Antibacterial Chemotherapy: Mechanisms of Resistance

Bacterial resistance

the quantitative assessment of the efficacy of an antibacterial agent for a specific organism having decreased or no susceptibility to the agent

Minimal inhibitory concentration

the lowest concentration of

antibacterial agent necessary to inhibit growth (cell division). Usually in µg/mL

Minimal Bactericidal concentration

the lowest concentration necessary to cause loss of

viability, referred to as thethe lowest concentration necessary to cause loss of

viability, referred to as the

MIC and MBC

Bacterial resistance can be determined/measured by both

Effectiveness of many agents

Resistance has eroded the

Resistance and virulence

separate properties but may be linked

Antimicrobials

Cell wall and outer membrane barriers to __________

Inability to traverse the outer membrane

____ __ ______ ____ ______ _____is the primary reason most β-

lactams are less active against Gram-negative than Gram-positive bacteria.

Drug penetration

Outer membrane protein porin channels may allow _____ ______

Inherent resistance to antimicrobial agents

Exclusion barrier is the Major reason for

PBP/transpeptidase

Important target of penicillin

Binding and inactivating their target

Antimicrobials act by

Reduced affinity for beta lactams

Altered PBPs (Pen.binding

protein) have

Chemically modifies it

Enzymatic inactivation Disrupts antimicrobial structure or

catalyzes a reaction that

higher level of resistance

the higher level of beta-lactamse produced =

breaking open beta-lactam ring

how does the beta-lactamase enzyme destroy penicillin, it does it by

Intrinsic resistance, acquired resistance, mutation

Resistance to antibiotics and biocides (primarily) occurs by 3 general processes:

Intrinsic resistance

Innate ability of a bacterium to resist deleterious properties of a particular antibacterial agent by virtue of its inherent physiological characteristics

Permeability barriers, enzyme production and Inducible enzymes

Intrinsic resistance components:

Acquired resistance

When a bacterium obtains the ability to resist deleterious properties of a particular antibacterial agent to which it was previously susceptible

Stable genetic variation

due to mutation or horizontal acquisition of resistant

genes from another source

Conjugation and transposition

Genetic exchange —- most common in human infections and are often combined

low frequency

mutation takes place at a regular but

Clinically significant resistance

Multiple mutations are required before

Transposon genes

move between chromosomes

and plasmids

Transduction

limited by bacteriophage specificity, transformation is underappreciated

Physiological adaptation

Resistance that occurs throughout the population by modification of a physiological property of the organism in the presence of a

Not stable

Parental phenotype is restored upon removal of the agent, therefore resistance is

acquired

what is the most dangerous resistance

Antimicrobial

creates selection for resistance

Transformation

Which of the following refers to the uptake of naked DNA from the surrounding environment?

Conjugation

The F plasmid is involved in which of the following processes?

Repressible

An operon of genes encoding enzymes in a biosynthetic pathway is likely to be which of the following?

Chemical modification of histones (post translational modification)

Which of the following is a type of regulation of gene expression unique to eukaryotes?

Lactose present, glucose absent

Which of the following conditions leads to maximal expression of lac operon?

Nonsense mutation

Which of the following is a change in the sequence that leads to the formation of stop codon?

Fructose 1 6 diphosphate

Aerobic bacteria mostly use en pathways due to lack of pfk enzyme and inability to produce

Substrate level phosphorylation

Formation in bacteria produce ATP by

Inhibition of protein biosynthesis

Which of the following processes is the mode of action of tetracyclin?

Beta lactamase

Identify the enzymes is responsible for destroying penicillin and conferring antibiotic resistance?