scholarly journals Mycobacterium tuberculosis H37Rv Strain Increases the Frequency of CD3+TCR+ Macrophages and Affects Their Phenotype, but Not Their Migration Ability

2021 ◽  
Vol 23 (1) ◽  
pp. 329
Author(s):  
Lucero A. Ramon-Luing ◽  
Claudia Carranza ◽  
Norma A. Téllez-Navarrete ◽  
Karen Medina-Quero ◽  
Yolanda Gonzalez ◽  
...  

In mycobacterial infections, the number of cells from two newly discovered subpopulations of CD3+ myeloid cells are increased at the infection site; one type expresses the T cell receptor (CD3+TCRαβ+) and the other does not (CD3+TCRαβ−). The role of Mycobacterium tuberculosis (Mtb) virulence in generating these subpopulations and the ability of these cells to migrate remains unclear. In this study, monocyte-derived macrophages (MDMs) infected in vitro with either a virulent (H37Rv) or an avirulent (H37Ra) Mtb strain were phenotypically characterized based on three MDM phenotypes (CD3−, CD3+TCRαβ+, and CD3+TCRαβ−); then, their migration ability upon Mtb infection was evaluated. We found no differences in the frequency of CD3+ MDMs at 24 h of infection with either Mtb strain. However, H37Rv infection increased the frequency of CD3+TCRαβ+ MDMs at a multiplicity of infection of 1 and altered the expression of CD1b, CD1c, and TNF on the surface of cells from both the CD3+ MDM subpopulations; it also modified the expression of CCR2, CXCR1, and CCR7, thus affecting CCL2 and IL-8 levels. Moreover, H37Rv infection decreased the migration ability of the CD3− MDMs, but not CD3+ MDMs. These results confirm that the CD3+ macrophage subpopulations express chemokine receptors that respond to chemoattractants, facilitating cell migration. Together, these data suggest that CD3+ MDMs are a functional subpopulation involved in the immune response against Mtb.

Rodriguésia ◽  
2020 ◽  
Vol 71 ◽  
Author(s):  
Stefhania Alzate Lozano ◽  
Aline Bastos Brilhante de Sousa ◽  
Julio Cezar de Souza ◽  
David Ribeiro da Silva ◽  
Marcos Gabriel Maciel Salazar ◽  
...  

Abstract Duroia saccifera (Rubiaceae) occurs in the Amazon rainforest and their extracts showed antibacterial properties. To obtain greater quantities of active substances, leaf segments from in vitro D. saccifera seedlings were used as explants for calli induction; calli were multiplied via multiple subcultures, dried and extracted with hexane followed by ethyl acetate (EtOAc) and methanol (MeOH). As D. macrophylla had been reported to produce antimycobacterial substances, we assayed calli extracts against Mycobacterium tuberculosis (H37Rv strain). Calli EtOAc extract was active, with a minimal inhibitory concentration (MIC) of ≤ 25 mg mL-1, IC90of 19.5 mg mL-1 and minimal bactericidal concentration (MBC) of 200 mg mL-1. EtOAc extract was analyzed by Thin Layer Chromatography (TLC) and Nuclear Magnetic Resonance (NMR) to determine its chemical profile, and was found to be rich in terpenes. Chromatographic fractionation of the EtOAc extract yielded a mixture of two sterols, β-sitosterol and stigmasterol (in proportion of 2:1), which were identified by 1H and 13C NMR analysis. As far as we know, this is the first report of Duroia saccifera in vitro cell culture, antituberculosis activity of calli extract and β-sitosterol and stigmasterol isolation from in vitro plant cell culture.


2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Tomasz Jagielski ◽  
Zofia Bakuła ◽  
Anna Brzostek ◽  
Alina Minias ◽  
Radosław Stachowiak ◽  
...  

ABSTRACTResistance ofMycobacterium tuberculosisto rifampin (RMP), mediated by mutations in therpoBgene coding for the beta-subunit of RNA polymerase, poses a serious threat to the efficacy of clinical management and, thus, control programs for tuberculosis (TB). The contribution of many individualrpoBmutations to the development and level of RMP resistance remains elusive. In this study, the incidence of mutations throughout therpoBgene among 115Mycobacterium tuberculosisclinical isolates, both resistant and susceptible to RMP, was determined. Of the newly discoveredrpoBmutations, the role of three substitutions in the causation of RMP resistance was empirically tested. The results fromin vitromutagenesis experiments were combined with the assessment of the prevalence ofrpoBmutations, and their reciprocal co-occurrences, across globalM. tuberculosispopulations. Twenty-two different types of mutations in therpoBgene were identified and distributed among 58 (89.2%) RMP-resistant strains. The MICs of RMP were within the range of 40 to 800 mg/liter, with MIC50and MIC90values of 400 and 800 mg/liter, respectively. None of the mutations (Gln429His, Met434Ile, and Arg827Cys) inspected for their role in the development of RMP resistance produced an RMP-resistant phenotype in isogenicM. tuberculosisH37Rv strain-derived mutants. These mutations are supposed to compensate for fitness impairment incurred by other mutations directly associated with drug resistance.


2020 ◽  
Author(s):  
Joanna Houghton ◽  
Angela Rodgers ◽  
Graham Rose ◽  
Kristine B. Arnvig

ABSTRACTAlmost 140 years after the identification of Mycobacterium tuberculosis as the etiological agent of tuberculosis, important aspects of its biology remain poorly described. Little is known about the role of post-transcriptional control of gene expression and RNA biology, including the role of most of the small RNAs (sRNAs) identified to date. We have carried out a detailed investigation of the M. tuberculosis sRNA, F6, and show it to be dependent on SigF for expression and significantly induced during in vitro starvation and in a mouse model of infection. However, we found no evidence of attenuation of a ΔF6 strain within the first 20 weeks of infection. A further exploration of F6 using in vitro models of infection suggests a role for F6 as a highly specific regulator of the heat shock repressor, HrcA. Our results point towards a role for F6 during periods of low metabolic activity similar to cold shock and associated with nutrient starvation such as that found in human granulomas in later stages of infection.


INDIAN DRUGS ◽  
2016 ◽  
Vol 53 (06) ◽  
pp. 18-23
Author(s):  
U. V. Laddi ◽  
◽  
S. R. Desai

Some new 5-[(((α-phenyl/methyl)benzylidene)amino)oxy]methyl/ethyl-2-[4-(substituted aryl)/allyl)] amino-1,3,4-oxadiazoles (4a-p), 3-[(((α-phenyl/methyl)- benzylidene) amino)oxy]methyl/ethyl-4-(4- substitutedaryl)/allyl-5-mercapto-1,2,4-triazoles (5a-p) and 5-[(((α-phenyl/methyl)-benzylidene)amino) oxy]- methyl/ethyl-2-[4-(substituted aryl)/allyl)]amino-1,3,4-thiadiazoles (6a-p) were prepared starting from α/β-[((α-(phenyl/methyl)benzylidene)amino)oxy acetic/propionic acid hydrazides (1a-d). The structures of all the compounds have been established by elemental and spectral (IR, 1HNMR and mass) analysis. All the newly synthesised compounds have been screened for their antimicrobial activity against Escherichia coli, Bacillus cirroflagellosus, Aspergillus niger and Rhizoctonia bataticola. Some of the newly synthesised compounds have been evaluated for antituberculosis activity against Mycobacterium tuberculosis H37Rv strain by BACTEC radiometric system at Southern Research Institute, Birmingham, AL and Frederick Research Centre, Frederick, MD. Significant antimicrobial activity is observed against Escherichia coli and Rhizoctonia bataticola. A few compounds also exhibited interesting antitubercular activity against Mycobacterium tuberculosis H37Rv strain.


2010 ◽  
Vol 14 (1) ◽  
pp. 47-52 ◽  
Author(s):  
L. Ouattara ◽  
J. Koudou ◽  
D.S. Karou ◽  
L. Giaco ◽  
G. Capelli ◽  
...  

2020 ◽  
Vol 8 (2) ◽  
pp. 228 ◽  
Author(s):  
Lilibeth Arias ◽  
Paula Cardona ◽  
Martí Català ◽  
Víctor Campo-Pérez ◽  
Clara Prats ◽  
...  

Cording was the first virulence factor identified in Mycobacterium tuberculosis (Mtb). We aimed to ascertain its role in the induction of active tuberculosis (TB) in the mouse strain C3HeB/FeJ by testing the immunopathogenic capacity of the H37Rv strain. We have obtained two batches of the same strain by stopping their growth in Proskauer Beck liquid medium once the mid-log phase was reached, in the noncording Mtb (NCMtb) batch, and two days later in the cording Mtb (CMtb) batch, when cording could be detected by microscopic analysis. Mice were challenged with each batch intravenously and followed-up for 24 days. CMtb caused a significant increase in the bacillary load at an early stage post-challenge (day 17), when a granulomatous response started, generating exudative lesions characterized by neutrophilic infiltration, which promoted extracellular bacillary growth together with cording formation, as shown for the first time in vivo. In contrast, NCMtb experienced slight or no bacillary growth and lesions could barely be detected. Previous Bacillus Calmette-Guérin (BCG) vaccination or low dose aerosol (LDA) Mtb infection were able to delay the progression towards active TB after CMtb challenge. While BCG vaccination also reduced bacillary load when NCMtb was challenged, LDA did not, and its proliferative lesions experienced neutrophil infiltration. Analysis of lung cytokine and chemokine profiles points to their capacity to block the production of CXCL-1 and further amplification of IL-1β, IL-17 and neutrophilic extracellular trap formation, all of which are essential for TB progression. These data highlight the key role of cording formation in the induction of active TB.


Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1740 ◽  
Author(s):  
Richard M. Beteck ◽  
Ronnett Seldon ◽  
Audrey Jordaan ◽  
Digby F. Warner ◽  
Heinrich C. Hoppe ◽  
...  

Co-infection of malaria and tuberculosis, although not thoroughly investigated, has been noted. With the increasing prevalence of tuberculosis in the African region, wherein malaria is endemic, it is intuitive to suggest that the probability of co-infection with these diseases is likely to increase. To avoid the issue of drug-drug interactions when managing co-infections, it is imperative to investigate new molecules with dual activities against the causal agents of these diseases. To this effect, a small library of quinolone-thiosemicarbazones was synthesised and evaluated in vitro against Plasmodium falciparum and Mycobacterium tuberculosis, the causal agents of malaria and tuberculosis, respectively. The compounds were also evaluated against HeLa cells for overt cytotoxicity. Most compounds in this series exhibited activities against both organisms, with compound 10, emerging as the hit; with an MIC90 of 2 µM against H37Rv strain of M. tuberculosis and an IC50 of 1 µM against the 3D7 strain of P. falciparum. This study highlights quinolone-thiosemicarabazones as a class of compounds that can be exploited further in search of novel, safe agents with potent activities against both the causal agents of malaria and tuberculosis.


2019 ◽  
Vol 14 (16) ◽  
pp. 1397-1415
Author(s):  
Pratibha Maan ◽  
Jagdeep Kaur

Aim: To elucidate the role of Rv2223c in Mycobacterium tuberculosis. Methods: Purified recombinant Rv2223c protein was characterized. Expression of rv2223c in the presence of different stress environment and subcellular localization were performed in M. tuberculosis H37Ra and Mycobacterium smegmatis ( MS_2223c). Effect of its overexpression on growth rate, infection and intracellular survival in THP-1/PBMC cells were studied. Results: rRv2223c demonstrated esterase activity with preference for pNP-octanoate and hydrolyzed trioctanoate to di- and mono-octanoate. Expression of rv2223c was upregulated in acidic and nutritive stress conditions. rRv2223c was identified in extracellular and cell wall fractions. MS_2223c exhibited enhanced growth, survival during in vitro stress, infection and intracellular survival. Conclusions: Rv2223c is a secretary, carboxyl-esterase, with enhanced expression under acidic and nutritive stress condition and might help in intracellular survival of bacteria.


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