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1.
Ann Agric Environ Med ; 28(4): 575-578, 2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-34969213

RESUMO

INTRODUCTION AND OBJECTIVE: In recent years, bovine tuberculosis (BTB) has become one of the major health hazards facing the European bison (EB, Bison bonasus), a vulnerable species that requires active protection, including regular and effective health monitoring. Monitoring of zoonotic disease in wildlife is also an important part of public health protection. The aim of the study was to determine whether BTB still influences the EB population in Poland. MATERIAL AND METHODS: During 2017-2019, mandibular, retropharyngeal and mediastinal lymph nodes were collected from 90 EB during post-mortem examination, and then cultivated on Lowenstein-Jensen and Stonebrink media. Isolated strains were subjected to molecular analysis to determine the species, spoligotype and MIRU-VNTR pattern. RESULTS: Lesions were found in lymph nodes originating from eight EB (8.89%). Positive microbiological cultures for mycobacteria were obtained in samples from six (6.67%) EB. The isolated strains were identified as Mycobacterium caprae (material from four EB) and atypical mycobacteria (material from two EB). For M. caprae strains spoligotype M. bovis 4_CA 1600 was identified and the MIRU-VNTR pattern was identified as 345751355413232. CONCLUSIONS: It is recommended that this potentially dangerous disease should be monitored in EB via a comprehensive strategy based on a combination of microbiological and molecular methods. Such monitoring will protect the health of both animals and humans.


Assuntos
Bison , Mycobacterium bovis , Tuberculose Bovina , Animais , Animais Selvagens , Bovinos , Mycobacterium bovis/genética , Polônia/epidemiologia
2.
Trop Anim Health Prod ; 53(5): 504, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34622357

RESUMO

This study aimed to determine whether cows detected as tuberculosis (bTB) reactors and seropositive to brucellosis (bBR), as well as co-positive to bBR and bTB (bBR-bTB) and with a complete lactation before slaughter, were associated with reduced milk production and fertility. A total of 8068 productive and reproductive records of high-yielding Holstein cows from a single large dairy herd with a high prevalence of bTB and bBR were collected from 2012 to 2015. Lactation derived either from calving (n = 6019) or hormonally induced lactation (n = 2049), and all cows received growth hormone throughout lactation. For cows not induced into lactation, pregnancy rate to first service for healthy cows (C; 26.6%) was higher (P < 0.01) than bBR (15.2%), bTB (15.8%), and bBR-bTB (1.3%) cows. For induced cows, pregnancy rate to first service did not differ significantly among C, bBR, and bTB (14.5-17.3%) cows, but the percentage success of first service was extremely low (1.3%; P < 0.01) in bBR-bTB cows. Services per pregnancy (only pregnant cows) were lowest for C (3.3 ± 2.9; P < 0.01) and highest (6.4 ± 3.4) for bBR-bTB non-induced cows. This variable was lowest for C (2.9 ± 2.5; P < 0.01) and highest for bBR-bTB non-induced cows (6.3 ± 3.1). Pregnancy rate to all services did not differed for C (79.5%), bBR (76.7%), and bTB (75.9%) but was lower (58.9%; P < 0.01) for bBR-bTB non-induced cows. For induced cows this variable was highest for bBR (53.3%) and lowest for bBR-bTB (34.1%; P < 0.01) non-induced cows. 305-d milk production was increased by 4%, and total milk yield by 7% in TB-positive cows compared to that of the negative cows non-induced hormonally into lactation. This study showed the negative impact of the co-positivity for bTB and bBR on the reproductive efficiency of Holstein cows, although positive bTB and bBR tests enhanced milk yield.


Assuntos
Brucelose Bovina/diagnóstico , Doenças dos Bovinos , Fertilidade , Leite , Tuberculose Bovina/diagnóstico , Animais , Bovinos , Doenças dos Bovinos/diagnóstico , Feminino , Lactação , Gravidez
3.
Prev Vet Med ; 196: 105477, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34482152

RESUMO

Abattoir surveillance is an integral component of a bovine tuberculosis (bTB) eradication programme. The objective of this study was to determine the prevalence of bTB among culled adult dairy cows in Wuhan, China and to further assess two diagnostic procedures as an adjunct to the confirmation of M. bovis in animals with TB-like lesions. The study was conducted in an abattoir located in Wuhan, China over a period of 41 days from June to July 2019. A total of 171 culled adult dairy cows were sampled and inspected, and blood samples collected from 134 of these. The viscera and lymph nodes of the carcasses were visually inspected and palpated for TB-like lesions. A total of 28.1 % (48/171) of the carcasses had gross TB-like lesions. 89.6 % (43/48) of the animals with TB-like lesions were positive to a PCR procedure for bTB. The sensitivity and specificity for post-mortem examination for TB-like lesions using a Bayesian latent class analysis model was estimated to be 60.8 % and 86.6 %, respectively. A seroprevalence of 20.9 % (28/134) was recorded for antibody response to M. bovis antigens MPB70 and MPB83 based on an ELISA procedure. There was a low-moderate agreement between the ELISA and PCR results in the detection of bTB (Kappa = 0.46, 95 % CI: 0.24-0.67). The study confirms a high prevalence of bTB among culled adult dairy cows in the abattoir and highlights the need to implement surveillance for bTB based on post-mortem examination and ELISA and PCR methods in association with backward tracing of infected dairy herds.


Assuntos
Mycobacterium bovis , Tuberculose Bovina , Matadouros , Abate de Animais , Animais , Teorema de Bayes , Bovinos , China/epidemiologia , Indústria de Laticínios , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Reação em Cadeia da Polimerase/veterinária , Prevalência , Sensibilidade e Especificidade , Estudos Soroepidemiológicos , Tuberculose Bovina/epidemiologia
4.
PLoS One ; 16(9): e0242586, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34478443

RESUMO

Road ecology has traditionally focused on the impact of in-situ and functional roads on wildlife. However, road construction also poses a major, yet understudied, threat and the implications for key aspects of animal behaviour are unknown. Badgers (Meles meles) have been implicated in the transmission of tuberculosis to cattle. There are concerns that environmental disturbances, including major road construction, can disrupt badger territoriality, promoting the spread of the disease to cattle. To address these knowledge gaps the ranging behaviour of a medium-density Irish badger population was monitored using GPS-tracking collars before, during, and after a major road realignment project that bisected the study area. We estimated badgers' home range sizes, nightly distances travelled, and the distance and frequency of extra-territorial excursions during each phase of the study and quantified any changes to these parameters. We show that road construction had a very limited effect on ranging behaviour. A small increase in nightly distance during road construction did not translate into an increase in home range size, nor an increase in the distance or frequency of extra-territorial excursions during road construction. In addition, suitable mitigation measures to prevent badger deaths appeared to ensure that normal patterns of ranging behaviour continued once the new road was in place. We recommend that continuous badger-proof fencing be placed along the entire length of new major roads, in combination with appropriately sited underpasses. Our analysis supports the view that road construction did not cause badgers to change their ranging behaviour in ways likely to increase the spread of tuberculosis.


Assuntos
Mustelidae , Territorialidade , Animais , Bovinos , Reservatórios de Doenças , Mycobacterium bovis , Tuberculose Bovina
6.
Front Immunol ; 12: 674643, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335572

RESUMO

Bovine tuberculosis is an important animal and zoonotic disease caused by Mycobacterium bovis. The innate immune response is the first line of defense against pathogens and is also crucial for the development of an efficient adaptive immune response. In this study we used an in vitro co-culture model of antigen presenting cells (APC) and autologous lymphocytes derived from peripheral blood mononuclear cells to identify the cell populations and immune mediators that participate in the development of an efficient innate response capable of controlling the intracellular replication of M. bovis. After M. bovis infection, bovine immune cell cultures displayed upregulated levels of iNOS, IL-22 and IFN-γ and the induction of the innate immune response was dependent on the presence of differentiated APC. Among the analyzed M. bovis isolates, only a live virulent M. bovis isolate induced an efficient innate immune response, which was increased upon stimulation of cell co-cultures with the M. bovis culture supernatant. Moreover, we demonstrated that an allelic variation of the early secreted protein ESAT-6 (ESAT6 T63A) expressed in the virulent strain is involved in this increased innate immune response. These results highlight the relevance of the compounds secreted by live M. bovis as well as the variability among the assessed M. bovis strains to induce an efficient innate immune response.


Assuntos
Imunidade Inata/imunologia , Mycobacterium bovis/imunologia , Tuberculose Bovina/imunologia , Animais , Antígenos de Bactérias/imunologia , Bovinos , Técnicas de Cocultura , Citocinas/metabolismo , Interferon gama/metabolismo , Macrófagos , Cultura Primária de Células
7.
Emerg Infect Dis ; 27(8): 2025-2032, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34286688

RESUMO

Infections with Mycobacterium microti, a member of the M. tuberculosis complex, have been increasingly reported in humans and in domestic and free-ranging wild animals. At postmortem examination, infected animals may display histopathologic lesions indistinguishable from those caused by M. bovis or M. caprae, potentially leading to misidentification of bovine tuberculosis. We report 3 cases of M. microti infections in free-ranging red deer (Cervus elaphus) from western Austria and southern Germany. One diseased animal displayed severe pyogranulomatous pleuropneumonia and multifocal granulomas on the surface of the pericardium. Two other animals showed alterations of the lungs and associated lymph nodes compatible with parasitic infestation. Results of the phylogenetic analysis including multiple animal strains from the study area showed independent infection events, but no host-adapted genotype. Personnel involved in bovine tuberculosis-monitoring programs should be aware of the fastidious nature of M. microti, its pathogenicity in wildlife, and zoonotic potential.


Assuntos
Cervos , Mycobacterium bovis , Tuberculose Bovina , Animais , Animais Selvagens , Áustria , Bovinos , Alemanha/epidemiologia , Mycobacterium bovis/genética , Filogenia
8.
Vet Rec ; 189(2): e140, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34297366

RESUMO

INTRODUCTION: This study aims to assess the most likely causes of Bovine tuberculosis (bTB) breakdowns in Spanish cattle herds and to identify the main risk factors at farm-level. METHODS: Causes of bTB breakdowns were assessed through a qualitative risk-assessment based on decision-trees by analysing surveillance data from 3819 bTB breakdowns detected during 2014-2016. Results were compared to veterinary officers' (VO) opinions. Risk factors were identified through a case-control study with data from 196 bTB cases and 160 controls collected during 2014-2018. RESULTS: The decision tree analysis identified residual infections and interactions with wildlife as the most frequent causes of breakdowns (36% each), followed by purchasing infected cattle (14%). These results were not supported by VOs' opinions. According to the regression models, the risk of bTB increased by sharing pastures (odds ratios [OR] = 2.7; 95% confidence interval [CI] = 1.6-4.4) and by increasing inwards cattle movements. The presence of wildlife reservoirs represented a significant risk for extensively-managed farms if other cattle farms are situated within a one-kilometre radius (OR = 2.3; 95% CI = 1.1-5.1). DISCUSSION: To prevent bTB breakdowns, efforts should be devoted to decrease the likelihood of residual infections and improve farm biosecurity. The adoption of biosecurity measures might be influenced by farmers' perceptions, which should be carefully evaluated to ensure the effectiveness of such strategies.


Assuntos
Tuberculose Bovina/epidemiologia , Tuberculose Bovina/etiologia , Animais , Estudos de Casos e Controles , Bovinos , Fazendas , Fatores de Risco , Espanha/epidemiologia
11.
PLoS One ; 16(7): e0254091, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34214106

RESUMO

Bovine tuberculosis (bTB) is an important disease for dairy productivity, as well as having the potential for zoonotic transmission. Previous prevalence studies of bTB in the dairy sector in central Ethiopia have suggested high prevalence, however, they have been limited to relatively small scale surveys, raising concerns about their representativeness. Here we carried out a cross sectional one-stage cluster sampling survey taking the dairy herd as a cluster to estimate the prevalence of bTB in dairy farms in six areas of central Ethiopia. The survey, which to date is by far the largest in the area in terms of the number of dairy farms, study areas and risk factors explored, took place from March 2016 to May 2017. This study combined tuberculin skin testing and the collection of additional herd and animal level data by questionnaire to identify potential risk factors contributing to bTB transmission. We applied the single intradermal cervical comparative tuberculin (SICCT) test using >4mm cut-off for considering an individual animal as positive for bTB; at least one reactor animal was required for a herd to be considered bTB positive. Two hundred ninety-nine dairy herds in the six study areas were randomly selected, from which 5,675 cattle were tested. The overall prevalence of bTB after standardisation for herd-size in the population was 54.4% (95% CI 48.7-60%) at the herd level, and it was 24.5% (95% CI 23.3-25.8) at the individual animal level. A Generalized Linear Mixed Model (GLMM) with herd and area as random effect was used to explore risk factors association with bTB status. We found that herd size, age, bTB history at farm, and breed were significant risk factors for animals to be SICCT positive. Animals from large herds had 8.3 times the odds of being tuberculin reactor (OR: 8.3, p-value:0.008) as compared to animals from small herds. The effect of age was strongest for animals 8-10 years of age (the oldest category) having 8.9 times the odds of being tuberculin reactors (OR: 8.9, p-value:<0.001) compared to the youngest category. The other identified significant risk factors were bTB history at farm (OR: 5.2, p-value:0.003) and cattle breed (OR: 2.5, p-value: 0.032). Our study demonstrates a high prevalence of bTB in central Ethiopia but with a large variation in within-herd prevalence between herds, findings that lays an important foundation for the future development of control strategies.


Assuntos
Indústria de Laticínios , Tuberculose Bovina/epidemiologia , Animais , Bovinos , Etiópia/epidemiologia , Análise Fatorial , Geografia , Análise Multivariada , Prevalência , Fatores de Risco , Tuberculina/metabolismo
12.
Res Vet Sci ; 138: 49-52, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34098415

RESUMO

As part of a bovine tuberculosis (bTB) control related Test and Vaccinate or Remove (TVR) badger research study in Northern Ireland, a project was launched evaluating whether badgers cross major roads (in this case the A1 dual carriageway linking Belfast/Newry/Dublin). This road formed the western boundary of the TVR study area and it was chosen to discourage badger movements in and out of the area. This was important in order to ensure that the badger study population was as stable as possible and also to get a better understanding of the risk of any spill over of bTB infection from the study area to the buffer area. Five badgers trapped close to the A1 were fitted with a Global Positioning System (GPS) collar in October 2017, which were set to record the badger location every 20 min between 19.20 and 03.00 h during a maximum of 84 days. Based on 4313 location points recorded, only 2 (0.05%) location points were located on the western side of the A1. Although this was a small sample, it can be concluded that generally badgers avoid crossing dual carriageways which is supported by evidence from other studies. This finding is important for informing on development of future badger intervention areas where major roads could be considered as strong borders. Furthermore, it adds to the body of knowledge in trying to understand drivers and barriers for badger dispersal behaviour.


Assuntos
Distribuição Animal , Mustelidae/fisiologia , Tuberculose Bovina/prevenção & controle , Animais , Bovinos , Feminino , Masculino , Movimento , Irlanda do Norte
13.
Vet Rec ; 188(11): 403, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34086318
15.
PLoS Comput Biol ; 17(6): e1009005, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34170901

RESUMO

Multi-host pathogens are particularly difficult to control, especially when at least one of the hosts acts as a hidden reservoir. Deep sequencing of densely sampled pathogens has the potential to transform this understanding, but requires analytical approaches that jointly consider epidemiological and genetic data to best address this problem. While there has been considerable success in analyses of single species systems, the hidden reservoir problem is relatively under-studied. A well-known exemplar of this problem is bovine Tuberculosis, a disease found in British and Irish cattle caused by Mycobacterium bovis, where the Eurasian badger has long been believed to act as a reservoir but remains of poorly quantified importance except in very specific locations. As a result, the effort that should be directed at controlling disease in badgers is unclear. Here, we analyse densely collected epidemiological and genetic data from a cattle population but do not explicitly consider any data from badgers. We use a simulation modelling approach to show that, in our system, a model that exploits available cattle demographic and herd-to-herd movement data, but only considers the ability of a hidden reservoir to generate pathogen diversity, can be used to choose between different epidemiological scenarios. In our analysis, a model where the reservoir does not generate any diversity but contributes to new infections at a local farm scale are significantly preferred over models which generate diversity and/or spread disease at broader spatial scales. While we cannot directly attribute the role of the reservoir to badgers based on this analysis alone, the result supports the hypothesis that under current cattle control regimes, infected cattle alone cannot sustain M. bovis circulation. Given the observed close phylogenetic relationship for the bacteria taken from cattle and badgers sampled near to each other, the most parsimonious hypothesis is that the reservoir is the infected badger population. More broadly, our approach demonstrates that carefully constructed bespoke models can exploit the combination of genetic and epidemiological data to overcome issues of extreme data bias, and uncover important general characteristics of transmission in multi-host pathogen systems.


Assuntos
Simulação por Computador , Reservatórios de Doenças , Mycobacterium bovis/isolamento & purificação , Filogenia , Tuberculose Bovina/transmissão , Animais , Bovinos , Mustelidae/microbiologia , Mycobacterium bovis/classificação , Mycobacterium bovis/genética , Tuberculose Bovina/microbiologia
16.
Prev Vet Med ; 193: 105417, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34192652

RESUMO

The buffalo herds in Brazil have been an alternative for increasing the economy in different biomes. For this reason, knowledge of the spatial distribution of diseases of mandatory notification in buffalo herds, such as brucellosis and tuberculosis, is essential to guarantee the quality of exported animal products, as well as assist in strategies of national control and eradication programs. In the present study, we aimed to evaluate the spatiotemporal distribution and temporal trends of brucellosis and tuberculosis in buffalo in Brazilian states between 2012-2019. During this period, 474 cases of brucellosis and 604 cases of tuberculosis were observed in buffalo in Brazil, with no significant differences between the total number of cases and incidence risk. The spatial distribution for the states was mostly heterogeneous, showing similarities of occurrences for both diseases in the south, north, and the states of Minas Gerais and Pernambuco. In the eight years evaluated, tuberculosis showed cyclical variation every 1-2 years; however, for brucellosis, there was a cyclical trend only between 2012-2015, with a significant decrease until 2018. Among Brazilian states, Pará had greater disease case numbers, with 34 % for brucellosis and 40.6 % for tuberculosis. Temporal trend analysis showed an increase for Pernambuco (annual percentage change [APC]: 21.0 [CI = 20.3; 21.8]), Paraná (APC: 27.1 [CI = 5.6; 53.0]), and Santa Catarina (APC: 10.4 [CI = 0.8; 21.0]) for brucellosis, and for tuberculosis, only for Santa Catarina state (APC: 24.1 [CI = 15.5; 33.3]). Spatiotemporally, there were four high-risk brucellosis clusters with a primary cluster, cluster A (relative risk [RRs] = 53.42, P < 0.001), involving the state of Amazonas between 2014-2015. For tuberculosis, there were three states of high risk, with a primary cluster, cluster E (RRs = 28.18, P < 0.001), involving the states of Pará, Roraima, Amazonas, Rondônia, and Acre in 2014. In conclusion, brucellosis and tuberculosis in buffalo in Brazil are heterogeneously distributed, with well-defined regions of high historical risk of infection. Among these regions, the states of Amazonas, Pará, Amapá, and Minas Gerais stand out due to the higher risk of infection for both brucellosis and tuberculosis, alerting Brazilian authorities to the need for disease control actions.


Assuntos
Brucelose , Búfalos/microbiologia , Tuberculose Bovina , Animais , Brasil/epidemiologia , Brucelose/epidemiologia , Brucelose/veterinária , Bovinos , Incidência , Análise Espaço-Temporal , Tuberculose Bovina/epidemiologia
17.
PLoS Negl Trop Dis ; 15(6): e0009502, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34138867

RESUMO

BACKGROUND: Bovine tuberculosis (bTB), caused by members of the Mycobacterium tuberculosis complex bacteria, mainly Mycobacterium bovis (M. bovis), is a major threat to public health and economic development. There has been no systematic epidemiological assessment concerning bTB in dairy cattle in China. METHODOLOGY/PRINCIPAL FINDINGS: Literature related to bTB in China was retrieved from China National Knowledge Infrastructure (CNKI), PubMed, ScienceDirect, VIP Chinese Journals Database, and Wan Fang Database to build the first meta-analysis for estimating the prevalence and infection moderators of bTB in dairy cattle in China. A total of 100 relevant studies published from 2010 to 2019 were included. We estimated the overall prevalence of bTB was 2.4% (95% CI: 2.1-2.8) during this decade. In the sampling year subgroup, the prevalence was lowest in 2017 or later at 0.8% (95% CI: 0.3-1.5). The lowest prevalence was 0.7% (95% CI: 0.5-1.0) in Northwestern China. The lowest prevalence was 2.1% (95% CI: 1.8-2.5) using SIT test. Heifer cows had the highest prevalence, which was 27.1% (95% CI: 9.7-49.2). The prevalence in scale farming was 3.7% (95% CI: 3.1-4.3), significantly higher than that in free-range farming (1.7%, 95% CI: 1.1-2.4). The prevalence of bTB was highest in summer at 4.0% (95% CI: 1.7-7.0). In addition, the influence of different geographical factors (altitude, longitude, latitude, precipitation, temperature, humidity) on the prevalence was analyzed. CONCLUSIONS/SIGNIFICANCE: The results showed that bTB was widespread in China but has been gradually reduced through concerted national intervention. It is suggested that different countries should formulate corresponding prevention and control measures according to the epidemic situation in its cattle industry. Enhanced monitoring of warm and humid areas may play an important role in reducing the incidence of bTB. In addition, when large-scale breeding is promoted, attention should be paid to standardizing breeding management and improving animal welfare to reduce the prevalence of bTB in cattle.


Assuntos
Criação de Animais Domésticos/métodos , Tuberculose Bovina/epidemiologia , Animais , Bovinos , China/epidemiologia , Clima , Indústria de Laticínios , Geografia , Mycobacterium bovis/isolamento & purificação , Prevalência , Estações do Ano
18.
PLoS One ; 16(6): e0253339, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34138949

RESUMO

Bovine tuberculosis (bTB) is a global zoonotic disease that has detrimental economic impacts worldwide. The NOS2A gene plays a key role in immunological control of many infectious diseases. However, research on the association between NOS2A polymorphisms and bTB infection in Holstein cattle reared on the Yunnan-Guizhou plateau of China is scarce. This study investigated a possible linkage between NOS2A polymorphisms and risk of developing bTB in Chinese Holstein cattle. The NOS2A gene was genotyped in 144 bTB-infected Holstein cows and 139 healthy controls were genotyped through nucleotide sequencing. Ten single-nucleotide polymorphisms (SNPs) were detected, six of which were associated with susceptibility/resistance patterns of bTB. Furthermore, the C/T genotypes of 671 and 2793, and T/T genotype of E22 (+15) were significantly associated with susceptibility risk; the G/A genotype of 2857, T/T genotype of E9 (+65), and C/C genotype of E9 (+114) probably increased resistance to bTB. In addition, the haplotypes of NOS2A-2 and NOS2A-9 were risk factors for bTB susceptibility, while the NOS2A-5 and NOS2A-8 haplotypes were contributing protective variants against tuberculosis. There is a significant association between variation in SNPs of NOS2A and tuberculosis susceptibility/resistance pattern. These findings suggest that substitution of genetic selection would be helpful for eradicating bTB. However, further investigation is required to study the underlying mechanism through which NOS2A polymorphisms affect bTB infection.


Assuntos
Predisposição Genética para Doença , Óxido Nítrico Sintase Tipo II/genética , Polimorfismo de Nucleotídeo Único , Tuberculose Bovina/genética , Alelos , Animais , Bovinos , Frequência do Gene , Genótipo , Haplótipos
20.
BMC Genomics ; 22(1): 343, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33980141

RESUMO

BACKGROUND: Bovine TB (bTB), caused by infection with Mycobacterium bovis, is a major endemic disease affecting global cattle production. The key innate immune cell that first encounters the pathogen is the alveolar macrophage, previously shown to be substantially reprogrammed during intracellular infection by the pathogen. Here we use differential expression, and correlation- and interaction-based network approaches to analyse the host response to infection with M. bovis at the transcriptome level to identify core infection response pathways and gene modules. These outputs were then integrated with genome-wide association study (GWAS) data sets to enhance detection of genomic variants for susceptibility/resistance to M. bovis infection. RESULTS: The host gene expression data consisted of RNA-seq data from bovine alveolar macrophages (bAM) infected with M. bovis at 24 and 48 h post-infection (hpi) compared to non-infected control bAM. These RNA-seq data were analysed using three distinct computational pipelines to produce six separate gene sets: 1) DE genes filtered using stringent fold-change and P-value thresholds (DEG-24: 378 genes, DEG-48: 390 genes); 2) genes obtained from expression correlation networks (CON-24: 460 genes, CON-48: 416 genes); and 3) genes obtained from differential expression networks (DEN-24: 339 genes, DEN-48: 495 genes). These six gene sets were integrated with three bTB breed GWAS data sets by employing a new genomics data integration tool-gwinteR. Using GWAS summary statistics, this methodology enabled detection of 36, 102 and 921 prioritised SNPs for Charolais, Limousin and Holstein-Friesian, respectively. CONCLUSIONS: The results from the three parallel analyses showed that the three computational approaches could identify genes significantly enriched for SNPs associated with susceptibility/resistance to M. bovis infection. Results indicate distinct and significant overlap in SNP discovery, demonstrating that network-based integration of biologically relevant transcriptomics data can leverage substantial additional information from GWAS data sets. These analyses also demonstrated significant differences among breeds, with the Holstein-Friesian breed GWAS proving most useful for prioritising SNPS through data integration. Because the functional genomics data were generated using bAM from this population, this suggests that the genomic architecture of bTB resilience traits may be more breed-specific than previously assumed.


Assuntos
Mycobacterium bovis , Tuberculose Bovina , Animais , Bovinos , Estudo de Associação Genômica Ampla , Genômica , Macrófagos Alveolares , Tuberculose Bovina/genética
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