Open research questions in Legionella and Acanthamoeba research
126 gap statements mined from Legionella and Acanthamoeba research papers in our 4.5M-paper local library, which holds 427 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.
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What the literature leaves open
The impact of wastewater on the microbiological quality of water was often overlooked during the COVID-19 pandemic. There is a need to expand the range of bacterial indicators for public health and environmental hygiene. The study aims to address the gap in evaluating the effectiveness of sequencing methods in pre-epidemic studies.
Re-Emerging Bacterial Pathogens, Resistance Genes and Promising Bioindicators in Raw and Treated Sewage—Addressing a Known Issue from a Different Angle and Perspective · 2026 · DOIThe lack of approved, effective, and safe treatments for free-living amoebae infections. The challenges of conducting clinical trials for these rare and rapidly lethal diseases. The need for a cost-effective strategy to accelerate therapeutic advances.
Promising Drug Repurposing Candidates Targeting Free-Living Amoebae: A Systematic and Critical Review of Laboratory-Based Evidence · 2026 · DOIFew studies have investigated the effect of chloramine disinfection on Legionnaires' disease outbreak. The researchers aim to fill this gap by studying the effect of chloramine disinfection on a Legionnaires' disease outbreak in a community water system.
Effect of Chloramine Disinfection of Community Water System on Legionnaires’ Disease Outbreak, Minnesota, USA, 2024 · 2026 · DOIThe need to distinguish between autoimmune flare and Legionella pneumonia in patients with similar symptoms.
Case Report: When muscle edema is not a myositis flare: Legionella pneumonia complicated by rhabdomyolysis and acute kidney injury in long-standing polymyositis · 2026 · DOIThe lack of awareness about the risks of using unboiled tap water for nasal rinsing among immunocompromised persons. The need for education on safe nasal rinsing practices to prevent free-living ameba infections. The importance of identifying the link between nasal rinsing and Acanthamoeba infection in immunocompromised patients.
It highlights the need to address the potential for genetic recombination and microevolution of the ST1905 strain. The study also notes the challenge of preventing further disease spread and ensuring public health preparedness.
Recurrence, Microevolution, and Spatiotemporal Dynamics of Legionella pneumophila Sequence Type 1905, Portugal, 2014–2022 · 2024 · DOIEctopic expression of Pels in mammalian cells results in distinct membrane localization, yet their subcellular localization and their role in the infection remain unknown.
Localization of the PelC and PelE effectors to the Legionella -containing vacuole through host-mediated prenylation and their role in intracellular proliferation · 2026 · DOIThe Dot/Icm type IV secretion system (T4SS) is essential for Legionella pneumophila infection, but its in situ architecture and mechanism remain incompletely understood.
Waste stabilization ponds (WSPs) represent a sustainable, low-cost wastewater treatment option, yet the ecological dynamics of microeukaryotic communities and their pathogenic potential remain underexplored.
Spatiotemporal dynamics and potential pathogen fate of microeukaryotic communities in a full-scale waste stabilization pond system · 2025 · DOILegionella infections are a major global health issue, yet there's limited research on their impact and trends.
The Global Burden and Trends of Legionella spp. Infection-Associated Diseases from 1990 to 2021: An Observational Study · 2025 · DOICyclic peptides exhibit a broad spectrum of antimicrobial activities but are underexplored for their antiamoebic activity.
Cyclic Peptide Natural Product Inspired Inhibitors of the Free-Living Amoeba Balamuthia mandrillaris · 2025 · DOIInnovative approaches to intentionally manipulate the microbial ecology to control Lp have been proposed but remain elusive.
Retrospective Analysis of Drinking Water Microcosm Microbiomes Reveals an Apparent Antagonistic Relationship between Neochlamydia and Legionella · 2025 · DOIInfections occur in seemingly healthy individuals and effective clinical options are lacking, thus a nearly 98% fatality rate.
Therapeutic glycan-specific antibody binding mediates protection during primary amoebic meningoencephalitis · 2024 · DOIYet, how Abs might interact with Naegleria in vivo or contribute to preventing lethal infection is not well understood.
Therapeutic glycan-specific antibody binding mediates protection during primary amoebic meningoencephalitis · 2024 · DOIEfficacious treatment options for these infections are lacking and the mortality rate remains >95% in the US.
Similarly, host factors that may alleviate cell death induced by these bacterial strains have not yet been investigated.
Legionella pneumophila exploits the endo-lysosomal network for phagosome biogenesis by co-opting SUMOylated Rab7 · 2024 · DOIThe bacterial factor directly responsible for inducing such cell death and the host factor involved in initiating the signaling cascade that leads to lysosome damage remain unknown.
Legionella pneumophila exploits the endo-lysosomal network for phagosome biogenesis by co-opting SUMOylated Rab7 · 2024 · DOIThe lack of standardized treatment has significantly contributed to the high fatality rates observed in reported cases.
Synthesis and Biological Evaluation of Cyanoacrylamides and 5-Iminopyrrol-2-Ones Against Naegleria fowleri · 2024 · DOIOur findings demonstrate an intriguing role of Lpg2444 in mitocytosis and highlight subjects that warrant further investigation in the future.
RETRACTED: Legionella pneumophila infection reduces the mitochondrial membrane potential through Lpg2444 ‐inhibited mitocytosis · 2024 · DOIThe impact of time to effective Legionella-directed therapy on mortality is not well defined.
Time to Effective Therapy and Mortality in Community-Acquired Legionella Pneumonia: A Multicenter Retrospective Cohort Study · 2026 · DOIT4bSS are well known to translocate soluble as well as transmembrane domain-containing effector proteins (TMD-effectors) but the mechanisms of secretion are still poorly understood.
The T4bSS of Legionella features a two-step secretion pathway with an inner membrane intermediate for secretion of transmembrane effectors · 2024 · DOIFurther studies on the effectiveness of sequencing methods in pre-epidemic studies, - Investigation of the cycling of genetic information in sewage, - Development of new markers for population well-being…
Re-Emerging Bacterial Pathogens, Resistance Genes and Promising Bioindicators in Raw and Treated Sewage—Addressing a Known Issue from a Different Angle and Perspective · 2026 · DOIFurther evaluation of the 166 compounds that showed substantial trophocidal activity, - Investigation of the potential of drug-repurposing for the treatment of FLA infections, - Development of new drugs from synthetic compounds…
Promising Drug Repurposing Candidates Targeting Free-Living Amoebae: A Systematic and Critical Review of Laboratory-Based Evidence · 2026 · DOICausation cannot be determined using these data, - Survival beyond the date of report cannot be confirmed, - Information regarding nasal rinsing practices were limited for some cases, - The small number of cases did not enable thorough assessment of practices that may be considered to increase risk…
Further studies are needed to investigate the effect of different disinfection methods on Legionella growth, - Research is needed to develop more effective methods for monitoring and controlling Legionella growth in community water systems, - Studies should be conducted to examine the effect of chloramine disinfection on Legionella growth in different types of water…
Effect of Chloramine Disinfection of Community Water System on Legionnaires’ Disease Outbreak, Minnesota, USA, 2024 · 2026 · DOI
Most-cited papers in Legionella and Acanthamoeba research
- Surveillance for Legionnaires' disease. Risk factors for morbidity and mortality · Archives of Internal Medicine · 1994 · 460 citations
- Surveillance for Legionnaires' Disease · Archives of Internal Medicine · 1994 · 378 citations
- Handbuch des Betäubungsmittelstrafrechts. (Böllinger) · Kriminologisches Journal · 2000 · 268 citations
- Human infections caused by free-living amoebae · Annals of Agricultural and Environmental Medicine · 2017 · 104 citations
- Opportunistic Pathogens in Drinking Water Distribution Systems—A Review · Microorganisms · 2024 · 81 citations
- Isolation of Legionella pneumophila from water systems: methods and preliminary results. · BMJ · 1981 · 80 citations
- A Large Community Outbreak of Legionnaires’ Disease Associated With a Cooling Tower in New York City, 2015 · Public Health Reports · 2017 · 70 citations
- Amoebae as training grounds for microbial pathogens · mBio · 2024 · 51 citations
- Understanding Acanthamoeba Keratitis: An In-Depth Review of a Sight-Threatening Eye Infection · Microorganisms · 2024 · 46 citations
- Cross‐reactivity of specific antibodies directed to heat shock proteins from periodontopathogenic bacteria of human origin · Oral Microbiology and Immunology · 1998 · 42 citations
Most recent work
- Mitochondrial proteome of Acanthamoeba delineates aerobic and anaerobic pathways dynamically regulated by oxygen · Cell · 2026
- Legionella Pneumonia in the Modern Era: Clinical Features and Predictors of Mortality · Clinical Infectious Diseases · 2026
- Acanthamoeba ATP synthase structure reveals the TCA cycle is tethered to OXPHOS · Cell · 2026
- Crystal structure of the Legionella pneumophila effector SidL (Lpg0437) in complex with its metaeffector LegA11 (Lpg0436) · Virulence · 2026
- Manipulation of the Unfolded Protein Response by Intracellular Bacterial Pathogens: Mechanisms of ER Hijacking and Therapeutic Implications · The FASEB Journal · 2026
- Mucin stimulates the growth of Legionella pneumophila · Microbiology · 2026
- PDIM drives the transition from repairable to catastrophic EsxA-mediated vacuole membrane damage during Mycobacterium marinum infection · bioRxiv · 2026
- Acanthamoeba myelopathy mimicking tropical spastic paraparesis in immunocompetent hosts: a case series · Neurological Sciences · 2026
- Regulation of ribosome hibernation controls Legionella survival, infection, antibiotic tolerance, and phenotypic heterogeneity · mBio · 2026
- Promising Drug Repurposing Candidates Targeting Free-Living Amoebae: A Systematic and Critical Review of Laboratory-Based Evidence · Pathogens · 2026
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