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Autophagy Jun 2022Mitophagy is a selective autophagy mechanism for eliminating damaged mitochondria and plays a crucial role in the immune evasion of some viruses and bacteria. Here, we...
Mitophagy is a selective autophagy mechanism for eliminating damaged mitochondria and plays a crucial role in the immune evasion of some viruses and bacteria. Here, we report that () utilizes host mitophagy to suppress host xenophagy to enhance its intracellular survival. is the causative agent of animal tuberculosis and human tuberculosis. In the current study, we show that induces mitophagy in macrophages, and the induction of mitophagy is impaired by PINK1 knockdown, indicating the PINK1-PRKN/Parkin pathway is involved in the mitophagy induced by . Moreover, the survival of in macrophages and the lung bacterial burden of mice are restricted by the inhibition of mitophagy and are enhanced by the induction of mitophagy. Confocal microscopy analysis reveals that induction of mitophagy suppresses host xenophagy by competitive utilization of p-TBK1. Overall, our results suggest that induction of mitophagy enhances growth while inhibition of mitophagy improves growth restriction. The findings provide a new insight for understanding the intracellular survival mechanism of in the host. BMDM: mouse bone marrow-derived macrophage; BNIP3: BCL2/adenovirus E1B interacting protein 3; BNIP3L/NIX: BCL2/adenovirus E1B interacting protein 3-like; BCL2L13: BCL2-like 13 (apoptosis facilitator); CCCP: carbonyl cyanide m-cholorophenyl hydrazone; FUNDC1: FUN14 domain-containing 1; FKBP8: FKBP506 binding protein 8; HCV: hepatitis C virus; HBV: hepatitis B virus; IFN: interferon; ; Mtb: ; Mdivi-1: mitochondrial division inhibitor 1; PINK1: PTEN-induced putative kinase 1; TBK1: TANK-binding kinase 1; TUFM: Tu translation elongation factor, mitochondrial; TEM: transmission electron microscopy.
Topics: Animals; Macroautophagy; Macrophages; Membrane Proteins; Mice; Mitochondrial Proteins; Mitophagy; Mycobacterium bovis
PubMed: 34720021
DOI: 10.1080/15548627.2021.1987671 -
African Health Sciences Aug 2011
Topics: Africa; Animals; Brucellosis; HIV Infections; Humans; Mycobacterium bovis; Oxidative Stress
PubMed: 22135632
DOI: No ID Found -
Microbiology (Reading, England) Aug 2020Biofilm-associated infections are difficult to eradicate because of their ability to tolerate antibiotics and evade host immune responses. Amoebae and/or their secreted...
Biofilm-associated infections are difficult to eradicate because of their ability to tolerate antibiotics and evade host immune responses. Amoebae and/or their secreted products may provide alternative strategies to inhibit and disperse biofilms on biotic and abiotic surfaces. We evaluated the potential of five predatory amoebae - , , , and - and their cell-free secretions to disrupt biofilms formed by methicillin-resistant (MRSA) and . The biofilm biomass produced by MRSA and was significantly reduced when co-incubated with , and , and their corresponding cell-free supernatants (CFS). spp. generally produced CFS that mediated biofilm dispersal rather than directly killing the bacteria; however, CFS demonstrated active killing of MRSA planktonic cells when the bacteria were present at low concentrations. The active component(s) of the CFS is resistant to freezing, but can be inactivated to differing degrees by mechanical disruption and exposure to heat. and its CFS also reduced preformed biofilms, whereas only decreased biofilm biomass when amoebae were added. These results highlight the potential of using select amoebae species or their CFS to disrupt preformed bacterial biofilms.
Topics: Amoebida; Antibiosis; Biofilms; Cell Survival; Culture Media, Conditioned; Methicillin-Resistant Staphylococcus aureus; Mycobacterium bovis; Species Specificity
PubMed: 32459167
DOI: 10.1099/mic.0.000933 -
Microbial Genomics Oct 2021Animal tuberculosis (TB) is an emergent disease caused by , one of the animal-adapted ecotypes of the complex (MTC). In this work, whole-genome comparative analyses of... (Comparative Study)
Comparative Study
Animal tuberculosis (TB) is an emergent disease caused by , one of the animal-adapted ecotypes of the complex (MTC). In this work, whole-genome comparative analyses of 70 . were performed to gain insights into the pan-genome architecture. The comparison across predicted genome composition enabled clustering into the core- and accessory-genome components, with 2736 CDS for the former, while the accessory moiety included 3897 CDS, of which 2656 are restricted to one/two genomes only. These analyses predicted an open pan-genome architecture, with an average of 32 CDS added by each genome and show the diversification of discrete subpopulations supported by both core- and accessory-genome components. The functional annotation of the pan-genome classified each CDS into one or several COG (Clusters of Orthologous Groups) categories, revealing ‘transcription’ (total average CDSs, =258), ‘lipid metabolism and transport’ (=242), ‘energy production and conversion’ (=214) and ‘unknown function’ (=876) as the most represented. The closer analysis of polymorphisms in virulence-related genes in a restrict group of from a multi-host system enabled the identification of clade-monomorphic non-synonymous SNPs, illustrating clade-specific virulence landscapes and correlating with disease severity. This first comparative pan-genome study of a diverse collection of encompassing all clonal complexes indicates a high percentage of accessory genes and denotes an open, dynamic non-conservative pan-genome structure, with high evolutionary potential, defying the canons of MTC biology. Furthermore, it shows that can shape its virulence repertoire, either by acquisition and loss of genes or by SNP-based diversification, likely towards host immune evasion, adaptation and persistence.
Topics: Animals; Cattle; Genome Size; Genome, Bacterial; Genomics; Lipid Metabolism; Mycobacterium bovis; Polymorphism, Single Nucleotide; Tuberculosis, Bovine; Virulence; Whole Genome Sequencing
PubMed: 34714230
DOI: 10.1099/mgen.0.000664 -
Vaccine Nov 2009The Bacillus Calmette-Guerin (BCG) is an attenuated strain of Mycobacterium bovis that has been broadly used as a vaccine against human tuberculosis. This live bacterial... (Review)
Review
The Bacillus Calmette-Guerin (BCG) is an attenuated strain of Mycobacterium bovis that has been broadly used as a vaccine against human tuberculosis. This live bacterial vaccine is able to establish a persistent infection and induces both cellular and humoral immune responses. The development of mycobacterial genetic systems to express foreign antigens and the adjuvanticity of BCG are the basis of the potential use of this attenuated mycobacterium as a recombinant vaccine. Over the years, a range of strategies has been developed to allow controlled and stable expression of viral, bacterial and parasite antigens in BCG. Herein, we review the strategies developed to express heterologous antigens in BCG and the immune response elicited by recombinant BCG constructs. In addition, the use of recombinant BCG as an immunomodulator and future perspectives of BCG as a recombinant vaccine vector are discussed.
Topics: BCG Vaccine; Genetic Vectors; Humans; Immunomodulation; Mycobacterium bovis; Tuberculosis; Vaccines, Attenuated; Vaccines, Synthetic
PubMed: 19720367
DOI: 10.1016/j.vaccine.2009.08.044 -
Brazilian Journal of Microbiology :... 2014Mycobacterium bovis is the main causative agent of animal tuberculosis (TB) and it may cause TB in humans. Molecular typing of M. bovis isolates provides precise... (Review)
Review
Mycobacterium bovis is the main causative agent of animal tuberculosis (TB) and it may cause TB in humans. Molecular typing of M. bovis isolates provides precise epidemiological data on issues of inter- or intra-herd transmission and wildlife reservoirs. Techniques used for typing M. bovis have evolved over the last 2 decades, and PCR-based methods such as spoligotyping and mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) have been extensively used. These techniques can provide epidemiological information about isolates of M. Bovis that may help control bovine TB by indicating possible links between diseased animals, detecting and sampling outbreaks, and even demonstrating cases of laboratory cross-contamination between samples. This review will focus on techniques used for the molecular typing of M. bovis and discuss their general aspects and applications.
Topics: Animals; Humans; Molecular Epidemiology; Molecular Typing; Mycobacterium bovis; Tuberculosis
PubMed: 25242917
DOI: 10.1590/s1517-83822014005000045 -
Microbial Genomics Jun 2022The increased accessibility of next generation sequencing has allowed enough genomes from a given bacterial species to be sequenced to describe the distribution of genes...
The increased accessibility of next generation sequencing has allowed enough genomes from a given bacterial species to be sequenced to describe the distribution of genes in the pangenome, without limiting analyses to genes present in reference strains. Although some taxa have thousands of whole genome sequences available on public databases, most genomes were sequenced with short read technology, resulting in incomplete assemblies. Studying pangenomes could lead to important insights into adaptation, pathogenicity, or molecular epidemiology, however given the known information loss inherent in analyzing contig-level assemblies, these inferences may be biased or inaccurate. In this study we describe the pangenome of a clonally evolving pathogen, , and examine the utility of gene content variation in outbreak investigation. We constructed the pangenome using 1463 assembled genomes. We tested the assumption of strict clonal evolution by studying evidence of recombination in core genes and analyzing the distribution of accessory genes among core monophyletic groups. To determine if gene content variation could be utilized in outbreak investigation, we carefully examined accessory genes detected in a well described outbreak in Minnesota. We found significant errors in accessory gene classification. After accounting for these errors, we show that has a much smaller accessory genome than previously described and provide evidence supporting ongoing clonal evolution and a closed pangenome, with little gene content variation generated over outbreaks. We also identified frameshift mutations in multiple genes, including a mutation in , which has recently been associated with antibiotic tolerance in . A pangenomic approach enables a more comprehensive analysis of genome dynamics than is possible with reference-based approaches; however, without critical evaluation of accessory gene content, inferences of transmission patterns employing these loci could be misguided.
Topics: Animals; Cattle; Disease Outbreaks; Mycobacterium bovis; Tuberculosis, Bovine
PubMed: 35763423
DOI: 10.1099/mgen.0.000839 -
Journal of Infection in Developing... May 2021Zoonotic tuberculosis is a disease of public health importance worldwide, especially in developing countries. The present study aimed to investigate the role played by...
INTRODUCTION
Zoonotic tuberculosis is a disease of public health importance worldwide, especially in developing countries. The present study aimed to investigate the role played by Mycobacterium bovis and other mycobacteria as etiologic agents of bubaline tuberculosis (TB) in the Brazilian Amazon region.
METHODOLOGY
Granulomatous lesions suggestive of TB obtained from 109 buffaloes (n =109) during sanitary inspection at slaughter were subjected to histopathological evaluation, immunohistochemical (IHC) detection of Mycobacterium antigens, and to molecular tests (PCR) to detect hsp65, IS6110 and RD4 genes, which are specific to Mycobacterium spp., Mycobacterium tuberculosis Complex (MTBC) and M. bovis, respectively.
RESULTS
PCR results indicated Mycobacterium infection in 87.2% of the cases, of which 69.5% were positive for M. bovis, 27.4% belonged to MTBC, and 3.1% were probably non-TB mycobacteria. There was good agreement between the genus-specific molecular technique and the histopathological analysis. This high frequency of TB cases caused by non-M. bovis suggests a diversified scenario of mycobacteria associated with bubaline TB in the Brazilian Amazon region.
CONCLUSIONS
The results reinforce the need of discussing the inclusion of more accurate techniques in examinations carried out by Inspection Services in Brazil.
Topics: Abattoirs; Animals; Brazil; Buffaloes; Humans; Mycobacterium bovis; Tuberculosis; Zoonoses
PubMed: 34106899
DOI: 10.3855/jidc.13558 -
PloS One 2017Mycobacterium bovis, the causative agent of the bovine tuberculosis (bTB), mainly affects cattle, its natural reservoir, but also a wide range of domestic and wild...
Mycobacterium bovis, the causative agent of the bovine tuberculosis (bTB), mainly affects cattle, its natural reservoir, but also a wide range of domestic and wild mammals. Besides direct transmission via contaminated aerosols, indirect transmission of the M. bovis between wildlife and livestock might occur by inhalation or ingestion of environmental substrates contaminated through infected animal shedding. We monitored the survival of M. bovis in two soil samples chosen for their contrasted physical and-chemical properties (i.e. pH, clay content). The population of M. bovis spiked in sterile soils was enumerated by a culture-based method after 14, 30, 60, 90, 120 and 150 days of incubation at 4°C and 22°C. A qPCR based assay targeting the IS1561' locus was also performed to monitor M. bovis in both sterile and biotic spiked soils. The analysis of survival profiles using culture-based method showed that M. bovis survived longer at lower temperature (4°C versus 22°C) whereas the impact of soil characteristics on M. bovis persistence was not obvious. Furthermore, qPCR-based assay detected M. bovis for a longer period of time than the culture based method with higher gene copy numbers observed in sterile soils than in biotic ones. Impact of soil type on M. bovis persistence need to be deepened in order to fill the gap of knowledge concerning indirect transmission of the disease.
Topics: Microbial Viability; Mycobacterium bovis; Soil; Temperature; Time Factors
PubMed: 28448585
DOI: 10.1371/journal.pone.0176315 -
PLoS Neglected Tropical Diseases Jan 2018Bovine tuberculosis is a zoonotic disease with largely unknown impact in Africa, with risk factors such as HIV and direct contact with animals or consumption of...
Bovine tuberculosis is a zoonotic disease with largely unknown impact in Africa, with risk factors such as HIV and direct contact with animals or consumption of Mycobacterium bovis infected animal products. In order to understand and quantify this risk and design intervention strategies, good epidemiological studies are needed. Such studies can include molecular typing of M. bovis isolates. The aim of this study was to apply these tools to provide novel information concerning the distribution of bovine tuberculosis in cattle in Mozambique and thereby provide relevant information to guide policy development and strategies to contain the disease in livestock, and reduce the risk associated with transmission to humans. A collection of 178 M. bovis isolates was obtained from cattle in Mozambique. Using spoligotyping and regions of difference analysis, we classified the isolates into clonal complexes, thus reporting the first characterisation of M. bovis strains in this region. Data from MIRU-VNTR typing was used to compare isolates from a number of African countries, revealing a deeply geographically structured diversity of M. bovis. Eastern Africa appears to show high diversity, suggesting deep evolution in that region. The diversity of M. bovis in Africa does not seem to be a function of recent importation of animals, but is probably maintained within each particular region by constant reinfection from reservoir animals. Understanding the transmission routes of M. bovis in Mozambique and elsewhere is essential in order to focus public health and veterinary resources to contain bovine tuberculosis.
Topics: Animals; Cattle; Disease Transmission, Infectious; Genetic Variation; Genotype; Molecular Epidemiology; Molecular Typing; Mozambique; Mycobacterium bovis; Tuberculosis, Bovine; Zoonoses
PubMed: 29346413
DOI: 10.1371/journal.pntd.0006147