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Article ; Online: A high-throughput screening assay based on automated microscopy for monitoring antibiotic susceptibility of Mycobacterium tuberculosis phenotypes.

Kalsum, Sadaf / Andersson, Blanka / Das, Jyotirmoy / Schön, Thomas / Lerm, Maria

BMC microbiology

2021 Volume 21, Issue 1, Page(s) 167

Abstract: Background: Efficient high-throughput drug screening assays are necessary to enable the discovery of new anti-mycobacterial drugs. The purpose of our work was to develop and validate an assay based on live-cell imaging which can monitor the growth of ... ...

Abstract	Background: Efficient high-throughput drug screening assays are necessary to enable the discovery of new anti-mycobacterial drugs. The purpose of our work was to develop and validate an assay based on live-cell imaging which can monitor the growth of two distinct phenotypes of Mycobacterium tuberculosis and to test their susceptibility to commonly used TB drugs. Results: Both planktonic and cording phenotypes were successfully monitored as fluorescent objects using the live-cell imaging system IncuCyte S3, allowing collection of data describing distinct characteristics of aggregate size and growth. The quantification of changes in total area of aggregates was used to define IC Conclusions: Our results emphasize the efficiency of using automated live-cell imaging and its potential in high-throughput whole-cell screening to evaluate existing and search for novel antimycobacterial drugs.
MeSH term(s)	Antitubercular Agents/pharmacology ; Automation ; High-Throughput Screening Assays/methods ; Humans ; Isoniazid/pharmacology ; Linezolid/pharmacology ; Microbial Sensitivity Tests/methods ; Microscopy/methods ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/genetics ; Mycobacterium tuberculosis/growth & development ; Phenotype ; Rifampin/pharmacology ; Tuberculosis/microbiology
Chemical Substances	Antitubercular Agents ; Linezolid (ISQ9I6J12J) ; Isoniazid (V83O1VOZ8L) ; Rifampin (VJT6J7R4TR)
Language	English
Publishing date	2021-06-05
Publishing country	England
Document type	Evaluation Study ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1471-2180
ISSN (online)	1471-2180
DOI	10.1186/s12866-021-02212-3
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Article ; Online: A high content screening assay for discovery of antimycobacterial compounds based on primary human macrophages infected with virulent Mycobacterium tuberculosis.

Kalsum, Sadaf / Otrocka, Magdalena / Andersson, Blanka / Welin, Amanda / Schön, Thomas / Jenmalm-Jensen, Annika / Lundbäck, Thomas / Lerm, Maria

Tuberculosis (Edinburgh, Scotland)

2022 Volume 135, Page(s) 102222

Abstract: Drug resistance in Mycobacterium tuberculosis is an emerging threat that makes the discovery of new candidate drugs a priority. In particular, drugs with high sterilizing activity within host cells are needed to improve efficacy and reduce treatment ... ...

Abstract	Drug resistance in Mycobacterium tuberculosis is an emerging threat that makes the discovery of new candidate drugs a priority. In particular, drugs with high sterilizing activity within host cells are needed to improve efficacy and reduce treatment duration. We aimed to develope and validate a High Content Screening assay based on Mycobacterium tuberculosis-infected primary human monocyte-derived macrophages as its natural reservoir. Infected primary human monocyte-derived macrophages were exposed to control antibiotics or tested compounds on 384 well plates. Intracellular bacterial growth and macrophage numbers were evaluated using an ImageXpress High Content Screening system and Z'-factor was calculated to assess the reproducibility. The combination of isoniazid and rifampicin as a positive control rendered a Z'-factor above 0.4, demonstrating suitability of the assay for screening and compound profiling purposes. In a validation experiment, isoniazid, rifampicin, moxifloxacin and levofloxacin all effectively inhibited intracellular growth as expected. Finally, a pilot screening campaign including 5700 compounds from diverse libraries resulted in the identification of three compounds with confirmed antimycobacterial activity in the low micromolar range and low host cell toxicity. The assay represents an attractive screening platform for both academic research on host-pathogen mechanisms in tuberculosis and for the identification and characterization of novel antimycobacterial compounds.
MeSH term(s)	Antitubercular Agents/pharmacology ; Humans ; Isoniazid/pharmacology ; Macrophages/microbiology ; Mycobacterium tuberculosis ; Reproducibility of Results ; Rifampin/pharmacology ; Tuberculosis, Lymph Node
Chemical Substances	Antitubercular Agents ; Isoniazid (V83O1VOZ8L) ; Rifampin (VJT6J7R4TR)
Language	English
Publishing date	2022-06-16
Publishing country	Scotland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2046804-0
ISSN	1873-281X ; 1472-9792
ISSN (online)	1873-281X
ISSN	1472-9792
DOI	10.1016/j.tube.2022.102222
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Article ; Online: Immunomodulatory Agents Combat Multidrug-Resistant Tuberculosis by Improving Antimicrobial Immunity.

Rao Muvva, Jagadeeswara / Ahmed, Sultan / Rekha, Rokeya Sultana / Kalsum, Sadaf / Groenheit, Ramona / Schön, Thomas / Agerberth, Birgitta / Bergman, Peter / Brighenti, Susanna

The Journal of infectious diseases

2021 Volume 224, Issue 2, Page(s) 332–344

Abstract: Background: Multidrug-resistant (MDR) tuberculosis has low treatment success rates, and new treatment strategies are needed. We explored whether treatment with active vitamin D3 (vitD) and phenylbutyrate (PBA) could improve conventional chemotherapy by ... ...

Abstract	Background: Multidrug-resistant (MDR) tuberculosis has low treatment success rates, and new treatment strategies are needed. We explored whether treatment with active vitamin D3 (vitD) and phenylbutyrate (PBA) could improve conventional chemotherapy by enhancing immune-mediated eradication of Mycobacterium tuberculosis. Methods: A clinically relevant model was used consisting of human macrophages infected with M. tuberculosis isolates (n = 15) with different antibiotic resistance profiles. The antimicrobial effect of vitD+PBA, was tested together with rifampicin or isoniazid. Methods included colony-forming units (intracellular bacterial growth), messenger RNA expression analyses (LL-37, β-defensin, nitric oxide synthase, and dual oxidase 2), RNA interference (LL-37-silencing in primary macrophages), and Western blot analysis and confocal microscopy (LL-37 and LC3 protein expression). Results: VitD+PBA inhibited growth of clinical MDR tuberculosis strains in human macrophages and strengthened intracellular growth inhibition of rifampicin and isoniazid via induction of the antimicrobial peptide LL-37 and LC3-dependent autophagy. Gene silencing of LL-37 expression enhanced MDR tuberculosis growth in vitD+PBA-treated macrophages. The combination of vitD+PBA and isoniazid were as effective in reducing intracellular MDR tuberculosis growth as a >125-fold higher dose of isoniazid alone, suggesting potent additive effects of vitD+PBA with isoniazid. Conclusions: Immunomodulatory agents that trigger multiple immune pathways can strengthen standard MDR tuberculosis treatment and contribute to next-generation individualized treatment options for patients with difficult-to-treat pulmonary tuberculosis.
MeSH term(s)	Antibiotics, Antitubercular/pharmacology ; Antimicrobial Peptides/immunology ; Cells, Cultured ; Cholecalciferol/pharmacology ; Humans ; Immunomodulating Agents/pharmacology ; Isoniazid/pharmacology ; Macrophages/immunology ; Macrophages/microbiology ; Mycobacterium tuberculosis ; Rifampin/pharmacology ; Tuberculosis, Multidrug-Resistant/drug therapy ; Tuberculosis, Multidrug-Resistant/immunology
Chemical Substances	Antibiotics, Antitubercular ; Antimicrobial Peptides ; Immunomodulating Agents ; Cholecalciferol (1C6V77QF41) ; Isoniazid (V83O1VOZ8L) ; Rifampin (VJT6J7R4TR)
Language	English
Publishing date	2021-02-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiab100
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Article ; Online: Polarization of M1 and M2 Human Monocyte-Derived Cells and Analysis with Flow Cytometry upon Mycobacterium tuberculosis Infection.

Mily, Akhirunnesa / Kalsum, Sadaf / Loreti, Marco Giulio / Rekha, Rokeya Sultana / Muvva, Jagadeeswara Rao / Lourda, Magda / Brighenti, Susanna

Journal of visualized experiments : JoVE

2020 , Issue 163

Abstract: Human macrophages are primary host cells of intracellular Mycobacterium tuberculosis (Mtb) infection and thus have a central role in immune control of tuberculosis (TB). We have established an experimental protocol to follow immune polarization of ... ...

Abstract	Human macrophages are primary host cells of intracellular Mycobacterium tuberculosis (Mtb) infection and thus have a central role in immune control of tuberculosis (TB). We have established an experimental protocol to follow immune polarization of myeloid-derived cells into M1 (classically activated) or M2 (alternatively activated) macrophage-like cells through assessment with a 10-color flow cytometry panel that allows visualization and deep-characterization of green-fluorescent-protein (GFP)-labeled Mtb in diverse macrophages subsets. Monocytes obtained from healthy blood donors were polarized into M1 or M2 cells using differentiation with granulocyte macrophage-colony-stimulating factor (GM-CSF) or macrophage-colony stimulating factor (M-CSF) followed by polarization with IFN-γ and lipopolysaccharide (LPS) or IL-4, respectively. Fully polarized M1 and M2 cells were infected with Mtb-GFP for 4 hours before detached Mtb-infected macrophages were stained with flow cytometry at 4- or 24-hours post-infection. Sample acquisition was performed with flow cytometry and the data was analyzed using a flow cytometry analysis software. Manual gating as well as dimensionality reduction with Uniform Manifold Approximation and Projection (UMAP) and phenograph analysis was performed. This protocol resulted in effective M1/M2 polarization characterized by elevated levels of CD64, CD86, TLR2, HLA-DR and CCR7 on uninfected M1 cells, while uninfected M2 cells exhibited a strong up-regulation of the M2 phenotype markers CD163, CD200R, CD206 and CD80. M1-polarized cells typically contained fewer bacteria compared to M2-polarized cells. Several M1/M2 markers were downregulated after Mtb infection, which suggests that Mtb can modulate macrophage polarization. In addition, 24 different cell clusters of different sizes were found to be uniquely distributed among the M1 and M2 uninfected and Mtb-infected cells at 24-hours post-infection. This M1/M2 flow cytometry protocol could be used as a backbone in Mtb-macrophage research and be adopted for special needs in different areas of research.
MeSH term(s)	Biomarkers/metabolism ; Cell Polarity ; Cells, Cultured ; Flow Cytometry/methods ; Humans ; Macrophages/cytology ; Macrophages/immunology ; Macrophages/metabolism ; Monocytes/cytology ; Tuberculosis/immunology ; Tuberculosis/metabolism
Chemical Substances	Biomarkers
Language	English
Publishing date	2020-09-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/61807
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Article: Polarization of m1 and m2 human monocyte-derived cells and analysis with flow cytometry upon Mycobacterium tuberculosis infection

Mily, Akhirunnesa / Kalsum, Sadaf / Loreti, Marco Giulio / Rekha, Rokeya Sultana / Muvva, Jagadeeswara Rao / Lourda, Magda / Brighenti, Susanna

Journal of visualized experiments. 2020 Sept. 18, , no. 163

2020

Abstract	Human macrophages are primary host cells of intracellular Mycobacterium tuberculosis (Mtb) infection and thus have a central role in immune control of tuberculosis (TB). We have established an experimental protocol to follow immune polarization of myeloid-derived cells into M1 (classically activated) or M2 (alternatively activated) macrophage-like cells through assessment with a 10-color flow cytometry panel that allows visualization and deep-characterization of green-fluorescent-protein (GFP)-labeled Mtb in diverse macrophages subsets. Monocytes obtained from healthy blood donors were polarized into M1 or M2 cells using differentiation with granulocyte macrophage-colony-stimulating factor (GM-CSF) or macrophage-colony stimulating factor (M-CSF) followed by polarization with IFN-γ and lipopolysaccharide (LPS) or IL-4, respectively. Fully polarized M1 and M2 cells were infected with Mtb-GFP for 4 hours before detached Mtb-infected macrophages were stained with flow cytometry at 4- or 24-hours post-infection. Sample acquisition was performed with flow cytometry and the data was analyzed using a flow cytometry analysis software. Manual gating as well as dimensionality reduction with Uniform Manifold Approximation and Projection (UMAP) and phenograph analysis was performed. This protocol resulted in effective M1/M2 polarization characterized by elevated levels of CD64, CD86, TLR2, HLA-DR and CCR7 on uninfected M1 cells, while uninfected M2 cells exhibited a strong up-regulation of the M2 phenotype markers CD163, CD200R, CD206 and CD80. M1-polarized cells typically contained fewer bacteria compared to M2-polarized cells. Several M1/M2 markers were downregulated after Mtb infection, which suggests that Mtb can modulate macrophage polarization. In addition, 24 different cell clusters of different sizes were found to be uniquely distributed among the M1 and M2 uninfected and Mtb-infected cells at 24-hours post-infection. This M1/M2 flow cytometry protocol could be used as a backbone in Mtb-macrophage research and be adopted for special needs in different areas of research.
Keywords	Mycobacterium tuberculosis ; computer software ; flow cytometry ; green fluorescent protein ; humans ; interleukin-4 ; lipopolysaccharides ; macrophages ; monocytes ; phenotype ; tuberculosis
Language	English
Dates of publication	2020-0918
Size	p. e61807.
Publishing place	Journal of Visualized Experiments
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/61807
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The Cording Phenotype of

Kalsum, Sadaf / Braian, Clara / Koeken, Valerie A C M / Raffetseder, Johanna / Lindroth, Margaretha / van Crevel, Reinout / Lerm, Maria

Frontiers in cellular and infection microbiology

2017 Volume 7, Page(s) 278

Abstract: The causative agent of tuberculosis, ...

Abstract	The causative agent of tuberculosis,
Language	English
Publishing date	2017
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2017.00278
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Article ; Online: Corticosteroids protect infected cells against mycobacterial killing in vitro.

Tükenmez, Hasan / Edström, Isabel / Kalsum, Sadaf / Braian, Clara / Ummanni, Ramesh / Fick, Stina Berglund / Sundin, Charlotta / Lerm, Maria / Elofsson, Mikael / Larsson, Christer

Biochemical and biophysical research communications

2019 Volume 511, Issue 1, Page(s) 117–121

Abstract: The effect of corticosteroids on human physiology is complex and their use in tuberculosis patients remains controversial. In a high-throughput screening approach designed to discover virulence inhibitors, several corticosteroids were found to prevent ... ...

Abstract	The effect of corticosteroids on human physiology is complex and their use in tuberculosis patients remains controversial. In a high-throughput screening approach designed to discover virulence inhibitors, several corticosteroids were found to prevent cytolysis of fibroblasts infected with mycobacteria. Further experiments with Mycobacterium tuberculosis showed anti-cytolytic activity in the 10 nM range, but no effect on bacterial growth or survival in the absence of host cells at 20 μM. The results from a panel of corticosteroids with various affinities to the glucocorticoid- and mineralocorticoid receptors indicate that the inhibition of cytolysis most likely is mediated through the glucocorticoid receptor. Using live-imaging of M. tuberculosis-infected human monocyte-derived macrophages, we also show that corticosteroids to some extent control intracellular bacteria. In vitro systems with reduced complexity are to further study and understand the interactions between bacterial infection, immune defense and cell signaling.
MeSH term(s)	Adrenal Cortex Hormones/pharmacology ; Antitubercular Agents/pharmacology ; Cell Line ; Cell Survival/drug effects ; Cells, Cultured ; Fibroblasts/cytology ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Fibroblasts/microbiology ; Humans ; Macrophages/cytology ; Macrophages/drug effects ; Macrophages/metabolism ; Macrophages/microbiology ; Mycobacterium tuberculosis/drug effects ; Protective Agents/pharmacology ; Receptors, Glucocorticoid/metabolism ; Tuberculosis/drug therapy ; Tuberculosis/metabolism ; Tuberculosis/microbiology
Chemical Substances	Adrenal Cortex Hormones ; Antitubercular Agents ; Protective Agents ; Receptors, Glucocorticoid
Language	English
Publishing date	2019-02-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2019.02.044
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Article ; Online: Effective delivery of the anti-mycobacterial peptide NZX in mesoporous silica nanoparticles.

Tenland, Erik / Pochert, Alexander / Krishnan, Nitya / Umashankar Rao, Komal / Kalsum, Sadaf / Braun, Katharina / Glegola-Madejska, Izabela / Lerm, Maria / Robertson, Brian D / Lindén, Mika / Godaly, Gabriela

PloS one

2019 Volume 14, Issue 2, Page(s) e0212858

Abstract: Background: Intracellular delivery of antimicrobial agents by nanoparticles, such as mesoporous silica particles (MSPs), offers an interesting strategy to treat intracellular infections. In tuberculosis (TB), Mycobacterium tuberculosis avoids components ...

Abstract	Background: Intracellular delivery of antimicrobial agents by nanoparticles, such as mesoporous silica particles (MSPs), offers an interesting strategy to treat intracellular infections. In tuberculosis (TB), Mycobacterium tuberculosis avoids components of the immune system by residing primarily inside alveolar macrophages, which are the desired target for TB therapy. Methods and findings: We have previously identified a peptide, called NZX, capable of inhibiting both clinical and multi-drug resistant strains of M. tuberculosis at therapeutic concentrations. In this study we analysed the potential of MSPs containing NZX for the treatment of tuberculosis. The MSPs released functional NZX gradually into simulated lung fluid and the peptide filled MSPs were easily taken up by primary macrophages. In an intracellular infection model, the peptide containing particles showed increased mycobacterial killing compared to free peptide. The therapeutic potential of peptide containing MSPs was investigated in a murine infection model, showing that MSPs preserved the effect to eliminate M. tuberculosis in vivo. Conclusions: In this study we found that loading the antimicrobial peptide NZX into MSPs increased the inhibition of intracellular mycobacteria in primary macrophages and preserved the ability to eliminate M. tuberculosis in vivo in a murine model. Our studies provide evidence for the feasibility of using MSPs for treatment of tuberculosis.
MeSH term(s)	Animals ; Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/pharmacokinetics ; Anti-Bacterial Agents/pharmacology ; Antimicrobial Cationic Peptides/chemistry ; Antimicrobial Cationic Peptides/pharmacokinetics ; Antimicrobial Cationic Peptides/pharmacology ; Disease Models, Animal ; Female ; Humans ; Mice ; Mice, Inbred BALB C ; Mycobacterium tuberculosis/growth & development ; Nanoparticles/chemistry ; Nanoparticles/therapeutic use ; Porosity ; Silicon Dioxide/chemistry ; Silicon Dioxide/pharmacokinetics ; Silicon Dioxide/pharmacology ; Tuberculosis, Pulmonary/drug therapy ; Tuberculosis, Pulmonary/metabolism ; Tuberculosis, Pulmonary/microbiology ; Tuberculosis, Pulmonary/pathology
Chemical Substances	Anti-Bacterial Agents ; Antimicrobial Cationic Peptides ; Silicon Dioxide (7631-86-9)
Language	English
Publishing date	2019-02-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0212858
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Article ; Online: A novel derivative of the fungal antimicrobial peptide plectasin is active against Mycobacterium tuberculosis.

Tenland, Erik / Krishnan, Nitya / Rönnholm, Anna / Kalsum, Sadaf / Puthia, Manoj / Mörgelin, Matthias / Davoudi, Mina / Otrocka, Magdalena / Alaridah, Nader / Glegola-Madejska, Izabela / Sturegård, Erik / Schmidtchen, Artur / Lerm, Maria / Robertson, Brian D / Godaly, Gabriela

Tuberculosis (Edinburgh, Scotland)

2018 Volume 113, Page(s) 231–238

Abstract: Tuberculosis has been reaffirmed as the infectious disease causing most deaths in the world. Co-infection with HIV and the increase in multi-drug resistant Mycobacterium tuberculosis strains complicate treatment and increases mortality rates, making the ... ...

Abstract	Tuberculosis has been reaffirmed as the infectious disease causing most deaths in the world. Co-infection with HIV and the increase in multi-drug resistant Mycobacterium tuberculosis strains complicate treatment and increases mortality rates, making the development of new drugs an urgent priority. In this study we have identified a promising candidate by screening antimicrobial peptides for their capacity to inhibit mycobacterial growth. This non-toxic peptide, NZX, is capable of inhibiting both clinical strains of M. tuberculosis and an MDR strain at therapeutic concentrations. The therapeutic potential of NZX is further supported in vivo where NZX significantly lowered the bacterial load with only five days of treatment, comparable to rifampicin treatment over the same period. NZX possesses intracellular inhibitory capacity and co-localizes with intracellular bacteria in infected murine lungs. In conclusion, the data presented strongly supports the therapeutic potential of NZX in future anti-TB treatment.
MeSH term(s)	Animals ; Antitubercular Agents/pharmacology ; Cells, Cultured ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Resistance, Multiple, Bacterial ; Female ; Humans ; Lung/drug effects ; Lung/microbiology ; Lung/ultrastructure ; Macrophages/drug effects ; Macrophages/microbiology ; Mice, Inbred BALB C ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/growth & development ; Peptide Fragments/pharmacology ; Peptides/pharmacology ; Time Factors ; Tuberculosis, Pulmonary/drug therapy ; Tuberculosis, Pulmonary/microbiology ; Tuberculosis, Pulmonary/pathology
Chemical Substances	Antitubercular Agents ; Peptide Fragments ; Peptides ; plectasin
Language	English
Publishing date	2018-10-30
Publishing country	Scotland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2046804-0
ISSN	1873-281X ; 1472-9792
ISSN (online)	1873-281X
ISSN	1472-9792
DOI	10.1016/j.tube.2018.10.008
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Article ; Online: Effective delivery of the anti-mycobacterial peptide NZX in mesoporous silica nanoparticles.

Erik Tenland / Alexander Pochert / Nitya Krishnan / Komal Umashankar Rao / Sadaf Kalsum / Katharina Braun / Izabela Glegola-Madejska / Maria Lerm / Brian D Robertson / Mika Lindén / Gabriela Godaly

PLoS ONE, Vol 14, Iss 2, p e

2019 Volume 0212858

Abstract: Background Intracellular delivery of antimicrobial agents by nanoparticles, such as mesoporous silica particles (MSPs), offers an interesting strategy to treat intracellular infections. In tuberculosis (TB), Mycobacterium tuberculosis avoids components ... ...

Abstract	Background Intracellular delivery of antimicrobial agents by nanoparticles, such as mesoporous silica particles (MSPs), offers an interesting strategy to treat intracellular infections. In tuberculosis (TB), Mycobacterium tuberculosis avoids components of the immune system by residing primarily inside alveolar macrophages, which are the desired target for TB therapy. Methods and findings We have previously identified a peptide, called NZX, capable of inhibiting both clinical and multi-drug resistant strains of M. tuberculosis at therapeutic concentrations. In this study we analysed the potential of MSPs containing NZX for the treatment of tuberculosis. The MSPs released functional NZX gradually into simulated lung fluid and the peptide filled MSPs were easily taken up by primary macrophages. In an intracellular infection model, the peptide containing particles showed increased mycobacterial killing compared to free peptide. The therapeutic potential of peptide containing MSPs was investigated in a murine infection model, showing that MSPs preserved the effect to eliminate M. tuberculosis in vivo. Conclusions In this study we found that loading the antimicrobial peptide NZX into MSPs increased the inhibition of intracellular mycobacteria in primary macrophages and preserved the ability to eliminate M. tuberculosis in vivo in a murine model. Our studies provide evidence for the feasibility of using MSPs for treatment of tuberculosis.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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