CHAPTER 19 THE GRAM-POSITIVE BACILLI OF MEDICAL IMPORTANCE
Gram-positive bacilli associated with infectious disease are presented. The bacilli are
separated into the endospore-forming bacilli (Bacillus and Clostridium), the non-sporeforming bacilli with consistent cellular morphology (Listeria and Erysipelothrix), the
non-spore-forming bacilli with inconsistent cellular morphology (Corynebacterium), and
the acid-fast bacilli (Mycobacterium). The general characteristics, clinical presentations,
host defenses, treatment, prevention, and identification of these bacteria and resultant
disease are outlined.
Learning Objectives
A student should learn the following concepts:
1. Many infections are caused by gram-positive bacilli; these bacteria are often
grouped according to their ability to produce endospores and whether they are
acid-fast.
2. Vegetative bacteria develop endospores (dense, protected structures) in response
to nutrient deprivation.
3. The genus Bacillus are aerobic, catalase-positive rods that can degrade a wide
variety of macromolecules, and are a common source of antibiotics.
4. Bacillus anthracis is the largest of the bacterial pathogens, develops spores under
a variety of conditions (excluding the body of the host), and produces a capsule
and exotoxins which are important virulence factors.
5. Inhalation of a small dose of anthrax spores can result in pulmonary anthrax.
6. Vaccines (for livestock and people) are available for anthrax.
7. Antibiotic therapy is available for the treatment of anthrax; however, antibiotic
therapy does not lessen the effects of toxemia.
8. Clostridium species are anaerobic, catalase-negative organisms that produce
exotoxins.
9. Clostridial diseases are separated into wound and tissue infections and food
intoxication.
10. Debridement of diseased tissue eliminates the environment that promotes many
wound infections.
11. Hyperbaric oxygen therapy increases the oxygen content of tissues and decreases
the severity of anaerobic bacterial infections.
12. Antibiotic-associated-colitis is the result of Clostridium difficile overgrowing the
normal flora of the intestine.
13. Tetanus (caused by Clostridium tetani) is a neuromuscular disease that occurs
when spores of Clostridium tetani are forced into injured tissues.
14. Clostridium botulinum produces a rare but severe intoxication (attributed to the
toxin botulin), whereas Clostridium perfringens produces a common mild
intestinal illness (attributed to its enterotoxin).
Chapter 19– Gram-Positive Bacilli of Medical Importance
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15. The species Listeria monocytogenes is non-spore forming, has flagella (one to
four), is facultatively anaerobic, and is resistant to cold, heat, salt, and pH
extremes.
16. Corynebacterium diphtheriae are aerobic, irregular, non-spore forming bacteria
which can cause upper respiratory tract or cutaneous infections (pathogenicity is
associated with the production of diphtherotoxin).
17. Propionibacterium acnes grow in skin follicles and can stimulate inflammation
and acne.
18. Mycobacterium species are aerobic, do not form capsules or spores, and have a
complex layered structure with a high lipid content (contributing to making it
impervious to many substances).
19. Mycobacterium tuberculosis does not produce exotoxins or enzymes, but
produces complex waxes and cord factor that contribute to its virulence.
20. Only about 5% of people infected with tuberculosis develop a clinical case of TB.
21. Isolation of M. tuberculosis provides a unique challenge because specimens can
become contaminated with rapid-growing bacteria that interfere with isolation of
M. tuberculosis.
22. Mycobacterium leprae has not been grown in artificial media or human tissue
cultures and has an extremely low rate of multiplication.
23. Actinomycetes are nonmotile, aerobic, and may be acid fast.
24. Actinomycosis is an endogenous infection by Actinomycetes living normally in
the human.
25. Pulmonary nocardiosis is a form of bacterial pneumonia with pathology and
symptoms similar to tuberculosis.
26. Nocardia brasiliensis causes pulmonary nocardiosis, especially in patients with
deficient immunity.
Chapter Outline (also see Chapter Summary with Key Terms p. 590)
19.1 Medically Important Gram-Positive Bacilli
19.2 Gram-Positive Spore-Forming Bacilli
 General Characteristics of the Genus Bacillus
o Bacillus anthracis and Anthrax
 Introduction
 Cutaneous Anthrax
 Pulmonary Anthrax
 Methods of Anthrax Control
 Biothrax
 Penicillin, Tetracycline, or Ciprofloxacin
o Other Bacillus Species Involved in Human Disease
 Bacillus cereus Food Poisoning
 The Genus Clostridium
o The Role of Clostridia in Infection and Disease
Chapter 19– Gram-Positive Bacilli of Medical Importance
o
o
o
o
o
 Wound and Tissue Infections
 Food Intoxications
Gas Gangrene/Myonecrosis
 Extent and Symptoms of Infection
 Treatment and Prevention of Gangrene
 Debridement
 Penicillin or Cefoxitin
 Hyperbaric Oxygen Therapy
Clostridium difficile-Associated Disease (CDAD)
 Antibiotic-Associated (Pseudomembranous) Colitis
Tetanus or Lockjaw
 The Course of Infection and Disease
 Tetanospasmin Toxin
 Risus sardonicus
 Treatment and Prevention of Tetanus
 Treatment
o Human Tetanus Immunoglobulin
o Penicillin or Tetracycline
o Muscle Relaxants
 Prevention
o DTaP Vaccine
Clostridial Food Poisoning
 Epidemiology of Botulinum Food Poisoning
 Botulism
 The Route of Pathogenesis
 Botulin Toxin
 Infant and Wound Botulism
 Treatment and Prevention of Botulism
 Trivalent Horse Antitoxins
 Proper Food Handling and Preparation
 Clostridial Gastroenteritis
Differential Diagnosis of Clostridial Species
19.3 Gram-Positive Regular Non-Spore-Forming Bacilli
 An Emerging Food-Borne Pathogen: Listeria monocytogenes
o Epidemiology and Pathology of Listeriosis
o Diagnosis and Control of Listeriosis
 Cold Enrichment
 Erysipelothrix rhusiopathiae: A Zoonotic Pathogen
o Epidemiology, Pathogenesis, and Control
 Erysipeloid
19.4 Gram-Positive Irregular Non-Spore-Forming Bacilli
 Corynebacterium diphtheriae
o Epidemiology of Diphtheria
o Pathology of Diphtheria
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Chapter 19– Gram-Positive Bacilli of Medical Importance


Introduction
 Local Infection
 Toxin Production and Toxemia
 Diphtherotoxin and Toxemia
 Pseudomembrane
 Toxemia
o Diagnostic Methods for Corynebacterium
 Alkaline Methylene Blue Stain
 Elek Test
o Treatment and Prevention of Diphtheria
 Diphtheria Antitoxin
 DTaP Vaccine
The Genus Propionibacterium
o Propionibacterium acnes
19.5 Mycobacteria: Acid-Fast Bacilli
 Mycobacterium tuberculosis: The Tubercle Bacillus
o Epidemiology and Transmission of Tuberculosis
o The Course of Infection and Disease
 Initial Infection and Primary Tuberculosis
 Tubercles
 Caseous Lesions
 Tuberculin Reaction
 Latent and Recurrent Tuberculosis
 Extrapulmonary Tuberculosis
o Clinical Methods of Detecting Tuberculosis
 Tuberculin Sensitivity and Testing
 Mantoux Test
 Induration
 Roentgenography and Tuberculosis
 Acid-Fast Staining
 Laboratory Cultivation and Diagnosis
o Management and Prevention of Tuberculosis
 Mycobacterium leprae: The Leprosy Bacillus
o Epidemiology and Transmission of Leprosy
o The Course of Infection and Disease
 Tuberculoid Leprosy
 Lepromatous Leprosy
o Diagnosing Leprosy
o Treatment and Prevention of Leprosy
 Infections by Nontuberculous Mycobacteria (NTM)
o Disseminated Mycobacterial Infections in AIDS
o Nontuberculous Lung Disease
o Miscellaneous Mycobacterial Infections
19.6 Actinomycetes: Filamentous Bacilli
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Chapter 19– Gram-Positive Bacilli of Medical Importance


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Actinomycosis
o Actinomyces israelii
Nocardiosis
o Nocardia brasiliensis
Student Activities
1. Have students design an educational campaign targeting individuals with TB
disease. Ask students to address the following issues in this campaign: importance
of the therapeutic regiment involving combined therapy, the importance of
complying with drug protocols (still taking antibiotics even after you feel better),
the risk of relapse with non-compliance, and the risk of bacteria developing multidrug resistance.
2. Ask students to investigate the natural reservoir(s) of Mycobacterium leprae.
Divide the group into classes and have them investigate different topics:
a. The possibility of an animal reservoir
http://svm369.vetmed.lsu.edu/images/truman/Human%20and%20Armadil
lo%20Leprosy.pdf,
b. The possibility of an environmental reservoir
http://medicine.plosjournals.org/perlserv?request=getdocument&doi=10.1371/journal.pmed.0020341,
c. The origin of leprosy (comparative genomics traces all cases back to a
single clone) http://www.sciencemag.org/cgi/content/short/308/5724/1040
and http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1322279,
d. And the geographic origin of leprosy
http://www.nih.gov/news/pr/may2005/niaid-12.htm.
e. Finally, have the students present their research to the rest of the class in a
PowerPoint presentation.
Classroom Discussion
1. Discuss the variety of antibiotics produced by Bacillus (polymyxin, difficidin,
subtilin, mycobacillin, bacitracin, pumulin, laterosporin, zwittermicin, gramicidin,
and tyrocidin). The range of activity of these antibiotics includes gram-positive
bacteria, gram-negative bacteria, and fungi. Bacillus are saprobic and the precise
role these antibiotics play in the growth and reproduction of Bacillus is unknown.
Ask students what role they feel these antibiotics play. Current hypotheses
involve possible competition between species, or regulation of sporulation and
maintenance of dormancy. The following article Researchers Eye “Predatory”
Bacterium for Novel Antimicrobial Strategies describes exploiting Bacillus to
help identify new antibiotics: http://jama.amaassn.org/cgi/content/extract/291/10/1188.
Chapter 19– Gram-Positive Bacilli of Medical Importance
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2. Review with students the important role the portal of entry plays in any infection.
Discuss the range in clinical presentations that can be seen with an anthrax
infection on the skin (enters through cuts and abrasions) as opposed to in the
lungs (inhalation of spores). Revisit Staphylococci and discuss the differences
between an individual who carries Staph but displays no symptoms, and the result
when Staph enters a wound. Remind students that infection is all about location,
location, location.
3. Discuss with students the “perfect” habitat for Clostridium perfringens. This
organism is adapted to surviving in conditions of low oxygen (the species
Clostridium perfringens is considered anaerobic). During an infection it is the
damaged or dead tissue that provides a suitable environment for gangrene. The
decreased blood flow (due to the damaged or dead tissue) not only decreases the
supply of oxygen to the site of the infection, but also decreases the chemotaxis of
WBCs that are carried in the blood (immune cells can’t get to where the infection
is). This organism has adapted to a very selective and specific niche, thus
accounting for its success.
4. Discuss the risks of long-term antibiotic therapy not only in terms of development
of resistant bacteria, but also in terms of the health of the host. Discuss antibioticassociated diarrhea. No pathogens are directly identified in antibiotic-associated
diarrhea; the diarrhea is due to changes in the composition of the normal intestinal
flora, most notably an overgrowth of C. difficile
(http://www.clevelandclinicmeded.com/diseasemanagement/gastro/antibioticdiarr
hea/antibioticdiarrhea.htm). This discussion should also revisit concepts presented
in Chapter 13, Resident Flora: The Human as a Habitat (p. 383), and Indigenous
Flora of Specific Regions (p. 385).
5. After presenting human tetanus immune globulin (TIG) (p. 572), ask students
how they think TIG is prepared. Where does it come from? Then distribute the
following information on BayTet (Tetanus Immune Globulin-Human) prepared
from plasma of donors immunized with tetanus toxoid (http://www.talecrispi.info/inserts/BayTet.pdf). WHO recommendations for the production, control,
and regulation of human plasma for fractionation is presented at this website:
http://www.who.int/biologicals/publications/ECBS%202005%20Annex%204%20
Human%20Plasma%20Fractionation.pdf. Finally discuss the antitoxins available
for C. botulinum. Ask students what kind of antitoxins they feel should be
available and where they might come from. Discuss the currently available horse
trivalent antitoxin.
6. Cord factor is briefly introduced (p. 580) as a virulence factor of mycobacteria.
Discuss with students the fact that mycobacteria do not produce exotoxins or
enzymes that destroy host tissue and contribute to infectiousness. Cord factor is a
potent inhibitor of neutrophil migration and prevents bacterial destruction by
macrophages, allowing mycobacteria to slip under the immune radar. Cord factor
is most abundantly produced by the most virulent strains of Mycobacterium
tuberculosis.
7. Introduce students to the concept of pathogenicity islands (PAIs). As the course
begins to focus more on specific bacteria and the virulence factors associated with
them, it is important for students to keep in mind the location of virulence factors
Chapter 19– Gram-Positive Bacilli of Medical Importance
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within the genome—and how these factors can be exchanged. The following
article Ecological fitness, genomic islands and bacterial pathogenicity provides
background on PAIs and discusses their role in pathogenicity:
http://www.nature.com/embor/journal/v2/n5/full/embor418.html.
8. Ask students how a latent TB infection might become an active TB infection, and
why (as discussed on p. 583) only 5% of people infected with TB develop a
clinical case. Discuss with students some of the many factors that may contribute
to a compromised immune system (age, stress, co-infection with HIV), and talk
about how the bacteria might then escape from their encapsulated area and spread
throughout the lung tissue.
Applicable Online Quizzes
www.mhhe.com/talaro7
A-B Exotoxins (Diphtheria Exotoxin)
Chapter Quiz
Key Terms and Phrases
Bacillus anthracis
anthrax
cutaneous anthrax
eschar
pulmonary anthrax
Bacillus cereus
Clostridium
exotoxins
Clostridium perfringens
gas gangrene
myonecrosis
debridement
Clostridium difficile
tetanus
Clostridium tetani
tetanospasmin
Clostridium botulinum
Clostridium perfringens
botulism
botulin
regular
listeriosis
Erysipelothrix
rhusiopathiae
erysipeloid
irregular
Corynebacterium
C. diptheriae
diphtheria
diphtherotoxin
pseudomembrane
toxemia
Corynebacterium
xerosis
Propionibacterium
P. acnes
pilosebaceous
Mycobacterium
acid-fastness
tubercle
caseous lesion
tuberculin reaction
extrapulmonary TB
mantoux test
induration
leprosy
tuberculoid leprosy
lepromatous leprosy
actinomycosis
nocardiosis
N. brasiliensis
cord factor
Instructors are encouraged to visit the Foundations in Microbiology ARIS (Assessment,
Review, Instruction System) site at www.mhhe.com/talaro7 for animations of key
processes, online quizzing, case presentations, and more.