Biology subjects

Bertolli, S. K.

Publications and source records attributed to Bertolli, S. K..

4 recordsLinked to original sources

bioRxiv2025

The type VI secretion system governs strain maintenance in a wild mammalian gut microbiome

Bacteria inhabiting the mammalian gut coexist in dense communities where contact-dependent antagonism mechanisms are widespread. The type VI secretion system (T6SS) is an interbacterial toxin delivery pathway prevalent among gut Bacteroidales, yet its function in naturally evolved microbiomes remains poorly defined. Here, we examine the role of the T6SS in Bacteroides within a physiologically relevant gut community derived from wild mice (the WildR microbiome). Using newly developed genetic tools and a strategy for functional replacement of strains within the WildR community, we demonstrate that the WildR isolate B. acidifaciens employs a T6SS to antagonize co-resident Bacteroidales. We also show that loss of T6SS function compromises the long-term maintenance of B. acidifaciens in the community but not its initial colonization, establishing the system as a determinant of strain persistence. The T6SS we identified resides on an integrative and conjugative element (ICE). ICE-seq, a targeted sequencing approach, reveals that the T6SS-ICE is distributed among select Bacteroidales and Muribaculaceae species in the WildR microbiome, between which it appears to be recently exchanged. We also show that transfer of the T6SS-ICE to WildR isolate Phocaeicola vulgatus confers transient colonization benefits in mice, but is linked to eventual population decline. Our findings demonstrate that the T6SS can stabilize the presence of specific strains within a complex, co-evolved gut microbiome, yet its value is context dependent and constrained by the ecological and physiological landscape of the host community.

microbiology↗

bioRxiv2025

Recognition of unique cell surface glycopolymers by diversified lectin domains specifies umbrella toxin targeting

The bacterial cell envelope provides structural integrity and is an essential conduit through which the organism interacts with its environment. However, the molecular structures of its constituents can also be exploited as receptors, permitting threats such as toxins and phage access to the cell. We previously demonstrated that Streptomyces coelicolor secretes an umbrella toxin particle that acts in a highly selective manner to inhibit the hyphal growth of competing Streptomyces strains. Here, we identify the receptor of umbrella toxins as teichuronic acid (TUA) oligosaccharides anchored to the cell surface through linkage to wall teichoic acids (WTA). We show that the carbohydrate portion of this previously undescribed hybrid TUA-WTA molecule is variable across species and that targeting specificity derives from its selective recognition by diversified lectin domains associated with umbrella particles. A cryo-EM structure of a lectin-TUA complex reveals the molecular basis for umbrella toxin cell targeting and, in conjunction with bioinformatic analyses, provides insights into a molecular arms race that we posit drives diversification of umbrella particles and the chemical composition of Streptomyces cell envelopes.

microbiology↗

bioRxiv2025

Pseudomonads coordinate innate defense against viruses and bacteria with a single regulatory system

Bacterial cells live under the constant existential threats imposed by other bacteria and viruses. Their mechanisms for contending with these threats are well documented; however, the regulation of these diverse defense elements remains poorly understood. Here we show that bacteria can mount a genome-wide, coordinated, and highly effective immune response against bacterial and viral threats using a single regulatory pathway. Bioinformatic analyses revealed that Pseudomonas species broadly possess a specialized form of the Gac/Rsm regulatory pathway (GRP), which our prior work in Pseudomonas aeruginosa implicated in activating interbacterial antagonism defense mechanisms in response to neighbor cell death. Proteomic studies comparing GRP-activated and -inactivated strains derived from diverse Pseudomonas species showed that the pathway regulates a large and variable suite of factors implicated in defense against both bacterial and phage threats. Focusing on P. protegens, we identify profound phenotypic consequences of these factors against multiple forms of bacterial antagonism and several phage. Together, our results reveal that bacteria, like more complex organisms, couple danger sensing to the activation of an immune system with antibacterial and antiviral arms.

microbiology↗

bioRxiv2021

Coordinately regulated interbacterial antagonism defense pathways constitute a bacterial innate immune system

Bacterial survival is fraught with antagonism, including that deriving from viruses and competing bacterial cells1-3 4. It is now appreciated that bacteria mount complex antiviral responses; however, whether a coordinated defense against bacterial threats is undertaken is not well understood. Previously we showed that Pseudomonas aeruginosa possess a danger sensing pathway that is a critical fitness determinant during competition against other bacteria5, 6. Here, we conducted genome-wide screens in P. aeruginosa that reveal three conserved and widespread interbacterial antagonism resistance clusters (arc1-3). We find that although arc1-3 are coordinately activated by the Gac/Rsm danger sensing system, they function independently and provide idiosyncratic defense capabilities, distinguishing them from general stress response pathways. Our findings demonstrate that Arc3 family proteins provide specific protection against phospholipase toxins by preventing the accumulation of lysophospholipids in a manner distinct from previously characterized membrane repair systems. These findings liken the response of P. aeruginosa to bacterial threats to that of eukaryotic innate immunity, wherein threat detection leads to the activation of specialized defense systems.

microbiology↗