jejuni and C. coli

cause most of the human infections of campylobacter infections

Helical gram negative

gram type and shape of campylobacter species

Bipolar

campylobacter have _____ flagella

Obligate microaerophile and non fermentative

campylobacter bacteria are ___ and _____ (oxygen type)

42

optimal growth for campylobacter species

Undercooked meat, often poultry

common source for campylobacter transmission which has a LOW infectious does

Inflammatory

what type of diarrhea does campylobacter cause in the lower GI tract

GI tract defense

the pH, digestive enzymes and bile salts, host microbiota takes up nutrient supplies and mucus layer is constantly shed

100 um/sec

campylobacter are extremely fast traveling at a speed of … where the helical shape contributes to penetration of mucus layer

Paracellularly

this type of invasion is preferred by campylobacter infection which is deeper penetration then an apical invasion

Fibronectin

this is more abundant on the basolateral surface and is why campylobacter infection prefers a paracellular infection

HtrA

the high temperature requirement protein A secreted by campylobacter spp to cleave tight junction components occuludin, claudin 8 and E cadherin which can reduce misfolded proteins appeared to be involved in adherence

CadF

campylobacter surface protein that is the adhesin to fibronectin

FlpA

fibronectin like protein A surface protein and separate from CadF but likely binds fibronectin in campy infections

JlpA

jejuni lipoprotein A surface liporprotein that binds surface HSP90alpha

Flagella

campylobacter secretion system is through

Cia

proteins invasion antigens used in the campylobacter flagellar secretion system

T3SS

while it is NOT this, the campylobacter flagellar secretion system is similar to ____

Fibronectin

provides a foundation for epithelial cells connected via integrins

CadF and FlpA

these bind to fibronectin and are associated to alpha 5 beta 1 integrin in campy infection

Rac1

binding of CadF and FlpA promotes FAK phosphorylation and Scr1 recruitment which leads to paxillin phosphorylation and then ____ activation

Membrane ruffling

Rac1 activation regulates actin remodeling and ________

Endocytosis

membrane ruffling is the process that leads to ____ which promotes campylobacter invasion

No

does the campylobacter containing vesicle associated with lysosomes

Cytolethal distending toxin

campylobacter tripartite AB2 toxin containing CdtA, CdtB, and CdtC

CdtA and CdtC

facilitate campy holotoxin binding ot host cell lipid rafts

CdtB

(campy infection) promotes endocytosis by cytoskeleton rearrangements, transported by the golgi and ER to nucleus, belongs to DNase A protein family leads to double strand breaks in host DNA,

DNA breakage

disables cell cycle and initiates apoptosis, a product of CDT CdtB and this leads to the release of proinflammatory cytokines

Neutrophil response

in campy infection _____ respond by phagocytosis, degranulating and making extracellular traps, sometimes campy can survive intracellularly

Macrophage response

in campy infection, monocytes are recruited to infection site and activated by LOS in TLR4 dependent manner and promotes cytokine secretion, then phagocytosis campy and kill in nitric oxide synthase 2 dependent manner

Catalase

bacterial ____ promotes survival in macrophages in campy infections

Guillain barre syndrome

LOS of campy mimics GM1alpha gangliosides which leads to autoantibody production and promotes complement activation and demyelination and peripheral paralysis and breathing complications.

Dr. Barry Marshall

Australian gastroenterologist that drank helicobacter to prove his experiments because there was no animal model to use for kochs postulate

Gastric and enterohepatic

the 35 helicobacter spp. are split into 2 groups which are

H. pylori

helicobacter spp. associated with human gastric infection (humans and non human primates can be infected (human primary))

Gastrointestinal tract and biliary tree

where do enterohepatic organisms colonize

H. hepaticus

in mice this spp is enterohepatic

Gram negative helical

gram type and shape of helicobacter spp

lophotrichous

type of flagella orientation on helicobacter

obligate microaerophile, metabolizes glucose by oxidative AND fermentative paths

helicobacter o2 preferences

37

optimal temp for helicobacter

Oral

transmission route is usually and will persist for life unless treated

HpNikR dependent

the pH of stomach activates this which promotes ureA gene transcription

UreA

urease that hydrolyzes gastric urea to carbonic acid and ammonia and is used as a diagnostic marker in helicobacter infections (by breathing into a bag)

Helical shape

this allows for helicobacter to be highly motile and to penetrate mucus layers which promotes survival in the stomach

Histological gastristis

helicobacter ass. disease which usually has no clinical manifestiations but is characterized by an influx of neutrophils and macrophages

10-20%

percent of individuals at risk for developing peptic ulcer disease in the gastric or duodenal tissue with 85 or 95% of those cases cause by H. pylori respectively

1-2%

percent of individuals at risk for developing gastric cancer, which is dependent on host factors

Hops

general name for the 30 different outer mem proteins which are some adhesions in helicobacter

Muc5a

mucins that H. pylori may specifically adhere to

BabA

expression of this adhesion molecule is associated with ulcers and gastric cancer in helicobacter infections

Cag pathogenicity island

encodes fro a type 4 secretion system that translocates CagA, about 40-70% of H. pylori, translocates pdg

Cytotoxin associated gene A

CagA is

VacA

50% of helicobacter strains secrete ____ which induces vacuolation in epithelial cells leads to variable activity, can stimulate inflammatory signalling, trafficked to mitochondria and induce apoptosis, form a mebrane channel and result in nutrient leakage, pass through tight junctions and inhibit T cell activation

Gram negative, diplococci

gram type and shape of Neisseria

Obligate aerobes, fastidious, fragile

descriptors of Neisseria spp.

N. gonorrhoeae and N. meningitidis

the two pathogenic spp. of Neisseria

Gonorrhea

Neisseria gonorrhoeae causes

Meningitis

Neisseria meningitidis causes

Natural competent

Neisseria spp. are _____ _which means they can uptake DNA from their environment

N. m. infection

infects upper respiratory tract and associate with non ciliated cells and are phagocytozed which is their method of reaching the apical side and then the blood vessels, commensal in nasopharynx of 5-10% of healthy individuals, but when in blood can disseminate to CNS (grows in CSF and cross BBB)

Africa belt

hyperendemic with N. m. periodic epidemics during dry season

N. g. infection

sexually transmitted, mostly symptomatic in men (less in women as we are a reservoir)

Men N. g. symptoms

onset of infection is rapid (4-20 days), painful urethritis and purulent urethral discharge as there is inflammatory cytokine production and recruitment of PMNs to the site of infection which leads to inflammation

Women N. g. symptoms

mostly asymptomatic, subtle onset w few symptoms, infection of uterus and fallopian tubes, PID, ectopic pregnancy and infertility

Antibiotic resistance

problem with attempting to treat N. g. infections

Pili, opa proteins, porin OM VG ion channel, LOS/LPS

shared adhesions between N. g. and N. m.

Pili

mediate N. g. and N. m. initial LOOSE adhesion and DNA uptake, twitching motility and biofilm formation

Opa proteins

transmembrane proteins which associate w bacterial OM and mediates the tight adhesion in N. g. and N. m. infection. 2 classes one binds with heparan sulfate proteoglycans and one binds CEACAMS

Porin

in N. g. and N. m, the OM VG ion channel that mediates ion exchange

LOS/LPS

in N. g. and N. m. used for adhesion to the asialoglycoprotein receptors in urethra, complement receptor 3 in cervix and lutropin choriogonadotropin hormone receptor in endometrium and fallopian

NadA, NhhA, MspA

unique adhesions to N. m.

Capsule

aids in airborne transmission of N. m.

Phase variation

on/off control of bacterial genes, usually reversible, most common in surface structures and helps bacteria to hide from immune response with methods such as invertible DNA segments, differential methylation and slip strand mispairing

Slip strand mispairing

modifies the reading frame and results in truncation or read throughs, if it occurs on the synthesis strand it is an addition and if it occurs on the template strand it’s a deletion

Homopolymeric repeats

runs of A, C or G on the coding strand found in LOS, pilC, capsule, polysialyltransferase siaA, repeats can also be in promoter regions and affect transcription efficiency

Short tandem repeats

tend to be more complex repeat structures of 3 to 5 bp elements and can be in the promoter region or CDS in multiples of 3

O antigen

Neisseria lack genes for ____ resulting in a rough LPS which is LOS and mimics human epithelial surfaces

N. m. capsule

the most important virulence factor for meningococcal disease with many subgroups and is what the serum antibody is directed to target, siaA has homopolymeric repeats

Antigenic variation

method of diversity to avoid immune servalliance where changes to peptide sequence occurs and only one variant is shown at a time, so Abs will be made, then it varies and they have to start over and make Abs against the new type

PilE

major component in the pilus, that has antigenic variation with 19 silent copies

Biofilm formation

contributes to treatment failure of Ng and Nm and is a surface adherent community which is used to compete with resident microbiota for resources and colonization and invasion of the epithelium

Def

active effort by human host to restrict availability of transition metals to invading pathogens

Transferrin

produced by the liver and major iron transporting protein in body, found in serum

Lactoferrin

iron binding protein found in milk and secretions

TonB dependent transporters

embedded in Om and help extract metals from metalloproteins, Neisseria does not synthesize siderophores so use the ones produced by other bacteria

LOS, factor I

one way N spp. subvert complement is by inactivating components to prevent MAC formation, ie C3b binds ____ and is inactivated by ____ which mediated cleavage

Factor H

expresses molecules on its surface that resemble host ie ____ binds to sialylated LOS to prevent complement cascade

Opa-CEACAM, LOS via unknown receptor, porin and pili interactions with CR3

in absence of opsonization, these will trigger the phagocytosis of Neisseria by neutrophils

Subvert ROS production

to survive in neutrophils after being phagocytosed, Neisseria spp must…