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Srinivasa, S.

Publications and source records attributed to Srinivasa, S..

4 recordsLinked to original sources

Functional impact of a type VI secretion system on RsmE-mediated spatial structure formation in Pseudomonas fluorescens Pf0-1

Bacteria naturally form densely structured populations wherein both space and nutrients become locally limited. In densely populated Pseudomonas fluorescens Pf0-1 colonies, spatiogenetic patches with drastically reduced cellular density naturally emerge through spontaneous mutations in rsmE. RsmE is a posttranscriptional regulator that binds to specific mRNAs, including those that consequently repress the production of extracellular secretions. We have previously shown that {Delta}rsmE produces an extracellular polysaccharide (EPS) and biosurfactant that collectively function to define the spatiogenetic structure and locally outcompete the WT. Here, we identify additional RsmE-regulated secretions through a combination of RNA-sequencing and LC-MS/MS. In particular, a type VI secretion system (T6SS) was exclusively produced by {Delta}rsmE. Confocal microscopy imaging of WT and genetically modified {Delta}rsmE cocultures showed that the T6SS kills WT cells that invade the low- density spatiogenetic structure. However, its impact on competition with the WT was both quantifiably and spatially limited in the absence of the normally co-produced EPS and biosurfactant, largely due to the consequently altered spatial structure. These results highlight the importance of understanding both the individual and collective spatial functions of extracellular secretions, especially in the ecological context of densely structured microbial populations. IMPORTANCEIn crowded wild type (WT) Pseudomonas fluorescens Pf0-1 colonies, rsmE mutants spontaneously emerge by forming a low cellular density spatial structure that is devoid of WT cells. RsmE functions primarily to repress the production of various extracellular secretions, including an extracellular polysaccharide and biosurfactant, that collectively form the unique spatial structure. Here, we describe an RsmE-regulated type VI secretion system that kills the invading WT cells and protect the low-density structure. Importantly, individual RsmE-regulated secretions carry out unique functions, but their efficacies largely depend on other co-regulated products. Extracellular secretions that are mechanistically similar to those described here are co- produced across diverse biofilm-forming and virulent bacterial species, where they also likely play complex molecular and ecological roles.

microbiology↗

Elucidation of Radical Degradation in Native Biofilms by EPR Sheds Light on Bacterial Resistance and Efficient DNP Solid-state NMR

Bacterial biofilms exhibit enhanced antimicrobial resistance, yet the mechanisms determining molecular transport and reactivity within these complex communities remain poorly understood. Here, we combine electron paramagnetic resonance (EPR), solid-state NMR (ssNMR), and dynamic nuclear polarization (DNP) ssNMR to determine how native Pseudomonas fluorescens Pf0-1 colony biofilms regulate nitroxide radicals. EPR measurements reveal that radical reduction depends on biofilm morphology, hydration, and composition of extracellular matrix (ECM). Wild-type biofilms exhibit slower nitroxide reduction than planktonic cells, while isolated ECM and dehydrated biofilms show no radical reduction, indicating that bacterial cells primarily drive radical reduction. Complementary ssNMR measurements identify polysaccharides and lipids within the ECM as primary interaction sites for nitroxide radicals. DNP-enhanced ssNMR further reveals compositional differences across biofilm morphologies, with increasingly polysaccharide-rich ECM environments correlating with slower reduction kinetics. These findings support a mechanism in which the ECM acts as a diffusion barrier and selective interaction region for nitroxide radicals to regulate cellular penetration. This work showcases an integrated magnetic resonance approach that provides molecular insight into how biofilm structure determines the fate of toxic redox-active small molecules. We also set the stage for high-sensitivity measurements of structure-function relationships in these medically relevant assemblies.

biophysics↗

High-Sensitivity Analysis of Native Bacterial Biofilms Using Dynamic Nuclear Polarization-Enhanced Solid-State NMR

Bacterial biofilms cause persistent infections that are difficult to treat and contribute greatly to antimicrobial resistance. However, high-resolution structural information on native bacterial biofilms remain very limited. This limitation is primarily due to methodological constraints associated with analyzing complex native samples. Although solid-state NMR (ssNMR) is a promising method in this regard, its conventional applications typically suffer from sensitivity limitations, particularly for unlabeled native samples. Through the use of Dynamic Nuclear Polarization (DNP), we applied sensitivity enhanced ssNMR to characterize native Pseudomonas fluorescens colony biofilms. The increased ssNMR sensitivity by DNP enabled ultrafast structural characterization of the biofilm samples without isotope-labelling, and chemical or physical modification. We collected 1D 13C and 15N, and 2D 1H-13C, 1H-15N and 13C-13C ssNMR spectra within seconds/minutes or hours, respectively which enabled us to identify biofilm components as polysaccharides, proteins, and eDNA effectively. This study represents the first application of ultrasensitive DNP ssNMR to characterize a native bacterial biofilm and expands the technical scope of ssNMR towards obtaining insights into the composition and structure of a wide array of in vitro and ex vivo biofilm applications. Such versatility should greatly boost efforts to develop structure-guided approaches for combating infections caused by biofilm-forming microbes.

microbiology↗

Tapping into the native Pseudomonas Bacterial Biofilm Structure by High-Resolution 1D and 2D MAS solid-state NMR

We present a high-resolution 1D and 2D magic-angle spinning (MAS) solid-state NMR (ssNMR) study to characterize native Pseudomonas fluorescens colony biofilms at natural abundance without isotope-labelling. By using a high-resolution INEPT-based 2D 1H-13C ssNMR spectrum and thorough peak deconvolution approach at the 1D ssNMR spectra, approximately 80/134 (in 1D/2D) distinct biofilm chemical sites were identified. We compared CP and INEPT 13C ssNMR spectra to different signals originating from the mobile and rigid fractions of the biofilm, and qualitative determined dynamical changes by comparing CP buildup behaviors. Protein and polysaccharide signals were differentiated and identified by utilizing FapC signals as a template, a biofilm forming functional amyloid from Pseudomonas. We also attempted to identify biofilm polysaccharide species by using 1H/13C chemical shifts obtained from the 2D spectrum. This study marks the first demonstration of high-resolution 2D ssNMR spectroscopy for characterizing native bacterial biofilms and expands the scope of ssNMR in studying biofilms. Our experimental pipeline can be readily applied to other in vitro biofilm model systems and natural biofilms and holds the promise of making a substantial impact on biofilm research, fostering new ideas and breakthroughs to aid in the development of strategic approaches to combat infections caused by biofilm-forming bacteria.

microbiology↗