General Principles of Medical Bacteriology
Dongwoo Shin
Laboratory of Molecular Bacteriology
Department of Molecular Cell Biology
Sungkyunkwan University School of Medicine
Features of Bacteria
-Unicellular organism
-Small size: 1~2 µm in length
-Haploid: number of a gene (or
allele) is one
-Short generation time: in the
case of E. coli, ~20 min
-Asexual replication
Structure of a Bacterial Cell
Classification of Bacteria
Introduction
Never Underestimate the Power of Bacteria!
 Why
bacteria are once again in the public health spotlight
• Antibiotics
-first introduced into widespread clinical use in the 1950s
-miracle drugs
-appeared to give humans the final victory over bacteria
• However....
-during the late 1980s, an increase in bacterial infections
-by 1995, bacterial infectious diseases became one of the top
five causes of death in the US (e.g. pneumonia, sepsis)
Introduction
 Why
bacteria are once again in the public health spotlight
• Emerging infectious diseases
-power of rapid evolution
-acquire genes that confer new virulence traits or resistance
to antibiotics
• Unfortunately....
-human victory over bacteria had not occurred and is not
going to occur anytime in the future
Introduction
 Current
public health issues caused by bacterial infections
• Emerging infectious diseases
-new diseases caused by newly discovered bacteria:
Legionella pneumophila
-long-known pathogens acquiring traits that make them more
dangerous: antibiotic-resistant bacteria (Streptococcus
pneumoniae, Staphylococcus aureus)
• Food-borne infections
-Outbreaks of Escherichia coli O157:H7 infections: in
Japanese schoolchildren, 1996
Introduction
 Current
public health issues caused by bacterial infections
• Modern medicine as a source of new diseases
-transplantation, cancer chemotherapy
-suppressed immune systems of patients
-increase in the chance of opportunistic infection:
Pseudomonas aeruginosa
• Microbiota shift diseases
-Outgrowth of pathogens in the large intestine by antibiotics
treatment
Human Microbiota
Commensal and Pathogenic Microbial Flora in Humans
The adult human intestine is...
- Home to an inconceivable number of microorganisms
: The size of population is up to 100 trillion, ~10 times
greater than the total number of our somatic and germ cells
“Thus, it is appropriate to view ourselves as a composite of
many species and our genetic landscape as an amalgam of genes
embedded in our Homo sapiens genome and in the genomes of
our affiliated microbial partners (the microbiome)”
- Jeffrey I. Gordon, Science (2005)
Commensal and Pathogenic Microbial Flora in Humans
 In
a healthy human,
- The internal tissues (e.g. brain, blood, muscles): normally
free of microorganisms
- Conversely, the surface tissues (e.g. skin and mucous
membrane): constantly in contact with environmental
microorganisms and become colonized by certain microbial
species
- Normal microbiota (= microflora, normal flora): mixture of
microorganisms regularly found at any anatomical site
- Bacteria make up most of the normal microbiota over the
fungi and protozoa
Commensal and Pathogenic Microbial Flora in Humans

Exposure of an individual to an organism
1. Transient (hours or days) colonization
2. Permanent colonization
3. Disease production (Infection)
Note: colonization vs. infection
Commensal and Pathogenic Microbial Flora in Humans
The Relationship between Normal Microbiota and the Host
 Normal
microbiota
- participates in the metabolism of food products → provides
essential growth factors
- protects against infections with virulent microorganisms
- stimulates immune response
“Without these organisms life would be impossible”
Commensal and Pathogenic Microbial Flora in Humans
The Relationship between Normal Microbiota and the Host
 Normal
microbiota for causing disease
- opportunistic pathogens: members of the patient’s normal
microbiota; no disease in normal setting but disease when
introduced into unprotected sites (e.g. blood, tissues);
immunocompromised patients are more susceptible
Staphylococcus aureus
Escherichia coli
- cf. strict pathogens: a few infections
Mycobacterim tuberculosis (tuberculosis)
Neisseria gonorrhoeae (gonorrhea)
Commensal and Pathogenic Microbial Flora in Humans
 Microbiota
IN and ON the human body
- A continual state of flux: determined by age, diet, hormones,
health, and hygiene
- Human fetus: in sterile environment
- Newborn human: exposed to microbes from the mother and
the environment; skin → oropharynx → gastrointestinal (GI)
tract → other mucosal surfaces
- Microbial population continues to change throughout the life
Commensal and Pathogenic Microbial Flora in Humans
 Current
knowledge of composition of human microbiota
- Based on culture methods: only a small proportion of the
microbes can be cultivated
- Human Microbiome Project (HMP): initiated 2008; a largescale project for characterization of comprehensive human
microbiota and analysis of its role in human health and
disease; genomic techniques
Commensal and Pathogenic Microbial Flora in Humans
Respiratory Tract and Head
 Upper Respiratory Tract: Mouth, Oropharynx, and Nasopharynx
- The most common anaerobic bacteria: Peptostreptococcus, Veillonella,
Actinomyces, Fusobacterium
- The most common aerobic bacteria: Streptococcus, Haemophilus,
Neisseria
- Rarely associated with disease unless introduced into sterile sites (e.g.
sinuses, middle ear, brain)
- Potential pathogens: Streptococcus pyogenes, Streptococcus
pneumoniae, Staphylococcus aureus, Neisseria meningitidis,
Heamophilus influenzae, and Enterobacteriaceae
Commensal and Pathogenic Microbial Flora in Humans
 Ear
- The most common bacteria colonizing out ear: coagulase (-)
Staphylococcus
- Potential pathogens: Streptococcus pneumoniae, Pseudomonas
aeruginosa, and Enterobacteriaceae
Commensal and Pathogenic Microbial Flora in Humans
 Eye
- The surface of the eye: colonized with coagulase (-) Staphylococcus
- S. pneumoniae, S. aureus, H. influenzae, N. gonorrhoeae, P. aeruginosa,
Chlamydia trachomatis, and Bacillus cereus: associated with disease
 Lower Respiratory Tract
- Larynx, trachea, bronchioles, and lower airways: generally sterile
- Acute disease of lower airways: virulent bacteria in mouth; S.
pneumoniae, S. aureus, Klebsiella
- Polymicrobial disease by chronic aspiration: Peptostreptococcus,
anaerobic cocci, and anaerobic gram-negative rods
Commensal and Pathogenic Microbial Flora in Humans
Gastrointestinal Tract
 Colonized with microbes at birth
 Home for diverse population of organisms throughout the life of the host
 The populations remains relatively constant: But, antibiotic treatment
disrupting the balanced flora
 Esophagus
- Most organisms isolated from the esophagus: transient colonizers
- Bacteria rarely cause disease of esophagus
 Stomach
- Only small numbers of acid-tolerant bacteria: HCl, and pepsinogen
- Helicobacter pylori: gastritis and ulcerative disease
Commensal and Pathogenic Microbial Flora in Humans
 Small intestine
- Colonized with many different anaerobic bacteria: Peptostreptococcus,
Porphyromonas, and Prevotella
- Gastroenteritis-causing bacteria: Salmonella and Campylobacter;
present in small numbers as asymptomatic residents
- Obstruction of small intestine (e.g. after surgery) → blind loop syndrome
(막힌 고리 증후군): colonization and proliferation of the microbes in the
large intestine → malabsorption syndrome (음식물 흡수 저해)
Commensal and Pathogenic Microbial Flora in Humans
 Large intestine
- The biggest populations of microbes in the human body: ~1011 bacteria /
g of feces
- The most common bacteria: Bifidobacterium, Eubacterium, Bacteroides,
Enterococcus, and Enterobacteriaceae (e.g. Escherichia coli)
- E. coli: present from birth to death, ~1% of the intestinal population but
the most common aerobe responsible for intraabdominal disease
- Bacteroides flagilis: a minor member of the intestinal flora but the most
common anaerobe responsible for intraabdominal disease
- Bifidobacterium and Eubacterium: the most common bacteria in large
intestine but harmless
Commensal and Pathogenic Microbial Flora in Humans
 Large intestine
- Antibiotic treatment:
 Rapidly alters the population
 Causes proliferation of antibiotic-resistant bacteria (e.g.
Enterococcus, Pseudomonas)
 Rapid growth of Clostridium difficile → psedomembranous
colitis (거짓막염)
- Infection by enteric pathogens:
 Shigella, and enterohemorrhagic E. coli
 Disruption of the colonic flora → intestinal disease
Commensal and Pathogenic Microbial Flora in Humans
Genitourinary Tract
 Only anterior urethra and vagina: permanent colonization by microbes
 Urinary bladder: transient colonization cleared by bactericidal activity of the
uroepithelial cells and flushing action of voided urine
 Anterior urethra
- Lactobacillus, Streptococcus, coagulase (-) Staphylococcus
- Transient colonization with fecal organisms: Enterococcus and
Enterobacteiaceae urinary tract infection (UTI)
- N. gonorrhoeae and C. trachomatis: common causes of urethritis
Commensal and Pathogenic Microbial Flora in Humans
 Vagina
- Diverse populations influenced by hormones
- Newborn girls: Lactobacillus at birth → declined maternal estrogen →
Staphylococcus, Streptococcus, and Enterobacteriaceae → estrogen
production at puberty → Lactobacillus (predominant), Staphylococcus,
Streptococcus, Enterococcus, Enterobacteiaceae
- N. gonorrhoeae: common cause of vaginitis
Commensal and Pathogenic Microbial Flora in Humans
Skin
-Coagulase (-) Staphylococcus
- Clostridium perfringens
- Acinetobacter
Power of Rapid Evolution of Bacteria
Bacterial Gene Transfer
 Inter-strain transfer of DNA provides ‘genetic
diversity’ of bacteria: Horizontal Gene Transfer
- e.g. Evolutionary process of pathogenic bacteria from
nonpathogenic bacteria
- e.g. Spread antibiotics resistance among bacteria
 Three ways of bacterial gene transfer
- Conjugation: by physical interaction
- Transformation: transfer of a naked DNA
- Transduction: by bacteriophages
Bacterial Plasmids
 Plasmid
-Small and circular dsDNA molecules that can exist independently
of host chromosome
-Contains own replication origin
-e.g. F plasmid
Bacterial Plasmids
 Major types of plasmids
Type
Names
Size (kb) Copy No.
Hosts
Phenotypes
Fertility Factor
F Factor 95-100
1-3
E. coli, Salmonella Conjugation
R plasmids
R1
80
1-3
G(-) bacteria
ApR, KmR, CmR
Col plasmids
ColE1
9
10-30
E. coli
Colicin production
83
E. coli
Enterotoxin
56
S. aureus
Enterotoxin B
75
Pseudomonas
Virulence plasmids Ent
pZA10
Metabolic plasmids TOL
Toluene degradation
Bacterial Conjugation
 Conjugation
- Transfer of genetic information by direct
cell to cell contact
 An electron micrograph of two E. coli cells
in an early stage of conjugation
Bacterial Conjugation
e.g. F+×F- mating
- Donor strain (F+) contains F factor
carrying the genes for pilus formation
and plasmid transfer
DNA Transformation
 Transformation
- Uptake of naked DNA by a cell
 ‘Competent’ cell
- One able to take up DNA and be
transformed
DNA Transformation
1. Natural transformation
- Streptococcus, Bacillus,
Thermoactinomyces, Haemophilus,
Neisseria, Moraxella, Acinetobacter,
Helicobacter, Pseudomonas
- Mechanism in S. pneumoniae
- DNA uptake machinery
2. Artificial transformation
- Treatment of E. coli with CaCl2
- Electric shock (electroporation)
Transduction
e.g. Generalized transduction
-Occurs during the lytic cycle
of phages and can transfer any
part of the bacterial genome
-Formation of transducing
particle
-E. coli P1 and Salmonella P22
phages
 Genetic mechanism of evolution of pathogenic E. coli
Biological Mechanisms of Drug Resistance
 Genetic mechanism of evolution of methicillin
and vancomycin resistant Staphylococcus aureus