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Euro Surveillance : Bulletin Europeen... May 2024Wastewater treatment plants (WWTPs) are increasingly identified as Legionnaires' disease (LD) sources. An outbreak investigation was initiated following five LD cases...
Wastewater treatment plants (WWTPs) are increasingly identified as Legionnaires' disease (LD) sources. An outbreak investigation was initiated following five LD cases reported in September 2022 in Houten, the Netherlands. Case identification was based on the European LD case definition, with symptom onset from 1 September 2022, residence in or within 5 km of Houten, or visit to Houten within the incubation period, without other likely sources. We sampled potential sources and genotyped environmental and clinical isolates. We identified 15 LD cases with onset between 13 September and 23 October 2022. A spatial source identification and wind direction model suggested an industrial (iWWTP) and a municipal WWTP (mWWTP) as potential sources, with the first discharging water into the latter. Both tested positive for serogroups 1 and 6 with multiple sequence types (ST). We detected sg1 ST42 in the mWWTP, matching with one of three available clinical isolates. Following control measures at the WWTPs, no further cases were observed. This outbreak underlines that municipal and industrial WWTPs can play an important role in community LD cases and outbreaks, especially those with favourable conditions for growth and dissemination, or even non-favourable conditions for growth but with the influx of contaminated water.
Topics: Legionnaires' Disease; Humans; Disease Outbreaks; Netherlands; Wastewater; Legionella pneumophila; Male; Middle Aged; Aged; Female; Water Microbiology; Water Purification; Adult; Genotype
PubMed: 38757288
DOI: 10.2807/1560-7917.ES.2024.29.20.2300506 -
International Immunopharmacology Jun 2024Patients with diabetes are particularly susceptible to Legionella pneumophila (LP) infection, but the exact pathogenesis of LP infection in diabetic patients is still...
BACKGROUND
Patients with diabetes are particularly susceptible to Legionella pneumophila (LP) infection, but the exact pathogenesis of LP infection in diabetic patients is still not fully understood. Herein, we investigated the effect of diabetes on immune function during LP infection in vitro and in vivo.
METHODS
The time course of LP infection in macrophages under normal and high-glucose (HG) conditions was examined in vitro. Western blot was used to determine nucleotide-binding oligomerization domain 1 (NOD1), kinase 1/2 (ERK1/2), mitogen-activated protein kinase p38 (MAPK p38), and c-Jun N-terminal kinases (JNK). Enzyme-linked immunosorbent assay (ELISA) was used to assess the secretion of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Cell Counting Kit-8 (CCK8) assay assessed U937 cell viability after treating cells with different concentrations of high sugar medium and ML130 (NOD1 inhibitor). For the in vivo study, normal and streptozocin-induced diabetic guinea pigs were infected with LP for 6, 24, and 72 h, after which NOD1, MAPK-related signals, TNF-α, and IL-6 expression in lung tissues were assessed using immunohistochemistry, western blot, and RT-PCR.
RESULTS
HG attenuated the upregulation of NOD1 expression and reduced TNF-α and IL-6 secretion caused by LP compared with LP-infected cells exposed to normal glucose levels (all p < 0.05). In diabetic guinea pigs, HG inhibited the upregulation of NOD1 expression in lung tissues and the activation of p38, ERK1/2, and cJNK caused by LP infection compared to control pigs (all p < 0.05).
CONCLUSION
HG attenuates the response of macrophages to LP infection by inhibiting NOD1 upregulation and the activation of MAPK signaling.
Topics: Nod1 Signaling Adaptor Protein; Animals; Humans; Macrophages; Legionella pneumophila; Glucose; Guinea Pigs; Male; Interleukin-6; Legionnaires' Disease; Diabetes Mellitus, Experimental; MAP Kinase Signaling System; U937 Cells; Tumor Necrosis Factor-alpha; Mice
PubMed: 38749333
DOI: 10.1016/j.intimp.2024.112254 -
PLoS Pathogens May 2024Legionella pneumophila strains harboring wild-type rpsL such as Lp02rpsLWT cannot replicate in mouse bone marrow-derived macrophages (BMDMs) due to induction of...
Legionella pneumophila strains harboring wild-type rpsL such as Lp02rpsLWT cannot replicate in mouse bone marrow-derived macrophages (BMDMs) due to induction of extensive lysosome damage and apoptosis. The 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. Similarly, host factors that may alleviate cell death induced by these bacterial strains have not yet been investigated. Using a genome-wide CRISPR/Cas9 screening, we identified Hmg20a and Nol9 as host factors important for restricting strain Lp02rpsLWT in BMDMs. Depletion of Hmg20a protects macrophages from infection-induced lysosomal damage and apoptosis, allowing productive bacterial replication. The restriction imposed by Hmg20a was mediated by repressing the expression of several endo-lysosomal proteins, including the small GTPase Rab7. We found that SUMOylated Rab7 is recruited to the bacterial phagosome via SulF, a Dot/Icm effector that harbors a SUMO-interacting motif (SIM). Moreover, overexpression of Rab7 rescues intracellular growth of strain Lp02rpsLWT in BMDMs. Our results establish that L. pneumophila exploits the lysosomal network for the biogenesis of its phagosome in BMDMs.
Topics: Legionella pneumophila; Animals; rab GTP-Binding Proteins; Mice; Phagosomes; rab7 GTP-Binding Proteins; Lysosomes; Macrophages; Legionnaires' Disease; Sumoylation; Mice, Inbred C57BL; Endosomes
PubMed: 38739652
DOI: 10.1371/journal.ppat.1011783 -
Current Microbiology May 2024Legionella pneumophila (Lp) is a Gram-negative bacterium found in natural and artificial aquatic environments and inhalation of contaminated aerosols can cause severe...
Legionella pneumophila (Lp) is a Gram-negative bacterium found in natural and artificial aquatic environments and inhalation of contaminated aerosols can cause severe pneumonia known as Legionnaires' Disease (LD). In Brazil there is hardly any information about this pathogen, so we studied the genetic variation of forty Legionella spp. isolates obtained from hotels, malls, laboratories, retail centers, and companies after culturing in BCYE medium. These isolates were collected from various sources in nine Brazilian states. Molecular identification of the samples was carried out using Sequence-Based Typing (SBT), which consists of sequencing and analysis of seven genes (flaA, pilE, asd, mip, mompS, proA, and neuA) to define a Sequence Type (ST). Eleven STs were identified among 34/40 isolates, of which eight have been previously described (ST1, ST80, ST152, ST242, ST664, ST1185, ST1464, ST1642) and three were new STs (ST2960, ST2962, and ST2963), the former identified in five different cooling towers in the city of São Paulo. The ST1 that is widely distributed in many countries was also the most prevalent in this study. In addition, other STs that we observed have also been associated with legionellosis in other countries, reinforcing the potential of these isolates to cause LD in Brazil. Unfortunately, no human isolates could be characterized until presently, but our observations strongly suggest the need of surveillance implementation system and control measures of Legionella spp. in Brazil, including the use of more sensitive genotyping procedures besides ST.
Topics: Brazil; Legionella pneumophila; Genetic Variation; Water Microbiology; Humans; Phylogeny; Genotype
PubMed: 38714565
DOI: 10.1007/s00284-024-03645-5 -
Microbiology Resource Announcements Jun 2024Legionnaires' disease is a severe form of pneumonia caused by spp. bacteria. According to the European Centre for Disease Prevention and Control, problems related to...
Legionnaires' disease is a severe form of pneumonia caused by 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.
PubMed: 38690889
DOI: 10.1128/mra.01154-23 -
MBio Jun 2024The causative agent of Legionnaires' disease, , is an environmental bacterium, that replicates in macrophages, parasitizes amoeba, and forms biofilms. employs the...
UNLABELLED
The causative agent of Legionnaires' disease, , is an environmental bacterium, that replicates in macrophages, parasitizes amoeba, and forms biofilms. employs the quorum sensing (Lqs) system and the transcription factor LvbR to control various bacterial traits, including virulence and biofilm architecture. LvbR negatively regulates the nitric oxide (NO) receptor Hnox1, linking quorum sensing to NO signaling. Here, we assessed the response of to NO and investigated bacterial receptors underlying this process. Chemical NO donors, such as dipropylenetriamine (DPTA) NONOate and sodium nitroprusside (SNP), delayed and reduced the expression of the promoters for flagellin (P) and the 6S small regulatory RNA (P). Marker-less mutant strains lacking individual (Hnox1, Hnox2, or NosP) or all three NO receptors (triple knockout, TKO) grew like the parental strain in media. However, in the TKO strain, the reduction of P expression by DPTA NONOate was less pronounced, suggesting that the NO receptors are implicated in NO signaling. In the Δ mutant, the promoter was upregulated, indicating that NosP negatively regulates LvbR. The single and triple NO receptor mutant strains were impaired for growth in phagocytes, and phenotypic heterogeneity of non-growing/growing bacteria in amoebae was regulated by the NO receptors. The single NO receptor and TKO mutant strains showed altered biofilm architecture and lack of response of biofilms to NO. In summary, we provide evidence that regulates virulence, intracellular phenotypic heterogeneity, and biofilm formation through NO and three functionally non-redundant NO receptors, Hnox1, Hnox2, and NosP.
IMPORTANCE
The highly reactive diatomic gas molecule nitric oxide (NO) is produced by eukaryotes and bacteria to promote short-range and transient signaling within and between neighboring cells. Despite its importance as an inter-kingdom and intra-bacterial signaling molecule, the bacterial response and the underlying components of the signaling pathways are poorly characterized. The environmental bacterium forms biofilms and replicates in protozoan and mammalian phagocytes. harbors three putative NO receptors, one of which crosstalks with the quorum sensing (Lqs)-LvbR network to regulate various bacterial traits, including virulence and biofilm architecture. In this study, we used pharmacological, genetic, and cell biological approaches to assess the response of to NO and to demonstrate that the putative NO receptors are implicated in NO detection, bacterial replication in phagocytes, intracellular phenotypic heterogeneity, and biofilm formation.
Topics: Biofilms; Legionella pneumophila; Nitric Oxide; Signal Transduction; Virulence; Gene Expression Regulation, Bacterial; Bacterial Proteins; Phenotype; Macrophages; Quorum Sensing
PubMed: 38682908
DOI: 10.1128/mbio.00710-24 -
Journal of Infection and Public Health Jun 2024Legionellers' desease accounts for 1-8 % of cases of severe community-acquired pneumonia (CAP). Legionella spp. Is the causative organism that can result in respiratory...
Legionellers' desease accounts for 1-8 % of cases of severe community-acquired pneumonia (CAP). Legionella spp. Is the causative organism that can result in respiratory failure, multi-organ dysfunction, sepsis, and death. Therefore, rapid diagnosis and efficient treatment are crucial. We report the clinical and microbiology study of a patient with community-acquired pneumonia caused by Legionella pneumophila, with fatal outcome. After death, the strain causing the infection was identified as Legionella pneumophila serogroup 1, Olda OLDA phenotype and sequence-type 1. This is the first reported case of septic shock and death associated with an isolate of these characteristics.
Topics: Humans; Community-Acquired Infections; Legionella pneumophila; Shock, Septic; Legionnaires' Disease; Fatal Outcome; Male; Aged; Serogroup; Middle Aged
PubMed: 38678725
DOI: 10.1016/j.jiph.2024.04.019 -
Emerging Infectious Diseases May 2024We investigated molecular evolution and spatiotemporal dynamics of atypical Legionella pneumophila serogroup 1 sequence type 1905 and determined its long-term...
We investigated molecular evolution and spatiotemporal dynamics of atypical Legionella pneumophila serogroup 1 sequence type 1905 and determined its long-term persistence and linkage to human disease in dispersed locations, far beyond the large 2014 outbreak epicenter in Portugal. Our finding highlights the need for public health interventions to prevent further disease spread.
Topics: Legionella pneumophila; Portugal; Humans; Legionnaires' Disease; Spatio-Temporal Analysis; Evolution, Molecular; Disease Outbreaks; History, 21st Century; Recurrence; Phylogeny; Serogroup
PubMed: 38666647
DOI: 10.3201/eid3005.231383 -
Case Reports in Pulmonology 2024Legionella bozemanii pneumonia is a rare form of Legionnaires' disease caused by the bacterium Legionella bozemanii. It is well known to cause pneumonia in...
Legionella bozemanii pneumonia is a rare form of Legionnaires' disease caused by the bacterium Legionella bozemanii. It is well known to cause pneumonia in immunocompromised patients and has rarely been reported in immunocompetent hosts. We describe a case of a 59-year-old immunocompetent female presented with pneumonia, acute respiratory failure, acute respiratory distress, and septic shock, who was treated with azithromycin, goal-directed resuscitation, and extracorporeal membrane oxygenation (ECMO) but did not survive. Clinicians should have high suspicion of rare legionella pathogens as causative agents for pneumonia.
PubMed: 38596699
DOI: 10.1155/2024/7571380 -
Cell Reports Apr 2024Small GTPases of the Ras subfamily are best known for their role as proto-oncoproteins, while their function during microbial infection has remained elusive. Here, we...
Small GTPases of the Ras subfamily are best known for their role as proto-oncoproteins, while their function during microbial infection has remained elusive. Here, we show that Legionella pneumophila hijacks the small GTPase NRas to the Legionella-containing vacuole (LCV) surface. A CRISPR interference screen identifies a single L. pneumophila effector, DenR (Lpg1909), required for this process. Recruitment is specific for NRas, while its homologs KRas and HRas are excluded from LCVs. The C-terminal hypervariable tail of NRas is sufficient for recruitment, and interference with either NRas farnesylation or S-acylation sites abrogates recruitment. Intriguingly, we detect markers of active NRas signaling on the LCV, suggesting it acts as a signaling platform. Subsequent phosphoproteomics analyses show that DenR rewires the host NRas signaling landscape, including dampening of the canonical mitogen-activated protein kinase pathway. These results provide evidence for L. pneumophila targeting NRas and suggest a link between NRas GTPase signaling and microbial infection.
Topics: Legionella pneumophila; Humans; Membrane Proteins; MAP Kinase Signaling System; GTP Phosphohydrolases; Bacterial Proteins; Down-Regulation; HEK293 Cells; Legionnaires' Disease; Vacuoles; Proto-Oncogene Proteins p21(ras)
PubMed: 38568811
DOI: 10.1016/j.celrep.2024.114033