Ask about this productRelated genes to: ESX1 Blocking Peptide
- Gene:
- ESX1 NIH gene
- Name:
- ESX homeobox 1
- Previous symbol:
- ESX1L
- Synonyms:
- ESXR1
- Chromosome:
- Xq22.2
- Locus Type:
- gene with protein product
- Date approved:
- 2001-03-14
- Date modifiied:
- 2014-11-19
Related products to: ESX1 Blocking Peptide
Related articles to: ESX1 Blocking Peptide
- , the causative agent of bovine tuberculosis, infects and persists within macrophages, triggering pro-inflammatory responses. While these mechanisms are well characterized for , less is known about host responses to . Inflammasome activation and IL-1β production have been linked to ESAT-6, a substrate of the ESX-1 secretion system present in both species. Here, we examined inflammasome activation in bovine macrophages infected with the virulent strain Mb04-303. AF2122/97 and NCTC10772 upregulated IL-1β transcription, whereas Mb04-303 and BCG did not. Unexpectedly, deletion of the genes encoding ESAT-6 and CFP-10 from Mb04-303 enhanced inflammasome activation, as evidenced by increased NLRP3 and IL-1β transcription. Complementation with either wild-type ESAT-6/CFP-10 or the T63A ESAT-6 variant restored downregulation of the response, indicating that this substitution does not alter inflammasome modulation. In contrast, deletion of ESAT-6/CFP-10 from an attenuated vaccine candidate reduced IL-1β transcription. No differences were observed between H37Rv and its ESAT-6-deficient mutant in bovine macrophages. Together, these findings demonstrate that ESAT-6/CFP-10-mediated modulation of inflammasome activation in bovine macrophages is highly dependent on the mycobacterial genetic background. - Source: PubMed
Publication date: 2026/05/03
Blanco Federico CarlosVazquez Cristina LourdesBigi María MercedesRocha Rosana ValeriaGarcía Elizabeth AndreaBigi Fabiana - Mycobacterium avium, a slow-growing nontuberculous mycobacterium (NTM), is the main cause of life-threatening NTM infections, which are globally on the rise. Unlike Mycobacterium tuberculosis and Mycobacterium marinum, M. avium lacks ESX-1, a subtype of Type VII secretion system (T7SS) and a key virulence determinant. The absence of ESX-1 in M. avium raises questions about its alternative intracellular survival strategies. To investigate M. avium pathogenesis, we exploited our recently established infection model in zebrafish larvae, enabling live imaging of early host-pathogen interactions. Macrophage depletion significantly increased M. avium burden and larval mortality, while neutrophil depletion had no major effect, emphasizing macrophages as key defenders against M. avium. In support, imaging of tnfa activation showed that macrophages polarized to a proinflammatory phenotype. However, like M. marinum, M. avium exploits chemokine receptor Cxcr3.2 signaling in macrophages for its expansion in granuloma-like clusters. Both M. avium and M. marinum preferentially infected macrophages, but M. avium-induced granuloma-like clusters were more compact and exhibited less cell death. Supporting this, lytic cell death pathways were enriched in M. marinum but not M. avium transcriptome signatures. Consequently, we investigated pyroptosis, an important form of inflammation-induced lytic cell death. We found that knockdown of critical mediators of pyroptosis, namely inflammatory caspase a (caspa) and gasdermin Eb (gsdmeb), produced opposing effects on the two mycobacterial pathogens, indicating a host-protective role during M. avium infection, while exacerbating M. marinum growth. These findings highlight the interaction with host cell death signaling as a determining factor for the pathogenic potential of mycobacterial species. - Source: PubMed
Publication date: 2026/04/30
Hu WanbinPagliaro FedericoSpaink Herman PMeijer Annemarie H - During infection, pathogenic mycobacteria reside within phagosomes of varying acidity based on the macrophage activation state. The ESX-1 secretion system (early secreted antigen 6 kilodaltons [ESAT-6] system 1) delivers protein virulence factors essential for phagosome lysis, facilitating infection. The mechanisms underlying ESX-1 lytic activity in heterogeneous environments remain unknown. Here, we show that the canonical Type VII secretion system, ESX-1, orchestrates substrate switching in response to different environments. Growing at acidic pH resulted in substrate switching . Substrate switching was accompanied by significant changes to the levels of ESX-1 substrate transcripts and to the levels of both ESX-1 substrates and chaperones at the protein level. We showed that specific ESX-1 transcripts were significantly upregulated and that distinct substrate sets are required in an acidic infection model. - Source: PubMed
Publication date: 2026/04/29
Collars Owen AHernandez Richard LWeaver Simon DPrest Rebecca JManu CalebViswanathan GopinathCronin Rachel MJones Bradley STobin David MChampion Matthew MChampion Patricia A - Tuberculosis (TB) is the leading cause of death from an infectious disease worldwide. Mutations arising in Mycobacterium tuberculosis complex (MTBC) strains during TB infection provide a record of bacterial adaptations, such as those needed to survive the attack of the immune system and antibiotic therapies. - Source: PubMed
Publication date: 2026/04/28
Zhang HelenMedina-Jaudes NaomiForcada-Nadal AliciaHarrison Ewan MColl Francesc - causes tuberculosis, an infectious disease; this acid-fast bacillus has various functions that enable it to survive within the host. Importantly, the type VII secretion system plays a vital role in host immune evasion. However, the early secretory antigenic target secretion system (ESX) component is crucial for mycobacteria survival, plays a significant role in bypassing the host immune response, and is linked to the prognosis of the disease. The review aims to analyze the ESX-associated genes' functions in defence mechanisms against host immune response. There are five types of ESX, with the ESX-1 effectors consisting of the heterodimers ESAT-6 and /CFP-10. The precise membranolytic role of remains unclear; however, mycobacterial mutants deficient in show reduced membrane lytic activity and lack the ability to perforate phagosomes. ESX-5 substrates, such as glycine-rich and repetitive proteins, are associated with immune evasion and pathogenicity. ESX-5 releases a substantial amount of PE and PPE proteins, along with various other immune-modulating substrates. In addition, ESX-3 facilitates iron acquisition through mycobactin and regulates metal homeostasis. ESX 4 has been studied in two fast-growing mycobacterial species: and . Notably, conjugal DNA transfer in the recipient strain of requires ESX-4. Therefore, the type VII secretion system of ESX-associated genes plays a crucial role in bacterial survival and action against autophagosome-lysosome fusion. Thus, studying this system will explore the effects of specific antigenic structures and their relationships with autophagy and mycobacterial self-defense mechanisms. - Source: PubMed
Publication date: 2026/04/07
Sundaram KarthikeyanRathinam SridharBethunaickan RamalingamRanganathan Uma DeviPrabhu VenkataramanDhanapal Madhavan