12/10/2024

• 3nd
• Overview to the Antibacterial
Agents including the
Bacteriostatic & the
Bactericidal Groups
 Mechanisms of Action of
Antimicrobial Drugs
) Inhibition of cell wall synthesis
) Inhibition of cell membrane function
) Inhibition of protein synthesis (i.e.
inhibition of translation and
transcription of genetic material)
) Inhibition of nucleic acid synthesis
 Inhibition of Nucleic Acid
Synthesis
Drugs are:
i
• Quinolones, -

• Pyrimethamine,
• Rifampin, Loading…
• Sulfonamides,
• Trimethoprim and trimetrexate.
 Inhibition of Nucleic Acid
Synthesis
• Rifampin inhibits bacterial growth by
binding strongly to the DNA-dependent
RNA polymerase of bacteria. Thus, it
inhibits-
>
bacterial RNA synthesis. Rai

• All Quinolones and Fluoroquinolones inhibit

microbial DNA synthesis by blocking DNA
gyrases, topoisomerase enzymes that play
key roles in DNA replication and repair.
 ciproflaxicin

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Mechanisms of quinolone resistance.
• (1) Target-mediated resistance. Mutations in
gyrase and topoisomerase weaken quinolone–
enzyme interactions.
• (2) Plasmid-mediated resistance. (2a) proteins
 (yellow) decrease topoisomerase–DNA
Inhibition of Nucleic Acid creation of Pholic
PABA-
Synthesis
Acid

For many microorganisms, P-aminobenzoic

acid (PABA) is an essential metabolite. The
specific mode of action of PABA involves an
adenosine triphosphate (ATP)-dependent
condensation of a pteridine with PABA to
yield dihydropteroic acid, which is
subsequently converted to folic acid. PABA
is involved in the synthesis of folic acid, an
important precursor to the synthesis of
nucleic acids.
 Inhibition of Nucleic Acid
Synthesis
Sulfonamide are structural analogs of PABA
and inhibit dihydropteroate synthesis.
Sulfonamides can enter into the reaction in
place of PABA and compete for the active
center of the enzyme. As a result,
nonfunctional analogs of folic acid are
formed, preventing further growth of the
bacterial cell.
The inhibiting action of sulfonamides on
bacterial growth can be counter-acted by
I
 RESISTANCE TO
ANTIMICROBIAL DRUGS
There are many mechanisms by which
microorganisms might exhibit resistance to
drugs.
1. Microorganisms produce enzymes that
destroy the active drug. Example:
Staphylococci resistant to penicillin G
produce a β-lactamase that destroys the
drug.
 RESISTANCE TO
ANTIMICROBIAL DRUGS
2. Microorganisms change their permeability
to the drug. Example: Resistance to
amikacin and to some other
aminoglycosides may depend on a lack of
permeability to the drugs.
3. Microorganisms develop an altered
structural target for the drug. Example:
Erythromycin-resistant organisms have an
altered receptor on the 50S subunit of the
ribosome.
 RESISTANCE TO
ANTIMICROBIAL DRUGS
4. Microorganisms develop an altered
metabolic pathway that bypasses the
reaction inhibited by the drug. Example:
Loading…bacteria.
Some sulfonamide-resistant
5. Microorganisms can develop efflux pumps
that transport the antibiotics out of the cell.
Many Gram-positive especially Gram-
negative organisms have developed this
mechanism for tetracyclines (common),
macrolides, fluoroquinolones, and even β-
Resistant mechanism in antimicrobial
I - Produce entime that destroy drug
lik:
Staphylococci Produce B-lactase

2-change The Permeability to drug

like :
Resistant to amikacin and

aminoglycosides
3- devolpment of alter structural target
like :
Erythromycin
4-devolpment of altered metabolic

Pathway lik: sulfonamides

,

. devolpment
5 of efflux pump that
transport drug out of cell
like
tetracyclines , fluoroquinolones
us

DNA
inhibitors
Gram-Positive Cocci

Prof. Dr. Haider Sabah Kadhim

PhD. Microbiology
 Staphylococci 13 min

• Genus: Staphylococcus
• Species: S. aureus, S. epidermidis,
-
> and
S. saprophyticus S SaProPhyticuS
.

Important properties
• S. aureus produce coagulase.
• S. epidermidis and S. saprophyticus are
coagulase- negative staphylococci
• Sta. aureus produces a golden color colonies in culture.
Sta. epidermidis produces white colonies.
• Sta. aureus usually ferments mannitol and hemolyzes
red blood cells, whereas the others do not.
 S. aureus
Important cell wall components and antigens:
1 Protein A ( virulence factor)
.
• The major protein. It is bind to IgG , thereby
preventing phagocytosis
Protein A is used in clinical laboratory.
2 Teichoic acids
.
• They mediate adherence of the staphylococci to
mucosal cells.
1. • Polysaccharide capsule:
Play a role in the virulence
induction factor.
of septic There are 11 serotypes
shock.
based on the antigenicity.
septic shock
= >

>
- shock
2. Surface receptors for specific bacteriophages , for epidemiologic caused by
Bactria
purposes.
3. The peptidoglycan it can stimulate macrophages to produce
cytokines.
 Transmission zomin &
S. aureus
• Nose and the skin of human especially of hospital.
• Hand contact
• Found in the vagina of approximately 5% of
women.
• Family members with boils.
• Human lesions contaminate fomites such as
towels and clothing.
• Compromised immune system.
 Transmission
• Sta. epidermidis is found primarily on the human skin and
can enter the blood stream at the site of
intravenous catheters.

• Sta. saprophyticus is found primarily on the mucosa of

the genital tract in young women and can ascend into the
urinary bladder to cause urinary tract infections.
 Pathogenesis
&
T
Pyogenic inflammation and toxins .
=>

• Abscess. Abscesses undergo central necrosis and

usually drain to the outside (e.g., furuncles
and boils), but organisms may disseminate
via the bloodstream as well.

• Sutures and intravenous catheters infected by Sta.

aureus.
 Pathogenesis
Toxins are produced by S.aureus.
A. Enterotoxin causes food poisoning characterized by:

1. Enterotoxins are produced when S aureus grows in

carbohydrate and protein foods.
2. Prominent vomiting and watery, nonbloody diarrhea.
3. Enterotoxin is heat-resistant and is therefore
usually not inactivated by brief cooking.
4. It is resistant to stomach acid and to enzymes in the
stomach and
jejunum.
 B.Toxic shock syndrome toxin (TSST)
1. Causes toxic shock Syndrome in
tampon-using menstruating women or in
individuals with wound infections, in nasal
packing used to stop bleeding from the nose.
2. The toxin enters the bloodstream, causing
a toxemia.
3. The toxin is associated with fever, shock,
and multisystem involvement, including
a skin rash.
C. Exfoliatin or Exfoliative toxin
Causes scalded skin syndrome in young children.
It is epidermolytic" acts as a protease that
cleaves desmoglein in desmosomes, leading to
the slough and separation of the epidermis .
D. Leukocidins:
kill leukocytes, and cause necrosis of tissues includes:
a. Alpha toxin(α toxin): Causes necrosis of the
skin and hemolysis by the formation of holes in the
cell membrane and loss of low- molecular-weight
substances from the damaged cell.
Scalded skin" syndrome
b . Panton-Valentine Leukocidin (P-V leukocidin)
It is a pore-forming toxin that kills cells, especially white
blood cells, by damaging cell membranes through which cell
contents leak out.

The gene encoding P-V leukocidin is located on a lysogenic

bacteriophage.

A sever necrotizing pneumonia, sever skin and soft

tissue infection is also caused by MRSA strains that
produce this leukocidin.
 The enzymes
Coagulase: Coagulase is an enzyme that causes plasma to clot by
activating prothrombin to form thrombin. Thrombin then activate the
fibrinogen to form the fibrin clot thereby retarding the migration of
=

neutrophils into the site.

Staphylokinase: is a fibrinolysin that can lyses thrombi.
Staphylokinase resulting in fibrinolysis.
Catalase: Staphylococci produce catalase, which converts hydrogen
peroxide into water and oxygen.
Hyal-uronidase: Spreading factor degrade hyaluronic acid in
connective, epithelial, and neural tissues.

Proteinases : degrade protein.

Lipases: degrade lipids

β-lactamase: degrade β-lactam ring in β-lactam drug.

 Clinical Findings
A. Skin infection
1. A pimple (boils or furuncles) hair follicle infection, or
pus- filled abscesses, cellulitis.

2. Impetigo, superficial skin infections characterized by a

honey color crusting of the skin.
3. Scalded skin syndrome in young children
4. Postoperative staphylococcal wound infection or
infection
following trauma. eg. , meningitis following skull fracture.
B. If S aureus disseminates cause bacteremia,
endocarditis, acute hematogenous osteomyelitis, meningitis
OR Pneumonia
or pneumonia.

Impetig
Pimple o
 Clinical Findings.
C. Food poisoning
Due to staphylococcal enterotoxin is characterized
by
• Short incubation period (1–8 hours)
• Violent nausea, vomiting, and diarrhea
• Rapid convalescence.
• There is no fever.
 Clinical Findings.
D. Toxic shock syndrome is manifested by:
An abrupt onset of high fever.
Vomiting and diarrhea .
Myalgias
A scarlatiniform rash (Scarlet fever) . Scarlatiniform rash
Hypotension with cardiac and renal failure in severe
cases occurs
within 5 days after the onset of menses in young
women who use tampons
It also occurs in children or in men with
staphylococcal wound
infections.
 Staphylococcus epidermidis &
Staphylococcus saprophyticus
These are two coagulase-negative staphylococci of
medical
importance.

Sta. epidermidis infections hospital-acquired.

Sta. saprophyticus infections community-acquired.

Coagulase-negative staphylococci do not produce exotoxins.

• They do not cause food poisoning or toxic shock syndrome.

• They do, however, cause pyogenic infections.

 Staphylococcus epidermidis Transmission

• It is part of the normal human flora of the skin and mucous membranes

• It can enter the bloodstream (bacteremia) and cause pyogenic infections.

• It commonly infects intravenous catheters and prosthetic implants, e.g.,

prosthetic heart valves (endocarditis), vascular grafts, and prosthetic
joints (hip joints arthritis or osteomyelitis.)

• Loading…
It is a major cause of sepsis in neonates
9 min

• Peritonitis in patients with renal failure undergo peritoneal dialysis through

an indwelling catheter.

• Cause cerebrospinal fluid shunt infections.

• Hospital personnel are a major reservoir for antibiotic-resistant strains of Sta.

epidermidis.
 Staphylococcus saprophyticus:

• Causes urinary tract infections

• This organism is second to Escherichia coli as a cause of

community-acquired urinary tract infections in
sexually active young women.
Growth Characteristics:
• The staphylococci produce catalase, which
differentiates them from the streptococci.
 Methicillin- resistant Staphylococcus
aureus, or MRSA
1. It Is a type of staph. considered as "superbug" because it
has become resistant to antibiotics commonly used to treat it,
resistant to methicillin, pencillin, amoxicillin, and oxacillin.
2. MRSA has been found to cause illness in hospitals,
nursing homes, prisons and other health facilities called
(health-care-associated MRSA or HA-MRSA).
3. It has also caused infections outside of healthcare
facilities, called community-associated MRSA (CA-
MRSA).
• Vancomycin intermediate staph aureus (VISA) strains
• Vancomycin resistance staph aureus (VRSA) strains are
typically methicillin-/nafcillin- vancomycin resistant, which
makes them very difficult to treat.
• 90% or more of S. aureus strains are resistant to penicillin G.
can be treated with nafcillin or methicillin , some
cephalosporins or vancomycin.
• The drug of choice for MRSA or NRSA is vancomycin,
gentamicin is sometimes added.
• Treatment with a combination of β -lactamase–
sensitive penicillin, e.g., amoxicillin, and a β -lactamase
inhibitor, e.g., clavulanic acid, is also useful.
• Trimethoprim-sulfamethoxazole or clindamycin in mild cases .
• Daptomycin (Cubicin) and Quinupristin- dalfopristin is
another useful choice.
• The last choice are Carbapenems (meropenem and imipenem)
• S. epidermidis : vancomycin, to which either rifampin
or an aminoglycoside can be added.

• Removal of the catheter or other device is often

necessary.

• S. saprophyticus urinary tract infections can be

treated with a quinolone, such as norfloxacin,
or with trimethoprim-sulfamethoxazole.

• Scalded skin syndrome is treated with

intravenous antibiotics and fluids to prevent
dehydration.
THANK
YOU
Prof. Dr. Haider Sabah Kadhim
PhD. Microbiology