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Microorganisms
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Intracellular Bacteria: From Basic Research to Clinics 2.0
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Intracellular Bacteria: From Basic Research to Clinics 2.0

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Molecular Microbiology and Immunology".

Deadline for manuscript submissions: closed (15 January 2024) | Viewed by 18150

Special Issue Editors

Prof. Dr. Gilbert Greub

E-Mail Website
Guest Editor
Institute of Microbiology, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland
Interests: antibiotics; bacteremia; Gram's stain; Enterobacteriaceae; Gram-negative bacteria; lasers; spectrometry; mass; matrix-assisted laser desorption-ionization; mass spectrometry; pathogenic organism; gram-negative bacteremia; ionization; empirical antibiotic therapy; blood culture; extended-spectrum beta lactamases; bloodstream infections; early diagnosis; time-of-flight mass spectrometry; time-of-flight; marseilleviruses
Special Issues, Collections and Topics in MDPI journals
Dr. Nicolas Jacquier

E-Mail Website
Guest Editor
Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Interests: antibiotics; bacteremia; Gram's stain; enterobacteriaceae; Gram-negative bacteria; lasers; spectrometry; mass; matrix-assisted laser desorption-ionization; mass spectrometry; pathogenic organism; Gram-negative bacteremia; ionization; empirical antibiotic therapy; blood culture; extended-spectrum beta lactamases; bloodstream infections; early diagnosis; time-of-flight mass spectrometry; time-of-flight; marseilleviruses
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In August 2022, a joint ESCCAR (European Society on Chlamydia, Coxiella, Anaplasma and Rickettsia)–ESCR (European Society for Chlamydia Research) international meeting took place in Lausanne (Switzerland). Intracellular bacteria, such as Chlamydia, Coxiella, Anaplasma and Rickettsia, are relevant human pathogens. This meeting addressed several important subjects regarding intracellular bacteria, such as diagnosis, epidemiology, pathogenesis, immunology and treatments, as well as the fundamental research performed on these bacteria, comprising host–cell interactions, genetics, evolution and cell biology, among others.

The organization of this meeting was a good opportunity to launch a Special Issue of Microorganisms, which will allow people in the field of intracellular bacteria to share their recent discoveries and/or opinions. Original research articles or reviews that bring a better understanding of the diverse aspects of intracellular bacteria are thus welcome for this Special Issue.

Prof. Dr. Gilbert Greub
Dr. Nicolas Jacquier
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Chlamydia
  • Coxiella
  • Anaplasma
  • Rickettsia
  • intracellular bacteria
  • host–cell interaction
  • pathogenicity
  • medical microbiology

Published Papers (10 papers)

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Research

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14 pages, 8368 KiB  
Article
Ticks and Chlamydia-Related Bacteria in Swiss Zoological Gardens Compared to in Contiguous and Distant Control Areas
by Vincent Vanat, Sébastien Aeby and Gilbert Greub
Microorganisms 2023, 11(10), 2468; https://doi.org/10.3390/microorganisms11102468 - 30 Sep 2023
Viewed by 1042
Abstract
Ticks are vectors of numerous agents of medical importance and may be infected by various Chlamydia-related bacteria, such as members of Parachlamydiaceae and Rhabdochlamydiaceae families, which are sharing the same biphasic life cycle with the pathogenic Chlamydia. However, the veterinary importance [...] Read more.
Ticks are vectors of numerous agents of medical importance and may be infected by various Chlamydia-related bacteria, such as members of Parachlamydiaceae and Rhabdochlamydiaceae families, which are sharing the same biphasic life cycle with the pathogenic Chlamydia. However, the veterinary importance of ticks and of their internalized pathogens remains poorly studied. Thus, we wondered (i) whether the prevalence of ticks was higher in zoological gardens than in control areas with similar altitude, vegetation, humidity and temperature, and (ii) whether the presence of Chlamydia-related bacteria in ticks may vary according to the environment in which the ticks are collected. A total of 212 Ixodes ricinus ticks were collected, and all were tested for the presence of DNA from any member of the Chlamydiae phylum using a pan-Chlamydiae quantitative PCR (qPCR). We observed a higher prevalence of ticks outside animal enclosures in both zoos, compared to in enclosures. Tick prevalence was also higher outside zoos, compared to in enclosures. With 30% (3/10) of infected ticks, the zoological gardens presented a prevalence of infected ticks that was higher than that in contiguous areas (13.15%, 10/76), and higher than the control distant areas (8.65%, 9/104). In conclusion, zoological gardens in Switzerland appear to contain fewer ticks than areas outside zoological gardens. However, ticks from zoos more often contain Chlamydia-like organisms than ticks from contiguous or distant control areas. Full article
(This article belongs to the Special Issue Intracellular Bacteria: From Basic Research to Clinics 2.0)
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9 pages, 3060 KiB  
Communication
Spontaneous Aberrant Bodies Formation in Human Pneumocytes Infected with Estrella lausannensis
by Aurelien Rovero, Carole Kebbi-Beghdadi and Gilbert Greub
Microorganisms 2023, 11(10), 2368; https://doi.org/10.3390/microorganisms11102368 - 22 Sep 2023
Cited by 1 | Viewed by 810
Abstract
Estrella lausannensis, a Chlamydia-related bacterium isolated from a Spanish river, is considered as a possible emerging human pathogen. Indeed, it was recently demonstrated to multiply in human macrophages, resisting oxidative burst and causing a strong cytopathic effect. In addition, a preliminary [...] Read more.
Estrella lausannensis, a Chlamydia-related bacterium isolated from a Spanish river, is considered as a possible emerging human pathogen. Indeed, it was recently demonstrated to multiply in human macrophages, resisting oxidative burst and causing a strong cytopathic effect. In addition, a preliminary study highlighted a correlation between antibody response to E. lausannensis and pneumonia in children. To clarify the pathogenic potential of these bacteria, we infected a human pneumocyte cell line with E. lausannensis and assessed its replication and cytopathic effect using quantitative real-time PCR and immunofluorescence, as well as confocal and electron microscopy. Our results demonstrated that E. lausannensis enters and replicates rapidly in human pneumocytes, and that it causes a prompt lysis of the host cells. Furthermore, we reported the spontaneous formation of aberrant bodies, a form associated with persistence in Chlamydiae, suggesting that E. lausannensis infection could cause chronic disorders in humans. Full article
(This article belongs to the Special Issue Intracellular Bacteria: From Basic Research to Clinics 2.0)
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12 pages, 975 KiB  
Article
Epidemiology of Zoonotic Coxiella burnetii in The Republic of Guinea
by Olesia V. Ohlopkova, Sergey A. Yakovlev, Kabwe Emmanuel, Alexey A. Kabanov, Dmitry A. Odnoshevsky, Mikhail Yu. Kartashov, Alexey D. Moshkin, Igor V. Tuchkov, Nikita Yu. Nosov, Andrey A. Kritsky, Milana A. Agalakova, Yuriy N. Davidyuk, Svetlana F. Khaiboullina, Sergey P. Morzunov, Magasuba N’Fally, Sanaba Bumbali, Mamadou Fode Camara, Mamadou Yero Boiro, Alexander P. Agafonov, Elena V. Gavrilova and Rinat A. Maksyutovadd Show full author list remove Hide full author list
Microorganisms 2023, 11(6), 1433; https://doi.org/10.3390/microorganisms11061433 - 29 May 2023
Cited by 1 | Viewed by 1524
Abstract
Background: Q fever is a zoonotic infectious disease characterized by fever, malaise, chills, significant weakness, and muscle pain. In some cases, the disease can become chronic and affect the inner membranes of the heart, such as the valves, leading to endocarditis and a [...] Read more.
Background: Q fever is a zoonotic infectious disease characterized by fever, malaise, chills, significant weakness, and muscle pain. In some cases, the disease can become chronic and affect the inner membranes of the heart, such as the valves, leading to endocarditis and a high risk of death. Coxiella burnetii (C. burnetii) is the primary causative agent of Q fever in humans. This study aims to monitor the presence of C. burnetii in ticks collected from small mammals and cattle in the Republic of Guinea (RG). Methods: Rodents were trapped in the Kindia region of RG during 2019–2020, and ticks were collected from cattle in six regions of RG. Total DNA was extracted using a commercial kit (RIBO-prep, InterLabService, Russia) following the manufacturer’s instructions. Real-time PCR amplification was conducted using the kit (AmpliSens Coxiella burnetii-FL, InterLabService, Russia) to detect C. burnetii DNA. Results and Conclusions: Bacterial DNA was detected in 11 out of 750 (1.4%) small mammals and 695 out of 9620 (7.2%) tick samples. The high number of infected ticks (7.2%) suggests that they are the main transmitters of C. burnetii in RG. The DNA was detected in the liver and spleen of a Guinea multimammate mouse, Mastomys erythroleucus. These findings demonstrate that C. burnetii is zoonotic in RG, and measures should be taken to monitor the bacteria’s dynamics and tick prevalence in the rodent population. Full article
(This article belongs to the Special Issue Intracellular Bacteria: From Basic Research to Clinics 2.0)
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14 pages, 1529 KiB  
Article
Novel Genetic Lineages of Rickettsia helvetica Associated with Ixodes apronophorus and Ixodes trianguliceps Ticks
by Yana Igolkina, Valeriy Yakimenko, Artem Tikunov, Tamara Epikhina, Aleksey Tancev, Nina Tikunova and Vera Rar
Microorganisms 2023, 11(5), 1215; https://doi.org/10.3390/microorganisms11051215 - 05 May 2023
Cited by 1 | Viewed by 1029
Abstract
Ixodes apronophorus is an insufficiently studied nidicolous tick species. For the first time, the prevalence and genetic diversity of Rickettsia spp. in Ixodes apronophorus, Ixodes persulcatus, and Ixodes trianguliceps ticks from their sympatric habitats in Western Siberia were investigated. Rickettsia helvetica [...] Read more.
Ixodes apronophorus is an insufficiently studied nidicolous tick species. For the first time, the prevalence and genetic diversity of Rickettsia spp. in Ixodes apronophorus, Ixodes persulcatus, and Ixodes trianguliceps ticks from their sympatric habitats in Western Siberia were investigated. Rickettsia helvetica was first identified in I. apronophorus with a prevalence exceeding 60%. “Candidatus Rickettsia tarasevichiae” dominated in I. persulcatus, whereas I. trianguliceps were infected with “Candidatus Rickettsia uralica”, R. helvetica, and “Ca. R. tarasevichiae”. For larvae collected from small mammals, a strong association was observed between tick species and rickettsiae species/sequence variants, indicating that co-feeding transmission in studied habitats is absent or its impact is insignificant. Phylogenetic analysis of all available R. helvetica sequences demonstrated the presence of four distinct genetic lineages. Most sequences from I. apronophorus belong to the unique lineage III, and single sequences cluster into the lineage I alongside sequences from European I. ricinus and Siberian I. persulcatus. Rickettsia helvetica sequences from I. trianguliceps, along with sequences from I. persulcatus from northwestern Russia, form lineage II. Other known R. helvetica sequences from I. persulcatus from the Far East group into the lineage IV. The obtained results demonstrated the high genetic variability of R. helvetica. Full article
(This article belongs to the Special Issue Intracellular Bacteria: From Basic Research to Clinics 2.0)
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17 pages, 2437 KiB  
Article
Temporal Dynamics of Anaplasma marginale Infections and the Composition of Anaplasma spp. in Calves in the Mnisi Communal Area, Mpumalanga, South Africa
by S. Marcus Makgabo, Kelly A. Brayton, Louise Biggs, Marinda C. Oosthuizen and Nicola E. Collins
Microorganisms 2023, 11(2), 465; https://doi.org/10.3390/microorganisms11020465 - 13 Feb 2023
Cited by 3 | Viewed by 1882
Abstract
Bovine anaplasmosis, caused by Anaplasma marginale, is one of the most important tick-borne diseases of cattle. Anaplasma marginale is known to be present in the Mnisi community, Mpumalanga Province, with frequent cases of anaplasmosis reported. This study investigated the infection dynamics in [...] Read more.
Bovine anaplasmosis, caused by Anaplasma marginale, is one of the most important tick-borne diseases of cattle. Anaplasma marginale is known to be present in the Mnisi community, Mpumalanga Province, with frequent cases of anaplasmosis reported. This study investigated the infection dynamics in calves (n = 10) in two habitats in the study area over 12 months. A duplex real-time PCR assay targeting the msp1β gene of A. marginale and the groEL gene of A. centrale confirmed the presence of A. marginale in five calves in a peri-urban area from the first month, but in only two calves at the wildlife–livestock interface and only after six months. These results were confirmed by 16S rRNA microbiome analysis. Over 50 A. marginale msp1α genotypes were detected in the calves along with five novel Msp1a repeats. Calves in the peri-urban area were more likely to be infected with A. marginale than calves in the wildlife–livestock interface. Cattle management, acaricide treatment, and cattle density could explain differences in infection prevalence in the two areas. Our results revealed that most calves were superinfected by distinct A. marginale strains within the study period, indicating continuous challenge with multiple strains that should lead to robust immunity in the calves and endemic stability in the area. Full article
(This article belongs to the Special Issue Intracellular Bacteria: From Basic Research to Clinics 2.0)
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15 pages, 2321 KiB  
Article
TLR4/CD14/MD2 Revealed as the Limited Toll-like Receptor Complex for Chlamydia trachomatis-Induced NF-κB Signaling
by Romana Klasinc, Claire Battin, Wolfgang Paster, Michael Reiter, Philipp Schatzlmaier, Peter Rhein, Andreas Spittler, Peter Steinberger and Hannes Stockinger
Microorganisms 2022, 10(12), 2489; https://doi.org/10.3390/microorganisms10122489 - 15 Dec 2022
Cited by 2 | Viewed by 1448
Abstract
Chlamydia trachomatis (Ct) is the most common cause of genital tract infections as well as preventable blindness worldwide. Pattern recognition receptors such as toll-like receptors (TLRs) represent the initial step in recognizing pathogenic microorganisms and are crucial for the initiation of an appropriate [...] Read more.
Chlamydia trachomatis (Ct) is the most common cause of genital tract infections as well as preventable blindness worldwide. Pattern recognition receptors such as toll-like receptors (TLRs) represent the initial step in recognizing pathogenic microorganisms and are crucial for the initiation of an appropriate immune response. However, our understanding of TLR-signaling in Chlamydia-infected immune cells is incomplete. For a better comprehension of pathological inflammatory responses, robust models for interrogating TLR-signaling upon chlamydial infections are needed. To analyze the TLR response, we developed and utilized a highly sensitive and selective fluorescent transcriptional cellular reporter system to measure the activity of the transcription factor NF-κB. Upon incubation of the reporter cells with different preparations of Ct, we were able to pinpoint which components of TLRs are involved in the recognition of Ct. We identified CD14 associated with unique characteristics of different serovars as the crucial factor of the TLR4/CD14/MD2 complex for Ct-mediated activation of the NF-κB pathway. Furthermore, we found the TLR4/CD14/MD2 complex to be decisive for the uptake of Ct-derived lipopolysaccharides but not for infection and replication of Ct. Imaging flow cytometry provided information about inclusion formation in myeloid- as well as lymphocytic cells and was highest for Ct L2 with at least 25% of inclusion forming cells. Ct E inclusion formation was eminent in Jurkat cells without CD14 expression (11.1%). Thus, our model enables to determine Ct uptake and signal induction by pinpointing individual components of the recognition and signaling pathways to better understand the immune response towards infectious pathogens. Full article
(This article belongs to the Special Issue Intracellular Bacteria: From Basic Research to Clinics 2.0)
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Review

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14 pages, 1164 KiB  
Review
Aberrant Bodies: An Alternative Metabolic Homeostasis Allowing Survivability?
by Thomas Kozusnik, Simone E. Adams and Gilbert Greub
Microorganisms 2024, 12(3), 495; https://doi.org/10.3390/microorganisms12030495 - 29 Feb 2024
Viewed by 1636
Abstract
The Chlamydiae phylum is comprised of obligate intracellular bacteria including human pathogens such as Chlamydia trachomatis and lesser-known Chlamydia-related bacteria like Waddlia chondrophila or Simkania negevensis. Despite broad differences, these bacteria share a similar development including a persistent state induced using [...] Read more.
The Chlamydiae phylum is comprised of obligate intracellular bacteria including human pathogens such as Chlamydia trachomatis and lesser-known Chlamydia-related bacteria like Waddlia chondrophila or Simkania negevensis. Despite broad differences, these bacteria share a similar development including a persistent state induced using stressors such as immune responses, nutrient starvation, or penicillin introduction. In microbiology, this persistent state is identified by enlarged bacteria, called aberrant bodies, which are unable to divide but are able to survive and resume the developmental cycle upon clearance of the stressor. Clinically, chlamydial persistence is thought to be linked to chronic disease and long-term infections with pathogenic strains. This review aims to share and discuss the latest discoveries made on the little-known mechanisms that take place during stress response. The results indicate that an inter-linked homeostasis between iron and tryptophan is required for effective bacterial proliferation. During stress, Chlamydiae attempt to compensate by inducing tight regulations of the tryptophan and iron acquisition operons. These compensations allow bacterial survival but result in the halting of cell division. As cell division is tightly linked to peptidoglycan synthesis and regulation, treatment with β-lactamase inhibitors can also exhibit an aberrant body phenotype. Full article
(This article belongs to the Special Issue Intracellular Bacteria: From Basic Research to Clinics 2.0)
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32 pages, 865 KiB  
Review
Concept about the Virulence Factor of Legionella
by Jin-Lei Yang, Danyang Li and Xiao-Yong Zhan
Microorganisms 2023, 11(1), 74; https://doi.org/10.3390/microorganisms11010074 - 27 Dec 2022
Cited by 5 | Viewed by 5527
Abstract
Pathogenic species of Legionella can infect human alveolar macrophages through Legionella-containing aerosols to cause a disease called Legionellosis, which has two forms: a flu-like Pontiac fever and severe pneumonia named Legionnaires’ disease (LD). Legionella is an opportunistic pathogen that frequently presents in [...] Read more.
Pathogenic species of Legionella can infect human alveolar macrophages through Legionella-containing aerosols to cause a disease called Legionellosis, which has two forms: a flu-like Pontiac fever and severe pneumonia named Legionnaires’ disease (LD). Legionella is an opportunistic pathogen that frequently presents in aquatic environments as a biofilm or protozoa parasite. Long-term interaction and extensive co-evolution with various genera of amoebae render Legionellae pathogenic to infect humans and also generate virulence differentiation and heterogeneity. Conventionally, the proteins involved in initiating replication processes and human macrophage infections have been regarded as virulence factors and linked to pathogenicity. However, because some of the virulence factors are associated with the infection of protozoa and macrophages, it would be more accurate to classify them as survival factors rather than virulence factors. Given that the molecular basis of virulence variations among non-pathogenic, pathogenic, and highly pathogenic Legionella has not yet been elaborated from the perspective of virulence factors, a comprehensive explanation of how Legionella infects its natural hosts, protozoans, and accidental hosts, humans is essential to show a novel concept regarding the virulence factor of Legionella. In this review, we overviewed the pathogenic development of Legionella from protozoa, the function of conventional virulence factors in the infections of protozoa and macrophages, the host’s innate immune system, and factors involved in regulating the host immune response, before discussing a probably new definition for the virulence factors of Legionella. Full article
(This article belongs to the Special Issue Intracellular Bacteria: From Basic Research to Clinics 2.0)
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Other

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7 pages, 921 KiB  
Brief Report
Rickettsial Infection in the COVID-19 Era: The Correlation between the Detection of Rickettsia aeschlimannii in Ticks and Storytelling Photography of a Presumable Human Rickettsiosis Case
by Donato Antonio Raele and Maria Assunta Cafiero
Microorganisms 2023, 11(11), 2645; https://doi.org/10.3390/microorganisms11112645 - 27 Oct 2023
Viewed by 1322
Abstract
Rickettsia aeschlimannii infection is an emerging human tick-borne disease with only a few recorded cases. We reported a presumable autochthonous case of rickettsiosis in an Italian cattle breeder associated with a Hyalomma marginatum bite. Rickettsia aeschlimannii DNA was detected in both the tick [...] Read more.
Rickettsia aeschlimannii infection is an emerging human tick-borne disease with only a few recorded cases. We reported a presumable autochthonous case of rickettsiosis in an Italian cattle breeder associated with a Hyalomma marginatum bite. Rickettsia aeschlimannii DNA was detected in both the tick specimen from the patient and the grazing cattle close to his farm. Full article
(This article belongs to the Special Issue Intracellular Bacteria: From Basic Research to Clinics 2.0)
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12 pages, 561 KiB  
Case Report
Coxiella burnetii Femoro-Popliteal Bypass Infection: A Case Report
by Farah Azouzi, Louis Olagne, Sophie Edouard, Serge Cammilleri, Pierre-Edouard Magnan, Pierre-Edouard Fournier and Matthieu Million
Microorganisms 2023, 11(9), 2146; https://doi.org/10.3390/microorganisms11092146 - 24 Aug 2023
Viewed by 928
Abstract
Cardiovascular infections are the most severe and potentially lethal among the persistent focalized Coxiella burnetii infections. While aortic infections on aneurysms or prostheses are well-known, with specific complications (risk of fatal rupture), new non-aortic vascular infections are increasingly being described thanks to the [...] Read more.
Cardiovascular infections are the most severe and potentially lethal among the persistent focalized Coxiella burnetii infections. While aortic infections on aneurysms or prostheses are well-known, with specific complications (risk of fatal rupture), new non-aortic vascular infections are increasingly being described thanks to the emerging use of 18-fluorodeoxyglucose positron emission tomography (18F-FDG PET-scan). Here, we describe an infection of a femoro-popliteal bypass that would not have been diagnosed without the use of PET-scan. It is well-known that vascular prosthetic material is a site favorable for bacterial persistence, but the description of unusual anatomical sites, outside the heart or aorta, should raise the clinicians’ awareness and generalize the indications for PET-scan, with careful inclusion of the upper and lower limbs (not included in PET-scan for cancer), particularly in the presence of vascular prostheses. Future studies will be needed to precisely determine their optimal management. Full article
(This article belongs to the Special Issue Intracellular Bacteria: From Basic Research to Clinics 2.0)
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