Biology subjects

Darisipudi, M. N.

Publications and source records attributed to Darisipudi, M. N..

4 recordsLinked to original sources

bioRxiv2026

A mouse-adapted Staphylococcus aureus strain enables lifelong neonatal colonization and elicits a Th17-dominated immune response

The opportunistic pathogen Staphylococcus aureus persistently colonizes the anterior nares of up to 20% of the human population, yet there were no persistent mouse colonization models to study host-pathogen interaction. Using the mouse-adapted S. aureus strain JSNZ (CC88-MSSA), we established a neonatal S. aureus colonization model in C57BL/6N mice. Natural neonatal colonization was achieved by vertical transmission in a JSNZ-positive breeding colony. Offspring were followed for up to 69 weeks and found persistently colonized in the nose and cecum with high bacterial loads. Adult mice were colonized by intranasal inoculation of JSNZ; controls received PBS. The colonization patterns and the S. aureus-specific T cell responses were then monitored over a period of 28 days and compared between age-matched mice colonized as neonates or adults. The neonatal group remained persistently colonized in nose and gut with high bacterial densities. In contrast, mice colonized as adults had lower and declining bacterial loads in the nose. Some eliminated S. aureus from the nares, while all remained colonized in the gut. Neonatally colonized mice exhibited reduced nasal chemokine levels, which may have favored the prolonged S. aureus persistence. Ex vivo re-stimulation of cervical lymph node cells with an S. aureus antigen cocktail revealed a Th17-dominated antigen-specific T cell response in both colonized groups. The lymph node cells secreted large amounts of IL-17, but Th1-, Th2-associated and regulatory cytokines were also detected. The cytokine patterns were similar in both colonized groups except for IL-5, which was more abundant upon neonatal colonization. In conclusion, vertical transmission of the mouse-adapted S. aureus strain JSNZ reliably establishes persistent high-density neonatal colonization, providing a physiologically relevant model for the study of S. aureus host interactions. Route and timing of colonization do not fundamentally affect the T cell response to S. aureus.

immunology↗

bioRxiv2025

The S. aureus serine protease-like protein B (SplB) is a potent allergen causing eosinophilic airway inflammation in mice

Background: Asthma is associated with Staphylococcus aureus colonization. Two hypotheses were proposed to explain this phenomenon: (1) the allergic environment in asthma favors S. aureus colonization and (2) S. aureus colonization creates a pro-allergic environment. Since several S. aureus virulence factors, such as the serine protease-like protein (Spl) B, elicit a type 2 biased immune response, we asked whether the pathogen itself can cause asthma. Objective: Test the ability of recombinant SplB of S. aureus to sensitize mice and induce allergic airway inflammation (AAI). Methods: Mice were treated with repeated intratracheal inoculations of either catalytically active SplB or an inactive mutant. AAI was assessed by evaluating airway hypersensitivity, immune cell infiltration, cytokines, mucus production, fibrosis, and specific serum IgE. We compared the outcome between wild-type and gene-deficient C57BL/6J mice, including recombination-activating gene knockout mice (Rag2-/-), interleukin-33 knockout mice (Il33 -/-), and protease-activated receptor 2 knockout mice (F2rl1-/-). Results: Intratracheal exposure to SplB sensitized the mice and caused eosinophilic airway inflammation and hyperresponsiveness. The development of asthma required both the proteolytic activity of SplB and a functional adaptive immune system. The soluble protease sensor IL-33 was necessary for eosinophil tissue invasion, whereas the membrane-bound protease sensor PAR2 was not. Conclusion: The serine protease SplB of S. aureus is a potent allergen. Based on this finding we propose a third mechanism to explain the relationship between S. aureus colonization and asthma: S. aureus can release allergens, such as SplB, that sensitize individuals and lead to the development of asthma.

immunology↗

bioRxiv2025

Spontaneous preputial gland adenitis in Staphylococcus aureus-colonized male C57Bl/6 mice triggers a Th17-driven immune response

Colonization with the pathobiont Staphylococcus aureus increases the risk of endogenous S. aureus infections if the balance between host and microbe is disturbed. We developed a model of persistent S. aureus colonization using the mouse-adapted strain JSNZ. The bacteria transfer from parents to offspring, producing lifelong, usually asymptomatic colonization. Here we report that S. aureus-colonized adult male mice frequently develop spontaneous preputial gland infections (preputial gland adenitis, PGA), which are characterized by pronounced pus production and gland enlargement. This study aimed to characterize PGA in terms of phenotype, causative agents, and the pathogen-specific antibody and T cell responses. We compared three groups: naive mice, colonized PGA-negative mice, and colonized PGA-positive mice. PGA occurred in 8/12 (67%) of male breeding animals and in 17/25 (68%) of adult male offspring. The infection did not self-resolve and persisted for several months. Genotyping identified the colonizing strain JSNZ as the causative agent. The infection caused purulent inflammation, with massive bacterial aggregates and neutrophil infiltrates filling the gland lumen. This inflammation completely disrupted the glandular architecture. PGA induced a strong but localized release of IL-1, IL-1{beta}, IL-17, MIP-1, and KC in the infected gland. T cells from PGA-draining lymph nodes, as well as splenocytes, reacted to in vitro re-stimulation with a S. aureus antigen cocktail with the proliferation of Th17 cells, and the release of IL-17 and IFN-{gamma}, corresponding to a type 3/1- immune response. Colonized PGA-positive mice also mounted a robust S. aureus-specific serum antibody response. In conclusion, the pathology of this spontaneous, chronic S. aureus infection is driven by a strong, type 3-biased immune response that, however, fails to clear the bacteria. This endogenous PGA model provides a valuable tool for studying host-pathogen interactions in natural S. aureus infection.

microbiology↗

bioRxiv2021

S. aureus-serine protease-like protein B (SplB) activates PAR2 and induces endothelial barrier dysfunction

Withdrawal StatementThe authors have withdrawn their manuscript owing to the following reason: Unfortunately, the preparation of the recombinant serine protease-like protein B (SplB) used in this study was found to contain impurities, so that the effects presented cannot be unambiguously attributed to the protease SplB. We therefore retract the manuscript from bioRxiv. We apologize for any inconvenience this may have caused. Therefore, the authors do not wish this work to be cited as reference for the project. We want to clarify that the issue was identified in the preparation of the SplB protein and does not reflect on the contributions of individual authors. If you have any questions, please contact the corresponding author.

immunology↗