Legionellosis Outbreaks Research Articles

Draft genome sequences from 127 Legionella spp. strains isolated in water systems linked to legionellosis outbreaks.

Legionnaires' disease is a severe form of pneumonia caused by Legionella spp. bacteria. According to the European Centre for Disease Prevention and Control, problems related to this pathogen showed a significant surge in recent years, making its monitoring critical.

Community Legionella outbreak linked to a cooling tower, 2022.

Thirty-five laboratory-confirmed legionellosis cases were reported to the Simcoe Muskoka District Health Unit (Ontario, Canada) between September 27, 2022, and October 15, 2022, resulting in one death and 29 hospitalizations. This article describes the Legionella outbreak and highlights activities for managing the outbreak, including various environmental and infrastructural controls associated with the public health response and some of the unique challenges and potential solutions to mitigate future outbreaks. All cases of legionellosis were reported to and investigated by the local provincial health unit. Within a 6 km radius around the community, 27 cooling towers (CTs) were identified as potential sources of Legionella. Environmental samples were collected from 19 CTs and a long-term care home. Of the 35 cases, 29 (83%) were hospitalized (including three long-term care residents) with two requiring intubation/ventilation. Of the five sputa (clinical isolates) collected from confirmed cases, four tested positive for Legionella pneumophila (one was positive for L. pneumophila serogroup 1-with the same sequence type as one of the CT isolates). Education and recommendations were provided by the local provincial health unit to operators to improve CT operation. Detection and management of community legionellosis outbreaks associated with CTs involve resources and time to properly identify and control risks. Measures for community risk mitigation included coordinating with provincial and community partners, developing methods to rapidly identify CTs as a likely source of infection and applying operational/maintenance/testing standards for CTs to control bacterial growth and minimize the dispersion of contaminated aerosols.

Environmental Investigation during Legionellosis Outbreak, Montérégie, Quebec, Canada, 2021.

In August 2021, a legionellosis outbreak involving 7 persons occurred within a 500-meter radius in the Montérégie region of Québec, Canada. Near real-time modeling of wind direction along with epidemiologic and environmental investigations identified the possible source. Modeling wind direction could help identify likely Legionella pneumophila sources during legionellosis outbreaks.

Characterization of reported legionellosis outbreaks associated with buildings served by public drinking water systems: United States, 2001-2017.

This study examined 184 legionellosis outbreaks in the United States reported to the Centers for Disease Control and Prevention's Waterborne Disease and Outbreak Surveillance System, from 2001 to 2017. Drinking water characteristics examined include source water type, disinfectant type, exposure setting, geographical distribution by U.S. Census Divisions, and the public water system size (population served). This study found that most of the reported drinking water-associated legionellosis outbreaks occurred in eastern United States, including 35% in the South Atlantic, 32% in the Middle Atlantic, and 16% in the East North Central Census Divisions were linked with building water systems in healthcare and hotel settings; and were associated with buildings receiving drinking water from public water systems serving >10,000 people. Targeted evaluations and interventions may be useful to further determine the combination of factors, such as disinfectant residual type and drinking water system size that may lead to legionellosis outbreaks.

Overview of the Clinical and Molecular Features of Legionella Pneumophila: Focus on Novel Surveillance and Diagnostic Strategies.

Legionella pneumophila (L. pneumophila) is one of the most threatening nosocomial pathogens. The implementation of novel and more effective surveillance and diagnostic strategies is mandatory to prevent the occurrence of legionellosis outbreaks in hospital environments. On these bases, the present review is aimed to describe the main clinical and molecular features of L. pneumophila focusing attention on the latest findings on drug resistance mechanisms. In addition, a detailed description of the current guidelines for the disinfection and surveillance of the water systems is also provided. Finally, the diagnostic strategies available for the detection of Legionella spp. were critically reviewed, paying the attention to the description of the culture, serological and molecular methods as well as on the novel high-sensitive nucleic acid amplification systems, such as droplet digital PCR.

European Surveillance of Legionnaires' Disease.

Legionnaires' disease and Pontiac fever are both diseases with important public health implications and require prompt and thorough responses to outbreaks for future prevention. Effective methods for defining, diagnosing, reporting and responding to legionellosis outbreaks ideally should be standardized across countries. Therefore, the European Union surveillance methods for countering Legionnaires' disease is a useful model especially for travel-associated Legionnaires' disease (TALD) cases which are on the rise. Multi-country surveillance in the EU and European Economic Area (EEA) has evolved since the first organizational efforts in the 1980's to the currently responsible, European Legionnaires' Disease Surveillance Network (ELDSNet). This chapter outlines the practices of the EU surveillance of Legionnaires' disease including their schemata, definitions, responsibilities of participating members, methods and the results of the data collected since the program's inception. Lastly, improvements must still be made as the incidence of Legionnaires' disease in the EU is likely underestimated due to underreporting and/or underdiagnosis. Nearly 70% of cases are reported from only four countries, France, Germany, Italy and Spain, which represent 50% of the EU population.

Legionella risk in evaporative cooling systems and underlying causes of associated breaches in health and safety compliance.

Legionella bacteria can colonise and proliferate in water systems in the built environment and can be spread by aerosol generation. If inhaled by a susceptible individual, this can lead to respiratory infections such as Legionnaires' Disease (LD), or the generally milder Pontiac fever. Evaporative cooling systems (ECS), including cooling towers, used in industrial processes to dissipate excessive heat are prone to contamination by Legionella. From these systems it is possible for contaminated aerosols to be dispersed over a wide area, potentially exposing workers on site, neighbouring workplaces or nearby members of the public. Analysis of reported data on outbreaks of LD in Great Britain, collated for a ten year period, identified 44 separate legionellosis outbreaks of which seven were attributed to ECS and were responsible for 229 infections and 10 fatalities. This prompted an examination of health and safety inspection records which revealed, over a five year period, 321 enforcement actions taken against failings in Legionella control, of which 31% were attributed to cooling towers. Based on this evidence, an intervention programme was undertaken by health and safety inspectors in which 1,906 sites with ECS were inspected. During these inspections, sites were rated against four topics that are used to demonstrate compliance with statutory requirements for Legionella control: Risk Assessment; Written Control Scheme; Implementation of Control Scheme; and Record Keeping. While there was compliance at the majority of sites, breaches of the legislation were found at 625 sites (33% of those inspected), leading to 409 Improvement Notices (compelling dutyholders to make improvements to health and safety breaches of law in a given timeframe) and 12 Prohibition Notices (compelling dutyholders to stop work until they have remedied breaches in health and safety law) being served at 229 sites (12.0% of those inspected). Data from the intervention programme was analysed to identify root causes of these breaches of legislation on Legionella control. The majority of Improvement Notices (53%) were issued for the 'lack of effective implementation of a Written Control Scheme', with 'Risk Assessment' and 'Written Control Scheme' both accounting for 23%. More detailed examination showed major problems to be lack of training; failure to maintain the cleanliness of cooling towers and the water within them; risk assessments either being absent or not up to date, i.e., no longer representing the risks present; and Written Control Schemes being absent or insufficiently detailed. This provides a valuable data resource for dutyholders, so that they can understand where they need to focus to achieve significant improvement in legal compliance and therefore reduce the risk of LD for employees and members of the public affected by their workplace, and valuable data for regulators to target future interventions aimed at improving dutyholder compliance leading to better protection of workers and members of the public.

Legionella Epidemiologic and Environmental Risks

Legionella bacteria cause Legionnaires’ disease (LD), a severe and potentially fatal pneumonia. Legionellosis has been increasing in the USA and in Europe. We reviewed the literature to describe host factors predisposing to LD, environmental factors facilitating Legionella proliferation, and transmission modes leading to legionellosis cases and outbreaks. Men, smokers, and persons 50 years and older, or with chronic pulmonary or immunocompromising conditions, are at risk for LD. Stagnated water and warm water temperature promote Legionella growth. Most legionellosis cases result from exposure to aerosolized contaminated water from man-made water systems, including hot tubs and whirlpool spas; hot water systems in large buildings, hotels, and hospitals; and cooling towers. Water management plans for hot water systems at hospitals, long-term care facilities, and large buildings are important to help prevent LD, and careful epidemiologic investigations remain essential in controlling and preventing legionellosis outbreaks.

Polymorphisms of a Collagen-Like Adhesin Contributes to Legionella pneumophila Adhesion, Biofilm Formation Capacity and Clinical Prevalence.

Legionellosis is a severe respiratory illness caused by the inhalation of aerosolized water droplets contaminated with the opportunistic pathogen Legionella pneumophila. The ability of L. pneumophila to produce biofilms has been associated with its capacity to colonize and persist in human-made water reservoirs and distribution systems, which are the source of legionellosis outbreaks. Nevertheless, the factors that mediate L. pneumophila biofilm formation are largely unknown. In previous studies we reported that the adhesin Legionella collagen-like protein (Lcl), is required for auto-aggregation, attachment to multiple surfaces and the formation of biofilms. Lcl structure contains three distinguishable regions: An N-terminal region with a predicted signal sequence, a central region containing tandem collagen-like repeats (R-domain) and a C-terminal region (C-domain) with no significant homology to other known proteins. Lcl R-domain encodes tandem repeats of the collagenous tripeptide Gly-Xaa-Yaa (GXY), a motif that is key for the molecular organization of mammalian collagen and mediates the binding of collagenous proteins to different cellular and environmental ligands. Interestingly, Lcl is polymorphic in the number of GXY tandem repeats. In this study, we combined diverse biochemical, genetic, and cellular approaches to determine the role of Lcl domains and GXY repeats polymorphisms on the structural and functional properties of Lcl, as well as on bacterial attachment, aggregation and biofilm formation. Our results indicate that the R-domain is key for assembling Lcl collagenous triple-helices and has a more preponderate role over the C-domain in Lcl adhesin binding properties. We show that Lcl molecules oligomerize to form large supramolecular complexes to which both, R and C-domains are required. Furthermore, we found that the number of GXY tandem repeats encoded in Lcl R-domain correlates positively with the binding capabilities of Lcl and with the attachment and biofilm production capacity of L. pneumophila strains. Accordingly, the number of GXY tandem repeats in Lcl influences the clinical prevalence of L. pneumophila strains. Therefore, the number of Lcl tandem repeats could be considered as a potential predictor for virulence in L. pneumophila isolates.

In vitro activities of antimicrobial peptides and ceragenins against Legionella pneumophila.

Legionella pneumophila is a waterborne intracellular pathogenic bacterium, the most frequent cause of human legionellosis and a relatively common cause of community-acquired and nosocomial pneumonia. Some legionellosis outbreaks are related to the presence of biofilms, which provide a reservoir for L. pneumophila strains. We investigated the in vitro activities of antibiotics; erythromycin and doxycycline, antimicrobial peptides AMPs; melittin, LL-37 and CAMA (cecropin A (1-7)-Melittin A (2-9) and ceragenins; CSA-8, CSA-13, CSA-44, CSA-131 and CSA-138 against L. pneumophila. Isolation of Legionella strains was conducted according to ISO 1998. Minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs) and minimum biofilm eradication concentrations (MBECs) were determined using microbroth dilution techniques. MIC ranges for melittin, LL-37, and CAMA were 0.25-1, 1-4, and 2-8 µg ml-1, respectively. MIC ranges for CSA-8, 13, 44, 131, and 138 were 0.5-2, 0.5-1, 1-4, 0.5-2, and 1-2 µg ml-1, respectively, and MBEC values for the ceragenins were 10-160 µg ml-1. These results demonstrate that AMPs and ceragenins display broad-spectrum, in vitro activity against L. pneumophila. In particular, CSA-8, CSA-13 and melittin gave the lowest MICs and MBCs. We also observed that ceragenins are active against established L. pneumophila biofilms.

Preventing legionellosis outbreaks by a quick detection of airborne Legionella pneumophila

Legionellosis is a severe pneumonic infection caused by inhaling bacteria of the genus Legionella. Most cases reported in the USA and Europe are associated with the species Legionella pneumophila. This Gram-negative bacterium can survive within a wide spectrum of temperatures, and be transmitted via aerosols from multiple aquatic sources: fountains, thermal spas and other water systems. Although the PCR is one of the most popular methods to verify its presence in environmental or clinical samples, the direct application of this technique to ambient air samples is unusual because of the scarce material in the specimens.Here, we have developed a two-PCR assay, carried out over the V3 and V5 hypervariable regions of the 16S rRNA gene, to detect specifically the pathogenic bacteria Legionella pneumophila in outdoor air samples with low concentration of DNA. The application of this protocol does not require culture and retrieves quick results to activate the corresponding public alerts to prevent legionellosis outbreaks.

Legionellosis Associated with Recreational Waters: A Systematic Review of Cases and Outbreaks in Swimming Pools, Spa Pools, and Similar Environments.

Legionella spp. is widespread in many natural and artificial water systems, such as hot water distribution networks, cooling towers, and spas. A particular risk factor has been identified in the use of whirlpools and hot tubs in spa facilities and public baths. However, there has been no systematic synthesis of the published literature reporting legionellosis cases or outbreaks related to swimming/spa pools or similar environments used for recreational purposes (hot springs, hot tubs, whirlpools, natural spas). This study presents the results of a systematic review of the literature on cases and outbreaks associated with these environments. Data were extracted from 47 articles, including 42 events (17 sporadic cases and 25 outbreaks) and 1079 cases, 57.5% of which were diagnosed as Pontiac fever, without any deaths, and 42.5% were of Legionnaires’ disease, with a fatality rate of 6.3%. The results are presented in relation to the distribution of Legionella species involved in the events, clinical manifestations and diagnosis, predisposing conditions in the patients, favourable environmental factors, and quality of the epidemiological investigation, as well as in relation to the different types of recreational water sources involved. Based on the epidemiological and microbiological criteria, the strength of evidence linking a case/outbreak of legionellosis with a recreational water system was classified as strong, probable, and possible; in more than half of the events the resulting association was strong.

Factors Mediating Environmental Biofilm Formation by Legionella pneumophila.

Legionella pneumophila (L. pneumophila) is an opportunistic waterborne pathogen and the causative agent for Legionnaires' disease, which is transmitted to humans via inhalation of contaminated water droplets. The bacterium is able to colonize a variety of man-made water systems such as cooling towers, spas, and dental lines and is widely distributed in multiple niches, including several species of protozoa In addition to survival in planktonic phase, L. pneumophila is able to survive and persist within multi-species biofilms that cover surfaces within water systems. Biofilm formation by L. pneumophila is advantageous for the pathogen as it leads to persistence, spread, resistance to treatments and an increase in virulence of this bacterium. Furthermore, Legionellosis outbreaks have been associated with the presence of L. pneumophila in biofilms, even after the extensive chemical and physical treatments. In the microbial consortium-containing L. pneumophila among other organisms, several factors either positively or negatively regulate the presence and persistence of L. pneumophila in this bacterial community. Biofilm-forming L. pneumophila is of a major importance to public health and have impact on the medical and industrial sectors. Indeed, prevention and removal protocols of L. pneumophila as well as diagnosis and hospitalization of patients infected with this bacteria cost governments billions of dollars. Therefore, understanding the biological and environmental factors that contribute to persistence and physiological adaptation in biofilms can be detrimental to eradicate and prevent the transmission of L. pneumophila. In this review, we focus on various factors that contribute to persistence of L. pneumophila within the biofilm consortium, the advantages that the bacteria gain from surviving in biofilms, genes and gene regulation during biofilm formation and finally challenges related to biofilm resistance to biocides and anti-Legionella treatments.

Combining Environmental Investigation and a Dual-Analytical Strategy to Isolate the Legionella longbeachae Strain Linked to Two Occupational Cases of Legionellosis.

Legionella has a global distribution, mainly in aquatic and man-made environments. Under the right conditions, this bacterium is a notorious human pathogen responsible for severe pulmonary illnesses. Legionellosis outbreaks are reported around the world, and exposure to water droplet aerosols containing Legionella pneumophila is usually the mechanism of its transmission. Even if L. pneumophila causes most outbreaks, Legionella longbeachae also accounts for some cases. Unlike most other Legionella strains, L. longbeachae is typically found in soil. Given the wide diversity and high concentration of microorganisms found in soil, isolating L. longbeachae by culture can be challenging. Because the chances of successfully isolating the strain are low, it is often not even attempted. This study reports the strategies used to successfully isolate L. longbeachae strain that was responsible of the two occupational legionellosis in Quebec. Fifteen random samples were collected from the soil of the metal recycling plant where the diagnosed workers were employed, covering 1.5% of the accessible surface of the plant. All samples were analyzed with both the quantitative polymerase chain reaction (qPCR) and culture methods. Four qPCR detection systems targeting Legionella spp, L. pneumophila, L. pneumophila serogroup 1, and L. longbeachae were used. Acid, heat, and acid/heat treatments were used for the culture method. For the qPCR method, all samples were positives for Legionella spp but only four were positives for L. longbeachae. For the culture method, only one isolate could be confirmed to be L. longbeachae. However, that strain proves to be the same one that caused the occupational legionellosis. Detecting the presence of L. longbeachae using the qPCR method made it possible to target the right samples to enable the cultivable strain of L. longbeachae to be isolated from the soil of the metal recycling plant. The complementarity of the two methods was established. This paper demonstrated the advantages of selecting the proper sampling and analytical strategies to achieve the isolation of the strain responsible for the infections. It also highlights for the first time in Quebec the potential occupational risks associated with L. longbeachae from soil and should motivate questioning soil exposures when all sources of water contamination have been eliminated from the causal analysis of legionellosis.

Quantification of viable and non-viable Legionella spp. by heterogeneous asymmetric recombinase polymerase amplification (haRPA) on a flow-based chemiluminescence microarray

Increasing numbers of legionellosis outbreaks within the last years have shown that Legionella are a growing challenge for public health. Molecular biological detection methods capable of rapidly identifying viable Legionella are important for the control of engineered water systems. The current gold standard based on culture methods takes up to 10 days to show positive results. For this reason, a flow-based chemiluminescence (CL) DNA microarray was developed that is able to quantify viable and non-viable Legionella spp. as well as Legionella pneumophila in one hour. An isothermal heterogeneous asymmetric recombinase polymerase amplification (haRPA) was carried out on flow-based CL DNA microarrays. Detection limits of 87 genomic units (GU) µL−1 and 26GUµL−1 for Legionella spp. and Legionella pneumophila, respectively, were achieved. In this work, it was shown for the first time that the combination of a propidium monoazide (PMA) treatment with haRPA, the so-called viability haRPA, is able to identify viable Legionella on DNA microarrays. Different proportions of viable and non-viable Legionella, shown with the example of L. pneumophila, ranging in a total concentration between 101 to 105GUµL−1 were analyzed on the microarray analysis platform MCR 3. Recovery values for viable Legionella spp. were found between 81% and 133%. With the combination of these two methods, there is a chance to replace culture-based methods in the future for the monitoring of engineered water systems like condensation recooling plants.

Legionella longbeachae detected in an industrial cooling tower linked to a legionellosis outbreak, New Zealand, 2015; possible waterborne transmission?

A legionellosis outbreak at an industrial site was investigated to identify and control the source. Cases were identified from disease notifications, workplace illness records, and from clinicians. Cases were interviewed for symptoms and risk factors and tested for legionellosis. Implicated environmental sources were sampled and tested for legionella. We identified six cases with Legionnaires' disease and seven with Pontiac fever; all had been exposed to aerosols from the cooling towers on the site. Nine cases had evidence of infection with either Legionella pneumophila serogroup (sg) 1 or Legionella longbeachae sg1; these organisms were also isolated from the cooling towers. There was 100% DNA sequence homology between cooling tower and clinical isolates of L. pneumophila sg1 using sequence-based typing analysis; no clinical L. longbeachae isolates were available to compare with environmental isolates. Routine monitoring of the towers prior to the outbreak failed to detect any legionella. Data from this outbreak indicate that L. pneumophila sg1 transmission occurred from the cooling towers; in addition, L. longbeachae transmission was suggested but remains unproven. L. longbeachae detection in cooling towers has not been previously reported in association with legionellosis outbreaks. Waterborne transmission should not be discounted in investigations for the source of L. longbeachae infection.

Vital Signs: Deficiencies in Environmental Control Identified in Outbreaks of Legionnaires’ Disease—North America, 2000–2014

Background The number of reported cases of Legionnaires’ disease, a severe pneumonia caused by the bacterium Legionella, is increasing in the United States. During 2000–2014, the rate of reported legionellosis cases increased from 0.42 to 1.62 per 100 000 persons; 4% of reported cases were outbreak-associated. Legionella is transmitted through aerosolization of contaminated water. A new industry standard for prevention of Legionella growth and transmission in water systems in buildings was published in 2015. CDC investigated outbreaks of Legionnaires’ disease to identify gaps in building water system maintenance and guide prevention efforts. Methods Information from summaries of CDC Legionnaires’ disease outbreak investigations during 2000–2014 was systematically abstracted, and water system maintenance deficiencies from land-based investigations were categorized as process failures, human errors, equipment failures, or unmanaged external changes. Results During 2000–2014, CDC participated in 38 field investigations of Legionnaires’ disease. Among 27 land-based outbreaks, the median number of cases was 10 (range = 3–82) and median outbreak case fatality rate was 7% (range = 0–80%). Sufficient information to evaluate maintenance deficiencies was available for 23 (85%) investigations. Of these, all had at least one deficiency; 11 (48%) had deficiencies in ≥2 categories. Fifteen cases (65%) were linked to process failures, 12 (52%) to human errors, eight (35%) to equipment failures, and eight (35%) to unmanaged external changes. Conclusions and Implications for Public Health Practice Multiple common preventable maintenance deficiencies were identified in association with disease outbreaks, highlighting the importance of comprehensive water management programs for water systems in buildings. Properly implemented programs, as described in the new industry standard, could reduce Legionella growth and transmission, preventing Legionnaires’ disease outbreaks and reducing disease.

Mass Gatherings and Respiratory Disease Outbreaks in the United States - Should We Be Worried? Results from a Systematic Literature Review and Analysis of the National Outbreak Reporting System.

BackgroundBecause mass gatherings create environments conducive for infectious disease transmission, public health officials may recommend postponing or canceling large gatherings during a moderate or severe pandemic. Despite these recommendations, limited empirical information exists on the frequency and characteristics of mass gathering-related respiratory disease outbreaks occurring in the United States.MethodsWe conducted a systematic literature review to identify articles about mass gathering-related respiratory disease outbreaks occurring in the United States from 2005 to 2014. A standard form was used to abstract information from relevant articles identified from six medical, behavioral and social science literature databases. We also analyzed data from the National Outbreaks Reporting System (NORS), maintained by the Centers for Disease Control and Prevention since 2009, to estimate the frequency of mass gathering-related respiratory disease outbreaks reported to the system.ResultsWe identified 21 published articles describing 72 mass gathering-related respiratory disease outbreaks. Of these 72, 40 (56%) were associated with agriculture fairs and Influenza A H3N2v following probable swine exposure, and 25 (35%) with youth summer camps and pandemic Influenza A H1N1. Outbreaks of measles (n = 1) and mumps (n = 2) were linked to the international importation of disease. Between 2009 and 2013, 1,114 outbreaks were reported to NORS, including 96 respiratory disease outbreaks due to Legionella. None of these legionellosis outbreaks was linked to a mass gathering according to available data.ConclusionMass gathering-related respiratory disease outbreaks may be uncommon in the United States, but have been reported from fairs (zoonotic transmission) as well as at camps where participants have close social contact in communal housing. International importation can also be a contributing factor. NORS collects information on certain respiratory diseases and could serve as a platform to monitor mass gathering-related respiratory outbreaks in the future.

Legionella DNA Markers in Tap Water Coincident with a Spike in Legionnaires’ Disease in Flint, MI

Two clusters of Legionnaires’ disease occurred in Flint, MI, subsequent to switching to a corrosive potable water source from April 2014 to October 2015. We hypothesized that the interrupted corrosion control and associated release of iron, nutrients, and depleted chlorine residual in the distribution system would lead to high levels of Legionella. A tap water survey conducted throughout Flint in August and October 2015 confirmed Legionella pneumophila in two hospitals (mean of 1890 ± 2220 gene copy numbers/mL, 48% positivity), but not small single-story buildings. The hospitals frequently had optimal Legionella growth temperatures and were located in high-water age zones of the distribution system (3 to >6 days). Relatively high concentrations of iron were present (mean of 51.0 ± 37.2 ppb), and Cl2 residual was sporadic (mean of 0.700 ± 0.775 mg/L) throughout the Flint distribution system. This study addresses knowledge gaps linking legionellosis outbreaks to changes in municipal water quality and distri...

Legionella pneumophila: The Paradox of a Highly Sensitive Opportunistic Waterborne Pathogen Able to Persist in the Environment.

Legionella pneumophila, the major causative agent of Legionnaires’ disease, is found in freshwater environments in close association with free-living amoebae and multispecies biofilms, leading to persistence, spread, biocide resistance, and elevated virulence of the bacterium. Indeed, legionellosis outbreaks are mainly due to the ability of this bacterium to colonize and persist in water facilities, despite harsh physical and chemical treatments. However, these treatments are not totally efficient and, after a lag period, L. pneumophila may be able to quickly re-colonize these systems. Several natural compounds (biosurfactants, antimicrobial peptides…) with anti-Legionella properties have recently been described in the literature, highlighting their specific activities against this pathogen. In this review, we first consider this hallmark of Legionella to resist killing, in regard to its biofilm or host-associated life style. Then, we focus more accurately on natural anti-Legionella molecules described so far, which could provide new eco-friendly and alternative ways to struggle against this important pathogen in plumbing.