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Water Research Feb 2017Mycobacterium avium complex (MAC) is a group of environmentally-transmitted pathogens of great public health importance. This group is known to be harbored, amplified,... (Review)
Review
Dose response models and a quantitative microbial risk assessment framework for the Mycobacterium avium complex that account for recent developments in molecular biology, taxonomy, and epidemiology.
Mycobacterium avium complex (MAC) is a group of environmentally-transmitted pathogens of great public health importance. This group is known to be harbored, amplified, and selected for more human-virulent characteristics by amoeba species in aquatic biofilms. However, a quantitative microbial risk assessment (QMRA) has not been performed due to the lack of dose response models resulting from significant heterogeneity within even a single species or subspecies of MAC, as well as the range of human susceptibilities to mycobacterial disease. The primary human-relevant species and subspecies responsible for the majority of the human disease burden and present in drinking water, biofilms, and soil are M. avium subsp. hominissuis, M. intracellulare, and M. chimaera. A critical review of the published literature identified important health endpoints, exposure routes, and susceptible populations for MAC risk assessment. In addition, data sets for quantitative dose-response functions were extracted from published in vivo animal dosing experiments. As a result, seven new exponential dose response models for human-relevant species of MAC with endpoints of lung lesions, death, disseminated infection, liver infection, and lymph node lesions are proposed. Although current physical and biochemical tests used in clinical settings do not differentiate between M. avium and M. intracellulare, differentiating between environmental species and subspecies of the MAC can aid in the assessment of health risks and control of MAC sources. A framework is proposed for incorporating the proposed dose response models into susceptible population- and exposure route-specific QMRA models.
Topics: Animals; Biofilms; Drinking Water; Humans; Mycobacterium avium; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Risk Assessment
PubMed: 27915187
DOI: 10.1016/j.watres.2016.11.053 -
Microbiology Spectrum Feb 2023Nontuberculous mycobacteria (NTM), including Mycobacterium avium, are clinically important pathogens in cystic fibrosis (CF). The innate immune response to M. avium...
Nontuberculous mycobacteria (NTM), including Mycobacterium avium, are clinically important pathogens in cystic fibrosis (CF). The innate immune response to M. avium remains incompletely understood. We evaluated the role of complement opsonization in neutrophil-mediated killing of M. avium. Killing assays were performed using neutrophils from healthy donors (HDs) and persons with CF (pwCF). Clinical isolates of M. avium were opsonized with plasma from HDs or pwCF, which was intact or heat-treated to inactivate complement. HD neutrophils had killing activity against M. avium opsonized with intact HD plasma and killing was significantly reduced when M. avium was opsonized with heat-inactivated HD plasma. When opsonized with HD plasma, CF neutrophils had killing activity against M. avium that was not different than HD neutrophils. When opsonized with intact plasma from pwCF, HD neutrophil killing of M. avium was significantly reduced. Opsonization of M. avium with C3-depleted serum or IgM-depleted plasma resulted in significantly reduced killing. Plasma C3 levels were elevated in pwCF with NTM infection compared to pwCF without NTM infection. These studies demonstrate that human neutrophils efficiently kill M. avium when opsonized in the presence of plasma factors from HD that include C3 and IgM. Killing efficiency is significantly lower when the bacteria are opsonized with plasma from pwCF. This indicates a novel role for opsonization in neutrophil killing of M. avium and a deficiency in complement opsonization as a mechanism of impaired M. avium killing in CF. Mycobacterium avium is a member of a group of bacterial species termed nontuberculous mycobacteria (NTM) that cause lung disease in certain populations, including persons with cystic fibrosis (CF). NTM infections are challenging to diagnose and can be even more difficult to treat. This study investigated how the immune system responds to M. avium infection in CF. We found that neutrophils, the most abundant immune cell in the lungs in CF, can effectively kill M. avium in individuals both with and without CF. Another component of the immune response called the complement system is also required for this process. Levels of complement proteins are altered in persons with CF who have a history of NTM compared to those without a history of NTM infection. These results add to our understanding of how the immune system responds to M. avium, which can help pave the way toward better diagnostic and treatment strategies.
Topics: Humans; Cystic Fibrosis; Neutrophils; Mycobacterium avium; Opsonization; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Complement System Proteins; Immunoglobulin M
PubMed: 36651756
DOI: 10.1128/spectrum.03279-22 -
PloS One 2022Paratuberculosis is debilitating chronic enteritis usually characterized by diarrhea, decreased milk production, and progressive cachexia. Mycobacterium avium subspecies...
BACKGROUND
Paratuberculosis is debilitating chronic enteritis usually characterized by diarrhea, decreased milk production, and progressive cachexia. Mycobacterium avium subspecies paratuberculosis (MAP) causes significant economic losses by affecting dairy herds globally. Development of protective vaccines is considered as one of the most effective controlling measures for MAP infections. In the current study, hydrophilic parts of MAP2191 and FAP-P proteins as two vaccine candidates were analyzed using immunoinformatics approaches.
METHODS
After selecting the most hydrophilic parts of MAP2191 and FAP-P, helper and cytotoxic T-cell epitopes of ht-MAP2191 and ht-FAP-P were identified. The immunogenic, toxicity and physicochemical properties were assessed. Secondary structures of these proteins were predicted, and their tertiary structures were modeled, refined, and validated. Linear and conformational epitopes of corresponding B-cells were recognized. Then ht-MAP2191 and ht-FAP-P epitopes were employed for molecular docking simulations.
RESULTS
The results indicated that ht-MAP2191 and ht-FAP-P were immunogenic, non-allergenic, and non-toxic and possess potent T-cell and B-cell epitopes. Eventually, these protein constructs were docked favorably against TLR4.
CONCLUSION
According to the findings, ht-MAP2191 and ht-FAP-P could be effective protein-based vaccine candidates for paratuberculosis. It should be noted that to examine their efficacy, further in vitro and in vivo experiments are underway.
Topics: Cattle; Animals; Paratuberculosis; Molecular Docking Simulation; Mycobacterium avium subsp. paratuberculosis; Cattle Diseases; Epitopes, B-Lymphocyte
PubMed: 36409703
DOI: 10.1371/journal.pone.0277751 -
BMC Genomics Oct 2023To date genomic studies on Map have concentrated on Type C strains with only a few Type S strains included for comparison. In this study the entire pan-genome of 261 Map...
BACKGROUND
To date genomic studies on Map have concentrated on Type C strains with only a few Type S strains included for comparison. In this study the entire pan-genome of 261 Map genomes (205 Type C, 52 Type S and 4 Type B) and 7 Mycobacterium avium complex (Mac) genomes were analysed to identify genomic similarities and differences between the strains and provide more insight into the evolutionary relationship within this Mycobacterial species.
RESULTS
Our analysis of the core genome of all the Map isolates identified two distinct lineages, Type S and Type C Map that is consistent with previous phylogenetic studies of Map. Pan-genome analysis revealed that Map has a larger accessory genome than Mycobacterium avium subsp. avium (Maa) and Type C Map has a larger accessory genome than Type S Map. In addition, we found large rearrangements within Type S strains of Map and little to none in Type C and Type B strains. There were 50 core genes identified that were unique to Type S Map and there were no unique core genes identified between Type B and Type C Map strains. In Type C Map we identified an additional CE10 CAZyme class which was identified as an alpha/beta hydrolase and an additional polyketide and non-ribosomal peptide synthetase cluster. Consistent with previous analysis no plasmids and only incomplete prophages were identified in the genomes of Map. There were 45 hypothetical CRISPR elements identified with no associated cas genes.
CONCLUSION
This is the most comprehensive comparison of the genomic content of Map isolates to date and included the closing of eight Map genomes. The analysis revealed that there is greater variation in gene synteny within Type S strains when compared to Type C indicating that the Type C Map strain emerged after Type S. Further analysis of Type C and Type B genomes revealed that they are structurally similar with little to no genetic variation and that Type B Map may be a distinct clade within Type C Map and not a different strain type of Map. The evolutionary lineage of Maa and Map was confirmed as emerging after M. hominissuis.
Topics: Animals; Mycobacterium avium subsp. paratuberculosis; Phylogeny; Genome; Synteny; Gene Rearrangement; Paratuberculosis; Mycobacterium avium
PubMed: 37907856
DOI: 10.1186/s12864-023-09752-0 -
Veterinary Research Jun 2015
Within- and between-host mathematical modeling of Mycobacterium avium subspecies paratuberculosis (MAP) infections as a tool to study the dynamics of host-pathogen interactions in bovine paratuberculosis.
Topics: Animals; Cattle; Cattle Diseases; Host-Pathogen Interactions; Models, Biological; Mycobacterium avium subsp. paratuberculosis; Paratuberculosis
PubMed: 26092284
DOI: 10.1186/s13567-015-0205-0 -
Frontiers in Cellular and Infection... 2020, an opportunistic intracellular pathogen, is a member of the non-tuberculous mycobacteria species. causes respiratory disease in immunosuppressed individuals and a...
, an opportunistic intracellular pathogen, is a member of the non-tuberculous mycobacteria species. causes respiratory disease in immunosuppressed individuals and a wide range of animals, including companion dogs and cats. In particular, the number of infected companion dogs has increased, although the underlying mechanism of pathogenesis in dogs has not been studied. Therefore, in the present study, the host immune response against in dogs was investigated by transcriptome analysis of canine peripheral blood mononuclear cells. was shown to induce different immune responses in canine peripheral blood mononuclear cells at different time points after infection. The expression of Th1-associated genes occurred early during infection, while that of Th17-associated genes increased after 12 h. In addition, the expression of apoptosis-related genes decreased and the abundance of intracellular increased in monocyte-derived macrophages after infection for 24 h. These results reveal the induces Th17 immune response and avoids apoptosis in infected canine cells. As the number of infection cases increases, the results of the present study will contribute to a better understanding of host immune responses to infection in companion dogs.
Topics: Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Immunity; Leukocytes, Mononuclear; Mycobacterium avium
PubMed: 33520738
DOI: 10.3389/fcimb.2020.609712 -
PloS One 2021Paratuberculosis a contagious and chronic disease in domestic and wild ruminants, is caused by Mycobacterium avium subspecies paratuberculosis (MAP). Typical clinical...
Paratuberculosis a contagious and chronic disease in domestic and wild ruminants, is caused by Mycobacterium avium subspecies paratuberculosis (MAP). Typical clinical signs include intractable diarrhea, progressive emaciation, proliferative enteropathy, and mesenteric lymphadenitis. Paratuberculosis is endemic to many parts of the world and responsible for considerable economic losses. In this study, different types of paratuberculosis and MAP in sheep and goats were investigated in Inner Mongolia, a northern province in China contiguous with two countries and eight other provinces. A total of 4434 serum samples were collected from six cities in the western, central, and eastern regions of Inner Mongolia and analyzed using the ELISA test. In addition, tissue samples were collected from seven animals that were suspected to be infected with MAP. Finally, these tissues samples were analyzed by histopathological examination followed by polymerase chain reaction (PCR), IS1311 PCR-restriction enzyme analysis (PCR-REA), and a sequence analysis of five genes. Among all 4434 ruminant serum samples collected from the six cities in the western, central, and eastern regions of Inner Mongolia, 7.60% (337/4434) measured positive for the MAP antibody. The proportions of positive MAP antibody results for serum samples collected in the western, central, and eastern regions were 5.10% (105/2058), 6.63% (85/1282), and 13.44% (147/1094), respectively. For the seven suspected infected animals selected from the herd with the highest rate of positivity, the gross pathology and histopathology of the necropsied animals were found to be consistent with the pathological features of paratuberculosis. The PCR analysis further confirmed the diagnosis of paratuberculosis. The rest of the results demonstrated that herds of sheep and goats in Inner Mongolia were infected with both MAP type II and type III. To the best of our knowledge, this is the first study of the two subtypes of MAP strains in sheep and goats in Inner Mongolia.
Topics: Animals; China; Enzyme-Linked Immunosorbent Assay; Genotype; Goat Diseases; Goats; Mycobacterium avium; Paratuberculosis; Serology; Sheep; Sheep Diseases
PubMed: 34492040
DOI: 10.1371/journal.pone.0256628 -
Microbiology Spectrum May 2024Tuberculostearic acid (TBSA) is a fatty acid unique to mycobacteria and some corynebacteria and has been studied due to its diagnostic value, biofuel properties, and...
Tuberculostearic acid (TBSA) is a fatty acid unique to mycobacteria and some corynebacteria and has been studied due to its diagnostic value, biofuel properties, and role in membrane dynamics. In this study, we demonstrate that TBSA production can be abrogated either by addition of pivalic acid to mycobacterial growth cultures or by a gene knockout encoding a flavin adenine dinucleotide (FAD)-binding oxidoreductase. subspecies () growth and TBSA production were inhibited in 0.5-mg/mL pivalic acid-supplemented cultures, but higher concentrations were needed to have a similar effect in other mycobacteria, including . While C-type strains, isolated from cattle and other ruminants, will produce TBSA in the absence of pivalic acid, the S-type strains, typically isolated from sheep, do not produce TBSA in any condition. A SAM-dependent methyltransferase encoded by and FAD-binding oxidoreductase are both required in the two-step biosynthesis of TBSA. However, S-type strains contain a single-nucleotide polymorphism in the gene, rendering the oxidoreductase enzyme vestigial. This results in the production of an intermediate, termed 10-methylene stearate, which is detected only in S-type strains. Fatty acid methyl ester analysis of a C-type knockout revealed the loss of TBSA production, but the intermediate was present, similar to the S-type strains. Collectively, these results demonstrate the subtle biochemical differences between two primary genetic lineages of and other mycobacteria as well as explain the resulting phenotype at the genetic level. These data also suggest that TBSA should not be used as a diagnostic marker for .IMPORTANCEBranched-chain fatty acids are a predominant cell wall component among species belonging to the genus. One of these is TBSA, which is a long-chain middle-branched fatty acid used as a diagnostic marker for . This fatty acid is also an excellent biolubricant. Control of its production is important for industrial purposes as well as understanding the biology of mycobacteria. In this study, we discovered that a carboxylic acid compound termed pivalic acid inhibits TBSA production in mycobacteria. Furthermore, strains from two separate genetic lineages (C-type and S-type) showed differential production of TBSA. Cattle-type strains of subspecies produce TBSA, while the sheep-type strains do not. This important phenotypic difference is attributed to a single-nucleotide deletion in sheep-type strains of . This work sheds further light on the mechanism used by mycobacteria to produce tuberculostearic acid.
Topics: Mycobacterium avium subsp. paratuberculosis; Animals; Paratuberculosis; Cattle; Bacterial Proteins; Sheep; Fatty Acids; Polymorphism, Single Nucleotide; Methyltransferases; Stearic Acids
PubMed: 38501867
DOI: 10.1128/spectrum.00508-24 -
PloS One 2022The Mycobacterium avium complex (MAC) comprises a widespread group of slowly-growing bacteria from the Mycobacteriaceae. These bacteria are responsible for opportunistic...
The Mycobacterium avium complex (MAC) comprises a widespread group of slowly-growing bacteria from the Mycobacteriaceae. These bacteria are responsible for opportunistic infections in humans and animals, including farm animals. The aim of the study was to determine whether it is possible to predict the presence of M. avium in pig lymph nodes based on the size and type of lesions found during post-mortem examination at a slaughterhouse. Lymph nodes were collected from 10,600 pigs subjected to such post-mortem examination. The nodes were classified with regard to their quality, and the number of tuberculosis-like lesions; following this, 86 mandibular lymph nodes with lesions and 113 without visible macroscopic lesions were selected for further study. Cultures were established on Löwenstein-Jensen and Stonebrink media, and a commercial GenoType Mycobacterium CM test was used to identify and differentiate M. avium species. The prevalence of M. avium was 56.98% in the lymph nodes with lesions and 19.47% in the unchanged ones. Statistical analysis indicated that visual assessment of lesions in the mandibular lymph nodes, in particular the number of tuberculous lesions, is a highly-efficient diagnostic tool. Similar results were obtained for estimated percentage area affected by the lesion, i.e. the ratio of the changed area of the lymph node in cross-section to the total cross-sectional area of the lymph node; however, this method is more laborious and its usefulness in slaughterhouse conditions is limited. By incising the lymph nodes and assessing the number of tuberculosis-like lesions, it is possible to limit the inclusion of meat from pigs infected with M. avium into the human food chain.
Topics: Animals; Humans; Lymph Nodes; Mycobacterium avium; Mycobacterium avium Complex; Swine; Swine Diseases; Tuberculosis
PubMed: 35839172
DOI: 10.1371/journal.pone.0269912 -
Journal of Medical Microbiology Jul 2020The incidence of complex (MAC) pulmonary disease (MAC PD), a refractory chronic respiratory tract infection, is increasing worldwide. MAC has three predominant colony...
The incidence of complex (MAC) pulmonary disease (MAC PD), a refractory chronic respiratory tract infection, is increasing worldwide. MAC has three predominant colony morphotypes: smooth opaque (SmO), smooth transparent (SmT) and rough (Rg). To determine whether colony morphotypes can predict the prognosis of MAC PD, we evaluated the virulence of SmO, SmT and Rg in mice and in human macrophages. We compared the characteristics of mice and human macrophages infected with the SmO, SmT, or Rg morphotypes of subsp. 104. C57BL/6 mice and human macrophages derived from peripheral mononuclear cells were used in these experiments. In comparison to SmO- or SmT-infected mice, Rg-infected mice revealed severe pathologically confirmed pneumonia, increased lung weight and increased lung bacterial burden. Rg-infected macrophages revealed significant cytotoxicity, increased bacterial burden, secretion of proinflammatory cytokines (TNF-α and IL-6) and chemokines (CCL5 and CCL3), and formation of cell clusters. Rg formed larger bacterial aggregates than SmO and SmT. Cytotoxicity, bacterial burden and secretion of IL-6, CCL5 and CCL3 were induced strongly by Rg infection, and were decreased by disaggregation of the bacteria. Rg, which is associated with bacterial aggregation, has the highest virulence among the predominant colony morphotypes.
Topics: Animals; Cytokines; Female; Humans; Incidence; Macrophages; Mice; Mice, Inbred C57BL; Mycobacterium avium; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Phenotype; Virulence
PubMed: 32589124
DOI: 10.1099/jmm.0.001224