External structures and drug targets in prokaryotic cells – PST05103 Pharmaceutical Microbiology

NTA Level 5 • Semester 1 • PST05103

External structures and drug targets in prokaryotic cells

Pharmaceutical Microbiology • Source Session/Topic 5
Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability.

Session 5: External structures and drug targets in prokaryotic cells

Total Session Time: 120 minutes

Pre-requisites

• Human anatomy and physiology

Students Learning Tasks

By the end of this session students are expected to be able to:

• Describe the structure of a bacterial cell
• List functions of different bacterial organelles/structures
• Describe various drug targets in the bacterial cell

Resources Needed:

• Flip charts, marker pens, and masking tape
• Black/white board and chalk/whiteboard markers

SESSION OVERVIEW

|Step |Time |Activity/ |Content |

| | |Method | |

|1 |5 minutes |Presentation |Introduction, Learning Tasks |

|2 |50 minutes |Presentation |External structures of prokaryotic|

| | | |cells |

|3 |25 minutes |Presentation |Drug Targets in Bacterial Cell |

| | | |Wall |

|4 |30 minutes |Presentation |Acid fast Bacilli |

|5 |5 minutes |Presentation |Key Points |

| 6|5 minutes |Presentation |Evaluation |

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing

STEP 2: Bacterial External Structures and Drug Targets (50 minutes)

• Bacterial External Structures

o External structures include the cell wall and structures external

to it

• Bacterial Cell wall

o A cell wall is a layer located outside the cell membrane found in

plants, fungi, bacteria, algae, and archaea.

o The bacterial cell wall is a rigid structure outside the cell

membrane (and inner to the capsule for capsulated bacteria)

composed of peptidoglycan layers making up a cell envelope around

the cell

o Peptidoglycan is composed of disaccharides and amino acids which

gives structural support to the bacteria

o Peptidoglycan is unique to bacteria

Figure 5.1: Structure of Peptidogycan

[pic]

▪ Molecules making up the peptidoglycan include;
• Alternating NAM and NAG chains
• A tetrapeptide chain
• A petaglycin chain

[pic]

o Bacteria are classified as being either Gram-positive or Gram-

negative based in differences in the structure of their

peptidoglycan cell wall

o Gram-positive bacteria are stained dark blue or violet by Gram

staining

o In Gram-positive bacteria, the cell wall is thick and consists of

several layers of peptidoglycan

o Gram negative bacteria lack the outer membrane envelope found in

Gram-negative bacteria

▪ They contain teichoic acids in the peptidoglycan.
• Teichoic acids are unique to the Gram-positive cell wall
• Teichoic acids are linear polymers of polyglycerol or

polyribitol substituted with phosphates and a few amino

acids and sugars

▪ immune response when the bacteria infect animals

o Functions of the bacterial cell wall;

▪ To enclose and protect the internal structures
▪ To protect the bacteria from osmotic lysis
▪ Provide shape to the bacteria
• Structures external to the cell wall include;
▪ Flagella
• Flagella are long protein filaments of uniform length that

are responsible for cell motility

• They are whip-like structure that allows a cell to move
• Types and examples of flagella

o Monotrichous –Single polar flagellum e.g. Vibrio

cholerae

o Amphitrichous –Single flagellum on both sides e.g.

Alkaligens faecalis

o Lophotrichous –Tufts of flagella at one or both sides

e.g. Spirillum

o Peritrichous–Numerous flagella all over the bacterial

body

▪ Pili
• Pili (singular: pilus) are hair-like appendages found on

the surface of some bacteria. They are made up of proteins

called pilins

• Pilli are classified into Ordinary pili or Sex pili

according to their morphology, distribution, and function

• The pilus is found on the surface of many gram-positive

bacteria and some gram-negative bacteria

• Pili function as adhesive factors for mucosal surface

attachment

▪ Capsule
• A capsule is a discrete detectable layer of polysaccharides

deposited outside the cell wall

• Capsule is attached tightly to the bacterium and has

definite boundaries

• Capsules are considered virulence factors because they

protect a bacterial cell from ingestion and destruction by

white blood cells (phagocytosis)

▪ Slime layer

• A slime layer in bacteria is an easily removable (e.g. by

centrifugation), unorganized layer of extracellular

material that surrounds bacteria cells

• A slime layer is loosely associated with the bacterium and

can be easily washed off

• The slime layer is usually composed of polysaccharides and

it may serve to trap nutrients, to aid in cell motility, to

bind cells together or to adhere to smooth surfaces

STEP 3: Drug Targets in Bacterial Cell Wall (25 minutes)

• Cell Biosynthetic Enzymes

o Fosfomycin

o Cycloserin

• Carrier Molecules

o Bacitracin

• Cell wall substrates

o Vancomycin

• Enzymes that Catalyse Crosslinking of peptidoglycan subunits

(Transpeptidases)

o Penicillins

o Cephalosporins

o Carbapenems

o Monobactams

STEP 4: Acid-fast Bacteria (30 minutes)

• Acid-Fast Bacteria possess a unique cell wall architecture different

from both gram negative and gram positive bacteria

• The Acid-Fast cell wall consists of a thick, outer lipid-rich layer

composed primarily of the fatty acid "Mycolic Acid"

• This lipid layer lies on top of a layer of peptidoglycan and the sugar

arabinogalactan which in turn invest the inner lipid membrane common

to all bacteria

• The thick outer mycolic acid layer renders acid-fast bacteria

resistant to gram stain.

• When stained with alternative dyes, the cell wall is resistant to

decolorization with acid alcohol, thus their name "Acid-Fast”

• The cell wall is characterized by;

o A thin layer of peptidoglycan

[pic]

• Function of the Cell wall components of Acid-fast bacilli

o The peptidoglycan prevents osmotic lysis

o The arabinogalactan layer is linked to both the peptidoglycan and

to the mycolic acid outer membrane and probably provides additional

strength to the cell wall

o The mycolic acids and other glycolipids also impede the entry of

chemicals causing the organisms to grow slowly and be more

resistant to chemical agents and lysosomal components of phagocytes

than most bacteria

▪ There are far fewer porins in the acid-fast cell wall compared

to the gram-negative cell wall and the pores are much longer

• The surface proteins in the acid-fast cell wall, depending on the

strain and species, carry out a variety of activities, including

functioning as enzymes and serving as adhesins, which enable the

bacterium to adhere intimately to host cells and other surfaces in

order to colonize and resist flushing

• The periplasm contains enzymes for nutrient breakdown

STEP 4: Key Points (5 minutes)

• Gram-positive and Gram-negative bacteria are protected by an external

cell wall composed of varying layers of peptidoglycan.

• Damage to bacterial cell wall compromises its integrity and creates

imbalance of electrolytes that trigger cell death.

• Some antibiotic classes act by inhibiting the synthesis of cell wall

building blocks leading to cell lysis and death

• Acid-Fast Bacteria possess a unique cell wall architecture different

from both gram negative and gram positive bacteria

• The acid-fast cell wall consists of a thin, inner layer of

peptidoglycan linked to a layer of arabinogalactin, which in turn is

linked to an outer membrane containing mycolic acids and overlaid with

a variety of polypeptides and glycolipids.

STEP 4: Evaluation (5 minutes)

• What is a cell wall?
• What is peptidoglycan?
• What is the importance of peptidoglycan in medicine?
• What are external structures of bacterial cell?

References

Hugo and Russell (2011), Pharmaceutical Microbiology 8th Edition, Willey-

Blackwel publications

Karen C. Carroll et al (2013); Jawetz, Melnick and Adelberg’s Medical

Microbiology 26th Ed. McGraw Hill Co. Inc.

Greenwood et al (2012); Medical Microbiology, 18th edition Churchill

Livingstone

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