Our health and medicine

Lecture 20
Nilkamal Mahanta
IIT Dharwad
Communicable/Infectious diseases
Communicable/Infectious diseases
Different pathogenic bacteria
 What are antibiotics?

Antibiotic (Greek anti, against and

bios, life) refers to microbial products
and their derivatives that kill susceptible
microorganisms or inhibit their growth

Bactericidal (Kill the bacteria)

Bacteriostatic (Inhibit the growth)

 History: The Discovery of
Penicillin

Classification and modes of

action

Chloramphenicol and
Outline Kanamycin

Antibiotic resistance

Antifungals and Antivirals

 Sir Joseph Lister (1827-1912) used carbolic
acid to inhibit sepsis after surgery
Paul Ehrlich (1854-1915) found that the dye trypan
red was active against the trypanosome that causes
African sleeping sickness (1904). Also found arsenic
based chemical Arsphenamine was active against
syphilis spirochete (Salvarsan, 1910)

Gerhard Domagk discovered sulfonamides/sulfa

drugs in 1927 (awarded Nobel prize in 1939)

History Alexander Fleming (1881-1955) accidently

discovered penicillin in 1928. Penicillium
notatum spore (fungus/mold) contaminated a
petri dish which has growing Staphylococci
Penicillin was later isolated and purified by
Florey, Chain and Heatley and tested on mice
and human trials done in 1940s
Selman Waksman (1888-1973) discovered
Streptomycin in 1944 from Streptomyces
griseus (first drug to treat Tuberculosis)-NP-1952
Chloramphenicol, Neomycin and tetracycline
were isolated from other Streptomyces species
(soil bacteria)
 Discovery of Penicillin: A life saver

Sir Alexander Fleming (Scotland) Staphylococcus aureus

Penicillium notatum

Penicillin (beta lactam antibiotic)

Alexander Fleming, Howard Florey and Ernst Chain (Oxford University)

(Nobel prize in 1945 for discovery and isolation of penicillin)
Antibiotics timeline
 Some terminologies regarding antibiotics
• Selective toxicity : Kills/inhibits the pathogen without affecting the host
• Therapeutic dose: The drug level required for clinical treatment of a particular infection
• Toxic dose: The drug level at which the agent becomes too toxic for the host
• Therapeutic index: Ratio of the toxic dose to the therapeutic dose. Larger the
therapeutic index, better the antibacterial agent
• Natural antibiotic : Produced by bacteria/fungi (Penicillin, Chloramphenicol)
• Synthetic antibiotic: Chemically prepared (Sulfonamides, Ciprofloxacin, Isoniazid,
Trimethoprim)
• Semi-synthetic antibiotic: Natural antibiotics which are chemically modified
(Ampicillin, Methicillin)
• Narrow-spectrum antibiotic: effective against only a limited variety of pathogens
(Vancomycin, Isoniazid)
• Broad-spectrum antibiotic: Effective against many different kinds of bacteria
(Chloramphenicol, Erythromycin, Kanamycin)
• Minimal inhibitory concentration (MIC): Lowest concentration of a drug that prevents
growth of a particular pathogen
• Minimal lethal concentration (MLC): Lowest drug concentration that kills the pathogen
 Natural vs Synthetic Vs Semi-synthetic antibiotic
Natural

Penicillin V (Phenoxymethylpenicillin) Penicillin G (Benzylpenicillin)

(Strep throat, Cellulitis, Rheumatic fever) (Pneumonia, syphilis, diphtheria, tetanus)
Semi-Synthetic

Amoxicillin Ampicillin Methicillin

(Ear infection, Skin infections, (RTI, UTI, Meningitis) (Skin infections)
Pneumonia, UTIs)

Synthetic

Ciprofloxacin Sulfanilamide Trimethoprim

(bone/joint infections, RTI, UTI) (UTIs) (Bladder infections)
Gram-positive vs Gram-negative bacteria
 How to test for an antibiotic
• Disk Diffusion test (Kirby-Bauer method)

• Microbroth Dilution test (to calculate MIC)

How antibiotics kill bacteria?
Antibiotics that affect important life processes
Mode of Action of Antibiotics
 Antibiotics that affect cell wall synthesis
• Penicillin: Blocks the enzyme catalyzing the transpeptidation reaction
that forms the peptidoglycan cross links. Thus formation of cell wall is
blocked leading to osmotic lysis
• Cephalosporin: Isolated in 1948 from the fungus Cephalosporium.
Inhibit transpeptidation reaction during peptidoglycan synthesis
• Vancomycin: Glycopeptide produced by Streptomyces orientalis.
Blocks transpeptidation by binding to D-Ala-D-Ala fragment

Cephalosporin
Antibiotics affecting protein synthesis
 Antibiotics affecting protein synthesis

• Aminoglycosides: Bind to the bacterial ribosome and

disrupt peptide elongation during translation
Kanamycin, Streptomycin, Neomycin

Kanamycin Neomycin
(Isolated in 1957 from Streptomyces kanamyceticus)
Isolated in 1949 by Waksman
Bacterial infections and Tuberculosis From Streptomyces fradiae
Skin infections
Tetracyclines

Tetracycline framework

Chlortetracycline Oxytetracycline
Produced by Streptomyces species
Bind 30S subunit of ribosome and inhibit protein synthesis
 Chloramphenicol

• Isolated from Streptomyces venezuelae

(from Caracas, Venezuela)
Two chiral centers, only the R, R isomer is active

It binds to the A-site of the ribosomal 50S subunit and inhibits the
movement of ribosomes along mRNA, by inhibiting the peptidyl transferase
reaction by which the peptide chain is extended

Broad spectrum but is toxic and has side effects (Bone marrow
suppression, nausea, diarrhea)
Used to treat conjunctivitis, meningitis, cholera, typhoid fever
Antibiotics affecting nucleic acid synthesis
• Inhibit DNA polymerase and topoisomerase to block replication
• Inhibit RNA polymerase to block replication
• Not as selective as other antibiotics because bacteria and
eukaryotes do not differ greatly w.r.t. nucleic acid synthesis

Quinolones

Ciprofloxacin Norfloxacin

Inhibit DNA gyrase and topoisomerase II

Antibiotics affecting metabolic pathways
Our health and medicine
Lecture 21
Nilkamal Mahanta
IIT Dharwad
 What are antibiotics?

Antibiotic (Greek anti, against and

bios, life) refers to microbial products
and their derivatives that kill susceptible
microorganisms or inhibit their growth

Bactericidal (Kill the bacteria)

Bacteriostatic (Inhibit the growth)

 Discovery of Penicillin: A life saver

Sir Alexander Fleming (Scotland) Staphylococcus aureus

Penicillium notatum

Penicillin (beta lactam antibiotic)

Alexander Fleming, Howard Florey and Ernst Chain (Oxford University)

(Nobel prize in 1945 for discovery and isolation of penicillin)
 Natural vs Synthetic Vs Semi-synthetic antibiotic
Natural

Penicillin V (Phenoxymethylpenicillin) Penicillin G (Benzylpenicillin)

(Strep throat, Cellulitis, Rheumatic fever) (Pneumonia, syphilis, diphtheria, tetanus)
Semi-Synthetic

Amoxicillin Ampicillin Methicillin

(Ear infection, Skin infections, (RTI, UTI, Meningitis) (Skin infections)
Pneumonia, UTIs)

Synthetic

Ciprofloxacin Sulfanilamide Trimethoprim

(bone/joint infections, RTI, UTI) (UTIs) (Bladder infections)
How antibiotics kill bacteria?
Mode of Action of Antibiotics
Antibiotic resistance
Antibiotic Resistance: Why we should care?
How Alarming is the situation: Superbugs

A Nevada woman dies of a superbug resistant

to every available antibiotic in the US

A pan-resistant form of Klebsiella pneumoniae killed a

70-year-old woman in Nevada in September, 2017
 Superbugs and some statistics
Nearly one million people die every year from bacterial infections
that cannot be treated with common antibiotics

1. Extensively drug-resistant Salmonella typhi

This highly contagious bacterium causes typhoid fever, a life-threatening infection that
affects about 21 million people around the world every year. About 1% of those
affected, or 223,000 people, will die. In November 2016, a strain of Salmonella
typhi emerged in Pakistan which was resistant to five antibiotics.

2. Extensively drug-resistant Mycobacterium tuberculosis

Mycobacterium tuberculosis is the world's leading infectious killer, causing more
than 1.7 million deaths every year. One of the reasons this bacteria is so deadly is its
ability to hide inside our cells.
People are required to take four different antibiotics continuously for six months.
Multidrug-resistant infections (MDR-TB) require treatment courses that are much
longer (generally 18 to 24 months) and use antibiotics that are expensive and toxic.
Extensively drug resistant (XDR-TB) cases are reported in 117 countries worldwide
3. Pandrug-resistant Klebsiella pneumoniae
Klebsiella pneumoniae is a common bacterium found in the skin, intestines and soil.
It causes a range of potentially deadly infections in people with compromised
immune systems. As this bacterium is particularly prevalent in hospitals, it's one of
the most critical drug-resistant threats to public health.
In 2016 a strain of Klebsiella pneumoniae was identified in the US that was resistant
to all 26 commonly available antibiotics (known as pandrug-resistant).

4. Pandrug-resistant Pseudomonas aeruginosa

Pseudomonas aeruginosa is a commonly found bacterium that causes infections
in people with compromised immune systems. Like Klebsiella pneumoniae, it's
particularly prevalent in hospitals. In the US, there are an estimated 51,000 health
care-associated Pseudomonas aeruginosa infections each year, with around 400
causing death. In the past five years, 29 cases of pandrug-resistant Pseudomonas
aeruginosa infection have been reported in hospitals in England.

5. Extensively drug-resistant Neisseria gonorrhoeae

There are an estimated 78 million global cases of Neisseria gonorrhoeae, which
causes gonorrhoea, a sexually transmitted infection affecting men and women.
Around one-third of all Neisseria gonorrhoeae infections are resistant to at least one
antibiotic. More worryingly, a new extensively drug-resistant "super gonorrhoeae",
resistant to all but one antibiotic, has been discovered, first reported in Australia.
Modes of antibiotic resistance

• Video

https://www.statnews.com/2017/01/12/nevada-woman-superbug-resistant/
Modes of antibiotic resistance
Beta-lactamase enzymes (Penicillinase)

Sensitive

Beta-lactamase crystal structure

Resistant
Fungal infections
 Different kinds of fungal infections
• Fungal infections are often categorized into different types according to the area they affect:

• Athlete’s foot, affecting the feet and hands

• Candidiasis or thrush, including oral thrush, urinary tract infection, and vaginal thrush

• Ringworm, infecting the scalp and skin

• Intertrigo, present in the skin folds

• Jock itch, affecting the groin

• Onychomycosis of the nails

• Pityriasis versicolor, or discoloration of the skin

 Ringworm
• Ringworm, also known as dermatophytosis, is a fungal infection
of the skin. It can affect both humans and animals. The infection
initially appears as red patches on the affected areas that later
spreads. It majorly affects the scalp, nails, feet, groin and beard.

The ringworm fungus grows well in moist environment such as showers, bathroom
floors and walls, swimming pools and also in between the skin folds. The vectors for
this disease include pets such as cats and dogs. There are multiple forms of ringworm
 Types of Ringworm
• Ringworm is classified based on the part of the body it affects.

1.Tinea capitis: This fungal infection affects the scalp. It is also known
by the name of scalp ringworm. (Tinea: Technical term for
ringworm.) (Capitis: Latin for “of the head“)

2.Tinea corporis: This fungal infection might occur in any part of the
body. Thus it is known as body ringworm. (Corporis: Latin for “of the
body”)

3.Tinea cruris: This fungal infection affects the skin around the inner
thighs, buttocks, and groin. It is also known as the Jock itch. (Cruris:
Latin for “of the leg”)

4.Tinea pedis: This fungal infection affects both the foot, in between
the fingernails and toenails. It is also known as Athlete’s foot.
(Pedis: Latin for “of the foot”)
 Causes of Ringworm

• Ringworm can be caused by the following ways:

• It spreads by skin contact with an infected person.

• It spreads from pets and cows. One should wash

hands properly after playing with the pets.

• The fungus causing ringworm might be found

lingering on clothes, comb, towels and brushes.

• These fungi are mainly present in the spores of soil

which may result in an infection. (Black fungus)
 Symptoms of Ringworm

• Ringworm symptoms vary depending upon the site of infection. The

following are the common characteristic symptoms of ringworm:

1.The skin of the feet becomes swollen and itchy between the toes. The
soles and heels of the feet may also be affected.

2.Itchy, scaly red spots appear on the groin area.

3.Ringworm appears like an itchy, scaly, inflamed bald spot on the scalp.

4.Ringworm on nails appear to be thick and abnormal in colour and shape.

5.In the beard, itchy, red spots appear on the chin, cheeks, and the upper
neck.
Diagnosis of Ringworm

• Common diagnostic procedures done by doctors to diagnose ringworms:

1.A black-light (also called UV-A or Wood’s lamp) is used to illuminate

affected areas on the body. Presence of the fungal infection will glow under
the light.

2.KOH exam- The scrapings of the infected skin is collected and mixed with
the prepared KOH solution. The KOH tests detect the fungi by removing the
unaffected cells and leaving the fungal cells aside. The test results are
checked under the microscope to detect ringworms.

3.Skin biopsy – A small section of skin tissue is cut and examined under a
microscope to detect fungi. It can detect a range of infections.

4.Fungal culture: A large swab is brushed over the infected areas. These
samples are then sent to a lab for analysis to identify the causative
microbes. This procedure helps to determine the best course of treatment.
 Ringworm Treatment
1.The best antifungal creams used for this infection are miconazole or
terbinafine, which should be applied twice in a day on the infected
region until the symptoms withdraw

2.Amphotericin B is a very powerful fungicide that is used in the most

serious cases of fungal infections

3. Using talcum powder is recommended as it helps to control sweating

4.Home remedies include neem, which is a particularly effective

antimicrobial and antifungal agent
 Antifungals
• Difficult as fungal cells are much more similar to human cells
• Fungistatic and have low therapeutic index
• Polyenes and Azoles: Both block fungal cell membrane
biosynthesis

• Amphotericin B (Polyene)

• Fluconazole, Miconazole (Azoles)

Athlete's foot
Symptoms of athlete's foot
Severe fungal infections can cause complications
• Fungal infections, especially the invasive types that affect
internal organs such as the brain and lungs, that are not treated
at the early stages can cause complications, including:

• Fever
• Sinus problem
• Seizures
• Paralysis
• Lung inflammation
• Blood in the sputum
BLACK FUNGUS AND
COVID-19
Our health and medicine
Lecture 22
Nilkamal Mahanta
IIT Dharwad
 What are viruses?
• Viruses are tiny parasites that can cause disease. They all contain genetic material, known as the viral
genome, and a surrounding shell made of proteins and lipids.

• A virus is a small collection of genetic code, either DNA or RNA, surrounded by a protein coat.

• A virus cannot replicate alone. Viruses must infect cells and use components of the host cell to make
copies of themselves. Often, they kill the host cell in the process, and cause damage to the host

• Researchers estimate that viruses outnumber bacteria by 10 to 1.

• Because viruses don’t have the same components as bacteria, they cannot be killed by antibiotics;

• Only antiviral medications or vaccines can eliminate or reduce the severity of viral diseases, including
AIDS, COVID-19, measles and smallpox.
Virus general structure
• Different types of viruses
Viral Diseases in Humans Virus
Common cold Rhinovirus

Smallpox Variola virus

Rabies Rabies lyssavirus

Hepatitis Hepatitis A virus, hepatitis B virus, Hepatitis C virus

Measles Rubeola virus

Poliomyelitis Poliovirus

Influenza Influenza virus (RNA virus)

Encephalitis Herpes Simplex Virus

Mumps Paramyxovirus
Other widespread viral infections are:

1. Chickenpox

2. HIV (human immunodeficiency virus)

3. HPV (human papillomavirus)

4. Shingles or herpes zoster (a viral infection that leads to the development of rash)

5. Viral pneumonia (a condition that occurs due to viruses that are responsible for flu and colds)

6. Viral hepatitis (inflammation of the liver that is caused by a virus)

7. Viral meningitis (viral infection wherein inflammation of the membranes that cover the brain occurs)

8. Rubella, mumps and measles

9. Herpes
Different ways that they can spread include:

1.Breathing in the germs present in airborne droplets when an infected person sneezes or
coughs

2.Coming in contact with the body fluids of an infected person during sexual activity

3.Indirect contact with these microorganisms when you touched inanimate objects
handled by an infected person

4.Viral infections can also spread through insect bites. Certain germs depend on insects as
carriers such as ticks and mosquitoes for moving from host to host

5.Having virus-contaminated water or food is another way in which viral infection can
spread from person to person.
 Common cold
• The common cold is usually caused by
a rhinovirus that is transmitted
through contact with the saliva or
nasal secretions infected person

Symptoms
•Sore throat
•Runny nose
•Nasal congestion
•Sneezing
•Cough
•Fatigue
•Minor muscle aches
•Headache
•Shivering /mild fever
Common cold vs Flu
Our health and medicine
Lecture 23
Nilkamal Mahanta
IIT Dharwad
Virus general structure
• Different types of viruses
 Common cold
• The common cold is usually caused by
a rhinovirus that is transmitted
through contact with the saliva or
nasal secretions infected person

Symptoms
•Sore throat
•Runny nose
•Nasal congestion
•Sneezing
•Cough
•Fatigue
•Minor muscle aches
•Headache
•Shivering /mild fever
Common cold vs Flu
HIV
HIV arrives from Congo
Worldwide
HIV attacks immune cells
 HIV stages

•This stage is also called asymptomatic HIV •The most severe phase of HIV infection.
infection or clinical latency.
•People have a large •People with AIDS have such badly
•HIV is still active but reproduces at low damaged immune systems that they get
amount of HIV in their
levels. an increasing number of severe illnesses,
blood. They are very
•People may not have any symptoms. called opportunistic infections.
contagious.
•Without taking HIV medicine, this period •People receive an AIDS diagnosis when
•Some people have flu-
may last a decade or so, but some progress their CD4 cell count drops below 200
like symptoms. This is
faster. cells/mm, or if they develop infections.
the body’s natural
response to infection.
•People can transmit HIV in this phase. •People with AIDS can have a high viral
•But some people may load and be very infectious.
•At the end of this phase, the amount of
not feel sick right away
HIV in the blood (called viral load) goes up •Without treatment, people with AIDS
or at all.
and the CD4 cell count goes down typically survive about three years.
increasing symptoms.
•Treatment: Antiretroviral drugs
 Azidothymidine (AZT, also called Zidovudine)
• Nucleoside analog reverse-transcriptase inhibitor against HIV

HIV is a retrovirus – its virus particles encode its genetic

information using single stranded RNA.

However, human cells only have the enzymatic capability to

make copies of DNA, not RNA.

For retroviruses to be able to replicate in the host cell, they

must encode a reverse transcriptase. By converting the viral
RNA to double stranded DNA, this enzyme is required for
copying the virus’s genetic material in newly infected cells.

AZT acts to inhibit this essential process.

AZT mechanism
 A movie on AZT
• The film tells the story of Ron Woodroof (Matthew McConaughey),
an AIDS patient diagnosed in the mid 1980s when HIV/AIDS
treatments were under-researched, while the disease was not
understood and highly stigmatized. As part of the experimental
AIDS treatment movement, he smuggled unapproved
pharmaceutical drugs (AZT) into Texas for treating his symptoms,
and distributed them to fellow people with AIDS by establishing the
"Dallas Buyers Club" while facing opposition from the Food and
Drug Administration (FDA). Won several Oscar awards.
Awareness programs
Videos related to HIV

https://www.youtube.com/watch?v=NOkBGeMaD6c

https://www.youtube.com/watch?v=FDVNdn0CvKI

https://www.youtube.com/watch?v=26AzXs0HwR8
Our health and medicine
Lecture 24
Nilkamal Mahanta
IIT Dharwad
HIV
•Treatment: Antiretroviral drugs
 Azidothymidine (AZT, also called Zidovudine)
• Nucleoside analog reverse-transcriptase inhibitor against HIV

HIV is a retrovirus – its virus particles encode its genetic

information using single stranded RNA.

However, human cells only have the enzymatic capability to

make copies of DNA, not RNA.

For retroviruses to be able to replicate in the host cell, they

must encode a reverse transcriptase. By converting the viral
RNA to double stranded DNA, this enzyme is required for
copying the virus’s genetic material in newly infected cells.

AZT acts to inhibit this essential process.

NOT YET, but
trials are going on
 Polio
• Polio (poliomyelitis) is an infectious disease that can cause permanent muscle weakness,
paralysis, can be life-threatening. Primarily affects children under age five

• It is caused by a virus known as the poliovirus, which is very contagious and is spread by
swallowing contaminated food or water, or by direct contact with an infected person.

• Polio is commonly known as a crippling disease, causing paralysis (the

inability to move) of muscles as a result of the virus invading the brain and
spinal column.

• Due to widespread vaccination, polio has been eradicated from many parts of the world.
Countries including Nigeria, Pakistan and Afghanistan, where polio infections still occur.
Two types of polio
 Highly effective vaccine
• Two types of vaccine are available worldwide:
• the inactivated poliomyelitis vaccine (IPV), which is given by injection; and
• the oral poliomyelitis vaccine (OPV), which is taken by mouth.
Hepatitis B
Vaccine and Diagnosis
Our health and medicine
Lecture 25
Nilkamal Mahanta
IIT Dharwad
 Corona virus

WIV
Seafood market
Timeline
Global outbreaks in history
SARS

A map of the infected countries of the epidemic of SARS between 2002-11-01 and 2003-08-07. Black: Countries
with confirmed deaths Red: Countries with confirmed infections Grey: Countries without confirmed cases
MERS
From where did
they come from?

Civet cat

Pangolins
Types of coronaviruses
SARS-CoV-2 attaches to ACE2 receptor on human cell

Spike protein
Modes of transmission
Covid-19 vaccines

Covishield

Covaxin
Johnsons and Johnsons
SARS-CoV-2 Variants: Mutations in the spike protein
Fantasy

2011
Effect of
lockdowns
in Covid 19
Related Video links

https://www.medscape.com/viewarticle/924314

https://www.youtube.com/watch?v=SvA1s5S9rQ0

https://www.youtube.com/watch?v=RN81h85V6D4