When you choose to publish with PLOS, your research makes an impact. Make your work accessible to all, without restrictions, and accelerate scientific discovery with options like preprints and published peer review that make your work more Open.

PLOS BLOGS ECR Community

Legionnaire’s in 2015: Cutting Edge Research Clashing with Public Health Unpreparedness

By Meredith Wright

In 1976, the American Legion, a veterans group still active today, met in Philadelphia, PA for a three-day convention. Shortly after the convention ended many of the Legionnaires became ill. By the end of the outbreak, 182 people contracted pneumonia and 29 people had died. Identification of the causative agent introduced Legionella pneumophila to the world, an intracellular bacteria which infects freshwater protozoa and causes bacterial pneumonia in humans. Almost 40 years later, New York City just experienced its worst outbreak of the disease, which started on July 12, 2015, in the Bronx and has grown to 124 reported cases, with 12 fatalities. While the outbreak is now considered over, questions remain concerning how a bacterium known to clinicians and public health officials since 1976 can cause such a large outbreak now. What do we know about L. pneumophila, and what is being done to prevent future outbreaks?

Image courtesty of NYC Department of Health and Mental Hygiene
Image courtesty of NYC Department of Health and Mental Hygiene

The Basics

L. pneumophila is an intracellular bacteria that naturally resides in warm water, where it is adapted to live inside protozoa, such as amoebae, and forms biofilms. Humans become infected by breathing in vapors or mist from contaminated water sources; it is not spread from human to human. Further, this bacterium is considered an opportunistic infection, meaning that it generally infects the elderly, those with chronic lung problems, or those who are immunocompromised for other reasons.

In humans, L. pneumophila infects alveolar macrophages, a cell type which is important for degrading pathogens and other foreign particles that have entered the lungs. Macrophages perform this vital task mainly through a process called phagosome-lysosome fusion, which involves the uptake of a foreign body, its packaging into a compartment called the phagosome, and then the maturing of the phagosome into the lysosome. The lysosome’s interior has harsher conditions than the phagosome and should result in the degradation of its contents (see Fig. 1b for a basic schematic of phagosome-lysosome fusion). Many pathogens have evolved methods for counteracting this human defense mechanism, including L. pneumophila. The Legionnaire’s disease bacterium co-opts phagosome-lysosome fusion to create a compartment that shelters the bacterium, known as the Legionella Containing Vacuole (LCV), depicted in Fig. 1a. L. pneumophila also impacts human macrophages through lipid remodeling, autophagy, and ubiquitin pathway changes. These processes work together to allow the replication of the bacterium at the cost of normal macrophage function, resulting in the pneumonia symptoms experienced by patients.

 Fig. 1: Legionella and phagosome-lysosome fusion. A: Basic schematic of the formation of the Legionella Containing Vacuole (LCV). B: Standard schematic of effective phagosome-lysosome fusion to contain a bacterium.

Fig. 1: Legionella and phagosome-lysosome fusion.
A: Basic schematic of the formation of the Legionella Containing Vacuole (LCV).
B: Standard schematic of effective phagosome-lysosome fusion to contain a bacterium. From Isberg et al, 2009.

The Latest Research

The molecular details of how L. pneumophila redirects the host cell for its nefarious purposes of building the LCV are not completely understood, but this is an area of active research. For example, recent work has identified Lpg0393, a previously unknown protein produced by the bacterium which activates Rab proteins, a family of proteins that play a critical role in the phagosome-lysosome fusion process. Additionally, recent structural studies on SidC, a known protein of L. pneumophila, has explained in better detail how this bacterial protein works to recruit necessary host proteins for sustaining the LCV and also lays the groundwork for utilizing proteins from this bacterium as a tool for other research. And perhaps most relevant for public health officials, it has recently been shown that not all decontamination techniques are created equal. A study published in PLOS ONE in August 2015 shows that suboptimal temperatures and chlorine concentrations reduce the benefits of treatments currently used for decontaminating water, and that these suboptimal conditions are usually what is found in the parts of water systems that are most likely to come in contact with human users.

Sources of Outbreaks

According to the CDC, common sources of the bacteria include hot tubs, cooling towers, hot water tanks, plumbing systems, and fountains. In the 1976 outbreak which gave L. pneumophila its name, Legionnaires who became ill were all staying in the same hotel; and while a precise source was not confirmed, it seems likely the bacteria came from contaminated water tanks connected to the air conditioning system, as the only hotel employee to become sick was an air conditioning repairman. According to testimony from Dr. Mary T. Bassett, Commissioner of the New York City Department of Health and Hygiene, a total of 18 cooling towers have tested positive for L. pneumophila in the South Bronx, an impoverished part of New York city. Cooling towers sit atop large buildings and are important for maintaining large air conditioning units. They have not previously been routinely tested for L. pneumophila in New York City, but this outbreak has spurred a Commissioner’s Order requiring all building owners to disinfect their cooling towers or provide evidence of prior disinfection. The city has also introduced legislation mandating regular testing of New York city cooling towers for the bacterium. The legislation, which was just signed into law on August 18th, plans to prevent and prepare for future outbreaks in a number of ways, with a heavy focus on the cooling towers which harbored the bacteria that started this outbreak. In particular, a registry of cooling towers will be created, and these towers will be inspected on a quarterly basis using guidelines issued by the New York City Health Department. According to NYC Mayor Bill deBlasio, this legislation is the first of its kind in any large city. Mandated testing will likely become more important over time, as an aging population creates a larger pool of susceptible individuals, and warmer temperatures in big cities require more large cooling towers.

Looking Ahead

It is unclear why these preventative testing measures were not already in place in New York city. There have been attempts to institute regular testing in the past, but they were unsuccessful. This outbreak in New York city hearkens back to the early days of the ongoing Ebola outbreak in West Africa, where officials scrambled to contain the outbreak after it was already well underway. But unlike Ebola, L. pneumophila is relatively well-understood by the scientific community, and there are simple measures which can be used to prevent the growth of L. pneumophila in urban water sources. In New York city’s defense, officials have been making efforts to educate the public about Legionnaire’s disease, holding a town hall meeting in the Bronx community on August 3rd and taking to social media to spread information (follow the New York City Health Department on Twitter at @nycHealthy).

 

Hopefully, this outbreak can serve as an example for other municipalities that systems for preventing and containing infectious disease are an essential part of a city’s infrastructure. As research uncovers more details about how L. pneumophila and other infectious diseases live and spread, these findings must be incorporated into continuously-updated public health policies.

References

1. David W. Fraser, M.D., Theodore R. Tsai, M.D., Walter Orenstein, M.D., William E. Parkin, D.V.M., DR. P.H., H. James Beecham, M.D., Robert G. Sharrar, M.D., John Harris, M.D., George F. Mallison, M.P.H., Stanley M. Martin, M.S., Joseph E. McDade, Ph.D., C, and the F. I. T. Legionnaire’s Disease: A Description of an Epidemic of Pneumonia. N. Engl. J. Med. 297, 1189–1197 (1977).

2. NYC Mayor_ Legionnaires’ Outbreak Has Claimed 12 Lives – ABC News.

3. Flannagan, R. S., Cosío, G. & Grinstein, S. Antimicrobial mechanisms of phagocytes and bacterial evasion strategies. 7, (2009).

4. Newton, H. J., Ang, D. K. Y., Van Driel, I. R. & Hartland, E. L. Molecular pathogenesis of infections caused by Legionella pneumophila. Clin. Microbiol. Rev. 23, 274–298 (2010).

5. Hubber, A. & Roy, C. R. Modulation of host cell function by Legionella pneumophila type IV effectors. Annu. Rev. Cell Dev. Biol. 26, 261–283 (2010).

6. Sohn, Y.-S. et al. Lpg0393 of Legionella pneumophila Is a Guanine-Nucleotide Exchange Factor for Rab5, Rab21 and Rab22. PLoS One 10, e0118683 (2015).

7. Luo, X. et al. Structure of the Legionella Virulence Factor, SidC Reveals a Unique PI(4)P-Specific Binding Domain Essential for Its Targeting to the Bacterial Phagosome. PLOS Pathog. 11, e1004965 (2015).

8. Isberg, R. R., O’Connor, T. J. & Heidtman, M. The Legionella pneumophila replication vacuole: making a cosy niche inside host cells. Nat. Rev. Microbiol. 7, 13–24 (2009).

9. Cervero-Aragó, S., Rodríguez-Martínez, S., Puertas-Bennasar, A. & Araujo, R. M. Effect of Common Drinking Water Disinfectants, Chlorine and Heat, on Free Legionella and Amoebae-Associated Legionella. PLoS One 10, e0134726 (2015).

10. NYC Dept. of Health and Mental Hygiene, Testimony of Mary T. Bassett regarding Cooling Towers Registration, and Inspection and Testing for Microbes and Preconsidered Intro. (2015).

11. Legionnaires’ death toll swells to 12; bacteria found in two more cooling towers – New York’s PIX11 – WPIX-TV.

12. Hygiene, N. D. of H. and M. Testimony of Mary T. Bassett regarding Cooling Towers Registration, and Inspection and Testing for Microbes. 1–5 (2015).

13. A Belated Look at New York’s Cooling Towers, Prime Suspect in Legionnaires’ Outbreak – The New York Times.

14. De Blasio Signs Cooling Tower Regulations Into Law In Wake Of Legionnaires’ Outbreak – CBS New York.

15. Mayor Bill de Blasio Signs First-In-Nation Legislation for Cooling Tower Maintenance – NYC.gov.

Discussion

Leave a Reply

Your email address will not be published. Required fields are marked *


Add your ORCID here. (e.g. 0000-0002-7299-680X)

Back to top