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Article ; Online: Glycosylating Effectors of

Belyi, Yury / Levanova, Nadya / Schroeder, Gunnar N

2022 Volume 12, Issue 2

Abstract: Work over the past two decades clearly defined a significant role of glycosyltransferase effectors in the infection strategy of the Gram-negative, respiratory ... ...

Abstract	Work over the past two decades clearly defined a significant role of glycosyltransferase effectors in the infection strategy of the Gram-negative, respiratory pathogen
MeSH term(s)	Bacterial Proteins/metabolism ; Glucosyltransferases/genetics ; Host-Pathogen Interactions ; Legionella pneumophila ; Protein Biosynthesis
Chemical Substances	Bacterial Proteins ; Glucosyltransferases (EC 2.4.1.-)
Language	English
Publishing date	2022-02-04
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12020255
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Article ; Online: The Toolbox for Uncovering the Functions of

Schroeder, Gunnar N

Frontiers in cellular and infection microbiology

2018 Volume 7, Page(s) 528

Abstract: The defective in organelle trafficking/intracellular multiplication (Dot/Icm) Type IVb secretion system (T4SS) is the essential virulence factor for the intracellular life style and pathogenicity ... ...

Abstract	The defective in organelle trafficking/intracellular multiplication (Dot/Icm) Type IVb secretion system (T4SS) is the essential virulence factor for the intracellular life style and pathogenicity of
MeSH term(s)	Bacteriological Techniques/methods ; Legionella/genetics ; Legionella/metabolism ; Molecular Biology/methods ; Substrate Specificity ; Type IV Secretion Systems/genetics ; Type IV Secretion Systems/metabolism ; Virulence Factors/metabolism
Chemical Substances	Type IV Secretion Systems ; Virulence Factors
Language	English
Publishing date	2018-01-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2017.00528
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Article ; Online: The

Lockwood, Daniel C / Amin, Himani / Costa, Tiago R D / Schroeder, Gunnar N

Microbiology (Reading, England)

2022 Volume 168, Issue 5

MeSH term(s)	Bacterial Proteins/genetics ; Genome, Bacterial ; Legionella pneumophila/genetics ; Type IV Secretion Systems/genetics
Chemical Substances	Bacterial Proteins ; Type IV Secretion Systems
Language	English
Publishing date	2022-04-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1180712-x
ISSN	1465-2080 ; 1350-0872
ISSN (online)	1465-2080
ISSN	1350-0872
DOI	10.1099/mic.0.001187
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Ud II Zs.140: Show issues

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Article ; Online: Editorial: Bacterial Effectors as Drivers of Human Disease: Models, Methods, Mechanisms.

Schroeder, Gunnar N / Pearson, Jaclyn S / Thurston, Teresa L M

Frontiers in cellular and infection microbiology

2021 Volume 11, Page(s) 708228

MeSH term(s)	Bacteria/genetics ; Bacterial Proteins ; Bacterial Secretion Systems ; Host-Pathogen Interactions ; Humans ; Virulence Factors
Chemical Substances	Bacterial Proteins ; Bacterial Secretion Systems ; Virulence Factors
Language	English
Publishing date	2021-07-08
Publishing country	Switzerland
Document type	Editorial ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2021.708228
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Article ; Online: A gas phase fractionation acquisition scheme integrating ion mobility for rapid diaPASEF library generation.

Penny, Jack / Arefian, Mohammad / Schroeder, Gunnar N / Bengoechea, José A / Collins, Ben C

Proteomics

2023 Volume 23, Issue 7-8, Page(s) e2200038

Abstract: Data independent acquisition (DIA/SWATH) MS is a primary strategy in quantitative proteomics. diaPASEF is a recent adaptation using trapped ion mobility spectrometry (TIMS) to improve selectivity/sensitivity. Complex DIA spectra are typically analyzed ... ...

Abstract	Data independent acquisition (DIA/SWATH) MS is a primary strategy in quantitative proteomics. diaPASEF is a recent adaptation using trapped ion mobility spectrometry (TIMS) to improve selectivity/sensitivity. Complex DIA spectra are typically analyzed with reference to spectral libraries. The best-established method for generating libraries uses offline fractionation to increase depth of coverage. More recently strategies for spectral library generation based on gas phase fractionation (GPF), where a representative sample is injected serially using narrow DIA windows that cover different mass ranges of the complete precursor space, have been introduced that performed comparably to deep offline fractionation-based libraries. We investigated whether an analogous GPF-based approach that accounts for the ion mobility (IM) dimension is useful for the analysis of diaPASEF data. We developed a rapid library generation approach using an IM-GPF acquisition scheme in the m/z versus 1/K0 space requiring seven injections of a representative sample and compared this with libraries generated by direct deconvolution-based analysis of diaPASEF data or by deep offline fractionation. We found that library generation by IM-GPF outperformed direct library generation from diaPASEF and had performance approaching that of the deep library. This establishes the IM-GPF scheme as a pragmatic approach to rapid library generation for analysis of diaPASEF data.
MeSH term(s)	Proteomics/methods ; Peptide Library ; Chemical Fractionation/methods ; Proteome/analysis
Chemical Substances	Peptide Library ; Proteome
Language	English
Publishing date	2023-03-10
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2032093-0
ISSN	1615-9861 ; 1615-9853
ISSN (online)	1615-9861
ISSN	1615-9853
DOI	10.1002/pmic.202200038
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Zs.A 5386: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.A 1868: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Precision-cut lung slices: A powerful ex vivo model to investigate respiratory infectious diseases.

Viana, Flávia / O'Kane, Cecilia M / Schroeder, Gunnar N

Molecular microbiology

2021 Volume 117, Issue 3, Page(s) 578–588

Abstract: Respiratory infections are a leading cause of mortality worldwide. Most of the research on the underlying disease mechanisms is based on cell culture, organoid, or surrogate animal models. Although these provide important insights, they have limitations. ...

Abstract	Respiratory infections are a leading cause of mortality worldwide. Most of the research on the underlying disease mechanisms is based on cell culture, organoid, or surrogate animal models. Although these provide important insights, they have limitations. Cell culture models fail to recapitulate cellular interactions in the lung and animal models often do not permit high-throughput analysis of drugs or pathogen isolates; hence, there is a need for improved, scalable models. Precision-cut lung slices (PCLS), small, uniform tissue slices generated from animal or human lungs are increasingly recognized and employed as an ex vivo organotypic model. PCLS retain remarkable cellular complexity and the architecture of the lung, providing a platform to investigate respiratory pathogens in a near-native environment. Here, we review the generation and features of PCLS, their use to investigate the pathogenesis of viral and bacterial pathogens, and highlight their potential to advance respiratory infection research in the future.
MeSH term(s)	Animals ; Communicable Diseases/pathology ; Lung/microbiology ; Lung/pathology
Language	English
Publishing date	2021-10-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	619315-8
ISSN	1365-2958 ; 0950-382X
ISSN (online)	1365-2958
ISSN	0950-382X
DOI	10.1111/mmi.14817
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Zs.A 2502: Show issues

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Article ; Online: The Galleria mellonella Infection Model for Investigating the Molecular Mechanisms of Legionella Virulence.

Frankel, Gad / Schroeder, Gunnar N

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

2019 Volume 1921, Page(s) 333–346

Abstract: Legionella species evolved virulence factors to exploit protozoa as replicative niches in the environment. Cell culture infection models demonstrated that many of these factors also enable the bacteria to thrive in human macrophages; however, these ... ...

Abstract	Legionella species evolved virulence factors to exploit protozoa as replicative niches in the environment. Cell culture infection models demonstrated that many of these factors also enable the bacteria to thrive in human macrophages; however, these models do not recapitulate the complex interactions between macrophages, lung epithelial, and additional immune cells, which are crucial to control bacterial infections. Thus, suitable infection models are required to understand which bacterial factors are important to trigger disease. Guinea pigs and, most frequently, mice have been successfully used as mammalian model hosts; however, ethical and economic considerations impede their use in high-throughput screening studies of Legionella isolates or small molecule inhibitors.Here, we describe the larvae of the lepidopteran Galleria mellonella as insect model of Legionella pathogenesis. Larvae can be obtained from commercial suppliers in large numbers, maintained without the need of specialized equipment, and infected by injection. Although lacking the complexity of a mammalian immune system, the larvae mount humoral and cellular immune responses to infection. L. pneumophila strain 130b and other prototype isolates withstand these responses and use the Defective in organelle trafficking/Intracellular multiplication (Dot/Icm) type IV secretion system (T4SS ) to inject effectors enabling survival and replication in hemocytes, insect phagocytes, ultimately leading to the death of the larvae. Differences in virulence between L. pneumophila isolates or gene deletion mutants can be analyzed using indicators of larval health and immune induction, such as pigmentation, mobility, histopathology, and survival. Bacterial replication can be measured by plating hemolymph or by immunofluorescence microscopy of isolated circulating hemocytes from infected larvae. Combined, these straightforward experimental readouts make G. mellonella larvae a versatile model host to rapidly assess the virulence of different Legionella isolates and investigate the role of specific virulence factors in overcoming innate host defense mechanisms.
MeSH term(s)	Animals ; Bacterial Load ; Bacterial Proteins/metabolism ; Cell Count ; Hemocytes/metabolism ; Hemocytes/microbiology ; Host-Pathogen Interactions ; Legionella/physiology ; Legionellosis/microbiology ; Macrophages/immunology ; Macrophages/metabolism ; Macrophages/microbiology ; Microscopy, Fluorescence ; Moths/microbiology ; Type IV Secretion Systems ; Virulence
Chemical Substances	Bacterial Proteins ; Type IV Secretion Systems
Language	English
Publishing date	2019-01-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-9048-1_22
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Article ; Online: Human mesenchymal stromal cells inhibit

Shaw, Timothy D / Krasnodembskaya, Anna D / Schroeder, Gunnar N / Doherty, Declan F / Silva, Johnatas Dutra / Tandel, Shikha M / Su, Yue / Butler, David / Ingram, Rebecca J / O'Kane, Cecilia M

Thorax

2024

Abstract: Introduction: Novel therapeutic strategies are urgently needed for : Methods: Human monocyte-derived macrophages (MDMs) were infected with : Results: MSCs reduced intracellular bacteria in MDMs over 72 hours (median 35% reduction, p=0.027). MSC ... ...

Abstract	Introduction: Novel therapeutic strategies are urgently needed for Methods: Human monocyte-derived macrophages (MDMs) were infected with Results: MSCs reduced intracellular bacteria in MDMs over 72 hours (median 35% reduction, p=0.027). MSC treatment increased extracellular concentrations of prostaglandin E2 (PGE2) (median 10.1-fold rise, p=0.002) and reduced tumour necrosis factor-α (median 28% reduction, p=0.025). Blocking MSC PGE2 production by cyclo-oxygenase-2 (COX-2) inhibition with celecoxib abrogated the antimicrobial effect, while this was restored by adding exogenous PGE2. MSC-treated mice had lower pulmonary CFUs (median 18% reduction, p=0.012), but no significant change in spleen or liver CFUs compared with controls. Conclusion: MSCs can modulate inflammation and reduce intracellular
Language	English
Publishing date	2024-03-20
Publishing country	England
Document type	Journal Article
ZDB-ID	204353-1
ISSN	1468-3296 ; 0040-6376
ISSN (online)	1468-3296
ISSN	0040-6376
DOI	10.1136/thorax-2023-220819
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Article ; Online: Host manipulation by bacterial type III and type IV secretion system effector proteases.

Viana, Flávia / Peringathara, Shruthi Sachidanandan / Rizvi, Arshad / Schroeder, Gunnar N

Cellular microbiology

2021 Volume 23, Issue 11, Page(s) e13384

Abstract: Proteases are powerful enzymes, which cleave peptide bonds, leading most of the time to irreversible fragmentation or degradation of their substrates. Therefore they control many critical cell fate decisions in eukaryotes. Bacterial pathogens exploit ... ...

Abstract	Proteases are powerful enzymes, which cleave peptide bonds, leading most of the time to irreversible fragmentation or degradation of their substrates. Therefore they control many critical cell fate decisions in eukaryotes. Bacterial pathogens exploit this power and deliver protease effectors through specialised secretion systems into host cells. Research over the past years revealed that the functions of protease effectors during infection are diverse, reflecting the lifestyles and adaptations to specific hosts; however, only a small number of peptidase families seem to have given rise to most of these protease virulence factors by the evolution of different substrate-binding specificities, intracellular activation and subcellular targeting mechanisms. Here, we review our current knowledge about the enzymology and function of protease effectors, which Gram-negative bacterial pathogens translocate via type III and IV secretion systems to irreversibly manipulate host processes. We highlight emerging concepts such as signalling by protease cleavage products and effector-triggered immunity, which host cells employ to detect and defend themselves against a protease attack. TAKE AWAY: Proteases irreversibly cleave proteins to control critical cell fate decisions. Gram-negative bacteria use type III and IV secretion systems to inject effectors. Protease effectors are integral weapons for the manipulation of host processes. Effectors evolved from few peptidase families to target diverse substrates. Effector-triggered immunity upon proteolytic attack emerges as host defence.
MeSH term(s)	Bacteria ; Bacterial Proteins ; Humans ; Peptide Hydrolases ; Type III Secretion Systems ; Type IV Secretion Systems ; Virulence Factors
Chemical Substances	Bacterial Proteins ; Type III Secretion Systems ; Type IV Secretion Systems ; Virulence Factors ; Peptide Hydrolases (EC 3.4.-)
Language	English
Publishing date	2021-08-30
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.13384
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Zs.A 5288: Show issues

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Article ; Online: A trans-kingdom T6SS effector induces the fragmentation of the mitochondrial network and activates innate immune receptor NLRX1 to promote infection.

Sá-Pessoa, Joana / López-Montesino, Sara / Przybyszewska, Kornelia / Rodríguez-Escudero, Isabel / Marshall, Helina / Ova, Adelia / Schroeder, Gunnar N / Barabas, Peter / Molina, María / Curtis, Tim / Cid, Víctor J / Bengoechea, José A

Nature communications

2023 Volume 14, Issue 1, Page(s) 871

Abstract: Bacteria can inhibit the growth of other bacteria by injecting effectors using a type VI secretion system (T6SS). T6SS effectors can also be injected into eukaryotic cells to facilitate bacterial survival, often by targeting the cytoskeleton. Here, we ... ...

Abstract	Bacteria can inhibit the growth of other bacteria by injecting effectors using a type VI secretion system (T6SS). T6SS effectors can also be injected into eukaryotic cells to facilitate bacterial survival, often by targeting the cytoskeleton. Here, we show that the trans-kingdom antimicrobial T6SS effector VgrG4 from Klebsiella pneumoniae triggers the fragmentation of the mitochondrial network. VgrG4 colocalizes with the endoplasmic reticulum (ER) protein mitofusin 2. VgrG4 induces the transfer of Ca
MeSH term(s)	Cullin Proteins/metabolism ; NF-KappaB Inhibitor alpha ; NF-kappa B/metabolism ; Reactive Oxygen Species/metabolism ; Immunity, Innate
Chemical Substances	Cullin Proteins ; NF-KappaB Inhibitor alpha (139874-52-5) ; NF-kappa B ; Reactive Oxygen Species
Language	English
Publishing date	2023-02-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-36629-3
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