Mutation and plasmid-mediated antibiotic resistance, bacterial pathogenesis Flashcards Preview

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Flashcards in Mutation and plasmid-mediated antibiotic resistance, bacterial pathogenesis Deck (23):
1

Features of episomes and plasmids

-Plasmid: extra-chromosomal genetic element (circular double-stranded DNA) that can replicate autonomously on the membrane
-Episome: type of plasmid that alternates btwn an autonomous state and a state where is is integrated into the chromosome (when integrated replication is controlled by chromosome)
-Factor: type of plasmid that is a transferable genetic element
-Plasmids carry genes that are not essential to the survival of the bacteria, but provide optional gene pools which confer an advantage to the bacteria

2

Transfer functions

-Conjugation (via pili, adhesins), transduction (via phage), transformation (naked DNA btwn plasmids)
-Not all plasmids are self-transferrable
-Large plasmids are conjugative, self-transmissible and contain tra genes (encode all functions for replication)
-Small plasmids are non-conjugative and rely on bacterial host for some replication functions
-Conjugation in GP bacteria via adhesins and pheromones, in GN bacteria by pili

3

Pathogenic properties encoded in plasmids

-Resistance to one or more antibios
-Synthesis of cell surface structures needed for adherence or colonization
-Production of toxins

4

Detection of plasmids

-Presumptive evidence: simultaneous, multiple drug resistance. Same patterns of antibio resistance in different strains. Drug resistant organisms at high frequencies among individuals w/ a common base of contact
-Proof: transfer of plasmid shown by genetic means. Isolation of extrachromosomal DNA by physical or biochemical means. Curability of plasmids by treating with UV, EtBr

5

R (resistance) factors

-Self-transmissible (large) plasmids widely distributed in GN bacteria
-One portion carries genes for transfer ability (analogous to tra genes in F factors) and autonomous replication (conjugative plasmids)
-Other portion carries genes for drug resistance
-Most common cause of acquired antibio resistance
-Transfer factors are widespread in natural bacterial populations (do not respect species boundaries but only transfer btwn GN bacteria)
-R factors were selected for, but not created by antibios

6

Resistance plasmids in GP bacteria

-Found in bacillus, streptococcus, staphylococcus, streptomyces, and clostridium
-Process of transferring conjugative plasmids is different from GN (which uses pili): sex pheromones are released by the plasmid-recipient bacteria. The pheromone causes the plasmid-donor to produce a protein adhesin allowing the bacteria to bind together
-Transfer occurs btwn these bacterial aggregates

7

Transposable elements (IS elements)

-DNA sequences that insert into multiple sites in chromosomes or plasmids and can move to a new position in the genome independent of DNA homology
-Insertion sequences (IS elements): small DNA pieces that only contain one gene for insertion functions (transposase). Will often form the boundaries of genetic information blocks integrated into DNA
-Insertion of IS elements into a gene usually deactivates the gene (if excised perfectly activity can be restored)
-Each contain an inverted repeat at each end, which serves as a recognition site for transposase

8

Transposable elements (transposons)

-Tn's contain genes flanked by IS elements
-Behaves like IS element (can move around the genome) but contains additional genes not associated w/ insertion functions
-Code for transposase and one or more other genes, cannot replicate autonomously
-Tn identified by loss of gene function (if Tn inserts into a gene) and acquisition of antibio resistance
-Have elements that regulate transcription of their own genes (acts as gene switches)
-Transposition process: recombination and replication, then one copy of Tn stays in original place and one copy goes else where. Insertion can stop gene function (after excision gene can be re-expresse)
-Speeds up genomic evolution

9

Plasmid vs. chromosomal resistance

-Chromosomal genes act by altering the structure of components such as ribosomes or cell wall
-Plasmid genes frequently mediate resistance by directing synthesis of nzs which modify and inactivate antibios

10

Stability of plasmid-mediated resistance

-Organisms w/ resistance genes on chromosomes grow more slowly and are gradually eliminated
-Plasmid-mediated resistance gives no competitive disadvantage (far more stable)
-Non-pathogenic bacteria serve as reservoirs for drug-resistance factors (most significant reservoir is the bowel)
-Selection can occur w/ long-term use of oral antibios
-Multiple drug resistance on plasmids is readily selected for because use of any one of the antibios selects for the entire group of resistance genes carried on the same plasmid

11

Prevention of antibio resistance

-Interrupt transmission of resistant bacteria from patient to patient via hand washing, gloves, sterilization, isolation procedures
-Discriminating use of antibios, including avoiding giving sub-inhibitory levels or abbreviated time courses of antibios, use of narrow-range antibios

12

Virulence plasmids and bacteriocinogenic factors

-Virulence plasmids encode proteins that are involved in pathogenic properties, like toxins
-Bacteriocinogenic factors: plasmids encoding bacteriocins (some are conjugative)
-These factors carry drug resistance genes
-Bacteriocins can be used to identify bacteria
-Utility of bacteriocins in mediating microbe competition

13

Bacteriocins

-Antibacterial protein substances that are released from bacteria and exert lethal effects on sensitive but closely related strains of bacteria (not producer bacteria)
-Bind to membrane receptors and use a variety of mechanisms to kill bacteria (specific colicin receptor sites are required)
-Confer a selective advantage for the bacteria that posses them

14

Stages of the infectious disease

-Incubation time: time btwn inoculation of the microbe and the appearance of symptoms
-Prodrome period: Time during which non-specific symptoms occur
-Specific illness period: characteristics of the disease are present
-Recovery time: time during which symptoms resolve

15

Types of symptoms

-Overt symptoms: caused by high levels of the microbe and host's immune system
-Asymptomatic: infection can only be detected by Ab titer or isolation of organism
-Latent state: organism stops replicating and becomes dormant, but can be reactivated
-Chronic carrier state: organism cannot be eliminated and continues to grow in host with or without producing symptoms (source of infection for others)

16

Scope of infections

-Endemic: constantly present at low levels
-Epidemic: occurring more frequently than usual
-Pandemic: infection on a worldwide scale

17

Entry, attachment and adherence

-Entry usually through nose, mouth, RT, ears, eyes, urogenital tract, skin, and anus
-Bacteria will adhere to the epithelial cell surface via adhesion-receptor binding
-Defenses against entry: intact skin, mucus, ciliated epithelium, antibacterial secretions (lysozyme), alveolar macrophages, IgA (in RT, GI, and genital tracts), bile and gastric acid, normal flora
-Outer membrane of GN bacteria make them more resistant to lysozyme, acid, and bile

18

Replication

-Many intracellular bacteria cause granulomatous lesions (when pathogen cannot be eliminated): mycobacterium, legionella, brucella, listeria
-Some bacteria can sense when populations are high enough to construct a biofilm (quorum sensing) and create a bacterial community on the biofilm

19

Destruction of tissue

-Endotoxins (LPS, only GN, and other cell wall components), exotoxins, and superantigens all facilitate tissue damage
-Endotoxins and super Ags both cause the release of inflammatory cytokines. Endotoxins activate B cells and macrophages. Superantigens non-specifically activate T cells
-TSST is a type of superantigen

20

Evasion of host defense

-Vary structure of surface Ags to prevent Ab binding
-Produce protease to degrade IgA, C5a
-Make IgG binding protein (protein A)
-Long O Ag chain in GN bacteria limits complement effectiveness
-Biofilms
-Prevent phagocytosis by killing cell or using capsules/biofilm
-Survive phagocytosis by preventing lysosome fusion, escaping the phagolysosome, or surviving with the phagolysosome

21

Exit/transmission

-Can be via airborne respiratory droplets, fecal oral route (two most common)
-Can also be via sexual contact, urine, skin, blood transfusion, insects, needles
-Can also be from other sources like water, soil, animals (zoonoses), fomites

22

Immunopathogenesis

-Symptoms cause by excessive host immune response
-Acute-phase response can be triggered by endotoxins and other cell wall components
-Tissue damage by neutrophils, macrophages and complement, also granuloma formation by CD4
-Rheumatic fever: Abs against bacterial protein M from S pyogenese can damage the heart
-Immune complexes can be deposited and cause damage (i.e. in kidney)

23

Diseases from normal flora imbalance

-Obesity (obese-prone microbiota in GI)
-Asthma (C section vs vaginal birth, vaginal has lower rate of asthma)
-Pseudomembraneous colitis: C difficile overgrowth due to suppression of normal flora from antibios
-Dental caries: overgrowth of bacteria
-Bacterial vaginosis: overgrowth of bacteria