Bacterial Persistence (1)

Phase variation

reversible process that allows bacteria to switch between expressing and not expressing certain genes somewhere in the promoter region that allows them to rapidly switch on/off genes

Slip strand mispairing, DNA methylation and site-specific recombination

types of phase variation

Surface structures

phase variation usually occurs on ____

Group B strep

associated w fetal infections (vaginal colonization) and has capsule variation between opaque or transparent

Opaque

this type of capsule colonies are less virulent in group B strep

Slipped strand mispairing

Group B strep uses ____ to do capsule variation

Transparent

group B strep group that is much more virulent

Antigenic variation

mechanism used by pathogens to evade host immune system by altering the structure of their surface antigens often with recombination events between active on and silent no promoter

Pilin

Neisseria gonorrhoeae ___ genes go through antigenic variation

pilS

the silent pilin gene that exchanged with the pilE genes for antigenic variation on Neisseria gonorrhoeae genes which allows the bacteria to produce variant pilin proteins

vlsE gene

this gene in Borrelia spp allows for antigenic variation in Lyme disease with 15 unexpressed cassettes of the gene

molecular mimicry

bacteria evolve proteins or molecules that closely resemble the hosts own molecules and allows for evasion of host immune system by presenting “self” antigens but this lead to autoimmune reactions

sialylation

this is a common molecular mimicry in eukaryotic glycoproteins

Group A streptococcus (GAS)

this bacterial M proteins aids in immune evasion by binding to host proteins which prevents phagocytosis and acting as a camouflage but this can lead to autoimmune response against heart tissue

Rheumatic fever

autoimmune response caused by GAS mimicking M protein and is similar to cardiac myosin because the antigens are too similar

Nutrient acquisition

pathogens have evolved ways to steal modify and transport host nutrients

Iron acquisition

use siderophores to cleat ___ from the host environment

Iron acquisition, metabolic flexibility, biofilm formation, virulence factors, adhesions, efflux pumps, quorum sensing

mechanisms of pathogen nutrient acquisition

Gram positive

for ____ bacteria they have a bacterial membrane anchored Fe binding proteins and membrane associated ABC transporter for nutrient acquisition

Gram negative

for ____ bacteria there is a host transferrin specific iron uptake system mediated by the bacterial receptor complex of the transferrin binding proteins A and B

Intracellular

bacteria that reside and replicated within the cells of their host organisms so they require the ability to invade host cells, evade end lysosomal fusion (or with other degradative compartments) and persist in intracellular environments and acquire nutrients from the host

Reduced genomes

intracellular bacteria often have a ________ because they utilize resources from their host cell and to help hide them from the host immune system

Internal

intracellular bacteria have 2 forms and the ___ form is metabolically active and NON infectious

External

intracellular bacteria have 2 forms and the ___ form is metabolically Inactive and infectious

Clathrin coated and caveolin coated

these type of vesicles deliver their contents to early endosomes which mature to late endosomes which eventually fuse th lysosomes and degrade what they are carrying

Phagosomes

these skip the early endosome stage and simply fuse directly to the lysosome

Coxiella

some pathogens need lysosome fusion ie …

Brucella

some pathogens tolerate lysosome fusion ie …

Avoid

most bacteria ____ lysosome fusion

pH event

triggers the maturation of an endosome to a lysosome

oxidative burst

what is the attack that the lysosome uses against bacteria in their compartments

persist in macrophages and create granulomas

how do TB bacteria evade phagocytosis

lipoarabinomannan (LAM)

interferes with the signaling pathways required for phagosome maturation and used by TB to evade phagocytosis and lysosome degradation

SapM

actively disrupt the formation of Pl3P which is essential for phagosome-lysosome fusion and used by TB to evade phagocytosis and lysosome degradation

Host tropism

the ability of bacteria to infect specific types of cell and pathogens select for specific niches/tissues

Biofilms

common in nature, often seen as layers of slime rocks or other objects in water or at water-air interface and contribute to human disease (legionnaires AC units, teeth plaques, CF, medical devices)

Biofilms

increases community fitness and can be on abiotic surfaces and increases genetic diversity of individuals

biofilm formation development

Absorption, irreversible attachment, microcolony growth, maturation, detachment

heterogeneity

in biofilms there is a ____ through differences in metabolic activity and locations of microbes which makes biofilms hard to treat

UV light, antibiotics, phagocytosis

protection made from biofilms

Rugose

phase variant of vibrio cholerae which produces a exopolysaccharide that facilitates biofilm formation and environment stress resistance (change from the smooth colony to this)

Slime layer

presence of an extracellular ____ is associated with biofilm formation

vps and rbmBCDEF

the gene and gene cluster that regulates rugose variant development

vpvC

single nucleotide change in ___ gene can control the variation between smooth and rugose phenotypes of vibrio cholerae

rbmB

deletion of ____ in vibrio cholerae increases colony corrugation