Mutation and plasmid-mediated antibiotic resistance, bacterial pathogenesis Flashcards

1
Q

Features of episomes and plasmids

A
  • 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
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2
Q

Transfer functions

A
  • 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
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3
Q

Pathogenic properties encoded in plasmids

A
  • Resistance to one or more antibios
  • Synthesis of cell surface structures needed for adherence or colonization
  • Production of toxins
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4
Q

Detection of plasmids

A
  • 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
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5
Q

R (resistance) factors

A
  • 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
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6
Q

Resistance plasmids in GP bacteria

A
  • 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
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7
Q

Transposable elements (IS elements)

A
  • 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
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8
Q

Transposable elements (transposons)

A
  • 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
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9
Q

Plasmid vs. chromosomal resistance

A
  • 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
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10
Q

Stability of plasmid-mediated resistance

A
  • 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
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11
Q

Prevention of antibio resistance

A
  • 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
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12
Q

Virulence plasmids and bacteriocinogenic factors

A
  • 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
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13
Q

Bacteriocins

A
  • 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
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14
Q

Stages of the infectious disease

A
  • 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
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15
Q

Types of symptoms

A
  • 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)
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16
Q

Scope of infections

A
  • Endemic: constantly present at low levels
  • Epidemic: occurring more frequently than usual
  • Pandemic: infection on a worldwide scale
17
Q

Entry, attachment and adherence

A
  • 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
Q

Replication

A
  • 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
Q

Destruction of tissue

A
  • 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
Q

Evasion of host defense

A
  • 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
Q

Exit/transmission

A
  • 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
Q

Immunopathogenesis

A
  • 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
Q

Diseases from normal flora imbalance

A
  • 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