Jaffal, H. | bioRxiv Science

bioRxiv2023

Phage-mediated dispersal of multicellular bacteria

Streptomyces are renowned for their prolific production of specialized metabolites with applications in medicine and agriculture. These multicellular bacteria present a sophisticated developmental cycle, and play a key role in soil ecology. Little is known about Streptomyces-phage interactions and the impact of phages on Streptomyces physiology. In this study, we investigated the conditions governing the expression and production of Samy, a prophage found in Streptomyces ambofaciens ATCC 23877. This siphoprophage is produced simultaneously with the activation of other mobile genetic elements. We show that Samy production increases bacterial dispersal under in vitro stress conditions. Altogether, we unveiled a new property of a bacteriophage infection that it is closely linked to the multicellular community life of Streptomyces bacteria. Graphical summary O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=163 SRC="FIGDIR/small/549817v2_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@126b3fcorg.highwire.dtl.DTLVardef@1f26808org.highwire.dtl.DTLVardef@18bfdcforg.highwire.dtl.DTLVardef@1c44be3_HPS_FORMAT_FIGEXP M_FIG C_FIG IMPORTANCEStreptomyces are multicellular bacteria producing valuable metabolites, including antibiotics, with applications in medicine and agriculture. In this study, we characterized a novel temperate phage, named Samy, and its impact on bacteria physiology. Remarkably, the presence and production of Samy increases bacterial dispersal under in vitro stress conditions. This constitutes an emerging property associated with bacteriophage infection that might enhance the spread of the species. Our study reveals a new aspect of bacteriophage infection in the context of multicellular aggregate dynamics.

microbiology↗

bioRxiv2022

Platelet phosphatidylserine is the critical mediator of thrombosis in heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a severe immune-mediated prothrombotic disorder caused by antibodies reactive to complexes of platelet factor 4 and heparin. Platelets (PLTs) and their interaction with different immune cells contribute to prothrombotic conditions in HIT. However, the exact mechanisms and the role of different PLT subpopulations to this prothrombotic enviroment remain poorly understood. In this study, we observed that HIT patient antibodies (Abs) induce relevant changes in PLT phenotype, with the key features being increased P-Selectin expression and procoagulant phosphatidylserine (PS) externalization. Formation of procoagulant PLTs was dependent on engagement of PLT Fc-gamma-RIIA by HIT Abs and resulted in significant increase of thrombin generation on the PLT surface. Using an ex vivo thrombosis model and multi-parameter assessment of thrombus formation, we observed that HIT Ab-induced procoagulant PLTs propagated formation of large PLT aggregates, leukocyte recruitment and most importantly, fibrin network generation. These prothrombotic conditions were prevented via the upregulation of PLTs intracellular cAMP with Iloprost, a clinically approved prostacyclin analogue. Additionally, the functional relevance of high P-Selectin and PS levels on procoagulant PLTs was dissected. While inhibition of P-Selectin did not affect thrombus formation, the specific blockade of PS with Lactadherin prevented HIT Ab-mediated thrombin generation and most importantly procoagulant PLT-mediated thrombus formation ex vivo. Taken together, our findings indicate that procoagulant PLTs are critical mediators of prothrombotic conditions in HIT. Upregulation of cAMP with Iloprost or PS targeting specifc therapeutics could be a promising approach to prevent thromboembolic events in HIT patients. Key points- HIT immune complexes drive procoagulant platelet formation - Phosphatidylserine blockade prevents HIT antibody-induced thrombus formation

immunology↗