Page 1 of 13

Legionella Pneumophilia

Clifton Torrence

Matt Wilkerson, Ph. D.

Galen College of Nursing

August 27, 2023

 Page 2 of 13

Legionella Pneumophilia

Legionella Pneumophilia was first identified in 1976 during the annual convention at the

American Legion. It began as an outbreak of a possible fatal form of pneumonia. During this

time, 182 cases were reported, and 29 of those cases ended up fatal (Iliadi et al., 2022).

Description of the Microorganism

Legionella Pneumophilia is a type of gram-negative, aerobic bacteria. The bacteria are

rod-shaped and are typically found singly or in pairs. They do not form spores but can survive

for long periods in the environment in a dormant state. Legionella can be difficult to culture and

is often visualized using fluorescent antibody staining or direct immunofluorescence microscopy.

The bacteria are motile under certain conditions, and some species form a characteristic darting

motility under dark field microscopy. Colonies on a solid medium are usually beige or gray and

are often characterized by their smooth, shiny appearance. In humans, Legionella can cause a

severe form of pneumonia known as Legionnaires’ disease, and it is commonly associated with

water systems like air conditioning units, hot water tanks, and cooling towers (Cassell &

Oliphant, 2020).

Virulence Factors

Legionella Pneumophilia is a waterborne pathogen that can cause severe respiratory

illness in humans by inhaling contaminated water droplets. It has a repertoire of virulence factors

that contribute to its pathogenicity. The two major virulence factors of Legionella are the

Dot/Icm type IV secretion system and the flagellum (Cassell & Oliphant, 2020).
 Page 3 of 13

The Dot/Icm system is responsible for delivering over 300 effector proteins into the host

cell, enabling Legionella to establish a replicative niche within the host cell. These effector

proteins manipulate various signaling pathways in the host cell, altering its structure and

function. For example, some effector proteins prevent fusion of the phagosome containing

Legionella with the lysosome of the host cell, allowing Legionella to evade destruction. The

Dot/Icm system also induces the formation of a unique organelle called the Legionella-

containing vacuole (LCV), in which Legionella can replicate and evade the host's immune

system. The Dot/Icm system is a critical determinant of the virulence of Legionella

Pneumophilia (Cassell & Oliphant, 2020).

The flagellum is another major virulence factor of Legionella. It helps the bacteria in

motility and chemotaxis, allowing it to move towards favorable conditions such as oxygen and

nutrients. Additionally, the flagellum is important in invading host cells, as it helps in adherence

to host cell surfaces. Once inside the host cell, the flagellum helps Legionella move around the

host cell and deliver effector proteins to different locations within the cell (Cassell & Oliphant,

2020).

These virulence factors of Legionella have various effects on the host. The Dot/Icm

system allows Legionella to establish a replicative niche within the host cell, which can cause

damage to the host cell. The altered signaling pathways in the host cell can lead to inflammation,

tissue damage, and even apoptosis. The flagellum enables Legionella to penetrate host cells,

leading to cellular damage. In addition, the flagellum and its movement in the host cell can

trigger an immune response, causing inflammatory responses within the host (Cassell &

Oliphant, 2020).
 Page 4 of 13

Overall, the virulence factors of Legionella contribute significantly to the bacteria's

pathogenicity and its ability to cause severe respiratory illness in humans. Understanding these

virulence factors can help in developing effective treatments and strategies to control the spread

of this waterborne pathogen (Cassell & Oliphant, 2020).

Immunity

The primary defense against Legionella pneumophilia infections is the innate immune

system, which includes physical barriers such as the skin and mucous membranes and immune

cells such as macrophages and neutrophils. These cells can recognize and engulf the pathogen,

preventing it from replicating and spreading (Centers for Disease Control and Prevention, n.d.).

Once the pathogen reaches the lungs, the adaptive immune system is activated, which

includes specific immune cells that target the pathogen. Specifically, Legionella pneumophilia

induces a cell-mediated immune response, which involves activating T-cells and releasing

cytokines to combat the infection (Centers for Disease Control and Prevention, n.d.).

Additionally, several vaccines have been developed to protect against Legionella

pneumophilia infections, particularly in high-risk populations, such as immunocompromised

individuals or those working in high-risk occupations. These vaccines stimulate the production

of antibodies that can prevent infection by neutralizing the pathogen (Centers for Disease

Control and Prevention, n.d.).

 Page 5 of 13

Infectious disease information

Legionella pneumophilia is responsible for causing a severe type of pneumonia called

Legionnaires' disease, as well as a milder, flu-like illness called Pontiac fever. These infections

affect the respiratory system, particularly the lungs. Legionella pneumophilia is an aerobic,

gram-negative bacillus that is naturally found in freshwater environments, such as lakes and

streams. It can also grow and proliferate in man-made water systems, such as hot tubs, air

conditioning systems, and cooling towers (Centers for Disease Control and Prevention, 2021).

In Legionnaires' disease, Legionella bacteria can cause lung inflammation (pneumonia),

leading to symptoms such as cough, fever, chest pain, muscle aches, headache, shortness of

breath, and sometimes abdominal pain, diarrhea, and confusion. Legionnaires' disease can be

fatal in severe cases, especially in individuals with underlying medical conditions, such as

immunosuppression, chronic lung disease, or kidney failure (Centers for Disease Control and

Prevention, 2021).

Pontiac fever, on the other hand, is characterized by flu-like symptoms, such as fever,

muscle aches, and headache. Unlike Legionnaires' disease, Pontiac fever does not cause

pneumonia and is usually self-limited, resolving within a few days (Centers for Disease Control

and Prevention, 2021).

Legionella pneumophilia infections are acute; they come on suddenly and can be severe

if left untreated. The complications of Legionnaires' disease can include respiratory failure,

kidney failure, septic shock, and even death in some cases (Centers for Disease Control and

Prevention, 2021).
 Page 6 of 13

Legionella pneumophilia is an opportunistic pathogen. It can cause disease only in people

with specific risk factors or predisposing conditions, such as a weakened immune system,

chronic lung disease, smoking, and advanced age. The bacteria are usually found in low levels in

natural water sources. However, they can grow to high levels in man-made water systems that

are not properly maintained, leading to an increased risk of contamination and infection (Centers

for Disease Control and Prevention, 2021).

Epidemiology

Legionella
Pneumophilia

Portal of Entry Infectious Agent Reservoir

Water Source
Droplets in the air
(Natural or Man-
Made). Also spread
through cough.

Portal of Exit

Airborne
Transmission Respiratory Droplets
 Page 7 of 13

Prevention

There is currently no vaccine recommended for routine childhood use against Legionella

bacteria, but there is a vaccine available for at-risk groups (CDC, n.d.).

The vaccine is called the Legionella pneumophilia SG1 Vaccine. It is recommended for individuals

who work in or who are visiting high-risk environments where the bacteria is likely to be present, such

as in healthcare settings, long-term care facilities, or hotels. The vaccine is administered in two doses, 28

days apart, and regular booster doses after the initial vaccination series may be required to maintain

immunity (Chen et al., 2016).

The Legionella pneumophilia SG1 vaccine is a subunit vaccine that is composed of a specific

antigen that triggers an immune response in the body. The vaccine produces antibodies in the body that

specifically target and neutralize the Legionella bacteria, preventing it from causing illness in the

individual (Fukuyama et al., 2014).

If there is no vaccine available, some measures that can be implemented to prevent

transmission of Legionella bacteria include:

1. Regular maintenance and disinfection of cooling towers, hot tubs, and other potential sources of

stagnant water to prevent Legionella from growing and contaminating the water supply.

2. Regular cleaning and disinfection of water systems and faucets.

3. Testing of water samples to ensure that they are free of Legionella (Harrison et al., 2018).
 Page 8 of 13

Treatment

The recommended chemotherapeutic agents for legionella pneumophilia include:

1. Azithromycin: It is a macrolide antibiotic and works by inhibiting bacterial protein synthesis.

Azithromycin concentrates within macrophages and epithelial cells, which are the primary

targets of legionella. It has been shown to be effective against legionella infections, including

Legionnaires’ disease (Mayo Clinic, 2021).

2. Levofloxacin: It is a fluoroquinolone antibiotic that inhibits DNA gyrase and topoisomerase

IV, which are essential enzymes for bacterial DNA replication and repair. Levofloxacin is

effective against many bacteria, including legionella pneumophilia (Mayo Clinic, 2021).

3. Doxycycline: It is a tetracycline antibiotic that prevents bacterial protein synthesis by binding

to the bacterial ribosome. Doxycycline is effective against many types of bacteria, including

legionella pneumophilia (Mayo Clinic, 2021).

The reason these agents are efficacious against legionella pneumophilia is that they target

essential bacterial functions, such as protein synthesis and DNA replication, which are necessary

for the bacteria to survive and replicate (Mayo Clinic, 2021).

Additional therapeutic agents or practices may include supportive care, such as oxygen

therapy, hydration, and fever control. In severe cases, hospitalization may be necessary, and

intravenous antibiotic therapy may be required to control the infection. Close monitoring of
 Page 9 of 13

respiratory function is also critical, particularly for patients who develop severe pneumonia

(Mayo Clinic, 2021).

Clinical Relevance

There are Multi-Drug Resistant (MDR) strains of Legionella pneumophilia, particularly

the serogroups 1, 3, 6, and 8. These MDR strains are of great concern and have been reported in

hospitals and long-term care facilities, making them a known healthcare-associated pathogen

(García-Vidal & Carratalà, 2018).

According to a study by the European Center for Disease Prevention and Control, the

highest rates of Legionella infections (including MDR strains) are observed among patients in

critical care units, followed by hematology/oncology and transplant units. Patients with

compromised immune systems, chronic lung disease, or a history of smoking are particularly at

risk of developing Legionella infections (European Centre for Disease Prevention and Control,

2019).

The treatment of MDR Legionella infections is challenging since these strains may be

resistant to the usual antibiotics. However, the use of a combination of antibiotics such as

fluoroquinolones (e.g., levofloxacin) and macrolides (e.g., azithromycin) has shown efficacy

against MDR strains of Legionella pneumophilia. Other antibiotics, such as tetracyclines (e.g.,

doxycycline), rifampin, and aminoglycosides, may also be effective. Treatment duration and

choice of antibiotics should be guided by susceptibility testing of the identified strain (García-

Vidal & Carratalà, 2018).

 Page 10 of 13

Conclusion

In conclusion, Legionella pneumophilia is a gram-negative bacterium that causes

Legionnaires' disease and Pontiac fever. The bacterium can be found in natural and human-made

water systems, and infection occurs through the inhalation of contaminated aerosols. Although

the mortality rate of Legionnaires' disease has reduced significantly with early diagnosis and

treatment, the emergence of Multi-Drug Resistant (MDR) strains of L. pneumophilia poses a

threat to public health.

Effective prevention and control measures should include surveillance of water systems,

routine disinfection and maintenance, and prompt reporting of outbreaks. Healthcare providers

should maintain a high level of clinical suspicion and follow recommended guidelines for

diagnosis, treatment, and prevention of Legionella infections. In addition, research on

epidemiology, pathogenesis, and treatment of MDR Legionella strains should be prioritized to

improve clinical outcomes.

In summary, while Legionella pneumophilia poses a risk to public health, through

effective prevention measures, improved diagnosis and treatment, and increased research, it is

possible to control and reduce the impact of this microorganism on human health.
 Page 11 of 13

References

Cassell, G. H., & Oliphant, C. M. (2020). Legionella and Legionnaires' Disease. In Mandell,

Douglas, and Bennett's Principles and Practice of Infectious Diseases (9th ed.) (pp. 2484–

2491). Elsevier.

Cassell, K. G., & Oliphant, C. M. (2020). Legionella: a persistent and evolving aquatic

opportunist. Journal of Applied Microbiology, 128(3), 712–731.

https://doi.org/10.1111/jam.14486

CDC. (n.d.). Legionella (Legionnaires' Disease and Pontiac Fever). Centers for Disease Control

and Prevention. https://www.cdc.gov/legionella/about/prevention.html

Centers for Disease Control and Prevention. (2021). Legionella (Legionnaires’ Disease and

Pontiac Fever): About the disease. https://www.cdc.gov/legionella/about/index.html

Chen, D. J., Provo, B. J., Hamilton, S. D., Carter, C., Thompson, C., Price, R., & Harriman, K.

H. (2016). Legionella pneumophila SG1 Vaccine Evaluation Study Group. Safety and

immunogenicity of a subunit vaccine against legionnaire's disease: a phase I randomized

controlled trial. Vaccine, 34(7), 916–923.

 Page 12 of 13

European Centre for Disease Prevention and Control. Legionnaires' disease in Europe, 2019.

https://www.ecdc.europa.eu/sites/default/files/documents/Legionnaires'-disease-2017-

EU-summary.pdf

Fukuyama, Y., & Takamura, S. (2014). Progress on the research for a Legionella pneumophilia

vaccine. Frontiers in Microbiology, 5, 511.

References

García-Vidal C, Carratalà J. A review of the management of Legionella pneumonia: therapeutic

strategies and clinical guidelines. Clin Respir J. 2018;12(6):1795-1803.

doi:10.1111/crj.12805

Harrison, T. G., Uldum, S. A., Alexiou‐Daniel, S., Bangsborg, J. M., Bernander, S., Wretlind, B.,

… Cianciotto, N. P. (2018). Legionella pneumophilia SG1 Vaccine Candidate

(LpSG1VCG) Derived from a Clinical Isolate Taxonomically Biomimetic to Progenitor

Environmental Strains. Molecular Informatics, 37(4), 1700128.

Iliadi, V., Staykova, J., Iliadis, S., Konstantinidou, I., Sivykh, P., Romanidou, G., Vardikov, D.

F., Cassimos, D., & Konstantinidis, T. G. (2022). Legionella pneumophilia: The Journey

from the Environment to the Blood. Journal of Clinical Medicine, 11(20).

https://doi.org/10.3390/jcm11206126

Legionella: Treatment and Drugs. Mayo Clinic. https://www.mayoclinic.org/diseases-

conditions/legionnaires-disease/diagnosis-treatment/drc-20352270. May 24, 2021.

Page 13 of 13