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Lecture Topic: Systemic Bacteriology

Mentor: Dr. Fahim Uddin Ahmad
MBBS, MD(Microbiology)
Assistant Professor of Microbiology
TMSS Medical College, Bogura
 Major Bacterial Pathogens

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 Gram-Positive Cocci
• Both staphylococci and streptococci are gram-positive cocci, but they
are distinguished by two main criteria:

• (1) Microscopically, staphylococci appear in grapelike clusters, whereas

streptococci are in chains.

• (2) Biochemically, staphylococci produce catalase (i.e., they degrade

hydrogen peroxide), whereas streptococci do not
 STAPHYLOCOCCUS- Diseases
• Staphylococcus aureus causes abscesses various pyogenic infections (e.g.,
endocarditis, septic arthritis, and osteomyelitis), food poisoning, scalded skin
syndrome, and toxic shock syndrome.
• It is one of the most common causes of hospital-acquired pneumonia, septicemia,
and surgical-wound infections.
• It is an important cause of skin and soft tissue infections, such as folliculitis ,
cellulitis, and impetigo .
• It is the most common cause of bacterial conjunctivitis
STAPHYLOCOCCUS- Diseases
 STAPHYLOCOCCUS- Diseases
• Staphylococcus epidermidis causes prosthetic valve endocarditis and
prosthetic joint infections. It is the most common cause of central nervous
system shunt infections and an important cause of sepsis in newborns.

• Staphylococcus saprophyticus causes urinary tract infections, especially

cystitis.

• Kawasaki syndrome is a disease of unknown etiology that may be caused by

certain strains of S. aureus
Staphylococci of Medical Importance
 Important Properties-STAPHYLOCOCCUS
• Staphylococci are spherical gram-positive cocci arranged in irregular
grapelike clusters . All staphylococci produce catalase.
 Important Properties-STAPHYLOCOCCUS

• Staphylococcus aureus produces a carotenoid pigment called

staphyloxanthin, which imparts a golden color to its colonies. This
pigment enhances the pathogenicity of the organism.
Important Properties-STAPHYLOCOCCUS

• More than 90% of S. aureus strains contain plasmids that encode β-

lactamase, the enzyme that degrades many, but not all, penicillins.
Some strains of S. aureus are resistant to the β-lactamase–resistant
penicillins, such as methicillin and nafcillin, by virtue of changes in
the penicillin-binding proteins (PBP) in their cell membrane. Genes on
the bacterial chromosome called mecA genes encode these altered
PBP.
MRSA
MRSA
• The drug of choice for these staphylococci(MRSA) is
• vancomycin, to which gentamicin is sometimes added.
• Daptomycin
• Trimethoprim-sulfamethoxazole or clindamycin.
• 5Th Generation cephalosporin Ceftarolin. (Note that MRSA strains are
resistant to almost all β-lactam drugs, including both penicillins and
cephalosporins)
Important Properties-STAPHYLOCOCCUS
• Strains of S. aureus with intermediate resistance to vancomycin (VISA)
and with full resistance to vancomycin (VRSA) have also been detected.

• These strains are typically methicillin-/nafcillin-resistant as well.

• Treatment of VISA:

Daptomycin (Cubicin)

Quinupristin-dalfopristin (Synercid)
Pathogenesis Staphylococcus aureus
• Staphylococcus aureus causes disease both by producing toxins and by inducing
pyogenic inflammation. The typical lesion of S. aureus infection is an abscess.

• Enterotoxin causes food poisoning characterized by prominent vomiting and watery,

nonbloody diarrhea. It acts as a superantigen within the gastrointestinal tract to
stimulate the release of large amounts of IL-1 and IL-2 from macrophages and
helper T cells, respectively
Pathogenesis Staphylococcus aureus
• Toxic shock syndrome toxin (TSST) causes toxic shock, especially in tampon-using
menstruating women or in individuals with wound infections TSST is a superantigen
and causes toxic shock by stimulating the release of large amounts of IL-1, IL-2 and
TNF.

• Exfoliatin causes “scalded skin” syndrome in young children. It is “epidermolytic”

and acts as a protease that cleaves desmoglein in desmosomes, leading to the
separation of the epidermis at the granular cell layer.
Pathogenesis Staphylococcus aureus
• Alpha toxin causes marked necrosis of the skin and hemolysis

• P-V leukocidin is a pore-forming toxin that kills cells, especially white

blood cells, by damaging cell membrane

• P-V leukocidin is an important virulence factor for CA-MRSA and

plays a role in the severe skin and soft tissue infection caused by this
organ
Important Features of Pathogenesis by
Staphylococci
Tolerant organism
• Some strains of staphylococci exhibit tolerance (i.e., they can be inhibited by
antibiotics but are not killed). (That is, the ratio of minimum bactericidal
concentration [MBC] to minimum inhibitory concentration [MIC] is very high.)

• Tolerance may result from failure of the drugs to inactivate inhibitors of autolytic
enzymes that degrade the organism. Tolerant organisms should be treated with drug
combinations.
STREPTOCOCCUS
• Streptococci cause a wide variety of infections. Streptococcus pyogenes
(group A Streptococcus) is the leading bacterial cause of pharyngitis , and
cellulitis .

• It is an important cause of impetigo , necrotizing fasciitis, and streptococcal

toxic shock syndrome.

• It is also the inciting factor of two important immunologic diseases, namely,

rheumatic fever and acute glomerulonephritis.
STREPTOCOCCUS
• Streptococcus agalactiae (group B Streptococcus) is the leading cause of
neonatal sepsis and meningitis.

• Enterococcus faecalis is an important cause of hospital-acquired urinary tract

infections and endocarditis.

• Viridans group streptococci are the most common cause of endocarditis .

Streptococcus bovis (also known as Streptococcus gallolyticus) is an
uncommon cause of endocarditis.
Streptococci of Medical Importance
Hemolysis of Streptococci
 Important Properties- STREPTOCOCCUS
• C carbohydrate determines the group of β-hemolytic streptococci.

• M protein is the most important virulence factor of S. pyogenes. It protrudes from the outer
surface of the cell and blocks phagocytosis (i.e., it is antiphagocytic). It inactivates C3b, a
component of complement that opsonizes the bacteria prior to phagocytosis.

• Strains of S. pyogenes that produce certain M protein types are rheumatogenic (i.e., cause
primarily rheumatic fever), whereas strains of S. pyogenes that produce other M protein types
are nephritogenic (i.e., cause primarily acute glomerulonephritis).
Pathogenesis
Streptococcus pyogenes-Pharyngitis and cellulitis
Endocarditis- Viridans streptococci
Treatment- Group A streptococcal infections
• Penicillin G or amoxicillin,
• oral penicillin V ( In rheumatic fever or AGN patients)
• erythromycin or azithromycin in In penicillin-allergic patients.
• Clindamycin can also be used in penicillin-allergic patients
• clindamycin and intravenous immunoglobulins (Invasive group A
streptococcal infections such as necrotizing fasciitis and streptococcal toxic
shock syndrome)
Endocarditis- Viridans streptococci-Treatemnt
• Endocarditis caused by most viridans streptococci is curable using prolonged
penicillin treatment.

• However, enterococcal endocarditis can be eradicated only by a penicillin or

vancomycin combined with an aminoglycoside

• VREs are now an important cause of nosocomial infections; there is no reliable

antibiotic therapy for these organisms. At present, two drugs are being used to treat
infections caused by VRE: linezolid (Zyvox) and daptomycin (Cubicin).
STREPTOCOCCUS PNEUMONIAE-Diease

• Streptococcus pneumoniae causes pneumonia, bacteremia, meningitis, and

infections of the upper respiratory tract such as otitis media, mastoiditis, and
sinusitis.

• Pneumococci are the most common cause of community-acquired

pneumonia, meningitis, sepsis in splenectomized individuals, otitis media,
and sinusitis.

• They are a common cause of conjunctivitis, especially in children.

Streptococcus pneumoniae—Gram stain
Important Properties

• Pneumococci possess polysaccharide capsules that have 91 antigenically distinct

types (serotypes)

• Another important surface component of S. pneumoniae is a teichoic acid in the

cell wall called C-substance (also known as C-polysaccharide). It reacts with a
normal serum protein made by the liver called C-reactive protein (CRP).

• CRP is not an antibody (which are γ-globulins) but rather a β-globulin.

• CRP is a nonspecific indicator of inflammation and is elevated in response to the

presence of many organisms, not just S. pneumoniae
Streptococcus pneumoniae-Optochin Sensitive and bile
soluble
Prevention-Streptococcus pneumoniae
• 13-valent pneumococcal conjugate vaccine

• The immunogen in this vaccine is the pneumococcal polysaccharide of

the 13 most prevalent serotypes conjugated (coupled) to a carrier protein
(diphtheria toxoid)
Gram-Negative Cocci-Neisseria
• Important Clinical Features of Neisseriae
Important Properties- Neisseria meningitidis
• Neisseria meningitidis (meningococcus) has a prominent polysaccharide
capsule that enhances virulence by its antiphagocytic action. The capsule also
is the immunogen in the vaccine that induces protective antibodies.

• Five serotypes cause most cases of meningitis and meningococcemia: A, B,

C, Y, and W-135.

• The organism grows best on chocolate agar incubated at 37°C in a in a 5%

CO2
Important Properties- Neisseria meningitidis
• Meningococci have four important virulence factors

• A polysaccharide capsule

• Endotoxin

• An immunoglobulin A (IgA) protease

• Factor H binding protein (FHBP)

Important Properties- Neisseria gonorrhoeae

• Neisseria gonorrhoeae (gonococcus) has no polysaccharide capsule but

has multiple serotypes based on the antigenicity of its pilus protein. There
is marked antigenic variation in the gonococcal pili.

• lipooligo saccharide (LOS) acts as endotoxin.

• They are oxidase-positive.

• IgA protease can hydrolyze secretory IgA.

Important Properties- Neisseria gonorrhoeae
• Gram-negative diplococci within PMNs in a urethral discharge specimen is
sufficient for diagnosis.

• Culture on Thayer-Martin medium, which is a chocolate agar containing

antibiotics (vancomycin, colistin, trimethoprim, and nystatin) to suppress the
normal flora.

• The organism is usually transmitted sexually; newborns can be infected

during birth.
Gram-Positive Rods-
• There are five medically important genera of gram-positive rods:

o Bacillus,

o Clostridium,

o Corynebacterium,

o Listeria, and

o Gardnerella.

• Bacillus and Clostridium form spores, whereas Corynebacterium, Listeria, and Gardnerella
do not.
Gram-Positive Rods of Medical Importance
Bacillus
cutaneous anthrax
CLOSTRIDIUM
• There are four medically important species:

❖Clostridium tetani,

❖Clostridium botulinum,

❖Clostridium perfringens (which causes either gas gangrene or food

poisoning), and

❖Clostridium difficile.
Important Features of Pathogenesis by Clostridium
Species
Clostridium botulinum
Infant Botulism
Botulinum toxin is absorbed from the gut and carried via the blood
to peripheral nerve synapses, where it blocks release of
acetylcholine.
Clostridium tetani
 Prevention and Treatment-tetanus

• The results of treatment of tetanus are not satisfactory.

• Therefore, prevention is all important. Prevention of tetanus

depends on

• (1) active immunization with toxoids,

• (2) proper care of wounds contaminated with soil

• (3) prophylactic use of antitoxin, and

• (4) administration of penicillin.

Clostridium difficile-Antibiotic associated diarrhoea and
pseudomembranous colitis
Clostridium perfringens
• Gas gangrene (myonecrosis, necrotizing fasciitis) is one of the two
diseases caused by C. perfringens .

• Necrotizing fasciitis is often called the “flesh-eating” disease.

• In addition to C. perfringens, Streptococcus pyogenes and methicillin-

resistant Staphylococcus aureus (MRSA) are important causes.
CORYNEBACTERIUM DIPHTHERIAE
❖Important Properties

• Gram-positive rods that appear club-shaped

• Have metacromatic granules

• Transmitted by airborne droplets and also by skin

• Diphtheria toxin inhibits protein synthesis by ADP-ribosylation of elongation factor-2

• A throat swab should be cultured on Loeffler’s medium

• Diphtheria are prevented by immunized with diphtheria toxoid (usually given as a combination of
diphtheria toxoid, tetanus toxoid, and acellular pertussis vaccine, often abbreviated as DTaP).
Diphtheria toxoid is prepared by treating the exotoxin with formaldehyde.
Clinical Findings- CORYNEBACTERIUM
DIPHTHERIAE
❖A local inflammation in the throat, with a fibrinous exudate that forms the
tough, adherent, gray pseudomembrane characteristic of the disease.
• There are three prominent complications:
• (1) Extension of the membrane into the larynx and trachea, causing airway
obstruction.
• (2) Myocarditis accompanied by arrhythmias and circulatory collapse.
• (3) Nerve weakness or paralysis, especially of the cranial nerves.
LISTERIA MONOCYTOGENES
• Listeria monocytogenes causes meningitis, abortion, and sepsis in
newborns, pregnant women, and immunosuppressed adults.

• It also causes outbreaks of febrile gastroenteritis.

• It is a major cause of concern for the food industry.

Important Properties-LISTERIA
MONOCYTOGENES
• Listeria monocytogenes is a small gram-positive rod

• The organism exhibits an unusual tumbling movement

• Listeria grows well at cold temperatures, can contaminate refrigerated

food.
 Pathogenesis- LISTERIA MONOCYTOGENES
• Listeria infections occur primarily in two clinical settings:
• (1) in the fetus or in a newborn as a result of transmission across the placenta or
during delivery and
• (2) in pregnant women and immunosuppressed adults, especially renal transplant
patients.

• Because Listeria preferentially grows intracellularly, cell-mediated immunity is a

more important host defense than humoral immunity. Suppression of cell-mediated
immunity predisposes to iListeria infections.
 GARDNERELLA VAGINALIS

• Gardnerella vaginalis is the main organism associated with bacterial

vaginosis.

• This disease is the most common vaginal infection of sexually active women.

• Bacterial vaginosis is characterized by a malodorous, white or gray-colored

vaginal discharge. The discharge has a characteristic “fishy” odor.
Laboratory Diagnosis- GARDNERELLA VAGINALIS

• Clue cells, which are vaginal epithelial cells covered with bacteria, are an important
laboratory finding seen in a microscopic examination of the vaginal discharge .

• In addition, the “whiff ” test, which consists of treating the vaginal discharge with 10%
KOH and smelling a pungent, “fishy” odor, is often positive.

• A pH of greater than 4.5 of the vaginal discharge supports the diagnosis of bacterial
vaginosis
Gram-Negative Rods Related to the Enteric Tract
• Categories of Gram-Negative Rods
 ENTEROBACTERIACEAE & RELATED
ORGANISMS
• The Enterobacteriaceae is a large family of gram-negative rods found primarily in the colon of
humans and other animals, many as part of the normal flora

• Features common to all members of this heterogeneous family are their anatomic location and the
following four metabolic processes:

▪ (1) they are all facultative anaerobes;

▪ (2) they all ferment glucose (fermentation of other sugars varies);

▪ (3) none have cytochrome oxidase (i.e., they are oxidase-negative); and

▪ (4) they reduce nitrates to nitrites as part of their energy generating process
Gram-Negative Rods Causing Diarrhea
Gram-Negative Rods Causing Urinary Tract
Infection or Sepsis
Diseases Caused by Members of the
Enterobacteriaceae
Clinical Aspects of Escherichia coli
Curved Gram-Negative Rods Affecting the
Gastrointestinal Tract
Gram-Negative Rods Related to the Respiratory
Tract
 HAEMOPHILUS

• Haemophilus influenzae used to be the leading cause of meningitis in young

children.
• It is one of the three important encapsulated pyogens, along with the
pneumococcus and the meningococcus.
• Of the six serotypes (a–f), type b is the most important. Type b used to cause most
of the severe, invasive diseases, such as meningitis and sepsis.
• Growth of the organism on laboratory media requires the addition of two
components, heme (factor X) and NAD (factor V).
Gram-Negative Rods Related to Animal Sources
(Zoonotic Organisms)
Mycobacteria
• Mycobacteria are aerobic, acid-fast bacilli.
Mycobacteria
• The major pathogens are Mycobacterium tuberculosis, the cause of
tuberculosis, and Mycobacterium leprae, the cause of leprosy. Atypical
mycobacteria, such as Mycobacterium avium-intracellulare complex
and Mycobacterium kansasii, can cause tuberculosis-like disease but
are less frequent pathogens.

• Rapidly growing mycobacteria, such as Mycobacterium chelonae,

occasionally cause human disease in immunocompromised patients or
those in whom prosthetic devices have been implanted
Medically Important Mycobacteria
MYCOBACTERIUM TUBERCULOSIS-Important
Properties
• Mycobacterium tuberculosis grows slowly (i.e., it has a doubling time of
18 hours. Because growth is so slow, cultures of clinical specimens must
be held for 6 to 8 weeks.

• Media used for its growth (e.g., Löwenstein-Jensen medium) contain

complex nutrients (e.g., egg yolk) and dyes (e.g., malachite green). The
dyes inhibit the unwanted normal flora present in sputum samples.
MYCOBACTERIUM TUBERCULOSIS-Important
Properties
• Mycobacterium tuberculosis is an obligate aerobe; this explains its
predilection for causing disease in highly oxygenated tissues such as the
upper lobe of the lung and the kidney.

• Cord factor (trehalose dimycolate) is correlated with virulence of the

organism. Virulent strains grow in a characteristic “serpentine” cordlike
pattern.
Pathogenesis
Immunity & Hypersensitivity
• After recovery from the primary infection, resistance to the organism is
mediated by cellular immunity (i.e., by CD4- positive T cells and
macrophages).

• The CD4-positive T cells are Th-1 helper T cells

• Prior infection can be detected by a positive tuberculin skin test result,

which is due to a delayed hypersensitivity reaction.
Immunity & Hypersensitivity
• PPD is used as the antigen in the tuberculin skin test. The intermediate-
strength preparation of PPD, which contains five tuberculin units, is
usually used.

• The skin test is evaluated by measuring the diameter of the induration

surrounding the skin test site). Note that induration (thickening), not
simply erythema (reddening), must be observed.
Tuberculine skin test
Immunity & Hypersensitivity
• The diameter required to judge the test as positive varies depending on the status of
the individual being tested. Induration of 15 mm or more is positive in a person who
has no known risk factors.
• Induration of 10 mm or more is positive in a person with high-risk factors, such as a
homeless person intravenous drug user, or a nursing home resident.
• Induration of 5 mm or more is positive in a person who has deficient cellmediated
immunity (e.g., AIDS patients) or has been in close contact with a person with
active tuberculosis.
Immunity & Hypersensitivity
• A positive skin test result indicates previous infection by the organism
but not necessarily active disease. The tuberculin test becomes positive
4 to 6 weeks after infection. Immunization with bacillus Calmette-
Guérin (BCG) vaccine) can cause a positive test, but the reactions are
usually only 5 to 10 mm and tend to decrease with time.

• Infection with measles virus can suppress cell-mediated immunity,

resulting in a loss of tuberculin skin test reactivity.
 Clinical Findings
• Pulmonary tuberculosis

• Scrofula which is mycobacterial cervical lymphadenitis

• Erythema nodosum, characterized by tender nodules along the extensor surfaces of the tibia
and ulna.

• Miliary tuberculosis is characterized by multiple disseminated lesions that resemble millet

seeds.

• Tuberculous meningitis and tuberculous osteomyelitis, especially vertebral osteomyelitis

(Pott’s disease), are important disseminated forms.
 Clinical Findings
• Gastrointestinal tuberculosis-ileocecal region is the site most often involved

• Oropharyngeal tuberculosis

• Renal tuberculosis, dysuria, hematuria, and flank pain occur. “Sterile pyuria”
is a characteristic finding. (Urine contains white blood cells, but cultures for
the common urinary tract bacterial pathogens show no growth).

• Most (approximately 90%) infections with M. tuberculosis are asymptomatic.

Asymptomatic infections, also known as latent infections,
 Clinical Findings
• MDR organisms is resistance to both INH and rifampin, but some
isolates are resistant to three or more drugs. The treatment of MDR
organisms usually involves the use of four or five drugs, including
ciprofloxacin, amikacin, ethionamide, and cycloserine.

• The strains of M. tuberculosis resistant to INH, rifampin, a

fluoroquinolone, and at least one additional drug are called extensively
drug-resistant (XDR) strains.
 Atypical Mycobacteria
• Group I (Photochromogens)
• Group II (Scotochromogens)
• Group III (Nonchromogens)
• Group IV (Rapidly Growing Mycobacteria)
 MYCOBACTERIUM LEPRAE-Pathogenesis
• There are two distinct forms of leprosy—tuberculoid and lepromatous—
with several intermediate forms between the two extremes

• Comparison of Tuberculoid and Lepromatous Leprosy:

 Actinomycetes
• Actinomycetes are a family of bacteria that form long, branching
filaments that resemble the hyphae of fungi . They are gram-positive,
but some (such as Nocardia asteroides) are also weakly acid-fast rods.
 Mycoplasma
• Mycoplasmas are a group of very small, wall-less organisms, of which Mycoplasma
pneumoniae causes “atypical” pneumonia.

• Atypical pneumonia is also caused by

❖Legionella pneumophila [Legionnaires’ disease],

❖Chlamydia pneumoniae,

❖Chlamydia psittaci [psittacosis],

❖Coxiella burnetii [Q fever], and

❖viruses such as such as influenza virus and adenovirus.

 Mycoplasma
• The extrapulmonary manifestations include Stevens-Johnson syndrome,
erythema multiforme, Raynaud’s phenomenon, cardiac arrhythmias,
arthralgias, hemolytic anemia, and neurologic manifestations such as
Guillain-Barré syndrom.

• They produce Cold agglutinins which are IgM autoantibodies against

type O red blood cells that agglutinate these cells at 4°C but not at 37°C.
Spirochetes of Medical Importance
 Treponema pallidum
• Treponema pallidum causes syphilis. It has three stages

• In primary syphilis, the spirochetes multiply at the site of inoculation, and a

local, nontender ulcer (chancre) usually forms in 2 to 10 weeks.

• One to 3 months later, the lesions of secondary syphilis may occur. These
often appear as a maculopapular rash, notably on the palms and soles or as
moist lesions (condylomata lata). These lesions are rich in spirochetes and are
highly infectious,
Treponema pallidum
 Treponema pallidum
• Tertiary syphilis may show granulomas (gummas), especially of skin
and bones; central nervous system involvement, also known as
neurosyphilis (e.g., tabes, paresis); or cardiovascular lesions (e.g.,
aortitis, aneurysm of the ascending aorta). In tertiary lesions,
treponemes are rarely seen.

• Treponema pallidum also causes congenital syphilis

 Laboratory Diagnosis
• Microscopy Spirochetes are demonstrated in the lesions of primary or
secondary syphilis, such as chancres or condylomata lata, by dark-field
microscopy or by direct fluorescent antibody (DFA) test. They are not
seen on a Gram-stained smear.

• Nonspecific Serologic Tests: VDRL and rapid plasma reagin RPR tests.
These tests are positive in most cases of primary syphilis and are almost
always positive in secondary syphilis
 Laboratory Diagnosis
• Nonspecific Serologic Tests : False-positive reactions occur in infections such
as leprosy, hepatitis B, and infectious mononucleosis and in various
autoimmune diseases. Therefore, positive results have to be confirmed by
specific tests. Results of nonspecific tests usually become negative after
treatment and should be used to determine the response to treatment

• These tests can also be falsely negative as a result of the prozone

phenomenon.
 Laboratory Diagnosis
• The laboratory diagnosis of congenital syphilis is based on the finding
that the infant has a higher titer of antibody in the VDRL test than the
mother

• Specific Serologic Tests: FTA-ABS is the fluorescent treponemal

antibody-absorbed test or hemagglutination (TPHA, MHA-TP) assays.
These tests remain positive for life.
Chlamydiae of Medical Importance
Rickettsial Diseases
 Thank you.

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