bacterial pathogenesis

primary (frank)

pathogen that causes disease by direct interaction with healthy host

opportunistic

pathogen that may be part of normal flora and causes disease when it has gained access to other tissue sites or host is immunocompromised

pathogenicity

ability of parasite to cause disease

abundance, pure culture, disease, re-isolated

Koch’s postulates (determine causal relationship between microbe and disease)

1. microbe must be found in ______ in diseased individual

2. microbe must be isolated from diseased individual and grown in _____

3. cultured microbe must cause ____ when re-introduced into healthy organism (animal model)

4. microbe must be _____ from animal model

Koch’s postulates

4 criteria for establishing a causal relationship between a microbe and a disease

viruses, bacteria, fungi, protozoa

infectious disease includes infections with ____, _____, _____, or _____

objective, subjective

signs are ___ changes in body that can be directly observed whereas symptoms are ____ changes experienced by patient

disease syndrome

set of characteristic signs and symptoms

incubation period, prodromal stage, period of illness, convalescence

• ____ is the period after pathogen entry but before signs

• ____ is the onset of signs/symptoms but not clear enough for diagnosis

• ____ is when the disease is most severe and has characteristic signs/symptoms

• ____ is when the signs/symptoms begin to disappear

vancomycin, negative, cell wall

____ can’t be used to treat gram _____ bacteria because outer membrane prevents large molecules from having access to _____

urethra, cervix (more rare: fallopian tubes, uterus, urethra)

N. gonorrhoeae is a gram negative, diplococcus bacteria that colonizes men’s ____ and women’s _____

macrolides

antibiotics that target bacterial protein synthesis (“super” gonorrhoea is resistant to azithromycin)

epithelial, monolayer, increases

early stage of N. gonorrhoeae infection

1. microcolony adheres to ____ cell surface (surrounded by microvilli)

2. microcolony disperse and bacteria adheres as _____

3. region of contact between bacteria and cell membrane _____

4. bacteria transverse the cell and exit other side

inflammation, complement, survives (exits macrophage as immune-resistant form)

N. gonorrhoeae transverse (enters) epithelium and induces ____. Its cell surface proteins inactivate ____ and it is phagocytosed by macrophages but ____

heterogeneous, homogeneous

genetic variation results in a _____ population whereas gene regulation due to an environmental stimulus results in a _____ population

pilin (PilE gene)

varying the ___ amino acid sequence → N. gonorrheoae able to escape adaptive immune response

pilin (pilE gene)

antibodies usually bind to N. gonorrhoeae ____ (acts as antigen) but the bacteria changes its amino acid sequence to prevent antibodies from binding and therefore escape the adaptive immune system

nosocomial (ex. Staphylococcus aureus)

pathogens that cause healthcare associated infections (infected while receiving healthcare at hospital)

20, 60, 20

Staphylococcus aureus infections of nasal carriage:

• ___% of people always carry it in their body (stable colonization)

• ___% of people carry it on and off (intermittent carriers)

• ___% of people will never carry it (non-carriers)

opportunistic, nosocomial

Staphylococcus is an _____ and _____ pathogen

iron, siderophores, heme/hemoglobin

Staphylococcus aureus extracts ____ from hosts, some scavenge _____ (molecule that scavenges this), and some extract it from ____

hemolysin

toxin produced by S. aureus that breaks down/lyses red blood cells (erythrocytes)

agr (accessory gene regulator)

quorum-sensing gene that controls expression of S. aureus hemolysin toxin (lyses host red blood cells)

quorum sensing

mechanism where a bacterial population can determine the abundance of itself and others in an environment (ex. agr gene that controls S. aureus hemolysin toxin expression)

autoinducing peptide (AIP)

quorum sensing Vibrio fischeri makes ____ to sense levels of itself

histidine-kinase sensor (AgrC)

• membrane bound sensor protein that detects autoinducing peptide (AIP) which is the molecule secreted by bacteria for quorum sensing so they can detect how much bacteria is present in environment

• part of agr gene that regulates gene expression of hemolysin toxin of S. aureus

response regulator (AgrA)

• cytoplasmic protein that is phosphorylated by AgrC (detects AIP) and activates expression of RNAIII

• part of agr gene that regulates gene expression of hemolysin toxin of S. aureus

RNAIII (regulatory RNA)

non-coding regulatory RNA that regulates expression of hemolysin in agr gene of S. aureus

sortase

• membrane protein in gram positive bacteria that attaches proteins to the cell wall

• attaches many virulence determinants to cell wall

mecA, penicillin binding protein (PBP2a), BlaR1

• methicillin resistance in S. aureus is mediated by ____ gene

• this gene encodes altered _____ which has low affinity for methicillin unlike normal PBPs (normally beta-lactams binds to PBP and inhibit it from building cell wall)

• this gene is regulated by ___ which is a membrane sensor for beta-lactams

cystic fibrosis

patients with ____ have increased resistance to Vibrio cholera

phage, 2

• the Cholera toxin is encoded by a ____

• the toxin consists of ___ subunits

toxin-coregulated pilus (TCP)

• type of pilus in V. cholera that self-aggregates to form microcolonies of V. cholerae on host cell

• acts as receptor for the CTX bacteriophage that encodes cholera toxin

cAMP

cholera toxin raises _____ levels in host epithelial cells → disruption of ion transport → water movement into gut (watery diarrhea)

rehydration salts (oral/IV)

treatment for cholera (toxin causes watery diarrhea)

mycolic acids, waxy

Mycobacterium tuberculosis is a gram positive bacterium that has outer layer of ____ around cell wall rather than an outer membrane and creates a ____ layer of protection

granuloma

strategy used by a host to wall-off a foreign substance that it can’t eliminate

lymphoid, fleas (blood meals)

the plague (Yersinia pestis) infects the ____ tissue and is transmitted through _____

phagocytosis

wild type Yersinia (plague) adheres to macrophages but is resistant to _____

type III secretion system

Yersinia (plague) uses _____ which is a needle-like molecular syringe that injects Yersinia outer proteins (YOPs) into host cells

Yersinia outer proteins (YOPs)

• Yersinia (plague) effector proteins that function to alter host processes and prevent phagocytosis

• inserted by needle-like syringe into host using type III secretion system by Yersinia