Bhaumik, R. | bioRxiv Science

bioRxiv2026

Uncovering the Role of the scs Pilus Within the Complex Surface Architecture of Stenotrophomonas maltophilia

Stenotrophomonas maltophilia is an emerging multidrug-resistant pathogen that encodes numerous surface structures mediating attachment, biofilm formation, motility, and virulence. How individual adhesive systems function within this complex and potentially redundant network remains unclear. Here, we investigated the scs locus, a conserved chaperone-usher pilus system, to define its contribution to surface-associated behaviors and infection. Deletion of scs alone produced minimal effects on biofilm formation under standard laboratory conditions. However, significant and reproducible phenotypic differences emerged when scs loss was combined with mutations in other pilus systems or when bacteria were evaluated in infection-relevant environments. Across assays of biofilm formation, surface piliation, motility, flagellar gene expression, and virulence, scs contributed differentially to enhancing the adhesion and motility defects associated with the smf-1 pili, cbl pili, and fliC flagellar gene loci. Transmission electron microscopy corroborated these findings, revealing differential expression and distinct alterations in predominantly the pilus architecture among mutant strains. These pilus associated phenotypes also largely corroborated infection in a Galleria melonella model. Given the abundance of adhesion associated gene loci in the pan-S. maltophilia genome, our results demonstrate that the scs locus functions as a context-dependent determinant of attachment and virulence, revealing a potential crosstalk between components of the surface landscape of the bacteria. ImportanceStenotrophomonas maltophilia is an emerging multidrug-resistant pathogen that relies on diverse surface structures, including chaperone-usher pili, to drive attachment, biofilm formation, and infection. Its rising clinical prevalence underscores the need to define how multiple chaperone-usher pili contribute to virulence and interact with other appendages such as flagella, which together shape pathogenic behaviors. Our work on the scs chaperone-usher pilus system advances this understanding by revealing its context-dependent role in virulence. We demonstrate how scs modulates defects in smf-1 and cbl pilin loci, and affects the fliC flagellar locus to reshape the cell surface pilus landscape, thereby illuminating how coordinated surface-structure interactions drive pathogenicity.

microbiology↗

bioRxiv2020

Membrane-associated α-tubulin is less acetylated in postmortem prefrontal cortex from depressed subjects relative to controls: cytoskeletal dynamics, HDAC6 and depression

Cytoskeletal proteins and post-translational modifications play a role in mood disorders. Post-translational modifications of tubulin also alter microtubule dynamics. Furthermore, tubulin interacts closely with Gs, the G-protein responsible for activation of adenylyl cyclase. Postmortem tissue derived from depressed suicide brain showed increased Gs in lipid-raft domains compared to normal subjects. Gs, when ensconced in lipid-rafts, couples less effectively with adenylyl cyclase to produce cAMP and this is reversed by antidepressant treatment. A recent in-vitro study demonstrated that tubulin anchors Gs to lipid-rafts and that increased tubulin acetylation (due to HDAC-6 inhibition) and antidepressant treatment decreased the proportion of Gs complexed with tubulin. This suggested that deacetylated-tubulin might be more prevalent in depression. This study, examined tubulin acetylation in whole tissue homogenate, plasma-membrane and lipid-raft membrane domains in tissue from normal control (NC) subjects, depressed suicides and depressed non-suicides. While tissue homogenate showed no changes in [<]-tubulin/tubulin acetylation between control, depressed suicides and depressed non-suicides, plasma-membrane associated tubulin showed significant decreases in acetylation in depressed suicides and depressed non-suicides compared to controls. No change was seen in expression of the enzymes responsible for tubulin acetylation or deacetylation. These data suggest that during depression, membrane localized tubulin maintains a lower acetylation state, permitting increased sequestration of Gs in lipid-raft domains, where it is less likely to couple to adenylyl cyclase for cAMP production. Thus, membrane tubulin may play a role in mood disorders which could be exploited for diagnosis and treatment. Significance StatementThere is little understanding about the molecular mechanisms involved in the development of depression and in severe cases, suicide. Evidence for the role of microtubule modifications in progression of depressive disorders is emerging. These postmortem data provide strong evidence for membrane tubulin modification leading to reduced efficacy of the G protein, Gs, in depression. This study reveals a direct link between decreased tubulin acetylation in human depression and the increased localization of Gs in lipid-raft domains responsible for attenuated cAMP signaling. The evidence presented here suggest a novel diagnostic and therapeutic locus for depression.

neuroscience↗