Mycobacterium tuberculosis PPE10 (Rv0442c) alters host cell apoptosis and cytokine profile via linear ubiquitin chain assembly complex HOIP-NF-κB signaling axis.

Tuberculosis caused by Mycobacterium tuberculosis infection remains one of the top ten causes of deaths worldwide. M. tuberculosis genome devoted 10% capacity for highly repeated PE/PPE genes family. To explore the role of PPE10 in host-pathogen interaction, PPE10 encoding gene Rv0442c was heterologously expressed in the nonpathogenic M. smegmatis strain. PPE10 altered the bacterial cell surface properties, colony morphology, and biofilm formation. Ms_PPE10 showed more resistance to stress conditions such as diamide, and low pH, as well as higher survival within the macrophage. Moreover, the host's cell apoptosis was regulated via decreased expression of caspases, IL-1, IL-6, and TNF-α through the Linear Ubiquitin Chain Assembly Complex (LUBAC) HOIP-NF-κB signaling axis. The study revealed novel insights into the mechanism of action of the PPE family.

Mycobacterium Von Willebrand factor protein MSMEG_3641 is involved in biofilm formation and intracellular survival.

Aim:Mycobacterium tuberculosis in vitro biofilm is associated with the virulence and persistence capability. Our aim is to delineate factors involved in biofilms development. Materials & methods: We performed transposon mutants screen and found that mutation of MSMEG_3641, a homolog of M. tuberculosis Rv1836c, can change M. smegmatis colony morphology and biofilm. Results: MSMEG_3641 contains a vWA domain that is highly conserved among Mycobacteria. The phenotypes of MSMEG_3641 mutants include disrupted biofilm, weakened migration ability and changed colony morphology. All phenotypes might be contributed to the enhanced cell wall permeability and declined cell aggregation ability. Conclusion: To our knowledge, this is the first report concerning the mycobacteria Von Willebrand factor domain function, especially in colony morphology and biofilm development.

Comparison of Microbiomes and Resistomes in Two Karst Groundwater Sites in Chongqing, China.

Karst groundwater is an important water resource, as it accounts for about 15% of the total landscape of the earth and supplies 20% of potable water worldwide. The antibiotics resistance is an emerging global concern, and antibiotics residual and increase of antibiotic resistance genes represent serious global concerns and emerging pollutants. There is no report on the antibiotic resistance genes in groundwater. To survey resistome and microbiome in karst groundwater, two karst water samples were chosen for metagenome and metatranscriptome study, namely the 37th spring (C) and Dongcao spring (R) in Beibei, Chongqing, China. The two sites differ significantly in sulfur content, geochemical parameters, community structure, antibiotic resistance genes, and mechanisms, and these results may be influenced by anthropogenic activities. Combining with the Antibiotic Resistance Genes Database, three types of resistance genes baca, sul2, sul1 are present in R and C, and ant3ia, ermc, tetpa are also present in R. The number of all resistance genes in R was more than C, and Proteobacteria, Bacteroidetes, Nitrospirae are the main sources of antibiotic resistance genes. In addition, a large number of genes related to antibiotic gene transmission and drug resistance were found in both samples. Karst groundwater is an important source of drinking water and a possible venue for the transmission of microbial antibiotic resistance genes. However, few studies addressed this issue in karst groundwater, despite its widespread and great importance to global ecosystem. Karst groundwater is a reservoir for antibiotic resistant genes, and measures to control these resistant genes are urgently needed.

Regulation of host cell pyroptosis and cytokines production by Mycobacterium tuberculosis effector PPE60 requires LUBAC mediated NF-κB signaling.

Tuberculosis, caused by Mycobacterium tuberculosis infection, remains a global public health threat. The success of M. tuberculosis largely contributes to its manipulation of host cell fate. The role of M. tuberculosis PE/PPE family effectors in the host destiny was intensively explored. In this study, the role of PPE60 (Rv3478) was characterized by using Rv3478 recombinant M. smegmatis. PPE60 can promote host cell pyroptosis via caspases/NLRP3/gasdermin. The production of pro-inflammatory cytokines, such as IL-1ß, IL-6, IL-12p40 and TNF-α was altered by PPE60. We found that LUBAC was involved in PPE60-elicited NF-κB signaling by using Linear Ubiquitin Chain Assembly Complex (LUBAC)-specific inhibitor gliotoxin. The PPE60 recombinant M. smegmatis survival rate within macrophages is increased, as well as elevated resistance to stresses such as low pH, surface stresses and antibiotics exposure. For a first time it is firstly reported that M. tuberculosis effector PPE60 can modulate the host cell fate via LUBAC-mediated NF-κB signaling.