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Virulence 2015In this issue of Virulence, Ramon-Garcia et al. demonstrate the requirement of a mycobacterial efflux pump during growth on cholesterol. In this editorial I replace the...
In this issue of Virulence, Ramon-Garcia et al. demonstrate the requirement of a mycobacterial efflux pump during growth on cholesterol. In this editorial I replace the study in the context of nutrient acquisition by Mycobacterium tuberculosis.
Topics: Bacterial Proteins; Cholesterol; Membrane Transport Proteins; Mycobacterium bovis
PubMed: 26126122
DOI: 10.1080/21505594.2015.1053688 -
Emerging Infectious Diseases Jun 2018Mycobacterium bovis infection in wild red foxes was found in southern France, where livestock and other wildlife species are infected. Foxes frequently interact with...
Mycobacterium bovis infection in wild red foxes was found in southern France, where livestock and other wildlife species are infected. Foxes frequently interact with cattle but have been underestimated as a reservoir of M. bovis. Our results suggest a possible role of the red fox in the epidemiology of bovine tuberculosis.
Topics: Animal Diseases; Animals; Bacterial Typing Techniques; Disease Reservoirs; Foxes; France; Livestock; Mycobacterium bovis; Tuberculosis; Zoonoses
PubMed: 29774850
DOI: 10.3201/eid2406.180094 -
Microbiology (Reading, England) Apr 2001Mycobacteria are likely to encounter acidic pH in the environments they inhabit; however intracellular pH homeostasis has not been investigated in these bacteria. In...
Mycobacteria are likely to encounter acidic pH in the environments they inhabit; however intracellular pH homeostasis has not been investigated in these bacteria. In this study, Mycobacterium smegmatis and Mycobacterium bovis [Bacille Calmette--Guérin (BCG)] were used as examples of fast- and slow-growing mycobacteria, respectively, to study biochemical and physiological responses to acidic pH. M. smegmatis and M. bovis BCG were able to grow at pH values of 4.5 and 5.0, respectively, suggesting the ability to regulate internal pH. Both species of mycobacteria maintained their internal pH between pH 6.1 and 7.2 when exposed to decreasing external pH and the maximum Delta pH observed was approximately 2.1 to 2.3 units for both bacteria. The Delta pH of M. smegmatis at external pH 5.0 was dissipated by protonophores (e.g. carbonyl cyanide m-chlorophenylhydrazone), ionophores (e.g. monensin and nigericin) and N,N'-dicyclohexylcarbodiimide (DCCD), an inhibitor of the proton-translocating F(1)F(0)-ATPase. These results demonstrate that permeability of the cytoplasmic membrane to protons and proton extrusion by the F(1)F(0)-ATPase plays a key role in maintaining internal pH near neutral. Correlations between measured internal pH and cell viability indicated that the lethal internal pH for both strains of mycobacteria was less than pH 6.0. Compounds that decreased internal pH caused a rapid decrease in cell survival at acidic pH, but not at neutral pH. These data indicate that both strains of mycobacteria exhibit intracellular pH homeostasis and this was crucial for the survival of these bacteria at acidic pH values.
Topics: Cell Membrane Permeability; Dicyclohexylcarbodiimide; Enzyme Inhibitors; Extracellular Space; Homeostasis; Hydrogen-Ion Concentration; Ionophores; Mycobacterium bovis; Mycobacterium smegmatis; Proton-Translocating ATPases
PubMed: 11283297
DOI: 10.1099/00221287-147-4-1017 -
Frontiers in Cellular and Infection... 2017Emerging antibiotic resistance in pathogenic bacteria like sp., poses a threat to human health and therefore calls for the development of novel antibacterial...
Emerging antibiotic resistance in pathogenic bacteria like sp., poses a threat to human health and therefore calls for the development of novel antibacterial strategies. We have recently discovered that bacterial membrane peptides, such as KdpF, possess anti-virulence properties when overproduced in pathogenic bacterial species. Overproduction of the KdpF peptide in BCG decreased bacterial replication within macrophages, without presenting antibacterial activity. We propose that KdpF functions as a regulatory molecule and interferes with bacterial virulence, potentially through interaction with the PDIM transporter MmpL7. We demonstrate here that KdpF overproduction in BCG, increased bacterial susceptibility to nitrosative stress and thereby was responsible for lower replication rate within macrophages. Moreover, in a bacterial two-hybrid system, KdpF was able to interact not only with MmpL7 but also with two membrane proteins involved in nitrosative stress detoxification (NarI and NarK2), and a membrane protein of unknown function that is highly induced upon nitrosative stress (Rv2617c). Interestingly, we showed that the exogenous addition of KdpF synthetic peptide could affect the stability of proteins that interact with this peptide. Finally, the exogenous KdpF peptide presented similar biological effects as the endogenously expressed peptide including nitrosative stress susceptibility and reduced intramacrophage replication rate for BCG. Taken together, our results establish a link between high levels of KdpF and nitrosative stress susceptibility to further highlight KdpF as a potent molecule with anti-virulence properties.
Topics: Adenosine Triphosphatases; Cell Line; Gene Expression; Humans; Macrophages; Microbial Viability; Mycobacterium bovis; Reactive Nitrogen Species
PubMed: 28428950
DOI: 10.3389/fcimb.2017.00115 -
Emerging Microbes & Infections 2019Mannose-capped lipoarabinomannan (ManLAM) is a high molecular mass amphipathic lipoglycan identified in pathogenic () and Bacillus Calmette-Guérin (BCG). ManLAM,... (Review)
Review
Mannose-capped lipoarabinomannan (ManLAM) is a high molecular mass amphipathic lipoglycan identified in pathogenic () and Bacillus Calmette-Guérin (BCG). ManLAM, serves as both an immunogen and a modulator of the host immune system, and its critical role in mycobacterial survival during infection has been well-characterized. ManLAM can be recognized by various types of receptors on both innate and adaptive immune cells, including macrophages, dendritic cells (DCs), neutrophils, natural killer T (NKT) cells, T cells and B cells. MamLAM has been shown to affect phagocytosis, cytokine production, antigen presentation, T cell activation and polarization, as well as antibody production. Exploring the mechanisms underlying the roles of ManLAM during mycobacterial infection will aid in improving tuberculosis (TB) prevention, diagnosis and treatment interventions. In this review, we highlight the interaction between ManLAM and receptors, intracellular signalling pathways triggered by ManLAM and its roles in both innate and adaptive immune responses.
Topics: Adaptive Immunity; Animals; Humans; Immunity, Innate; Immunologic Factors; Lipopolysaccharides; Mannose; Mycobacterium bovis; Mycobacterium tuberculosis; Receptors, Immunologic; Signal Transduction
PubMed: 31379262
DOI: 10.1080/22221751.2019.1649097 -
PloS One 2013Tuberculosis is a major human and animal disease of major importance worldwide. Genetically, the closely related strains within the Mycobacterium tuberculosis complex...
Tuberculosis is a major human and animal disease of major importance worldwide. Genetically, the closely related strains within the Mycobacterium tuberculosis complex which cause disease are well-characterized but there is an urgent need better to understand their phenotypes. To search rapidly for metabolic differences, a working method using Biolog Phenotype MicroArray analysis was developed. Of 380 substrates surveyed, 71 permitted tetrazolium dye reduction, the readout over 7 days in the method. By looking for ≥5-fold differences in dye reduction, 12 substrates differentiated M. tuberculosis H37Rv and Mycobacterium bovis AF2122/97. H37Rv and a Beijing strain of M. tuberculosis could also be distinguished in this way, as could field strains of M. bovis; even pairs of strains within one spoligotype could be distinguished by 2 to 3 substrates. Cluster analysis gave three clear groups: H37Rv, Beijing, and all the M. bovis strains. The substrates used agreed well with prior knowledge, though an unexpected finding that AF2122/97 gave greater dye reduction than H37Rv with hexoses was investigated further, in culture flasks, revealing that hexoses and Tween 80 were synergistic for growth and used simultaneously rather than in a diauxic fashion. Potential new substrates for growth media were revealed, too, most promisingly N-acetyl glucosamine. Osmotic and pH arrays divided the mycobacteria into two groups with different salt tolerance, though in contrast to the substrate arrays the groups did not entirely correlate with taxonomic differences. More interestingly, these arrays suggested differences between the amines used by the M. tuberculosis complex and enteric bacteria in acid tolerance, with some hydrophobic amino acids being highly effective. In contrast, γ-aminobutyrate, used in the enteric bacteria, had no effect in the mycobacteria. This study proved principle that Phenotype MicroArrays can be used with slow-growing pathogenic mycobacteria and already has generated interesting data worthy of further investigation.
Topics: Coloring Agents; Culture Media; Glycolysis; Humans; Hydrocarbons; Hydrogen-Ion Concentration; Microarray Analysis; Mycobacterium bovis; Mycobacterium tuberculosis; Nitrogen Compounds; Oxidation-Reduction; Phenotype; Phosphorus Compounds; Sodium Chloride; Species Specificity; Sulfur Compounds; Tetrazolium Salts
PubMed: 23326347
DOI: 10.1371/journal.pone.0052673 -
BMC Microbiology Mar 2020Bovine tuberculosis (bTB) affects cattle and wildlife in South Africa with the African buffalo (Syncerus caffer) as the principal maintenance host. The presence of a...
BACKGROUND
Bovine tuberculosis (bTB) affects cattle and wildlife in South Africa with the African buffalo (Syncerus caffer) as the principal maintenance host. The presence of a wildlife maintenance host at the wildlife/livestock interface acting as spill-over host makes it much more challenging to control and eradicate bTB in cattle. Spoligotyping and mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) genotyping methods were performed to investigate the genetic diversity of Mycobacterium bovis (M. bovis) isolates from cattle and wildlife, their distribution and transmission at the wildlife/livestock interface in northern Kwa-Zulu Natal (KZN), South Africa.
RESULTS
SB0130 was identified as the dominant spoligotype pattern at this wildlife/livestock interface, while VNTR typing revealed a total of 29 VNTR profiles (strains) in the KZN province signifying high genetic variability. The detection of 5 VNTR profiles shared between cattle and buffalo suggests M. bovis transmission between species. MIRU-VNTR confirmed co-infection in one cow with three strains of M. bovis that differed at a single locus, with 2 being shared with buffalo, implying pathogen introduction from most probably unrelated wildlife sources.
CONCLUSION
Our findings highlight inter and intra species transmission of bTB at the wildlife/livestock interface and the need for the implementation of adequate bTB control measures to mitigate the spread of the pathogen responsible for economic losses and a public health threat.
Topics: Animals; Animals, Wild; Buffaloes; Cattle; Evolution, Molecular; Genetic Variation; Genotyping Techniques; Livestock; Minisatellite Repeats; Mycobacterium bovis; Phylogeny; South Africa; Tuberculosis, Bovine
PubMed: 32131736
DOI: 10.1186/s12866-020-01736-4 -
BMC Microbiology May 2019Vitamin B (V) is a crucial dietary nutrient and essential cofactor for several key enzymes in the regulation of cellular and metabolic processes, and more importantly in...
BACKGROUND
Vitamin B (V) is a crucial dietary nutrient and essential cofactor for several key enzymes in the regulation of cellular and metabolic processes, and more importantly in the activation of immune system. To date, the precise role of V in Mycobacterium tuberculosis remains to be fully understood.
RESULTS
In this study, the transcriptional and metabolic profiles of V-treated Mycobacterium. bovis BCG were analyzed by RNA-sequencing and LC-MS (Liquid chromatography coupled to mass spectrometry). The selection of BCG strain was based on its common physiological features shared with M. tuberculosis. The results of cell growth assays demonstrated that V inhibited the BCG growth rate in vitro. Transcriptomic analysis revealed that the expression levels of genes related to fatty acid metabolism, cholesterol metabolism, glycolipid catabolism, DNA replication, protein translation, cell division and cell wall formation were significantly downregulated in M. bovis BCG treated with V In addition, the metabolomics LC-MS data indicated that most of the amino acids and adenosine diphosphate (ADP) were decreased in M. bovis BCG strain after V treatment.
CONCLUSIONS
This study provides the molecular and metabolic bases to understand the impacts of V on M.bovis BCG.
Topics: Bacterial Proteins; Chromatography, Liquid; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Mass Spectrometry; Metabolome; Metabolomics; Mycobacterium bovis; Sequence Analysis, RNA; Thiamine
PubMed: 31117936
DOI: 10.1186/s12866-019-1492-9 -
International Journal of Infectious... Oct 2017To determine genetic diversity by comparing the whole genome sequences of cattle and human Mycobacterium bovis isolates from Baja California.
OBJECTIVES
To determine genetic diversity by comparing the whole genome sequences of cattle and human Mycobacterium bovis isolates from Baja California.
METHODS
A whole genome sequencing strategy was used to obtain the molecular fingerprints of 172 isolates of M. bovis obtained from Baja California, Mexico; 155 isolates were from cattle and 17 isolates were from humans. Spoligotypes were characterized in silico and single nucleotide polymorphism (SNP) differences between the isolates were evaluated.
RESULTS
A total of 12 M. bovis spoligotype patterns were identified in cattle and humans. Two predominant spoligotypes patterns were seen in both cattle and humans: SB0145 and SB1040. The SB0145 spoligotype represented 59% of cattle isolates (n=91) and 65% of human isolates (n=11), while the SB1040 spoligotype represented 30% of cattle isolates (n=47) and 30% of human isolates (n=5). When evaluating SNP differences, the human isolates were intimately intertwined with the cattle isolates.
CONCLUSIONS
All isolates from humans had spoligotype patterns that matched those observed in the cattle isolates, and all human isolates shared common ancestors with cattle in Baja California based on SNP analysis. This suggests that most human tuberculosis caused by M. bovis in Baja California is derived from M. bovis circulating in Baja California cattle. These results reinforce the importance of bovine tuberculosis surveillance and control in this region.
Topics: Animals; Bacterial Typing Techniques; Cattle; DNA, Bacterial; Humans; Mexico; Mycobacterium bovis; Polymorphism, Single Nucleotide; Tuberculosis; Tuberculosis, Bovine; Whole Genome Sequencing
PubMed: 28739421
DOI: 10.1016/j.ijid.2017.07.012 -
Emerging Infectious Diseases Dec 2019Human infection with Mycobacterium bovis is reported infrequently in the United Kingdom. Most cases involve previous consumption of unpasteurized milk. We report a rare...
Human infection with Mycobacterium bovis is reported infrequently in the United Kingdom. Most cases involve previous consumption of unpasteurized milk. We report a rare occurrence of 2 incidents of cat-to-human transmission of M. bovis during a cluster of infection in cats.
Topics: Adolescent; Adult; Animals; Cats; Genome, Bacterial; Genomics; Genotype; Humans; Mycobacterium bovis; Phylogeny; Tuberculosis; Young Adult; Zoonoses
PubMed: 31742516
DOI: 10.3201/eid2512.190012