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Aschtgen, M.-S.

Publications and source records attributed to Aschtgen, M.-S..

2 recordsLinked to original sources
bioRxiv2026

Klebsiella pneumoniae T6SS exacerbates gut inflammation promoting tumorigenesis.

Dysbiosis and bacterial pathobionts contribute to inflammation in IBD and CRC, yet the molecular drivers of this process remain unclear. We identify the Klebsiella pneumoniae type VI secretion system (T6SS) as a key promoter of intestinal inflammation and tumor progression. Metagenomic analyses revealed enrichment of T6SS encoding genes in the gut microbiota of IBD patients during inflammatory flares. In zebrafish and mouse models, K. pneumoniae T6SS activity exacerbated inflammation and promoted colorectal tumor growth. Mechanistically, T6SS firing enhanced the secretion of LPS via outer membrane vesicles (OMVs), driving NF-{kappa}B activation and interferon signalling in host cells. In vivo, T6SS-dependent inflammation was associated with the expansion of regulatory T-cell subsets and an immunosuppressive tumor microenvironment. These findings redefine the T6SS as a microbial determinant of host inflammation and cancer progression, highlighting T6SS inhibition as a potential therapeutic approach for IBD and CRC. HighlightsO_LIT6SS-encoding Enterobacteria are enriched in the gut microbiota of IBD patients C_LIO_LIKlebsiella pneumoniae T6SS exacerbates colitis in mice C_LIO_LIT6SS activity enhances outer membrane vesicle secretion and LPS release C_LIO_LIT6SS promotes colorectal tumorigenesis and immune dysregulation C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=186 HEIGHT=200 SRC="FIGDIR/small/715367v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@1c99341org.highwire.dtl.DTLVardef@e2d0eborg.highwire.dtl.DTLVardef@1021387org.highwire.dtl.DTLVardef@1502c97_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗
bioRxiv2026

Chemical tools to Detect and Inhibit IgA1 Proteases in Haemophilus influenzae

Non-encapsulated ("non-typeable") Haemophilus influenzae is a major cause of mucosal infections such as otitis media, conjunctivitis, and exacerbations of chronic obstructive pulmonary disease. Rising antibiotic resistance has increased interest in anti-virulence strategies that reduce pathogenicity without exerting selective pressure for resistance. A key virulence factor of H. influenzae is immunoglobulin A1 protease (IgA1P), a secreted serine protease that promotes colonization by cleaving human IgA1 at the hinge region and enabling immune evasion. Despite its therapeutic promise, progress has been limited by the lack of chemical tools to probe IgA1P activity in its native biological environment. Here, we report the first activity-based probes that enable direct detection of active IgA1Ps in complex samples and H. influenzae clinical isolates. Competitive activity-based screening using these probes identified novel IgA1P inhibitors, and structure-activity relationship guided optimization yielded a potent lead IgA1P inhibitor. This inhibitor preserves IgA1 at the bacterial surface, demonstrating effective inhibition of IgA1P activity in its native context and chemical disruption of an IgA1P-dependent immune-evasion mechanism. Together, these chemical tools establish a versatile platform for elucidating IgA1Ps role in H. influenzae colonization and virulence, and for validating IgA1Ps as diagnostic markers and antivirulence targets.

microbiology↗