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Article ; Online: One size does not fit all: Lysosomes exist in biochemically and functionally distinct states.

Bussi, Claudio / Gutierrez, Maximiliano G

2024 Volume 22, Issue 3, Page(s) e3002576

Abstract: Single-organelle resolution approaches have the potential to advance our knowledge of the heterogeneity of lysosome function. Challenging population-based models, we propose a "lysosome states" concept that links single lysosomes to function. ...

Abstract	Single-organelle resolution approaches have the potential to advance our knowledge of the heterogeneity of lysosome function. Challenging population-based models, we propose a "lysosome states" concept that links single lysosomes to function.
MeSH term(s)	Lysosomes ; Organelles
Language	English
Publishing date	2024-03-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2126776-5
ISSN	1545-7885 ; 1544-9173
ISSN (online)	1545-7885
ISSN	1544-9173
DOI	10.1371/journal.pbio.3002576
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Zs.A 6193: Show issues

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Article ; Online: Intracellular niche switching as host subversion strategy of bacterial pathogens.

Gutierrez, Maximiliano G / Enninga, Jost

Current opinion in cell biology

2022 Volume 76, Page(s) 102081

Abstract: Numerous bacterial pathogens "confine" themselves within host cells with an intracellular localization as main or exclusive niche. Many of them switch dynamically between a membrane-bound or cytosolic lifestyle. This requires either membrane damage and/ ... ...

Abstract	Numerous bacterial pathogens "confine" themselves within host cells with an intracellular localization as main or exclusive niche. Many of them switch dynamically between a membrane-bound or cytosolic lifestyle. This requires either membrane damage and/or repair of the bacterial-containing compartment. Niche switching has profound consequences on how the host cell recognizes the pathogens in time and space for elimination. Moreover, niche switching impacts how bacteria communicate with host cells to obtain nutrients, and it affects the accessibility to antibiotics. Understanding the local environments and cellular phenotypes that lead to niche switching is critical for developing new host-targeted antimicrobial strategies, and has the potential to shed light into fundamental cellular processes.
MeSH term(s)	Bacteria ; Cytosol ; Host-Pathogen Interactions
Language	English
Publishing date	2022-04-26
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1026381-0
ISSN	1879-0410 ; 0955-0674
ISSN (online)	1879-0410
ISSN	0955-0674
DOI	10.1016/j.ceb.2022.102081
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Zs.A 2963: Show issues

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Article ; Online: Quantitative Spatio-temporal Analysis of Phagosome Maturation in Live Cells.

Arévalo, Patricia Rosell / Aylan, Beren / Gutierrez, Maximiliano G

Methods in molecular biology (Clifton, N.J.)

2023 Volume 2692, Page(s) 187–207

Abstract: Phagocytosis and phagosome maturation are central processes to the development of the innate and adaptive immune response. Phagosome maturation is a continuous and dynamic process that occurs rapidly. In this chapter we describe fluorescence-based live ... ...

Abstract	Phagocytosis and phagosome maturation are central processes to the development of the innate and adaptive immune response. Phagosome maturation is a continuous and dynamic process that occurs rapidly. In this chapter we describe fluorescence-based live cell imaging methods for the quantitative and temporal analysis of phagosome maturation of beads and M. tuberculosis as two phagocytic targets. We also describe simple protocols for monitoring phagosome maturation: the use of the acidotropic probe LysoTracker and analyzing the recruitment of EGFP-tagged host proteins by phagosomes.
MeSH term(s)	Phagocytosis ; Phagosomes/metabolism ; Mycobacterium tuberculosis ; Spatio-Temporal Analysis
Language	English
Publishing date	2023-06-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-3338-0_13
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Host cell environments and antibiotic efficacy in tuberculosis.

Day, Nathan J / Santucci, Pierre / Gutierrez, Maximiliano G

Trends in microbiology

2023 Volume 32, Issue 3, Page(s) 270–279

Abstract: The aetiologic agent of tuberculosis (TB), Mycobacterium tuberculosis (Mtb), can survive, persist, and proliferate in a variety of heterogeneous subcellular compartments. Therefore, TB chemotherapy requires antibiotics crossing multiple biological ... ...

Abstract	The aetiologic agent of tuberculosis (TB), Mycobacterium tuberculosis (Mtb), can survive, persist, and proliferate in a variety of heterogeneous subcellular compartments. Therefore, TB chemotherapy requires antibiotics crossing multiple biological membranes to reach distinct subcellular compartments and target these bacterial populations. These compartments are also dynamic, and our understanding of intracellular pharmacokinetics (PK) often represents a challenge for antitubercular drug development. In recent years, the development of high-resolution imaging approaches in the context of host-pathogen interactions has revealed the intracellular distribution of antibiotics at a new level, yielding discoveries with important clinical implications. In this review, we describe the current knowledge regarding cellular PK of antibiotics and the complexity of drug distribution within the context of TB. We also discuss the recent advances in quantitative imaging and highlight their applications for drug development in the context of how intracellular environments and microbial localisation affect TB treatment efficacy.
MeSH term(s)	Humans ; Tuberculosis/drug therapy ; Tuberculosis/microbiology ; Antitubercular Agents/pharmacology ; Antitubercular Agents/therapeutic use ; Antitubercular Agents/metabolism ; Mycobacterium tuberculosis/metabolism ; Host-Pathogen Interactions ; Treatment Outcome
Chemical Substances	Antitubercular Agents
Language	English
Publishing date	2023-09-12
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1158963-2
ISSN	1878-4380 ; 0966-842X
ISSN (online)	1878-4380
ISSN	0966-842X
DOI	10.1016/j.tim.2023.08.009
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Zs.A 3738: Show issues

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Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Human stem cell-based models for studying host-pathogen interactions.

Pellegrino, Enrica / Gutierrez, Maximiliano G

Cellular microbiology

2021 Volume 23, Issue 7, Page(s) e13335

Abstract: The use of human cell lines and primary cells as in vitro models represents a valuable approach to study cellular responses to infection. However, with the advent of new molecular technologies and tools available, there is a growing need to develop more ... ...

Abstract	The use of human cell lines and primary cells as in vitro models represents a valuable approach to study cellular responses to infection. However, with the advent of new molecular technologies and tools available, there is a growing need to develop more physiologically relevant systems to overcome cell line model limitations and better mimic human disease. Since the discovery of human stem cells, its use has revolutionised the development of in vitro models. This is because after differentiation, these cells have the potential to reflect in vivo cell phenotypes and allow for probing questions in numerous fields of the biological sciences. Moreover, the possibility to combine the advantages of stem cell-derived cell types with genome editing technologies and engineered 3D microenvironments, provides enormous potential for producing in vitro systems to investigate cellular responses to infection that are both relevant and predictive. Here, we discuss recent advances in the use of human stem cells to model host-pathogen interactions, highlighting emerging technologies in the field of stem cell biology that can be exploited to investigate the fundamental biology of infection. TAKE AWAYS: hPSC overcome current limitations to study host-pathogen interactions in vitro. Genome editing can be used in hPSC to study cellular responses to infection. hPSC, 3D models and genome editing can recreate physiological in vitro systems.
MeSH term(s)	Cell Line ; Host-Pathogen Interactions ; Humans ; Models, Biological ; Stem Cells/cytology
Language	English
Publishing date	2021-05-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1468320-9
ISSN	1462-5822 ; 1462-5814
ISSN (online)	1462-5822
ISSN	1462-5814
DOI	10.1111/cmi.13335
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Zs.A 5288: Show issues

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Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: High content quantitative imaging of Mycobacterium tuberculosis responses to acidic microenvironments within human macrophages.

Aylan, Beren / Botella, Laure / Gutierrez, Maximiliano G / Santucci, Pierre

FEBS open bio

2023 Volume 13, Issue 7, Page(s) 1204–1217

Abstract: Intracellular pathogens such as Mycobacterium tuberculosis (Mtb) have evolved diverse strategies to counteract macrophage defence mechanisms including phagolysosomal biogenesis. Within macrophages, Mtb initially resides inside membrane-bound phagosomes ... ...

Abstract	Intracellular pathogens such as Mycobacterium tuberculosis (Mtb) have evolved diverse strategies to counteract macrophage defence mechanisms including phagolysosomal biogenesis. Within macrophages, Mtb initially resides inside membrane-bound phagosomes that interact with lysosomes and become acidified. The ability of Mtb to control and subvert the fusion between phagosomes and lysosomes plays a key role in the pathogenesis of tuberculosis. Therefore, understanding how pathogens interact with the endolysosomal network and cope with intracellular acidification is important to better understand the disease. Here, we describe in detail the use of fluorescence microscopy-based approaches to investigate Mtb responses to acidic environments in cellulo. We report high-content imaging modalities to probe Mtb sensing of external pH or visualise in real-time Mtb intrabacterial pH within infected human macrophages. We discuss various methodologies with step-by-step analyses that enable robust image-based quantifications. Finally, we highlight the advantages and limitations of these different approaches and discuss potential alternatives that can be applied to further investigate Mtb-host cell interactions. These methods can be adapted to study host-pathogen interactions in different biological systems and experimental settings. Altogether, these approaches represent a valuable tool to further broaden our understanding of the cellular and molecular mechanisms underlying intracellular pathogen survival.
MeSH term(s)	Humans ; Mycobacterium tuberculosis ; Macrophages ; Tuberculosis/microbiology ; Phagosomes/microbiology
Language	English
Publishing date	2023-01-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2651702-4
ISSN	2211-5463 ; 2211-5463
ISSN (online)	2211-5463
ISSN	2211-5463
DOI	10.1002/2211-5463.13537
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A sandPIT for Salmonella to play with efferosomes.

Morrison, Rebecca / Luk, Chak Hon / Gutierrez, Maximiliano G

Cell host & microbe

2022 Volume 30, Issue 2, Page(s) 141–143

Abstract: In this issue of Cell Host and Microbe, Hiyoshi et al. show that Salmonella uses a type III secretion system (T3SS-2) to damage the Salmonella-containing vacuole, leading to complement deposition on intracellular bacteria followed by neutrophil ... ...

Abstract	In this issue of Cell Host and Microbe, Hiyoshi et al. show that Salmonella uses a type III secretion system (T3SS-2) to damage the Salmonella-containing vacuole, leading to complement deposition on intracellular bacteria followed by neutrophil efferocytosis that protects intracellular bacteria from the respiratory burst.
MeSH term(s)	Bacterial Proteins/metabolism ; Neutrophils/metabolism ; Salmonella/metabolism ; Type III Secretion Systems/metabolism
Chemical Substances	Bacterial Proteins ; Type III Secretion Systems
Language	English
Publishing date	2022-02-07
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2278004-X
ISSN	1934-6069 ; 1931-3128
ISSN (online)	1934-6069
ISSN	1931-3128
DOI	10.1016/j.chom.2022.01.008
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Zs.A 6578: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: High content quantitative imaging of Mycobacterium tuberculosis responses to acidic microenvironments within human macrophages

Aylan, Beren / Botella, Laure / Gutierrez, Maximiliano G. / Santucci, Pierre

FEBS Open Bio. 2023 July, v. 13, no. 7 p.1204-1217

2023

Abstract	Intracellular pathogens such as Mycobacterium tuberculosis (Mtb) have evolved diverse strategies to counteract macrophage defence mechanisms including phagolysosomal biogenesis. Within macrophages, Mtb initially resides inside membrane‐bound phagosomes that interact with lysosomes and become acidified. The ability of Mtb to control and subvert the fusion between phagosomes and lysosomes plays a key role in the pathogenesis of tuberculosis. Therefore, understanding how pathogens interact with the endolysosomal network and cope with intracellular acidification is important to better understand the disease. Here, we describe in detail the use of fluorescence microscopy‐based approaches to investigate Mtb responses to acidic environments in cellulo. We report high‐content imaging modalities to probe Mtb sensing of external pH or visualise in real‐time Mtb intrabacterial pH within infected human macrophages. We discuss various methodologies with step‐by‐step analyses that enable robust image‐based quantifications. Finally, we highlight the advantages and limitations of these different approaches and discuss potential alternatives that can be applied to further investigate Mtb–host cell interactions. These methods can be adapted to study host–pathogen interactions in different biological systems and experimental settings. Altogether, these approaches represent a valuable tool to further broaden our understanding of the cellular and molecular mechanisms underlying intracellular pathogen survival.
Keywords	Mycobacterium tuberculosis ; acidification ; biogenesis ; fluorescence microscopy ; humans ; lysosomes ; macrophages ; pH ; pathogen survival ; pathogenesis ; phagosomes ; tuberculosis
Language	English
Dates of publication	2023-07
Size	p. 1204-1217.
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	2651702-4
ISSN	2211-5463
ISSN	2211-5463
DOI	10.1002/2211-5463.13537
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Mycobacterium tuberculosis infection of host cells in space and time.

Bussi, Claudio / Gutierrez, Maximiliano G

FEMS microbiology reviews

2019 Volume 43, Issue 4, Page(s) 341–361

Abstract: Tuberculosis (TB) caused by the bacterial pathogen Mycobacterium tuberculosis (Mtb) remains one of the deadliest infectious diseases with over a billion deaths in the past 200 years (Paulson 2013). TB causes more deaths worldwide than any other single ... ...

Abstract	Tuberculosis (TB) caused by the bacterial pathogen Mycobacterium tuberculosis (Mtb) remains one of the deadliest infectious diseases with over a billion deaths in the past 200 years (Paulson 2013). TB causes more deaths worldwide than any other single infectious agent, with 10.4 million new cases and close to 1.7 million deaths in 2017. The obstacles that make TB hard to treat and eradicate are intrinsically linked to the intracellular lifestyle of Mtb. Mtb needs to replicate within human cells to disseminate to other individuals and cause disease. However, we still do not completely understand how Mtb manages to survive within eukaryotic cells and why some cells are able to eradicate this lethal pathogen. Here, we summarise the current knowledge of the complex host cell-pathogen interactions in TB and review the cellular mechanisms operating at the interface between Mtb and the human host cell, highlighting the technical and methodological challenges to investigating the cell biology of human host cell-Mtb interactions.
MeSH term(s)	Host-Pathogen Interactions/physiology ; Humans ; Microbial Viability ; Mycobacterium tuberculosis ; Research Design ; Tuberculosis/microbiology ; Tuberculosis/physiopathology
Language	English
Publishing date	2019-03-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	283740-7
ISSN	1574-6976 ; 0168-6445
ISSN (online)	1574-6976
ISSN	0168-6445
DOI	10.1093/femsre/fuz006
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Zs.A 2165: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: LRRK2 in Infection: Friend or Foe?

Herbst, Susanne / Gutierrez, Maximiliano G

ACS infectious diseases

2019 Volume 5, Issue 6, Page(s) 809–815

Abstract: In the field of Parkinson's disease (PD) research, leucine-rich repeat kinase 2 (LRRK2) remains one of the most enigmatic kinases. LRRK2 pathogenic mutations result in increased kinase activity, making LRRK2 an attractive therapeutic target for PD. For ... ...

Abstract	In the field of Parkinson's disease (PD) research, leucine-rich repeat kinase 2 (LRRK2) remains one of the most enigmatic kinases. LRRK2 pathogenic mutations result in increased kinase activity, making LRRK2 an attractive therapeutic target for PD. For over 10 years, the identification of a bona fide substrate and a physiological function for LRRK2 has been elusive, and only recently, Rab GTPases were identified as substrates for LRRK2 kinase activity. Additionally, LRRK2 gene expression data shows that LRRK2 is expressed at low levels in neurons and at high levels in cells of the immune system. These findings shifted research efforts from neuronal toxicity of LRRK2 mutations to the function of LRRK2 in both vesicle trafficking and the immune system, which has resulted in novel insights into the role of LRRK2 during infection and immunity. In this Perspective, we summarize the latest findings highlighting LRRK2 as a central regulator of vesicular trafficking, infection, immunity, and inflammation, speculating how LRRK2 function could influence neuronal pathology in PD.
MeSH term(s)	Humans ; Inflammation ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/immunology ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/physiology ; Mutation ; Neurons/immunology ; Neurons/pathology ; Parkinson Disease/drug therapy ; Parkinson Disease/enzymology ; Phosphorylation ; Protein Transport
Chemical Substances	LRRK2 protein, human (EC 2.7.11.1) ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 (EC 2.7.11.1)
Language	English
Publishing date	2019-04-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2373-8227
ISSN (online)	2373-8227
DOI	10.1021/acsinfecdis.9b00051
Database	MEDical Literature Analysis and Retrieval System OnLINE

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