scholarly journals Stabilization of Hypoxia-Inducible Factor Promotes Antimicrobial Activity of Human Macrophages Against Mycobacterium tuberculosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Sebastian F. Zenk ◽  
Sebastian Hauck ◽  
Daniel Mayer ◽  
Mark Grieshober ◽  
Steffen Stenger
Keyword(s):  
Antimicrobial Activity ◽  
Mycobacterium Tuberculosis ◽  
Oxygen Sensor ◽  
Expression Patterns ◽  
Hypoxia Inducible Factor ◽  
Antimycobacterial Activity ◽  
P38 Map Kinase ◽  
Microbial Pathogens ◽  
Prolyl Hydroxylases ◽  
Human Macrophages

Hypoxia-inducible factor (HIF) is a key oxygen sensor that controls gene expression patterns to adapt cellular metabolism to hypoxia. Pharmacological inhibition of prolyl-hydroxylases stabilizes HIFs and mimics hypoxia, leading to increased expression of more than 300 genes. Whether the genetic program initialized by HIFs affects immune responses against microbial pathogens, is not well studied. Recently we showed that hypoxia enhances antimicrobial activity against Mycobacterium tuberculosis (Mtb) in human macrophages. The objective of this study was to evaluate whether the oxygen sensor HIF is involved in hypoxia-mediated antimycobacterial activity. Treatment of Mtb-infected macrophages with the prolyl-hydroxylase inhibitor Molidustat reduced the release of TNFα and IL-10, two key cytokines involved in the immune response in tuberculosis. Molidustat also interferes with the p38 MAP kinase pathway. HIF-stabilization by Molidustat also induced the upregulation of the Vitamin D receptor and human β defensin 2, which define an antimicrobial effector pathway in human macrophages. Consequently, these immunological effects resulted in reduced proliferation of virulent Mtb in human macrophages. Therefore, HIFs may be attractive new candidates for host-directed therapies against infectious diseases caused by intracellular bacteria, including tuberculosis.

scholarly journals Polyketides from an Endophytic Aspergillus fumigatus Isolate Inhibit the Growth of Mycobacterium tuberculosis and MRSA

2015 ◽  
Vol 10 (10) ◽  
pp. 1934578X1501001 ◽  
Author(s):  
Andrew J. Flewelling ◽  
Amanda L Bishop ◽  
John A. Johnson ◽  
Christopher A. Gray
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Mycobacterium Tuberculosis ◽  
Aspergillus Fumigatus ◽  
Crude Extract ◽  
Antimycobacterial Activity ◽  
Methicillin Resistant ◽  
Bioassay Guided Fractionation ◽  
Chaetoglobosin A

The crude extract of Aspergillus fumigatus isolate AF3-093A, an endophyte of the brown algaFucus vesiculosus, showed significant antimicrobial activity in initial bioactivity screens. Bioassay-guided fractionation of the extract led to the isolation of flavipin, chaetoglobosin A and chaetoglobosin B, all of which inhibited the growth of Staphylococcus aureus, methicillin-resistant S. aureus and Mycobacterium tuberculosis H37Ra. The antimycobacterial activity of these compounds has not been previously reported.

scholarly journals Antimicrobial activity of essential oils from Lippia alba, Lippia sidoides, Cymbopogon citrates, Plectranthus amboinicus, and Cinnamomum zeylanicum against Mycobacterium tuberculosis

2018 ◽  
Vol 48 (6) ◽  
Author(s):  
Aquiles Paulino Peres Mota ◽  
João Carlos Pinheiro Dantas ◽  
Cristiane Cunha Frota
Keyword(s):  
Antimicrobial Activity ◽  
Mycobacterium Tuberculosis ◽  
Essential Oils ◽  
Antimycobacterial Activity ◽  
Effective Control ◽  
Cinnamomum Zeylanicum ◽  
Promising Alternative ◽  
Lippia Sidoides ◽  
Lippia Alba ◽  
Plectranthus Amboinicus

ABSTRACT: The rise in cases of antibiotic-resistant Mycobacterium tuberculosis has become a major obstacle to the effective control of tuberculosis (TB) worldwide. Essential oils (EO) are complex mixtures that may contain between 20 and 60 components, with two or three major compounds at relatively high concentrations (20-70%) that are responsible for their pharmacological properties. The objective of this study was to assess the antimicrobial activity of the EOs, bushy lippia (Lippia alba), rosemary pepper (Lippia sidoides), lemon grass (Cymbopogon citratus), Mexican mint or Indian borage (Plectranthus amboinicus), and true cinnamon (Cinnamomum zeylanicum), against Mycobacterium tuberculosis H37Rv. Chemical characterization of the EOs was performed by gas chromatography coupled to mass spectrometry. The minimum inhibitory concentration (MIC) was determined by the microdilution-based resazurin microtiter assay. Four EOs were able to inhibit the growth of M. tuberculosis, with MICs of 286.5±130.2μg/mL (C. zeylanicum), 299.5±117.2μg/mL (L. sidoides), 351.6±39.06μg/mL (P. amboinicus), and 1,250μg/mL (C. citratus). Only the EO of L. alba showed no antimycobacterial activity at the tested concentrations, with an MIC greater than 1,250µg/mL. Results of this study suggested that C. zeylanicum, L. sidoides, and P. amboinicus could be important sources of bactericidal compounds against M. tuberculosis and require further investigation. The activity against M. tuberculosis of these three EOs has not been reported previously. The results show the high potential of the tested antimycobacterial EOs, making them a promising alternative for TB treatment. This data also confirms the importance of bioprospecting studies for active substances with antimycobacterial activity, which are still scarce.

Zanthoxylum capense constituents with antimycobacterial activity against Mycobacterium tuberculosis in vitro and ex vivo within human macrophages

2013 ◽  
Vol 146 (1) ◽  
pp. 417-422 ◽  
Author(s):  
Xuan Luo ◽  
David Pires ◽  
José A. Aínsa ◽  
Begoña Gracia ◽  
Noélia Duarte ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Ex Vivo ◽  
Antimycobacterial Activity ◽  
Human Macrophages

scholarly journals CD23 Mediates Antimycobacterial Activity of Human Macrophages

2009 ◽  
Vol 77 (12) ◽  
pp. 5537-5542 ◽  
Author(s):  
M. Djavad Mossalayi ◽  
Ioannis Vouldoukis ◽  
Maria Mamani-Matsuda ◽  
Tina Kauss ◽  
Jean Guillon ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Human Monocyte ◽  
Antimycobacterial Activity ◽  
Mycobacterial Infection ◽  
Interleukin 10 ◽  
Functional Surface ◽  
Necrosis Factor Alpha ◽  
Human Macrophages ◽  
Tnf Α ◽  
Human Immune

ABSTRACT Engagement of surface receptors contributes to the antimicrobial activity of human immune cells. We show here that infection of human monocyte-derived macrophages (MDM) with live Mycobacterium avium induced the expression of CD23 on their membrane. Subsequent cross-linking of surface CD23 by appropriate ligands induced a dose-dependent antibacterial activity of MDM and the elimination of most infected cells. The stimulation of inducible nitric oxide synthase-dependent generation of NO from MDM after CD23 activation played a major role during their anti-M. avium activity. CD23 activation also induced tumor necrosis factor alpha (TNF-α) production from MDM. Mycobacteria reduction was partially inhibited by the addition of neutralizing anti-TNF-α antibody to cell cultures without affecting NO levels, which suggested the role of this cytokine for optimal antimicrobial activity. Finally, interleukin-10, a Th2 cytokine known to downregulate CD23 pathway, is shown to decrease NO generation and mycobacteria elimination by macrophages. Therefore, (i) infection with M. avium promotes functional surface CD23 expression on human macrophages and (ii) subsequent signaling of this molecule contributes to the antimicrobial activity of these cells through an NO- and TNF-α-dependent pathway. This study reveals a new human immune response mechanism to counter mycobacterial infection involving CD23 and its related ligands.

scholarly journals Inhibitory Effect of NO-Releasing Ciprofloxacin (NCX 976) on Mycobacterium tuberculosis Survival

2003 ◽  
Vol 47 (7) ◽  
pp. 2299-2302 ◽  
Author(s):  
R. Ciccone ◽  
F. Mariani ◽  
A. Cavone ◽  
T. Persichini ◽  
G. Venturini ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Antimycobacterial Activity ◽  
Inhibitory Effect ◽  
Human Macrophages ◽  
H37rv Strain ◽  
Free Model ◽  
A Cell ◽  
Marked Activity

ABSTRACT Here, we report the antimycobacterial activity of NCX 976, a new molecule obtained adding a NO moiety to the fluoroquinolone ciprofloxacin, on Mycobacterium tuberculosis H37Rv strain, both in a cell-free model and in infected human macrophages. Unlike unaltered ciprofloxacin, NCX976 displayed a marked activity also at low-nanomolar concentrations.

New Groups of Potential Antituberculotics: Bis(1-aryltetrazol-5-yl) Disulfides. Structure Activity Relationship

1994 ◽  
Vol 59 (1) ◽  
pp. 234-238 ◽  
Author(s):  
Karel Waisser ◽  
Jiří Kuneš ◽  
Alexandr Hrabálek ◽  
Želmíra Odlerová
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Minimum Inhibitory Concentration ◽  
Inhibitory Concentration ◽  
Antimycobacterial Activity ◽  
Activity Relationship ◽  
Active Derivative ◽  
Structure Activity ◽  
Medium Activity ◽  
Substituent Constants ◽  
Atypical Strains

Oxidation of 1-aryltetrazole-5-thiols afforded bis(1-aryltetrazol-5-yl) disulfides. The compounds were tested for antimycobacterial activity against Mycobacterium tuberculosis, M. kansasii, M. avium and M. fortuitum. In the case of M. tuberculosis, the logarithm of minimum inhibitory concentration showed a parabolic dependence on hydrophobic substituent constants. Although the compounds exhibited low to medium activity, the most active derivative, bis(4-chlorophenyltetrazol-5-yl) disulfide (III) was more effective against atypical strains than are the commercial tuberculostatics used as standards.

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