PMID- 34473918
OWN - NLM
STAT- MEDLINE
DCOM- 20220113
LR  - 20220113
IS  - 1868-503X (Electronic)
IS  - 1868-5021 (Linking)
VI  - 12
IP  - 1
DP  - 2021 Sep 2
TI  - 3D host cell and pathogen-based bioassay development for testing 
      anti-tuberculosis (TB) drug response and modeling immunodeficiency.
PG  - 117-128
LID - 10.1515/bmc-2021-0013 [doi]
AB  - Tuberculosis (TB) is a global health threat that affects 10 million people 
      worldwide. Human Immunodeficiency Virus (HIV) remains one of the major 
      contributors to the reactivation of asymptomatic latent tuberculosis (LTBI). Over 
      the recent years, there has been a significant focus in developing in-vitro 3D 
      models mimicking early events of Mycobacterium tuberculosis (Mtb) pathogenesis, 
      especially formation of the granuloma. However, these models are low throughput 
      and require extracellular matrix. In this article, we report the generation of a 
      matrix-free 3D model, using THP-1 human monocyte/macrophage cells and 
      mCherry-expressing Mycobacterium bovis BCG (Bacilli Camille Guerin), henceforth 
      referred as 3D spheroids, to study the host cell-bacterial interactions. Using 
      mCherry-intensity-based tracking, we monitored the kinetics of BCG growth in the 
      3D spheroids. We also demonstrate the application of the 3D spheroids for testing 
      anti-TB compounds such as isoniazid (INH), rifampicin (RIF), as well as a 
      host-directed drug, everolimus (EVR) as single and combinational treatments. We 
      further established a dual infection 3D spheroid model by coinfecting THP-1 
      macrophages with BCG mCherry and pseudotype HIV. In this HIV-TB co-infection 
      model, we found an increase in BCG mCherry growth within the 3D spheroids 
      infected with HIV pseudotype. The degree of disruption of the granuloma was 
      proportional to the virus titers used for co-infection. In summary, this 3D 
      spheroid assay is an useful tool to screen anti-TB response of potential 
      candidate drugs and can be adopted to model HIV-TB interactions.
CI  - (c) 2021 Shilpaa Mukundan et al., published by Sciendo.
FAU - Mukundan, Shilpaa
AU  - Mukundan S
AD  - Department of Biomedical Engineering, Rutgers, The State University of New 
      Jersey, NJ 08854.
FAU - Bhatt, Rachana
AU  - Bhatt R
AD  - Department of Biomedical Engineering, Rutgers, The State University of New 
      Jersey, NJ 08854.
FAU - Lucas, John
AU  - Lucas J
AD  - Department of Biomedical Engineering, Rutgers, The State University of New 
      Jersey, NJ 08854.
FAU - Tereyek, Matthew
AU  - Tereyek M
AD  - Department of Biomedical Engineering, Rutgers, The State University of New 
      Jersey, NJ 08854.
FAU - Chang, Theresa L
AU  - Chang TL
AD  - Public Health Research Institute, New Jersey Medical School, Rutgers, The State 
      University of New Jersey, NJ 07103.
FAU - Subbian, Selvakumar
AU  - Subbian S
AD  - Public Health Research Institute, New Jersey Medical School, Rutgers, The State 
      University of New Jersey, NJ 07103.
FAU - Parekkadan, Biju
AU  - Parekkadan B
AD  - Department of Biomedical Engineering, Rutgers, The State University of New 
      Jersey, NJ 08854; Department of Medicine, Rutgers Biomedical Health Sciences, 
      Rutgers, The State University of New Jersey, NJ 08854.
LA  - eng
PT  - Journal Article
DEP - 20210902
PL  - Germany
TA  - Biomol Concepts
JT  - Biomolecular concepts
JID - 101518829
RN  - 0 (Antitubercular Agents)
RN  - 0 (Pharmaceutical Preparations)
SB  - IM
MH  - Antitubercular Agents/pharmacology
MH  - Biological Assay
MH  - Humans
MH  - *Mycobacterium tuberculosis
MH  - *Pharmaceutical Preparations
MH  - *Tuberculosis/veterinary
OTO - NOTNLM
OT  - Bioassay
OT  - Drug response
OT  - HIV-TB co-infection
OT  - Human Immunodeficiency Virus
OT  - Tuberculosis
OT  - anti-tuberculosis drugs
OT  - granuloma
EDAT- 2021/09/03 06:00
MHDA- 2022/01/14 06:00
CRDT- 2021/09/02 17:53
PHST- 2021/05/20 00:00 [received]
PHST- 2021/06/24 00:00 [accepted]
PHST- 2021/09/02 17:53 [entrez]
PHST- 2021/09/03 06:00 [pubmed]
PHST- 2022/01/14 06:00 [medline]
AID - bmc-2021-0013 [pii]
AID - 10.1515/bmc-2021-0013 [doi]
PST - epublish
SO  - Biomol Concepts. 2021 Sep 2;12(1):117-128. doi: 10.1515/bmc-2021-0013.