Week 4: Mar.

3-4, 2025

Microbiology
&
Parasitology
Marjonel L. Acedera, RMT, MLS(ASCPi)CM, DTA, MPH
NS
Antimicrobial Agents
This presentation explores antimicrobial agents, their mechanisms of action, and how
bacteria develop resistance. We'll cover the characteristics of ideal antimicrobials,
classification methods, and the growing concern of drug resistance in infection control.

ZZ
What are Antimicrobial Agents?
1 Antimicrobials or 2 They can be derived 3 Examples include
antibiotics are from natural sources penicillin (from
substances that can like fungi and Penicillium fungus),
inhibit or destroy bacteria, or produced polymyxin and
microorganisms, even synthetically in bacitracin (from
at low concentrations. laboratories. Bacillus spp.), and
tetracycline,
chloramphenicol, and
streptomycin (were all
from Actinomyces).
Characteristics of Ideal
Antimicrobial Agents

Effective Broad Spectrum Safe Stable

Able to kill or inhibit Active against a wide No damage or adverse Remains stable when
microbial growth range of effects to the patient stored in either solid or
microorganisms liquid form
Characteristics of Ideal
Antimicrobial Agents

Long-lasting Fast-acting Selective Toxicity

Remains in specific body tissues Kills organism before it can Toxic to microbial cells but not
long enough to be effective mutate and develop resistance to host cells
Classification of Antimicrobials
Spectrum of Activity
Broad spectrum (wide coverage against a wide spectrum of microorganisms) or narrow
spectrum (limited coverage, effective only against a limited number of microorganisms)

Antimicrobial Activity
Bactericidal (kills bacteria) or bacteriostatic (inhibits growth)
Absorbability
Locally-acting (limited to site administered, like topicals or eyedrops) or systemically-acting
(affects several body systems, like antibiotics administered through IV or IM)

Mechanism of Action
How the drug affects microorganisms
Agents Interfering with
Cell Wall Synthesis
β-lactam Antibiotics Glycopeptides

Penicillins and cephalosporins inhibit Vancomycin and other glycopeptides

peptidoglycan synthesis by targeting inhibit transglycosylase and
penicillin-binding proteins (PBPs). This transpeptidase enzymes, which are
results in weakly cross-linked essential for completing peptidoglycan
peptidoglycan, making bacteria synthesis in the bacterial cell wall.
susceptible to cell lysis and death.
Agents Altering
Cell Membrane Function
1 Importance of Cell 2 Types of Agents 3 Example:
Membrane Polymyxins
Agents targeting the
The microbial cell cell membrane can be Polymyxin B and
membrane is crucial classified into cationic, colistemethate
for survival, acting as a anionic, and neutral (polymyxin E) disrupt
selective barrier and agents. the outer membrane
the site of ATP structure, inhibit
production. metabolic processes,
and depolarize the cell
membrane.
Agents Altering
Cell Membrane Function

Polyenes Azoles

Antifungal drugs like nystatin and Clotrimazole, ketoconazole, miconazole,

amphotericin B alter the permeability of and fluconazole interfere with the
the fungal cell membrane. synthesis of ergosterol, a major
component of the fungal cell membrane.
Agents Inhibiting Protein Synthesis
Effects
Ribosome Binding
Binding results in failure to
These agents bind to either initiate protein synthesis,
1 interference with protein
the 30S or 50S ribosomal
2
subunits, or both. elongation, or production of
deformed proteins.

50S Inhibitors
4 30S Inhibitors
Chloramphenicol, 3
Aminoglycosides and
macrolides, and
tetracyclines primarily interfere
lincosamides inhibit the
with the initiation process.
elongation process of
protein synthesis.
30S Ribosomal Subunit Inhibitors
Aminoglycosides Spectinomycin Tetracycline

Cause formation of Binds to a protein in the Targets bacterial 30S

nonfunctional complexes 30S ribosome, different ribosomal subunit. It is
and misreading of genetic from aminoglycosides' only bacteriostatic, but
code. target. like spectinomycin, both
are able to inhibit a wide
variety of bacteria
including Chlamydia and
Mycoplasma.
 50S Ribosomal Subunit Inhibitors
Chloramphenicol Macrolides Lincinoids
Binds to peptidyl Interfere with peptidyl Clindamycin is the most
transferase enzyme, transferase reaction or important and has a similar
inhibiting peptide bond translocation. Erythromycin target as macrolides and is
formation. Effective is the most popular bacteriostatic.
against gram-positive macrolide and is effective
and gram-negative against certain gram-positive Kanamycin and gentamycin
organisms. bacteria, Haemophilus, are able to bind both 30S
Mycoplasma, Chlamydia, and 50S ribosomal subunits.
Note: New classes include azithromycin and
and Legionella.
clarithromycin which have broader spectrums

than erythromycin.
Agents Acting on Nucleic Acid
DNA Topoisomerase Fluoroquinolones RNA Synthesis
Inhibitors Inhibitors
Newer generation
Quinolones target DNA quinolones with wider Rifampicin, a first-line
gyrase, a type II spectrum of activity than drug for tuberculosis
topoisomerase essential first-generation treatment, specifically
for prokaryotic survival. quinolones. inhibits bacterial RNA
First-generation synthesis by interfering
quinolones include with the β-subunit of RNA
nalidixic acid and oxolinic polymerase.
acid.
Agents Inhibiting Microbial
Metabolic Pathways
1 Folic Acid Metabolism 2 Importance of Folic 3 Mechanism of Action
Inhibitors Acid
Trimethoprim and Tetrahydrofolic acid is Sulfonamides inhibit
sulfonamides interfere crucial for DNA, RNA, formation of
with folic acid and bacterial cell wall dihydrofolic acid, while
metabolism, acting as synthesis. Bacteria trimethoprim inhibits
competitive inhibitors cannot utilize formation of
of tetrahydrofolic acid preformed folic acid tetrahydrofolic acid by
synthesis. from the environment. inhibiting
dihydrofolate
reductase.
Drug Resistance: A Growing Concern

Definition Types of Resistance

An organism is considered resistant to an Resistance can be innate (intrinsic) or

antibiotic if it is no longer affected by that acquired. Innate resistance is a stable
particular drug. genetic property encoded in the
chromosome, while acquired resistance
develops over time due to constant
exposure to antimicrobial agents.
Factors Contributing to Antimicrobial
Resistance

Overprescription Misdiagnosis Improper Use Livestock Use

Overuse of broad- Incorrect diagnosis Indiscriminate or Use of antibiotics as
spectrum leading to improper use of additives in animal
antibiotics is the unnecessary antibiotics by feed
most common antibiotic use patients
cause
Genetic Exchange in Acquired
Resistance Note: Resistance acquired through genetic exchange
can occur through any of these three ways.

Transformation Transduction Conjugation

Free microbial DNA Transfer of genetic Transfer of genetic
inserts itself into the DNA material by a material through the sex
of the same species. This bacteriophage pilus, often involving
is the simplest and plasmids which carry the
earliest form of genetic resistance gene.
exchange studies.
Mechanisms of Drug Resistance:
Drug Modification or Inactivation
Enzymatic Hydrolysis Example: Beta-
Inactivation lactamases
Some resistance genes
Resistance genes may produce enzymes that Certain bacteria produce beta-
code for enzymes that cause hydrolysis of lactamases which hydrolyze
alter the chemical antibiotics, destroying the beta-lactam bonds in
structure of antibiotics, them. penicillins and cephalosporins,
leading to their rendering them ineffective.
inactivation. This is the most common
mechanism of beta-lactam
resistance.
Mechanisms of Drug Resistance:
Prevention of Cellular Uptake or Efflux
1 Outer Membrane 2 Efflux Pumps 3 Examples
Modification Both Gram-positive This mechanism is
Some Gram-negative and Gram-negative observed in bacterial
bacteria alter their bacteria can develop resistance to
outer membrane lipid efflux pumps that tetracyclines and
composition, prevent antibiotic fluoroquinolones.
preventing antibiotics accumulation within
from reaching their the cell.
cellular targets.
Mechanisms of Drug Resistance:
Target Site Modification
Structural Changes Example: Penicillin Multiple Mechanisms
Resistance
Bacteria can alter the Some bacteria, like
structure of antibiotic Streptococcus Staphylococcus aureus,
target sites, preventing the pneumoniae can develop combine target site
drug from exerting its resistance to penicillin by modification with other
action. altering its penicillin- resistance mechanisms
binding proteins (PBPs). like beta-lactamase
production.
Examples of Modified Antibiotic Target Sites
Target site modified Antibiotic involved

Peptide subunits of peptidoglycan Glycopeptides

Ribosome subunits Macrolides, tetracyclines, aminoglycosides

Metabolic enzymes Sulfa drugs, sulfones, trimethoprim

Lipopolysaccharide structure Polymyxins

DNA gyrase Fluoroquinolones

RNA polymerase Rifampin

Mechanisms of Drug Resistance:
Overproduction or Bypass of Target Enzyme

1 Target Enzyme 2 Alternative 3 Example

Overproduction Pathways
Both these
Bacteria can Some bacteria mechanisms are
overproduce the develop alternative involved in bacterial
target enzyme of an metabolic pathways resistance to
antibiotic, ensuring that can serve as sulfonamides.
enough enzyme substitutes for the
remains free to carry target enzyme.
out essential
metabolic reactions.
Mechanisms of Drug Resistance:
Target Mimicry
Concept Example

Bacteria produce proteins similar in Mycobacterium tuberculosis can produce

structure to the target sites of antibiotics, a protein that mimics the structure of
diverting the drug from its intended DNA, selectively binding fluoroquinolones
target. and preventing their interaction with
bacterial DNA.
Summary of Antibiotic Resistance
Mechanisms
Blocked Penetration
Efflux pump B-lactams, tetracyclines,
Fluoroquinolones, 2 fluoroquinolones
1
aminoglycosides, tetracyclines, B-
lactams, macrolides Target Modification
Fluoroquinolones, rifamycin,
3
vancomycin, B-lactams,
5
Inactivation of Enzymes macrolides, aminoglycosides
B-lactams, aminoglycosides, 4
macrolides, rifamycin Note: It is important to know how
antibiotic resistance works.