bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nontuberculous mycobacteria induce mitochondrial dysfunction in macrophages
Authors: Sadikot Ruxana T 
Published: January 2021

Aims and Objectives:
The incidence of nontuberculous mycobacterial (NTM) disease continues to rise, especially in developed countries. While NTM can affect almost any organ system, pulmonary infection is more prevalent than disseminated disease and can occur in patients with COPD, non-cystic fibrosis (CF) bronchiectasis, and CF. Mitochondria are the powerhouse of the cell, but it is unknown what role they play in the host response to NTM infection. Using electron microscopy, we have previously shown that mitochondrial morphology is altered upon infection with Mycobacterium avium intracellulare (MAI). Thus, we hypothesize that mitochondrial damage leading to changes in mitochondrial function and dynamics impair host response to infection with MAI and Mycobacterium abscessus (MAB).

Methods:
We infected MH-S cells (murine alveolar macrophages) and bone marrow-derived macrophages (BMDM) with clinical strains of MAI or MAB (multiplicity of infection [MOI] of 25) for 6 and 24 hours. We determined the expression of mitochondrial DNA fragments mt79 and mt230 that are associated with mitochondrial DNA damage using RT-qPCR; we calculated the fold change of these fragments relative to GAPDH and determined a ratio of these fragments. We also determined the expression of key mitochondrial quality control genes, including peroxisome proliferator activated receptor gamma coactivator (PGC)-1α, transcription factor A mitochondrial (TFAM), and mitofusin (MFN)-2, using RT-qPCR.

Results:
We found that in MH-S cells, the mt79:mt230 ratio was increased at 6 and 24 hours for both MAI and MAB relative to controls infected with PBS. Furthermore, expression of genes involved in mitochondrial biogenesis, PGC-1 α and TFAM, were both decreased at 6 and 24 hours. MFN2 was also decreased at both 6 and 24 hours for MAI and MAB. These data were consistent in BMDM, with a more significant decrease in these genes noted at 24 hours.

Conclusions:
These data suggest that there is an increase in mitochondrial damage as indicated by the mt79:230 ratio when macrophages are infected with NTM. The infected macrophages exhibit decreased mitochondrial biogenesis and also have impaired mitochondrial quality control, including mitochondrial fusion and fission. The functional impact of these impaired mitochondria on host response to NTM infection needs to be further explored as there may be a role for pharmacologic interventions, like PGC-1 α activators, that can augment bacterial killing in patients infected with NTM.
An interactive panel for monitoring the spread of bovine tuberculosis and brucellosis in colombia
Authors: Arenas Nelson Enrique , Ávila Edier F. , Correa Edwin D. , Rueda Wendy N. , López Gina M. , Moren Vilma , Diego Arbil , Torres Jehison , Soto Carlos Y. 
Published: January 2021

Aims & objectives:
Bovine tuberculosis (BTB) and brucellosis are communicable diseases that require epidemiological surveillance in real-time as a key strategy to control and eradicate outbreaks. Thus, our purpose was to design an epidemiological tool to monitor BTB and brucellosis in Colombia.

Methods:
We collected the epidemiological data from the epidemiological bulletins of the Colombian Agricultural and Livestock Institute (ICA) between 2004-2019. Data analysis was conducted using multiple correspondence analysis (MCA) and a Chi-square test in Factominer and Factoextra packages executed in the R software (v3.6). We designed a user-friendly dashboard with epidemiological information using the ArcGIS platform coupled with the Esri's Map-Viewer tool.

Results:
Our final dataset included 529 BTB and 739 brucellosis cases reported in Colombia for 15 years. The variables location and case number for both diseases were significantly associated. Our tool's analysis showed that Cundinamarca and Valle del Cauca provinces have been epidemic areas for bovine BTB and brucellosis, respectively (p-value <0.001). Furthermore, increased case detection was reported in 2012 for bovine BTB and brucellosis (p-value <0.001) during 2019. We implemented a user-friendly dashboard for the mapping of both diseases during the observation period to focus on program control actions.

Conclusions:
We expect that our GIS-based tool will support disease control strategies, tracking disease hotspots, and identify trends over time to provide useful information for animal health authorities tailoring new strategies for control programs. Dashboard availability: https://arcg.is/1uvSLv
The burden of disease and the cost of illness attributable to tuberculosis and HIV/aids associated to massive migration between colombia and venezuela
Authors: Arenas Nelson E. , Cuervo Laura I. , Avila Edier F. , Duitama-Leal Alejandro , Pineda-Peña Andrea-Clemencia 
Published: January 2021

Aims & objectives:
The Venezuelan socio-political crisis has boosted massive exodus of Venezuelan citizens due to the shortage of medicines and spread of some preventable infectious diseases. We aimed to assess the impact of tuberculosis (TB) and HIV burden, health expenditure and the cost of illness under the framework of Colombian-Venezuelan migration flow focused on Norte de Santander, Santander, and La Guajira provinces.

Methods:
A retrospective study was conducted including TB and HIV data between 2009-2018. A database was made based on the records from the Colombian Surveillance System (SIVIGILA), official reports of the World Health Organization, Indexmundi, Global Health Observatory, IHME HIV Atlas and UNAIDS. Disability metrics in terms of DALYs (Disability Adjusted Life Years) and YLDs (Years Lived with Disability), were compared between both countries. Interactive maps were carried out by using ArcGIS program and the official migration data of Venezuelan citizens. We performed a phylogenetic analysis by retrieving pol sequences based in HIV cases from Venezuela and Colombia by using MEGA X and HIV Alamos database.

Results:
TB country profiles from Colombia and Venezuela were identical in terms of disease burden in 2017 and 2018. However, the Colombian public health settings reported an increase in the TB incidence above national average (22.1 cases per 100,000 inhabitants) in Santander, Norte de Santander and La Guajira provinces during the last years. Similar situation was observed regarding TB multidrug-resistant, prolonged hospital stays (150 days) and low-testing rates for cases of multidrug-resistant TB (67%) and HIV/AIDS (60%). We identified an underfunding for HIV/AIDS control programs and patient care. Our DALY analysis showed an increased disability in HIV/AIDS patients (362.35 for 2017). Moreover, our phylogenetic analysis shows three defined clusters, which indicate specific linages through specific areas, and shared cluster in the Colombo-Venezuela border.

Conclusions:
This study suggests that the massive migration and program underfunding in Venezuela might exacerbate the dual burden of TB and HIV in Colombia, especially towards the Colombo-Venezuelan border.
Cell-penetrating peptidomimetics derived from cathelicidin CAP-18 showed inhibition of Na+ /K+, Cu(I) and Zn(II)ATPases in mycobacterial plasma membrane
Authors: Chingaté S , Guzmán Fanny , Salazar L 
Published: January 2021

Aims & objectives:
Mycobacterium tuberculosis is the etiological agent of tuberculosis (TB), which is one of the ten most deadly diseases and the first cause of death by bacterial origin around the world. One of the causes that increase the problem are the M. tuberculosis resistant strains to conventional antibiotics, multi-drug resistant tuberculosis (MDR-TB) and extensively-drug resistant tuberculosis (XDR-TB); so it is necessary to develop new drugs with different mechanisms of action.

Methods:
In this study, the effect on the mycobacterial cell membrane ATPase activity of CAP-18 derived peptide with unnatural amino acids was assessed. Using bioinformatic tools, the amino acid sequence of CAP-18 with the best features of helical structure and antibacterial activity was determined; the corresponding peptide had changes for D-Lys and N-methyl-Gly in the sequence, generating the peptides CAP18-BD and CAP18-CD and the peptoid CAP18-BP.

Results:
In vitro assesament of the peptides and peptidomimetics were tested in plasma membrame from Mycobacterium smegmatis mc2 155. The inorganic phosphate released (Pi) was quantified during the ATP hydrolysis reaction by the action of ATPases, using the Fiske and Subarrow method modified by Cariani et al., in the presence and absence of the peptidic sequences to be evaluated, where the basal ATPase activity in the absence corresponds to zero percent inhibition of these enzymes, and 100% of the residual ATPase activity, understood as the enzymatic activity present with or without peptide treatment.

Conclusions:
The results showed inhibition of basal ATPase activity and Na+ /K+, Cu(I), Zn (II) pumps in the plasma membrane, which is associated with its mechanism of action, which suggests that CAP18-BD, CAP18-CD and CAP18-BP can be considered as a potential antimycobacterial compounds targeting cell membrane ATPases.
Cationic peptidomimetics derived from CAP-18 cathelicidin shown activity in vitro against mycobacterium tuberculosis H37RA and synergy combined with isoniazid
Authors: Chingaté S , Salazar L , Guzmán Fanny 
Published: January 2021

Aims & objectives:
Tuberculosis (TB) is the infectious disease that results in the largest number of deaths around the world caused by a bacterial infectious agent. According to the World Health Organization (WHO), there were 10 million new cases and 1.2 million deaths caused by TB in 2018. The problem increases due to drug resistance and HIV/AIDS coinfection, which is why it is necessary to develop new anti-TB compounds with different mechanisms of action. Antimicrobial peptides are molecules gener42ated in the innate immune response of the host with an effect on pathogens. This is the case of the cathelicidins present in mammals involved in the formation of channels in the bacterial cell membrane that leads to cell lysis.

Methods:
In this study, the antimycobacterial activity and the possible mechanism of action of peptides derived from CAP-18 with unnatural amino acids were evaluated. Using bioinformatic tools, the epitope of the native sequence with the best characteristics of helical structure, amphipathicity and antibacterial value was determined. The corresponding peptides, CAP18-B and CAP18-C, had changes from L-Lys to D-Lys and from L-Gly to N-methyl-Gly in the sequence, generating the peptides CAP18-BD, CAP18-CD and the peptoid CAP18-BP. Peptides and peptoids were synthesized using the Fmoc strategy, purified by RP-HPLC and characterized by ESI-MS, circular dichroism and H1 -NMR. The in vitro assesament of the designed sequences was carried out in Mycobacterium smegmatis mc2 155 and

Results:
Mycobacterium tuberculosis H37Ra, obtaining a minimum inhibitory concentration increase from 2 to 6 times in the ranges from 1200 to 60 μg/mL, less than 10% hemolytic activity and no cytotoxic activity on U937 monocytes with LC50 values at least 10 times higher than the MIC and synergy combined with isoniazid. Confocal microscopy showed the insertion of peptides and peptoids in Mycobacterium smegmatis mc2 155 and transmission electron microscopy showed alterations in the cell membrane of Mycobacterium smegmatis mc2 155 evidenced in the formation of blisters, microspheres, channels and cell lysis.

Conclusions:
The results suggest that analogous sequences derived from CAP-18 can be considered as potential antimycobacterial compounds.
Transmissibility study of two vaccine candidates against bovine tuberculosis
Authors: Muñiz Ximena Ferrara , García Elizabeth , Blanco Federica Carlos , Bigi Fabiana , Zumarraga Martín José , Cataldi Angel , Eirin María Emilia 
Published: January 2021

Aims & Objective:
We studied the transmissibility in mice of two candidate vaccine M. bovis strains, M. bovis Δmce2 and M. bovis Δmce2ΔphoP, attenuated by gene knock out. The parental strain M. bovis UK (NCTC10772) and a M. bovis wild boar isolate (Mb04-303) were inoculated as controls.

Methods:
Groups of animals including 3 non-inoculated + 3 subcutaneously inoculated with every strain (1.105 CFU) were placed in the same cage (in duplicate). Necropsy was performed at 60 and 90 days post inoculation (dpi) in search of visible tuberculosis lesions (VTL) in lungs and spleens. Organs were analyzed to determine the bacterial load.

Results:
None of the animals presented VTL and no M. bovis was detectable in the non-inoculated group at 60 and 90 dpi. M. bovis was isolated from spleen of all the inoculated mice and from lungs of mice inoculated with control strains. The candidate vaccines were not isolated from lungs.

Conclusions:
This study shows the absence of transmissibility up to 90 days. Recovery of viable control strains from lungs and spleen suggests that the administration route would not alter the capacity of virulent strains to colonize organs. Contrasting, the candidate vaccines were only isolated from spleen. Longer periods should be assayed to evaluate transmissibility of these strains in mice.
IS900 RFLP Analysis of Mycobacterium avium subsp. Paratuberculosis of iranian isolates and analyze using bioinformatics tools
Authors: Khiav Lida Abdolmohammadi , Mosavari Nader , Haghkhah Masoud , Tadayon Keyvan 
Published: January 2021

Aims and objectives:
Mycobacterium avium subspecies paratuberculosis was first diagnosed and reported in imported cattle from England during 1962-1965. Further studies have shown that paratuberculosis is scattered throughout Iranian ruminants population. In spite of heavy economic loses; little genetic information is available. So, present study was carried out in order to obtain a better understanding of the MAP genetic diversity in Iranian isolates.

Methods:
During a 7-month period, 36 isolates of MAP was collected from milk and feces obtained from sheep, goat and cattle originating 10 provinces plus a further eleven archived MAP isolates and two MAP vaccine strains (MAP 316F & III &V) and two D4 reference strains (Weybridge and Turkish) were included and digested by restriction endonucleases PstI. Digested DNA was hybridised with a standard IS900 probe. Genomic fingerprints were scanned by camera and analysed using the software Gel pro analyzer & Bionumerix software package version 6.5 (Applied Maths Belgium). Dendrogram and Minimum Spanning Tree was draw using arithmetic averages (UPGMA) for Iranian isolates and vaccine strains.

Results:
ten RFLP (Pst I) types were detected and designated as B (bovine, ovine and caprine), and G (bovine, and caprine) and eight new type (three of them singletons and five cluster) in accordance with the study by pavlik et al 1999. The largest cluster (G strain) contained 45.8% of Iranian isolates (n = 22) then type II (B strain), represented by 11 isolates, recovered from all the three animals in six provinces. A single type was identified only in cattle from three provinces. The identical RFLP type was shown by MAP vaccine strains were different from the Iranian isolates. Two D4 reference strains had restriction pattern but did not hybridize to IS900 sequence. Dendrogram result showed B profiles close to G profile and MAP vaccine strains profiles (>98). The results of Minimum Spanning Tree also showed that all of the clusters and orphan were derived directly or indirectly from B profile with multiple hosts throughout the country. This pattern has been seen from throughout the world and multiple hosts.

Conclusions:
RFLP analysis showed that the Iranian isolates have perhaps originated from B specific profile but it still need to more future works using genotyping methods.
Performance comparison of GenoTypeMTBDRs/Version 1 and version 2 for rapid detection of resistance to fluoroquinolones and injectable drugs among multidrug-resistant mycobacterium tuberculosis in a low MDR-TB setting
Authors: Mokaddas Eiman , Mishari Noura , Ahmed Suhail 
Published: January 2021

Aims and objectives:
Fluoroquinolones (FQs) are potent antibiotics against multidrug-resistant Mycobacterium tuberculosis (MDR-TB) and resistance to FQs is associated with higher patient mortality. Rapid and accurate drug susceptibility testing (DST) against FQs and injectable drugs is essential for successful treatment of MDR-TB. FQ resistance mutation detection is equivalent to culture-based DST for predicting MDR-TB treatment outcome. This study compared performance of GenoTypeMTBDRsl Version 1 and Version 2 for detection of resistance to FQs and injectable drugs among MDR-TB strains in Kuwait, a country with low incidence of MDR-TB.

Methods:
MDR-TB strains (n=93) cultured from 74 pulmonary and 19 extra-pulmonary specimens from 93 patients were analyzed by GenoTypeMTBDRsl Version 1 and Version 2 for FQ and injectable drug resistance-associated mutation detection. Repeat isolates from 22 patients, 50 pansusceptible isolates and M. tuberculosis H37 Rv (as control) were also tested. Results were confirmed by PCR-sequencing of gyrA, gyrB, rrs, embB and eis genes. Fingerprinting of isolates was done by spoligotyping.

Results:
Among 93 MDR-TB strains, GenoTypeMTBDRsl Version 1 with/without PCR-sequencing identified 10 isolates with gyrA mutation (A90V, n=2; D94G, n=4; D94A, n=2; D94N, n=1; D94Y, n=1), seven isolates with rrs mutation (A1401G) and 51 isolates with an embB mutation. GenoTypeMTBDRsl Version 2 with/without PCR-sequencing confirmed Version 1 results for gyrA/rrs genes and additionally identified two isolates with gyrB mutation (T500N, n=1; N538D, n=1) and one isolate with eis mutation (-10 G/A). Repeat isolates yielded expected results. No mutation was detected in 50 pansusceptible isolates. Spoligotyping identified 10 Shared International Types among 12 isolates with gyrA/B mutation.

Conclusions:
Our data show that GenoTypeMTBDRsl Version 2 is superior to Version 1 as it identified two additional isolates with gyrB mutations. Improved detection of FQ resistance by GenoTypeMTBDRsl Version 2 will help in proper management of MDR-TB patients in low MDR-TB settings. Supported by KURS grant MI01/18.
Forecasting the Incidence of Tuberculosis in Algeria
Authors: Selmane Scherhazad 
Published: January 2021

Aims and objectives:
Tuberculosis (TB) remains a health public issue in Algeria. In spite of the great efforts made for controlling the disease, the number of new reported cases exceeds the twenty thousand cases per year. One worthy of note epidemiological characteristics of TB is its seasonality. The seasonality of TB has been explored in some countries but no study has been conducted in Algeria. The aim of this study is to find out the seasonal pattern and the trend of TB incidence in Algeria.

Methods:
The monthly TB notification data from January 2008 to December 2017 extracted from the National Health Tuberculosis Register were examined to find out the seasonal pattern and trend of TB in Algeria. The seasonal autoregressive integrated moving average (SARIMA) model was used in analysing and predicting TB cases from 2008 to 2016. Cases registered in 2017 were used to assess the prediction accuracy of the selected models. The metrics mean square error (MSE) and mean absolute error (MAE) were applied to assess the better performance of prediction between the selected models.

Results:
From January 2008 to December 2017 there were 215,581 TB notified cases in Algeria with a yearly average 21,467 cases leading to an average annualized morbidity rate of 56,7 per 100,000 inhabitants. The monthly mean was 1796.5, the maximum number (2499) of reported cases was registered in April 2015 and the minimum (1202) in November 2009. The monthly TB data are normally distributed. The incidence of notified pulmonary TB cases decreased from 24 cases per 100,000 inhabitants in 2008 to 15 cases per 100,000 inhabitants in 2017; thus registering a drop of 37.6%, whereas the incidence of notified extrapulmonary TB cases increased from 27.5 cases per 100,000 inhabitants in 2008 to 35.8 cases per 100,000 inhabitants in 2017; thus registering an increase of 29.9%. The heatmap of TB incidence per quarter per province showed a significant temporal and geospatial variation. Time series analysis revealed seasonality with peaks in spring and summer and troughs in autumn and winter and showed that a (3,1,6)×(1,0,1)12 SARIMA model offered the best fit to the TB surveillance data for the period 2008-2016. This model was used to predict TB cases for the year 2017, and the fitted data showed considerable agreement with the actual data.

Conclusions:
Our findings are optimistic for forecasting TB by means of SARIMA models and afford useful information to public health policy makers in formulating targeted prevention and preparedness measures.
Identification of drug resistant tuberculosis
Authors: Varma-Basil Mandira 
Published: January 2021

Aims and objectives:
Multidrug resistant TB (MDR-TB) and extensively drug resistant (XDR) are responsible for significant obstruction to global control of tuberculosis (TB). Drug resistance in Mycobacterium tuberculosis mainly occurs through chromosomal mutations in genes encoding for drug target or drug activating enzymes. However, alternative mechanisms, such as efflux pumps may also be responsible for drug resistance.

Methods:
Insight into the mechanisms of drug resistance would help in limiting the disease through the use and development of better diagnostic and therapeutic tools. The importance of rapid and effective methods of identification of drug resistance in M. tuberculosis cannot be over emphasized. Traditional laboratory techniques are time consuming and cumbersome and not sufficiently sensitive or specific to fight this menace.

Results:
Though rapid molecular methods such as GeneXpert and line probe assays are vital tools in the fight against drug resistant TB, major advances in next generation sequencing (NGS) technology are allowing increasingly rapid and accurate sequencing of entire bacterial genomes, providing unprecedented depth of information.

Conclusion:
NGS has the ability to cause a revolutionary paradigm shift in the diagnosis of drug resistant tuberculosis and in understanding the evolution of drug resistance. However, certain challenges need to be overcome to enable the use of this promising technology in routine diagnosis and research, especially in resource limited regions of the world.