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This article discusses the use of rifampin in clinical drug-drug interaction (DDI) studies. Rifampin is an antibiotic that is commonly used as an inducer of drug-metabolizing enzymes and transporters. However, recent reports of a nitrosamine impurity called 1-methyl-4-nitrosopiperazine (MNP) in rifampin products have raised concerns. The FDA has set a limit for MNP in rifampin products, and this has led to the search for alternative inducers for DDI studies. The authors argue that rifampin should continue to be used in these studies due to its well-established induction effects, pleiotropic effects, and safety profile compared to alternative inducers like carbamazepine and phenytoin. [Extracted from the article]

In the summer of 1976, prior to the United States presidential election between Gerald Ford and Jimmy Carter, an outbreak of Legionnaires' disease occurred in Philadelphia. After an epidemiological survey, 221 people with pneumonia or similar symptoms were identified, 34 of whom died. The outbreak prompted the advancement of legislation to exempt companies that produced influenza vaccines from liability for damages, resulting in significant losses for the government. The outbreak was a major economic blow to the Bellevue Stratford Hotel, an iconic historical hotel in Philadelphia, which was forced to close 16 days after the election. Following the outbreak, media coverage was extensive, and there was frustration over the inability to determine the cause of the outbreak in Philadelphia. The critical factor was that the cause of the outbreak was not determined to be rod‐shaped bacteria, later named Legionella pneumophila, before the election date. While many aspects had an impact, it is possible that the Legionnaires' disease outbreak may have affected the outcome of the election, particularly in Pennsylvania. This study does not make definitive causal links but focuses on Legionnaires' disease and the 1976 elections. [ABSTRACT FROM AUTHOR]

Understanding how the infectious disease burden was affected throughout the COVID‐19 pandemic is pivotal to identifying potential hot spots and guiding future mitigation measures. Therefore, our study aimed to analyze the changes in the rate of new cases of Poland's most frequent infectious diseases during the entire COVID‐19 pandemic and after the influx of war refugees from Ukraine. We performed a registry‐based population‐wide study in Poland to analyze the changes in the rate of 24 infectious disease cases from 2020 to 2023 and compared them to the prepandemic period (2016–2019). Data were collected from publicly archived datasets of the Epimeld database published by national epidemiological authority institutions. The rate of most of the studied diseases (66.6%) revealed significantly negative correlations with the rate of SARS‐CoV‐2 infections. For the majority of infectious diseases, it substantially decreased in 2020 (in case of 83%) and 2021 (63%), following which it mostly rebounded to the prepandemic levels and, in some cases, exceeded them in 2023 when the exceptionally high annual rates of new cases of scarlet fever, Streptococcus pneumoniae infections, HIV infections, syphilis, gonococcal infections, and tick‐borne encephalitis were noted. The rate of Clostridioides difficile enterocolitis was two‐fold higher than before the pandemic from 2021 onward. The rate of Legionnaires' disease in 2023 also exceeded the prepandemic threshold, although this was due to a local outbreak unrelated to lifted COVID‐19 pandemic restrictions or migration of war refugees. The influx of war migrants from Ukraine could impact the epidemiology of sexually transmitted diseases. The present analysis indicates that continued efforts are needed to prevent COVID‐19 from overwhelming healthcare systems again and decreasing the control over the burden of other infectious diseases. It also identifies the potential tipping points that require additional mitigation measures, which are also discussed in the paper, to avoid escalation in the future. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Legionnaires' disease, often presenting as pneumonia, can uncommonly manifest with extrapulmonary symptoms such as cerebellar involvement and rhabdomyolysis. This case emphasizes the successful resolution of dysarthria and renal dysfunction with prompt Legionella treatment, underscoring the importance of vigilance for diverse manifestations in Legionella infections. Legionnaires' disease usually presents with pneumonia and a few extrapulmonary manifestations, such as neurological, musculoskeletal, and cutaneous manifestations. However, cerebellar involvement and rhabdomyolysis as an association with Legionella are not frequently encountered. We present a case of Legionella‐induced rhabdomyolysis requiring hemodialysis and dysarthria that resolved with Legionella treatment. [ABSTRACT FROM AUTHOR]

This article presents a case report of a 35-year-old Chinese woman who initially presented with symptoms resembling idiopathic inflammatory myopathy (IIM), a rare autoimmune disorder affecting muscles. However, further investigation revealed that she had legionnaire's disease (LD), a bacterial infection that mimicked the symptoms of IIM. The patient's diagnosis was confirmed through pathogen screening, and she was successfully treated with antibiotics. The case highlights the importance of considering infectious etiologies when diagnosing conditions that mimic IIM and emphasizes the need for a comprehensive diagnostic approach. [Extracted from the article]

The article discusses the importance of maintaining water quality in buildings and the role that water utilities can play in this process. While utilities are not responsible for water quality within buildings, they can implement measures such as secondary disinfection and corrosion control strategies to help building owners and operators maintain water quality. The article also highlights the efforts of the American Water Works Association's Premise Plumbing Committee (PPC) in synthesizing industry knowledge and providing guidance on topics such as controlling microbial growth and managing lead and copper in building plumbing systems. The PPC is also working towards creating a training and certification program for building water system (BWS) operators to ensure adequate management of BWSs and the control of microbial pathogens and other contaminants. [Extracted from the article]

Legionella pneumophila is a gram‐negative bacteria found in natural and anthropogenic aquatic environments such as evaporative cooling towers, where it reproduces as an intracellular parasite of cohabiting protozoa. If L. pneumophila is aerosolized and inhaled by a susceptible person, bacteria may colonize their alveolar macrophages causing the opportunistic pneumonia Legionnaires' disease. L. pneumophila utilizes an elaborate regulatory network to control virulence processes such as the Dot/Icm Type IV secretion system and effector repertoire, responding to changing nutritional cues as their host becomes depleted. The bacteria subsequently differentiate to a transmissive state that can survive in the environment until a replacement host is encountered and colonized. In this review, we discuss the lifecycle of L. pneumophila and the molecular regulatory network that senses nutritional depletion via the stringent response, a link to stationary phase‐like metabolic changes via alternative sigma factors, and two‐component systems that are homologous to stress sensors in other pathogens, to regulate differentiation between the intracellular replicative phase and more transmissible states. Together, we highlight how this prototypic intracellular pathogen offers enormous potential in understanding how molecular mechanisms enable intracellular parasitism and pathogenicity. [ABSTRACT FROM AUTHOR]

Legionnaires' disease is caused by Legionella (L.) pneumophila. Inhaling aerosolized water containing this bacteria is the most common transmission route. Shower heads used in the catering industry's dishwashing units are also potential amplifying systems for bacteria and possible sources of infection by generating droplets and aerosols. Therefore, these systems should not contain pathogenic bacteria. This study aims to monitor the microbial quality, Legionnaires' disease risk and L. pneumophila presence in tap water samples from the water outlet of the shower‐type dishwashing unit of mass catering establishments for a year. Seventy‐two tap water samples were microbiologically tested for total mesophilic aerobic bacteria count, coliform, Escherichia (E.) coli and L. pneumophila. DNA was isolated from L. pneumophila‐positive samples, and their serogroup was characterized by real‐time PCR. The correlation between seasonal variation and prevalence of L. pneumophila serogroup and L. pneumophila and other indicator bacteria were statistically tested by Spearman rank test (p < 0.05). Findings showed that 17 (24%) samples had microbial growth, 14 (19.4%) were positive for L. pneumophila and 13 isolates were characterized as L. pneumophila serogroup 1. The statistical analysis showed no significant correlation between seasonal variation (p = 0.491) and L. pneumophila and total mesophilic aerobic bacteria count, coliform and E. coli (p = 0.923). Overall, Legionella spp. is an essential indicator of the microbial quality in the tap water from mass catering establishments and should be regularly monitored for public health independently from seasonal variation and other indicator bacteria. [ABSTRACT FROM AUTHOR]

Inorganic pyrophosphate (PPi) is generated as an intermediate or byproduct of many fundamental metabolic pathways, including DNA/RNA synthesis. The intracellular concentration of PPi must be regulated as buildup can inhibit many critical cellular processes. Inorganic pyrophosphatases (PPases) hydrolyze PPi into two orthophosphates (Pi), preventing the toxic accumulation of the PPi byproduct in cells and making Pi available for use in biosynthetic pathways. Here, the crystal structure of a family I inorganic pyrophosphatase from Legionella pneumophila is reported at 2.0 Å resolution. L. pneumophila PPase (LpPPase) adopts a homohexameric assembly and shares the oligonucleotide/oligosaccharide‐binding (OB) β‐barrel core fold common to many other bacterial family I PPases. LpPPase demonstrated hydrolytic activity against a general substrate, with Mg2+ being the preferred metal cofactor for catalysis. Legionnaires' disease is a severe respiratory infection caused primarily by L. pneumophila, and thus increased characterization of the L. pneumophila proteome is of interest. [ABSTRACT FROM AUTHOR]

Legionella longbeachae is the most common cause of Legionnaires' disease in Australasia. Legionella species are considered a rare cause of pleural infection, and empyema and lung abscess due to L. longbeachae has not previously been reported. Our patient presented with a 2–3 week history of breathlessness, lethargy, dry cough and headaches. Initial chest radiograph showed extensive left sided consolidation with an associated pleural effusion. An area of necrotising pneumonia evident on computed tomography scan evolved into a multiloculated intrapulmonary abscess. Sputum culture isolated L. longbeachae, which prompted culture of pleural fluid on buffered charcoal yeast extract agar and isolation of the organism. This case provides evidence that L. longbeachae can cause both empyema and lung abscess, and in areas where it is prevalent, increased use of Legionella specific agar for pleural fluid culture should be considered. [ABSTRACT FROM AUTHOR]

Lipid droplets (LDs) are dynamic and versatile organelles present in most eukaryotic cells. LDs consist of a hydrophobic core of neutral lipids, a phospholipid monolayer coat, and a variety of associated proteins. LDs are formed at the endoplasmic reticulum and have diverse roles in lipid storage, energy metabolism, membrane trafficking, and cellular signaling. In addition to their physiological cellular functions, LDs have been implicated in the pathogenesis of several diseases, including metabolic disorders, cancer, and infections. A number of intracellular bacterial pathogens modulate and/or interact with LDs during host cell infection. Members of the genera Mycobacterium, Legionella, Coxiella, Chlamydia, and Salmonella exploit LDs as a source of intracellular nutrients and membrane components to establish their distinct intracellular replicative niches. In this review, we focus on the biogenesis, interactions, and functions of LDs, as well as on their role in lipid metabolism of intracellular bacterial pathogens. [ABSTRACT FROM AUTHOR]

The conservation of freshwater is of both global and national importance, and in the United States, agriculture is one of the largest consumers of this resource. Reduction of the strain farming puts on local surface or groundwater is vital for ensuring resilience in the face of climate change, and one possible option is to irrigate with a combination of freshwater and reclaimed water from municipal wastewater treatment facilities. However, this wastewater can contain pathogens that are harmful to human health, such as Legionella pneumophila, which is a bacterium that can survive aerosolization and airborne transportation and cause severe pneumonia when inhaled. To assess an individual adult's risk of infection with L. pneumophila from a single exposure to agricultural spray irrigation, a quantitative microbial risk assessment was conducted for a scenario of spray irrigation in central Illinois, for the growing seasons in 2017, 2018, and 2019. The assessment found that the mean risk of infection for a single exposure exceeded the safety threshold of 10–6 infections/exposure up to 1 km from a low‐pressure irrigator and up to 2 km from a high‐pressure irrigator, although no median risk exceeded the threshold for any distance or irrigator pressure. These findings suggest that spray irrigation with treated municipal wastewater could be a viable option for reducing freshwater consumption in Midwest farming, as long as irrigation on windy days is avoided and close proximity to the active irrigator is limited. [ABSTRACT FROM AUTHOR]

Legionella pneumophila replicates in macrophages and amoeba within a unique compartment, the Legionella‐containing vacuole (LCV). Hallmarks of LCV formation are the phosphoinositide lipid conversion from PtdIns(3)P to PtdIns(4)P, fusion with ER‐derived vesicles and a tight association with the ER. Proteomics of purified LCVs indicate the presence of membrane contact sites (MCS) proteins possibly implicated in lipid exchange. Using dually fluorescence‐labeled Dictyostelium discoideum amoeba, we reveal that VAMP‐associated protein (Vap) and the PtdIns(4)P 4‐phosphatase Sac1 localize to the ER, and Vap also localizes to the LCV membrane. Furthermore, Vap as well as Sac1 promote intracellular replication of L. pneumophila and LCV remodeling. Oxysterol binding proteins (OSBPs) preferentially localize to the ER (OSBP8) or the LCV membrane (OSBP11), respectively, and restrict (OSBP8) or promote (OSBP11) bacterial replication and LCV expansion. The sterol probes GFP‐D4H* and filipin indicate that sterols are rapidly depleted from LCVs, while PtdIns(4)P accumulates. In addition to Sac1, the PtdIns(4)P‐subverting L. pneumophila effector proteins LepB and SidC also support LCV remodeling. Taken together, the Legionella‐ and host cell‐driven PtdIns(4)P gradient at LCV‐ER MCSs promotes Vap‐, OSBP‐ and Sac1‐dependent pathogen vacuole maturation. Synopsis: Legionella pneumophila replicates intracellularly within a unique "Legionella‐containing vacuole" (LCV). Dually fluorescence‐labeled Dictyostelium discoideum amoeba reveal that LCVs and the ER form membrane contact sites and Legionella‐ as well as host cell‐driven lipid flux promotes pathogen vacuole remodeling. The Legionella‐containing vacuole (LCV) engages in membrane contact sites (MCS) with the ER.The MCS components VAMP‐associated protein (Vap), oxysterol binding proteins (OSBPs), and the PtdIns(4)P 4‐phosphatase Sac1 localize to the ER and/or the LCV membrane.Host cell factors (Vap, OSBPs, Sac1) as well as bacterial effector proteins (LepB, SidC) modulate lipid exchange, LCV remodelling and intracellular growth of L. pneumophila. [ABSTRACT FROM AUTHOR]

During an ongoing outbreak of Legionnaires' disease in Belgium, residents of the affected area took part in an online field experiment. The impact of four distinct crisis messages used by the Belgian authorities was tested on uncertainty, fear and trust. After receiving any of these messages, participants felt less insecure, less anxious and had more trust in the authorities as compared to before they saw the information. The extent of this positive impact of crisis information depended, however, on the message that was offered. Two messages offering comprehensive instructing and adjusting information appeared more effective than two messages offering only limited (predominantly adjusting) information. The use of visuals, by means of an infographic, did not seem to hinder or increase the effectiveness of the message in this particular study. Organizations and authorities responsible for managing a health crisis are recommended to actively communicate a complete overview of information about what is going on as well as specific information regarding what the public can (or cannot) do to address the matter. While visual aids may not be necessary, they can be helpful to effectively communicate a comprehensive overview of information through social media. [ABSTRACT FROM AUTHOR]

In the summer of 1984, Professor Haas had the opportunity under the AAAS Environmental Science and Engineering Fellowship to spend 10 weeks in Washington, DC and learn about federal science and technology policy formation. At that time in Illinois the expansion of solid waste landfills required showing a need at the county level, and Professor Haas testified at several county board hearings to support the needs assessment. Former student and now colleague Patrick Gurian's thoughts: Chuck is probably best known for his contributions to developing dose response models for pathogenic microorganisms and for using these to informing water quality regulations and bioterrorism response plans. Chuck Haas was attracted to science as a young child. [Extracted from the article]

The pathogen Legionella pneumophila, which is the causative agent of Legionnaires' disease, secrets hundreds of effectors into host cells via its Dot/Icm secretion system to subvert host‐cell pathways during pathogenesis. VipF, a conserved core effector among Legionella species, is a putative acetyltransferase, but its structure and catalytic mechanism remain unknown. Here, three crystal structures of VipF in complex with its cofactor acetyl‐CoA and/or a substrate are reported. The two GNAT‐like domains of VipF are connected as two wings by two β‐strands to form a U‐shape. Both domains bind acetyl‐CoA or CoA, but only in the C‐terminal domain does the molecule extend to the bottom of the U‐shaped groove as required for an active transferase reaction; the molecule in the N‐terminal domain folds back on itself. Interestingly, when chloramphenicol, a putative substrate, binds in the pocket of the central U‐shaped groove adjacent to the N‐terminal domain, VipF remains in an open conformation. Moreover, mutations in the central U‐shaped groove, including Glu129 and Asp251, largely impaired the acetyltransferase activity of VipF, suggesting a unique enzymatic mechanism for the Legionella effector VipF. [ABSTRACT FROM AUTHOR]

Summary: The environmental bacterium Legionella pneumophila causes the pneumonia Legionnaires' disease. The opportunistic pathogen forms biofilms and employs the Icm/Dot type IV secretion system (T4SS) to replicate in amoebae and macrophages. A regulatory network comprising the Legionella quorum sensing (Lqs) system and the transcription factor LvbR controls bacterial motility, virulence and biofilm architecture. Here we show by comparative proteomics that in biofilms formed by the L. pneumophila ΔlqsR or ΔlvbR regulatory mutants the abundance of proteins encoded by a genomic 'fitness island', metabolic enzymes, effector proteins and flagellar components (e.g. FlaA) varies. ∆lqsR or ∆flaA mutants form 'patchy' biofilms like the parental strain JR32, while ∆lvbR forms a 'mat‐like' biofilm. Acanthamoeba castellanii amoebae migrated more slowly through biofilms of L. pneumophila lacking lqsR, lvbR, flaA, a functional Icm/Dot T4SS (∆icmT), or secreted effector proteins. Clusters of bacteria decorated amoebae in JR32, ∆lvbR or ∆icmT biofilms but not in ∆lqsR or ∆flaA biofilms. The amoeba‐adherent bacteria induced promoters implicated in motility (PflaA) or virulence (PsidC, PralF). Taken together, the Lqs‐LvbR network (quorum sensing), FlaA (motility) and the Icm/Dot T4SS (virulence) regulate migration of A. castellanii through L. pneumophila biofilms, and – apart from the T4SS – govern bacterial cluster formation on the amoebae. [ABSTRACT FROM AUTHOR]

The bacterium Legionella pneumophila is a causative agent of Legionnaires' disease. It utilizes the Dot/Icm type IV secretion system (T4SS) to deliver over 300 effector proteins into the host cell, leading to modification of cellular processes and creating a safe environment for bacterial proliferation. Dot/Icm is a multi‐subunit molecular machine. The effectors are recognized by the inner membrane‐embedded coupling complex (T4CC), which then delivers them to the translocation apparatus. This T4CC subcomplex is made up of DotL, DotM, DotN, IcmS, IcmW, LvgA, DotY and DotZ, and its structure was recently determined by cryo‐EM. DotY is a highly mobile component of this subcomplex and its structure was only partially defined. DotY is a unique component of the T4SS that is only found in the Legionella genus. Here, the crystal structure of DotY on its own is presented and its fold and the connectivity of its secondary‐structure elements are established. The protein is divided into three segments. The first and last segments form a four‐helix bundle domain, while the middle segment forms an α/β domain that has a unique fold. The flexibility of the interdomain linkers allows the reorientation of the two domains between that observed in the crystal structure and that assumed within the T4CC subcomplex. [ABSTRACT FROM AUTHOR]

Legionella pneumophila is a human pathogen that causes Legionnaires' disease, a severe form of pneumonia. It can be found in various aquatic environments ranging from cooling towers to ponds. In addition to causing disease in humans, it can also infect free‐living amoebae commonly found in various aquatic environments. Once inside a human lung macrophage, it creates a niche called the Legionella‐containing vacuole where it can evade phagolysosomal degradation and replicate. During infection, normal cellular functions are hijacked by proteins that are secreted by the pathogen, called bacterial effectors. Here, the structural characterization of the effector LegA15/AnkD is reported. The protein contains an ankyrin‐repeat domain followed by a cysteine protease‐like (CPL) domain with a putative catalytic triad consisting of His268–Asn290–Cys361. The CPL domain shows similarity to the CE clan in the MEROPS database, which contains ubiquitin‐like hydrolases. The C‐terminal segment of LegA15, including the CPL domain, shows structural similarity to another effector, LegA3/AnkH, while they share only 12% sequence identity. When expressed in mammalian cells, LegA15 is localized within the cytoplasm, in contrast to LegA3, which localizes to the nucleus. [ABSTRACT FROM AUTHOR]

Legionella pneumophila is a facultative intracellular bacterial pathogen, causing the severe form of pneumonia known as Legionnaires' disease. Legionella actively alters host organelle trafficking through the activities of "effector" proteins secreted via a type‐IVB secretion system, in order to construct the bacteria‐laden Legionella‐containing vacuole (LCV) and prevent lysosomal degradation. The LCV is created with membrane derived from host endoplasmic reticulum (ER), secretory vesicles and phagosomes, although the precise molecular mechanisms that drive its synthesis remain poorly understood. In an effort to characterize the in vivo activity of the LegC7/YlfA SNARE‐like effector protein from Legionella in the context of eukaryotic membrane trafficking in yeast, we find that LegC7 interacts with the Emp46p/Emp47p ER‐to‐Golgi glycoprotein cargo adapter complex, alters ER morphology and induces aberrant ER:endosome interactions, as measured by visualization of ER cargo degradation, reconstitution of split‐GFP proteins and enhanced oxidation of the ER lumen. LegC7‐dependent toxicity, disruption of ER morphology and ER:endosome fusion events were dependent upon endosomal VPS class C tethering complexes and the endosomal t‐SNARE, Pep12p. This work establishes a model in which LegC7 functions to recruit host ER material to the bacterial phagosome during infection by driving ER:endosome contacts, potentially through interaction with host membrane tethering complexes and/or cargo adapters. [ABSTRACT FROM AUTHOR]

Legionellosis I Legionella i is a pathogenic bacterium that causes legionellosis, resulting in three distinct illnesses: Legionnaires' disease, Pontiac fever, and extrapulmonary legionellosis. The CDC recommends setting hot water tank temperatures at a minimum of 140 °F to minimize I Legionella i risk because at this temperature, 90% of the bacteria will die within two minutes, according to the World Health Organization (2007). Keywords: Legionella; Distribution Systems; Water Quality; Premise Plumbing; Opportunistic Pathogens EN Legionella Distribution Systems Water Quality Premise Plumbing Opportunistic Pathogens 88 91 4 07/05/21 20210701 NES 210701 GLO:KNS/01jul21:awwa1753-gra-0001.jpg PHOTO (COLOR): . gl I Legionella pneumophila i , the bacterium that can cause Legionnaires' disease, is shown here growing on specialized microbiological media. [Extracted from the article]

Legionellapneumophila (Lp) is a waterborne bacterium able to infect human alveolar macrophages, causing Legionnaires' disease. Lp can survive for several months in water, while searching for host cells to grow in, such as ciliates and amoeba. In Lp, the sigma factor RpoS is essential for survival in water. A previous transcriptomic study showed that RpoS positively regulates the small regulatory RNA Lpr10. In the present study, deletion of lpr10 results in an increased survival of Lp in water. Microarray analysis and RT‐qPCR revealed that Lpr10 negatively regulates the expression of RpoS in the postexponential phase. Electrophoretic mobility shift assay and in‐line probing showed that Lpr10 binds to a region upstream of the previously identified transcription start sites (TSS) of rpoS. A third putative transcription start site was identified by primer extension analysis, upstream of the Lpr10 binding site. In addition, nlpD TSS produces a polycistronic mRNA including the downstream gene rpoS, indicating a fourth TSS for rpoS. Our results suggest that the transcripts from the third and fourth TSS are negatively regulated by the Lpr10 sRNA. Therefore, we propose that Lpr10 is involved in a negative regulatory feedback loop to maintain expression of RpoS to an optimal level. [ABSTRACT FROM AUTHOR]

Legionella pneumophila is a deadly bacterial pathogen that has caused numerous Legionnaires' disease outbreaks, where cooling towers were the most common source of exposure. Bacterial culturing is used for L. pneumophila detection, but this method takes approximately 10 days to complete. In this work, an RNA‐cleaving fluorogenic DNAzyme, named LP1, was isolated. Extensive characterization revealed that LP1 is reactive with multiple infectious isolates of L. pneumophila but inactive with 25 other common bacterial species. LP1 is likely activated by a protein target, capable of generating a detectable signal in the presence of as few as 10 colony‐forming units of L. pneumophila, and able to maintain its activity in cooling tower water from diverse sources. Given that similar DNAzymes have been incorporated into many sensitive assays for bacterial detection, LP1 holds the potential for the development of biosensors for monitoring the contamination of L. pneumophila in exposure sources. [ABSTRACT FROM AUTHOR]

Legionnaires' disease is caused by infection with the intracellularly replicating Gram‐negative bacterium Legionella pneumophila. This pathogen uses an unconventional way of ubiquitinating host proteins by generating a phosphoribosyl linkage between substrate proteins and ubiquitin by making use of an ADPribosylated ubiquitin (UbADPr) intermediate. The family of SidE effector enzymes that catalyze this reaction is counteracted by Legionella hydrolases, which are called Dups. This unusual ubiquitination process is important for Legionella proliferation and understanding these processes on a molecular level might prove invaluable in finding new treatments. Herein, a modular approach is used for the synthesis of triazole‐linked UbADPr, and analogues thereof, and their affinity towards the hydrolase DupA is determined and hydrolysis rates are compared to natively linked UbADPr. The inhibitory effects of modified Ub on the canonical eukaryotic E1‐enzyme Uba1 are investigated and rationalized in the context of a high‐resolution crystal structure reported herein. Finally, it is shown that synthetic UbADPr analogues can be used to effectively pull‐down overexpressed DupA from cell lysate. [ABSTRACT FROM AUTHOR]

Summary: The detection and quantification of Legionella pneumophila (responsible for legionnaire's disease) in water samples can be achieved by various methods. However, the culture‐based ISO 11731:2017, which is based on counts of colony‐forming units per ml (CFU·ml‐1) is still the gold standard for quantification of Legionella species (spp.). As a powerful alternative, we propose real‐time monitoring of the growth of L. pneumophila using an isothermal microcalorimeter (IMC). Our results demonstrate that, depending on the initial concentration of L. pneumophila, detection times of 24–48 h can be reliably achieved. IMC may, therefore, be used as an early warning system for L. pneumophila contamination. By replacing only visual detection of growth by a thermal sensor, but otherwise maintaining the standardized protocol of the ISO 11731:2017, the new procedure could easily be incorporated into existing standards. The exact determination of the beginning of metabolic heat is often very difficult because at the beginning of the calorimetric signal the thermal stabilization and the metabolic heat development overlap. Here, we propose a new data evaluation based on the first derivation of the heat flow signal. The improved evaluation method can further reduce detection times and significantly increase the reliability of the IMC approach. [ABSTRACT FROM AUTHOR]

The Flint water crisis is one of the most significant environmental contamination events in recent American history. In April 2014, the city of Flint, Michigan, while under the control of an emergency manager appointed by the governor, switched its drinking water supply from Lake Huron water treated and distributed by the Detroit Water and Sewerage Department to the Flint River. Failure to treat the water properly at the Flint Water Treatment Plant led to a variety of problems with water quality and public health. Low chlorine in parts of the water system fostered bacterial growth and contributed to an historic outbreak of Legionnaires' disease in 2014–2015. High levels of trihalomethanes brought the city into violation of the Safe Drinking Water Act in late 2014. Finally, systemic lead contamination—revealed through a collaborative sampling effort by local activists and engineers in the summer of 2015—resulted from corrosive water eating into lead pipes and other lead‐bearing components of Flint's water infrastructure. In October 2015, after considerable public pressure, the city switched back to Lake Huron water. Efforts by federal, state, and local officials to respond to the crisis have focused on restoring water quality, repairing and replacing dangerous and damaged pipes, and addressing public health needs. At the popular level, residents and activists have continued to fight for accountability, reparations, and restoration. A variety of causal explanations for the crisis have been put forward, some focusing on water treatment, regulation, and infrastructure, others on the political context created by state takeover of the city, and others on historical factors like structural racism, deindustrialization, and depopulation. This article is categorized under: Science of Water > Water QualityEngineering Water > Water, Health, and SanitationHuman Water > Water Governance [ABSTRACT FROM AUTHOR]

We report an acute clinical course of pneumonia caused by Legionella pneumophila in a patient receiving chemotherapy for lung cancer and corticosteroid therapy. A 57‐year‐old man presented with fever and dyspnoea and was admitted to our hospital. Chest computed tomography revealed a new left lower lung infiltrate, tumour progression in the right upper lung region, metastases to lymph nodes and pleural effusion. The urinary antigen test for Legionella was positive. The patient's oxygen requirement increased on the day of admission, and he died the day after hospitalization. Legionnaires' disease may manifest with an acute presentation, and patients in Japan with physical risk factors for this disease could get infected despite the absence of environmental risk factors. Early treatment for suspected Legionnaire's disease should be considered. [ABSTRACT FROM AUTHOR]

Wagner also keeps the focus for each chapter on only one or a few researchers which makes it easier to keep track of all the individuals in the book. Wagner does an excellent job describing the rapid ecological transitions that occurred in the Mount St. Helens area after the blast, but the transformation of Spirit Lake is arguably the most surprising. Rather than telling the events as they happened, Wagner describes the events through the lens of the many researchers who have worked in the Mount St. Helens area since the eruption. [Extracted from the article]

GLO:81V/01jun21:jpc15108-fig-0003.jpg PHOTO (COLOR): 3 A chest computed tomography showed multiple, cystic changes in the bilateral lungs. gl Discussion I Legionella i pneumonia is rare among healthy children and is reported found in only 1% of paediatric, community-acquired pneumonia cases. I Legionella i pneumonia is rare among healthy children and is reported in only 1% of paediatric community-acquired pneumonia cases. The present case demonstrated cavitation in the lungs and intractable pneumothorax as complications of I Legionella i pneumonia. [Extracted from the article]

The Migratory Bird Conservation Commission has approved $28 million in funding for various wetland conservation projects. The report's conclusions and recommendations are intended to improve management of I Legionella i contamination of water systems and consequently improve control of Legionnaires' disease in the United States. Scottsdale will continue to meet customer needs through its diverse water supply portfolio, which includes using indirect potable reuse to recharge the aquifer. Through its partnership with the Planet Water Foundation, a US-based nonprofit organization that works to bring clean water to the world's most impoverished communities, Watts employees and five of its customers built "AquaTowers" at two schools in the Sa Kaeo province. [Extracted from the article]

The oxidation number, or valence, is a number assigned to each element that indicates the number of electrons lost, gained, or shared by its atom in the compound formation. Similarly, an atom that gains electrons, gains negative charges equal to the number of electrons gained. As in the formation of different compounds, the same element may have a different number of electrons involved, so it may have more than one oxidation number. Metals lose electrons and thus have positive oxidation numbers, and nonmetals gain electrons and have negative oxidation numbers. [Extracted from the article]

Protective immunity against intracellular pathogens, including bacteria, usually relies on cellular immunity. However, antibodies are also implicated in mediating protection against intracellular bacteria. In case of airway infection with Legionella pneumophila (Lpn), the causative agent of Legionnaires' disease, pre‐existing Lpn‐specific antibodies were shown to afford protection within two days of infection. Here we dissected the early kinetics of Ab‐mediated protection against airway Lpn infection and observed two kinetically and mechanistically distinct phases of protection by passively administered antibodies. Within the first hour of infection, Lpn‐opsonizing antibodies provided almost 10‐fold protection in an antibody Fc‐dependent, but FcR‐independent manner. Later on, by two days post infection, Lpn‐specific Ab‐mediated protection strictly involved FcγR, Syk kinase activity in alveolar macrophages and induction of reactive oxygen species (ROS). The findings presented here contribute to the understanding of the mechanisms of Ab‐mediated control of Lpn infection in actively or passively immunized individuals. [ABSTRACT FROM AUTHOR]

Legionellosis, manifesting as either Legionnaires' disease or Pontiac fever, is a serious concern in the United States. Water providers and property owners must do their part to control Legionella. [ABSTRACT FROM AUTHOR]

Legionella pneumophila, regularly found within premise plumbing distribution systems of many large and complex buildings, is responsible for 90% of legionellosis cases. When properly applied and maintained, onsite water treatment offers options for pathogen inactivation and health protection. The addition of copper and silver ions by copper–silver ionization (CSI) is reviewed here. A literature survey was conducted to assess current knowledge about the biocidal mechanisms of copper and silver ions against Legionella spp. and their survival responses and resistance mechanisms. Understanding how copper and silver ions affect bacteria, how bacteria defend against metal ions, and environmental conditions that affect CSI efficacy may help better define conditions under which CSI, alone or in combination with other treatment(s), might offer reliable control of Legionella. Elevated dissolved oxygen, the sodium content of the water, combined disinfectants, and higher temperature may provide conditions under which Legionella spp. may be more susceptible to metal ions. [ABSTRACT FROM AUTHOR]

Abstract: Diverse species of Legionella and Legionella‐like amoebal pathogens (LLAPs) have been identified as intracellular bacteria in many amoeboid protists. There are, however, other amoeboid groups such as testate amoeba for which we know little about their potential to host such bacteria. In this study, we assessed the occurrence and diversity of Legionella spp. in cultures and environmental isolates of freshwater arcellinid testate amoebae species, Arcella hemispherica, Arcella intermedia, and Arcella vulgaris, via 16S rRNA gene sequence analyses and fluorescent in situ hybridization (FISH). Analysis of the 16S rRNA gene sequences indicated that A. hemispherica, A. intermedia, and A. vulgaris host Legionella‐like bacteria with 94–98% identity to other Legionella spp. based on NCBI BLAST search. Phylogenetic analysis placed Legionella‐like Arcella‐associated bacteria (LLAB) in three different clusters within a tree containing all other members of Legionella and LLAPs. The intracellular localization of the Legionella within Arcella hosts was confirmed using FISH with a Legionella‐specific probe. This study demonstrates that the host range of Legionella and Legionella‐like bacteria in the Amoebozoa extends beyond members of “naked” amoebae species, with members of the testate amoebae potentially serving an ecological role in the dispersal, protection, and replication of Legionella spp. in natural environments. [ABSTRACT FROM AUTHOR]

The article offers information on Legionella which is the leading cause of U.S. waterborne disease outbreaks. It mentions that Legionella is different from waterborne pathogens, as the exposure is inhalation than ingestion. It mentions that inhalation of Legionella, lead to severe pneumonia or lung inflammation called Legionnaires’ disease.

Legionnaires' disease ( LD) can be fatal among high-risk transplant recipients. To understand the epidemiology of LD, we reviewed 15-year longitudinal data from a center in Seattle, Washington that cares for both solid organ transplant ( SOT) and hematopoietic cell transplant ( HCT) recipients. We identified all laboratory-confirmed LD and extracted data on species, diagnostic modalities, clinical presentation, management, and outcomes from medical records. Among 32 patients with LD, transplant recipients made up the majority of diagnoses (22, 69%; SOT 10, HCT 12). Approximately 0.8% of transplant recipients who underwent Legionella-specific testing were positive. Non- pneumophila Legionella species ( LNLP), which are not detected by urinary antigen test, accounted for half the cases, led by Legionella micdadei (32%). The severity and outcome between Legionella pneumophila and LNLP infections were similar (attributed mortality, 36% vs 27%); all LNLP deaths occurred in transplant recipients with L. micdadei. The clinical and radiological features mimicked other opportunistic pathogens; 32% (n=7) were not on empiric treatment at the time of diagnosis. These data add to the emerging literature describing the importance of LD and highlight the need for both routine Legionella testing on transplant recipients with pulmonary findings and empiric Legionella-active antibiotic therapy. [ABSTRACT FROM AUTHOR]

Background and objective Legionella longbeachae is a predominant cause of Legionnaires' disease in some parts of the world, particularly in Australasia. Clinical reports of L. longbeachae infection are limited to case reports or small case series, and culture-confirmed cases. Methods We reviewed the clinical characteristics and outcomes of L. longbeachae pneumonia in a large case series from Christchurch, New Zealand during a 4-year period when both PCR and cultures were used as routine diagnostic tools for Legionnaires' disease. Cases of Legionella pneumophila pneumonia were reviewed for comparison. Results A total of 107 cases of L. longbeachae infection were identified by PCR and/or culture . The median age was 65 years (range 25-90 years), 63% were male, and most became unwell during spring or summer. Presenting clinical features were similar to those reported for community-acquired pneumonia, with headache, myalgia and diarrhoea being common. Elevated C-reactive protein, hyponatraemia and abnormal liver function tests were also common. History of productive cough, involvement of both lungs, and high bacterial load were independently associated with culture of Legionella from lower respiratory samples. One quarter required intensive care unit admission, and 5% died. Among patients given antimicrobial therapy before admission, those given agents without anti- Legionella activity were more likely to be admitted to the intensive care unit. Limited comparisons were made with the 19 L. pneumophila cases over the same time period. Conclusion Characteristics of L. longbeachae pneumonia are broadly similar to those reported for community-acquired pneumonia from a variety of other populations, except for the spring/summer seasonality. [ABSTRACT FROM AUTHOR]

Amino acids represent the prime carbon and energy source for Legionella pneumophila, a facultative intracellular pathogen, which can cause a life-threatening pneumonia termed Legionnaires' disease. Genome, transcriptome and proteome studies indicate that L. pneumophila also utilizes carbon substrates other than amino acids. We show here that glycerol promotes intracellular replication of L. pneumophila in amoeba or macrophages (but not extracellular growth) dependent on glycerol-3-phosphate dehydrogenase, GlpD. An L. pneumophila mutant strain lacking glpD was outcompeted by wild-type bacteria upon co-infection of amoeba, indicating an important role of glycerol during infection. Isotopologue profiling studies using 13C-labelled substrates were performed in a novel minimal defined medium, MDM, comprising essential amino acids, proline and phenylalanine. In MDM, L. pneumophila utilized 13C-labelled glycerol or glucose predominantly for gluconeogenesis and the pentose phosphate pathway, while the amino acid serine was used for energy generation via the citrate cycle. Similar results were obtained for L. pneumophila growing intracellularly in amoeba fed with 13C-labelled glycerol, glucose or serine. Collectively, these results reveal a bipartite metabolism of L. pneumophila, where glycerol and carbohydrates like glucose are mainly fed into anabolic processes, while serine serves as major energy supply. [ABSTRACT FROM AUTHOR]

Two excellent examples of this type of thinking can be seen in chapters 7 and 10 on SARS and COVID-19, respectively because public health experts had to investigate not only human health but animal health and how the diseases thrived in the built environments as well. One Hundred Years of Panic, Hysteria, and Hubris by Mark Honigsbaum is exactly the book of a person trying to gain a broad knowledge of public health pandemic needs. One Health scientists believe that in order to address diseases, human, animal, and environmental health must be considered simultaneously when addressing disease etiology. [Extracted from the article]

Transplant recipients are at risk of developing Legionnaires' disease ( LD) because of impaired cellular immunity. Here, we describe a renal transplant recipient who developed LD at least 10 days after hospital admission and transplantation. The hospital water network was initially suspected, but further testing determined that the probable source was the patient's domestic water supply. Our report also suggests that the patient's immunosuppressed state may have switched potential colonization to pneumonia. [ABSTRACT FROM AUTHOR]

The article discusses the facilitation of supplemental disinfection for Legionella pneumophila control in plumbing systems. Topics discussed include an increase in U.S. legionellosis cases from 2000 to 2009, supplemental disinfection technology application at sites in plumbing systems, and the regulation of Legionella under the Safe Drinking Water Act.

The environmental bacterium L egionella pneumophila is the causative agent of Legionnaires' disease, a life-threatening pneumonia. For cell-cell communication the bacteria employ the autoinducer LAI-1 (3-hydroxypentadecane-4-one), which is produced and detected by the Lqs ( L egionella quorum sensing) system. The system comprises the autoinducer synthase LqsA, the putative sensor kinases LqsS and LqsT, and the prototypic response regulator LqsR. Lqs-regulated processes include L . pneumophila-phagocyte interactions, production of extracellular filaments, and natural competence. Using biochemical approaches we show here that LqsS and LqsT are autophosphorylated by [γ-32 P]- ATP at a conserved histidine residue ( H200 or H204) located in their cytoplasmic histidine kinase domain. Pull-down assays revealed that LqsS and LqsT are bound by LqsR or phospho- LqsR. Dependent on the conserved receiver domain aspartate ( D108), the response regulator prevented autophosphorylation of both sensor kinases by catalysing the dephosphorylation of phospho- LqsS or phospho- LqsT. Moreover, LqsR formed dimers upon phosphorylation at D108 by either acetyl-phosphate or phospho- LqsT. Finally, upon heterologous production in E scherichia coli, LqsT (but not LqsS) was autophosphorylated by ATP, and LqsR prevented the autophosphorylation by catalysing the dephosphorylation of phospho- LqsT. In summary, these results indicate that phosphorylation signalling through the L egionella quorum sensing histidine kinases LqsS and LqsT converges on the response regulator LqsR. [ABSTRACT FROM AUTHOR]

Evaporative cooling towers are water systems used in, e.g., industry and telecommunication to remove excess heat by evaporation of water. Temperatures of cooling waters are usually optimal for mesophilic microbial growth and cooling towers may liberate massive amounts of bacterial aerosols. Outbreaks of legionellosis associated with cooling towers have been known since the 1980's, but occurrences of other potentially pathogenic bacteria in cooling waters are mostly unknown. We examined the occurrence of mycobacteria, which are common bacteria in different water systems and may cause pulmonary and other soft tissue infections, in cooling waters containing different numbers of legionellae. Mycobacteria were isolated from all twelve cooling systems and from 92% of the 24 samples studied. Their numbers in the positive samples varied from 10 to 7.3 × 104 cfu/L. The isolated species included M. chelonae/abscessus, M. fortuitum, M. mucogenicum, M. peregrinum, M. intracellulare, M. lentiflavum, M. avium/nebraskense/scrofulaceum and many non-pathogenic species. The numbers of mycobacteria correlated negatively with the numbers of legionellae and the concentration of copper. The results show that cooling towers are suitable environments for potentially pathogenic mycobacteria. Further transmission of mycobacteria from the towers to the environment needs examination. [ABSTRACT FROM AUTHOR]

Statistical methods used in spatio-temporal surveillance of disease are able to identify abnormal clusters of cases but typically do not provide a measure of the degree of association between one case and another. Such a measure would facilitate the assignment of cases to common groups and be useful in outbreak investigations of diseases that potentially share the same source. This paper presents a model-based approach, which on the basis of available location data, provides a measure of the strength of association between cases in space and time and which is used to designate and visualise the most likely groupings of cases. The method was developed as a prospective surveillance tool to signal potential outbreaks, but it may also be used to explore groupings of cases in outbreak investigations. We demonstrate the method by using a historical case series of Legionnaires' disease amongst residents of England and Wales. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Legionella pneumophila is an intracellularly surviving pathogen that releases about 270 different proteins into the host cell during infection. A set of secreted proteins takes control of the vesicular trafficking regulator Rab1. Legionella LepB inactivates Rab1 by acting as a GTPase-activating protein (GAP). We present the crystal structure of the Rab1b:LepB complex together with a thorough biochemical analysis and show that the GAP domain of LepB consists of an unusual fold. LepB acts by an atypical RabGAP mechanism that is reminiscent of classical GAPs and therefore sets the protein apart from mammalian TBC-like GAPs. Surprisingly, LepB can function as a GAP for Rab3, Rab8, Rab13 and Rab35, too, suggesting that it has a broader cellular role than previously thought. [ABSTRACT FROM AUTHOR]

Legionella species are intracellular gram-negative bacilli that require specific culture media for growth. Transplant recipients with impaired cellular immunity are at particular risk for infection with this pathogen. Most human disease is caused by Legionella pneumophila; disease caused by non- L. pneumophila species is reported mainly in immunosuppressed patients with the exception of Legionella longbeachae. L. longbeachae is a common cause of Legionnaires' disease in Australia and New Zealand, and is associated with exposure to potting soil. We report the case of a patient, 26 years post kidney transplant, who presented with severe and rapidly progressive respiratory illness. L. longbeachae serogroup 1 was isolated from respiratory cultures. Further investigation revealed that she had significant soil exposure before the onset of illness. We highlight the importance of following safe living strategies to prevent exposure-related illness even in long-term transplant recipients. [ABSTRACT FROM AUTHOR]