Mycobacterium tuberculosis , as a facultative intracellular pathogen, can interact with host macrophages and modulate macrophage function to influence innate and adaptive immunity. Proteins secreted by the ESX-1 secretion system are involved in this relationship. Although the importance of ESX-1 in host-pathogen interactions and virulence is well-known, the primary role is ascribed to EsxA (EAST-6) in mycobacterial pathogenesis and the functions of individual components in the interactions between pathogens and macrophages are still unclear. Here, we investigated the effects of EspC on macrophage activation. The EspC protein is encoded by an espA/C/D cluster, which is not linked to the esx-1 locus, but is essential for the secretion of the major virulence factors of ESX-1, EsxA and EsxB. Our results showed that both EspC protein and EspC overexpression in M. smegmatis induced pro-inflammatory cytokines and enhanced surface marker expression. This mechanism was dependent on Toll-like receptor 4 (TLR4), as demonstrated using EspC-treated macrophages from TLR4 −/− mice, leading to decreased pro-inflammatory cytokine secretion and surface marker expression compared with those from wild-type mice. Immunoprecipitation and immunofluorescence assays showed that EspC interacted with TLR4 directly. Moreover, EspC could activate macrophages and promote antigen presentation by inducing mitogen-activated protein kinase (MAPK) phosphorylation and nuclear factor-κB activation. The EspC-induced cytokine expression, surface marker upregulation, and MAPK signaling activation were inhibited when macrophages were blocked with anti-TLR4 antibodies or pretreated with MAPK inhibitors. Furthermore, our results showed that EspC overexpression enhanced the survival of M. smegmatis within macrophages and under stress conditions. Taken together, our results indicated that EspC may be another ESX-1 virulence factor that not only modulates the host innate immune response by activating macrophages through TLR4-dependent MAPK signaling but also plays an important role in the survival of pathogenic mycobacteria in host cells.

Tuberculosis caused by the Mycobacterium tuberculosis complex (MTBC) has become one of the leading causes of death in humans and animals. Current research suggests that the transmission of MTBC in the environment indirectly transmit to humans and animals with subsequent impact on their wellbeing. Therefore, it is of great significance to take One Health approach for understanding the role of MTBC in not only the interfaces of humans and animals, but also environment, including soil, water, pasture, air, and dust, etc., in response to the MTBC infection. In this review, we present the evidence of MTBC transmission from environment, as well as detection and control strategies in this interface, seeking to provide academic leads for the global goal of End Tuberculosis Strategy under multidisciplinary and multisectoral collaborations.

Background Glycerol kinase ( glpK ) is essential for the first step of glycerol catabolism in Mycobacterium tuberculosis . However, Mycobacterium bovis has been known to grow poorly in glycerol media because of a base insertion in the glpK gene. Methods We analyzed the glpK gene sequences of 60 clinical M. bovis isolates, and determined the minimum inhibitory concentration of 14 drugs by microdilution method to evaluate the effect of frameshift mutations on drug sensitivity. The effect of M. bovis growth rate on its drug sensitivity was investigated using bacteria grown on glycerol or pyruvate. Results A total of 44 (73.33%) clinical M. bovis isolates have frameshift mutations in a homopolymeric tract of 7 cytosines in the glpK gene. 15.00% M. bovis isolates showed phenotypic drug resistance. Glycerol metabolism-deficient M. bovis showed reduced susceptibility to 9 out of 14 tested drugs. Mutations in the glpK gene can lead to impaired growth in glycerol-based media, while the minimal inhibitory concentration values of slow-growing M. bovis were higher. Conclusion Mutations in the glpK gene can lead to slowed growth and reduced susceptibility to drugs in M. bovis , which may contribute to the emergence of drug-resistant M. bovis and pose a threat to human health owing to the zoonotic capacity of M. bovis .

Mycobacterium bovis is the cause of bovine tuberculosis, and it can also cause disease in humans, with symptoms similar to those caused by M. tuberculosis. However, our understanding of its genomic diversity, biogeography, and drug resistance remains incomplete. We performed a comparative and phylogenetic analysis of 3228 M. bovis genomes from 24 countries. Following drug susceptibility testing, we applied a bacterial genome-wide association study to capture associations between genomic variation and drug resistance in 74 newly isolated strains from China. The data show that the cattle-adapted M. bovis were divided into six lineages with a strong phylogeographical population structure. Lineages 1 and 6 are the most widespread globally, while others show a strong geographical restriction. Note that 17.39% of M. bovis isolates were resistant to at least one drug in China. Furthermore, we identify genomic variations associated with an increased risk of resistance acquisition. This study furthers our knowledge of M. bovis diversity, biogeography, and drug resistance and will facilitate more deeply informed genomic tracking and surveillance to minimize its threat to human health, as a cause of zoonotic tuberculosis.

In the title compound, C 16 H 16 N 4 O 3 ÁCH 3 OH, the aromatic rings form a dihedral angle of 0.4 (2). The nitro group is twisted from the attached benzene ring by 7.5 (2). In the crystal, N-HÁ Á ÁO and O-HÁ Á ÁO hydrogen bonds link alternating hydrazone and methanol molecules into chains in [100]. The crystal packing exhibitsinteractions between aromatic rings from neighbouring chains [centroid-centroid distances = 3.734 (3) and 3.903 (3) Å ].