Persistent Colonization Research Articles

Altered genomic methylation promotes Staphylococcus aureus persistence in hospital environment

Staphylococcus aureus can cause outbreaks and becomes multi-drug resistant through gene mutations and acquiring resistance genes. However, why S. aureus easily adapts to hospital environments, promoting resistance and recurrent infections, remains unknown. Here we show that a specific S. aureus lineage evolved from a clone that expresses the accessory gene regulator (Agr) system to subclones that reversibly suppressed Agr and caused an outbreak in the hospital setting. S. aureus with flexible Agr regulation shows increased ability to acquire antibiotic-resistant plasmids, escape host immunity, and colonize mice. Bacteria with flexible Agr regulation shows altered cytosine genomic methylation, including the decreased 5mC methylation in transcriptional regulator genes (pcrA and rpsD), compared to strains with normal Agr expression patterns. In this work, we discover how altered genomic methylation promotes flexible Agr regulation which is associated with persistent pathogen colonization in the hospital environment.

Functional redundancy in Candida auris cell surface adhesins crucial for cell-cell interaction and aggregation

Candida auris is an emerging nosocomial fungal pathogen associated with life-threatening invasive disease due to its persistent colonization, high level of transmissibility and multi-drug resistance. Aggregative and non-aggregative growth phenotypes for C. auris strains with different biofilm forming abilities, drug susceptibilities and virulence characteristics have been described. Using comprehensive transcriptional analysis we identified key cell surface adhesins that were highly upregulated in the aggregative phenotype during in vitro and in vivo grown biofilms using a mouse model of catheter infection. Phenotypic and functional evaluations of generated null mutants demonstrated crucial roles for the adhesins Als4112 and Scf1 in mediating cell-cell adherence, coaggregation and biofilm formation. While individual mutants were largely non-aggregative, in combination cells were able to co-adhere and aggregate, as directly demonstrated by measuring cell adhesion forces using single-cell atomic force spectroscopy. This co-adherence indicates their role as complementary adhesins, which despite their limited similarity, may function redundantly to promote cell-cell interaction and biofilm formation. Functional diversity of cell wall proteins may be a form of regulation that provides the aggregative phenotype of C. auris with flexibility and rapid adaptation to the environment, potentially impacting persistence and virulence.

Effects of parental care on skin microbial community composition in poison frogs.

Parent-offspring interactions constitute the first contact of many newborns with their environment, priming community assembly of microbes through priority effects. Early exposure to microbes can have lasting influences on the assembly and functionality of the host's microbiota, leaving a life-long imprint on host health and disease. Studies of the role played by parental care in microbial acquisition have primarily focused on humans and hosts with agricultural relevance. Anuran vertebrates offer the opportunity to examine microbial community composition across life stages as a function of parental investment. In this study, we investigate vertical transmission of microbiota during parental care in a poison frog (Family Dendrobatidae), where fathers transport their offspring piggyback-style from terrestrial clutches to aquatic nurseries. We found that substantial bacterial colonization of the embryo begins after hatching from the vitelline envelope, emphasizing its potential role as microbial barrier during early development. Using a laboratory cross-foster experiment, we demonstrated that poison frogs performing tadpole transport serve as a source of skin microbes for tadpoles on their back. To study how transport impacts the microbial skin communities of tadpoles in an ecologically relevant setting, we sampled frogs and tadpoles of sympatric species that do or do not exhibit tadpole transport in their natural habitat. We found more diverse microbial communities associated with tadpoles of transporting species compared to a non-transporting frog. However, we detected no difference in the degree of similarity between adult and tadpole skin microbiotas, based on whether the frog species exhibits transporting behavior or not. Using a field experiment, we confirmed that tadpole transport can result in the persistent colonization of tadpoles by isolated microbial taxa associated with the caregiver's skin, albeit often at low prevalence. This is the first study to describe vertical transmission of skin microbes in anuran amphibians, showing that offspring transport may serve as a mechanism for transmission of parental skin microbes. Overall, these findings provide a foundation for further research on how vertical transmission in this order impacts host-associated microbiota and physiology.

Clinical efficacy and safety of a silver ion-releasing foam dressing on hard-to-heal wounds: a meta-analysis.

Delayed or stalled healing in open wounds can result from persisting chronic inflammation related to infection and/or persistent bacterial colonisation and biofilm. Treatment of hard-to-heal wounds focuses on debridement and exudate management, but also on infection prevention and control. Silver dressings have been evaluated in randomised clinical trials (RCTs); this meta-analysis evaluated the efficacy and safety of a silver ion-releasing foam dressing (Biatain Ag; Coloplast A/S, Denmark) to treat hard-to-heal wounds. Literature databases (PubMed and Cochrane Library) were searched for studies on silver ion-releasing foam dressings in the treatment of hard-to-heal wounds. Individual patient data from four RCTs were obtained and included in the meta-analysis. Findings showed that treatment with the silver ion-releasing foam dressing was associated with a significantly higher relative reduction in wound area after four (least squares-mean difference (LS-MD): -12.55%, 95% confidence interval (CI): (-15.95, -9.16); p<0.01) and six weeks of treatment (LS-MD: -11.94%, 95%CI: (-17.21, -6.68); p<0.01) compared with controls. Significant benefits were also observed for time to disappearance of odour (hazard ratio: 1.61, 95%CI: (1.31, 1.98); p<0.01), relative reduction of exudate (LS-MD: -5.15, 95%CI: (-7.36, -2.94); p<0.01), proportion of patients with periwound erythema (relative risk (RR): 0.81, 95%CI: (0.69; 0.94); p<0.01), and less pain at dressing removal (LS-MD: -0.35, 95%CI: (-0.63, -0.06); p=0.02). No differences regarding safety outcomes were identified. This meta-analysis has demonstrated beneficial outcomes and a good tolerability profile for silver ion-releasing foam dressings in the treatment of moderate-to-highly exuding wounds with delayed healing compared with control dressings.

Forty-year single-center experience of Burkholderia cystic fibrosis airway infections

ObjectivesTo resolve the epidemiology of airway infections with Burkholderia cepacia complex (Bcc) in patients with cystic fibrosis (pwCFs) over 40 years at a single treatment center. MethodsAll Bcc and Burkholderia gladioli airway isolates were collected from pwCFs who presented at the cystic fibrosis outpatient and the lung transplantation clinics from 1983 to 2022. ResultsThe collection of 1205 strains is dominated by B. multivorans (56%), followed by B. cenocepacia (16%), B. stabilis (10%), and B. orbicola (9%). A total of 27 pwCFs experienced a single self-limiting episode of airway infection with Bcc. A total of 13 pwCFs were harboring Bcc for 1.7-13.6 years and 15 pwCFs were persistently infected with Bcc. A total of 16 Bcc-positive pwCFs received a lung transplant. Fatal post-transplant sepsis happened in one patient with B. multivorans, two with B. cenocepacia, and two with B. orbicola. ConclusionsAfter the first acquisition of Bcc, transient carriage was 2.7 times more frequent than persistent colonization. Infections with B. cenocepacia or B. orbicola confer a higher risk for post-transplant sepsis than an infection with B. multivorans.

Commensal consortia decolonize Enterobacteriaceae via ecological control

Persistent colonization and outgrowth of potentially pathogenic organisms in the intestine can result from long-term antibiotic use or inflammatory conditions, and may perpetuate dysregulated immunity and tissue damage1,2. Gram-negative Enterobacteriaceae gut pathobionts are particularly recalcitrant to conventional antibiotic treatment3,4, although an emerging body of evidence suggests that manipulation of the commensal microbiota may be a practical alternative therapeutic strategy5–7. Here we isolated and down-selected commensal bacterial consortia from stool samples from healthy humans that could strongly and specifically suppress intestinal Enterobacteriaceae. One of the elaborated consortia, comprising 18 commensal strains, effectively controlled ecological niches by regulating gluconate availability, thereby re-establishing colonization resistance and alleviating Klebsiella- and Escherichia-driven intestinal inflammation in mice. Harnessing these activities in the form of live bacterial therapies may represent a promising solution to combat the growing threat of proinflammatory, antimicrobial-resistant Enterobacteriaceae infection.

Non-releasing poly (ionic liquid) based hydrogel accelerates diabetic wound healing

Persistent bacterial colonization, abnormal inflammatory responses, and impaired angiogenesis pose significant challenges to effective wound repair, particularly in diabetic wounds. Employing exogenous bioactive substances in wound dressings is a recognized approach to dynamically respond to the wound microenvironment and accelerate the repair process. However, this strategy can lead to the development of drug resistance and induce further tissue damage. To address these challenges, we are synthesizing a novel hydrogel for diabetic wound treatment using functional poly (ionic liquid) and modified dextran. The hydrogel is characterized by its excellent tissue adhesion, exceptional self-healing capacity, and substantial compressive deformation. It exhibits broad antibacterial activity, reduces the expression of pro-inflammatory cytokines and enhances the healing in diabetic wounds. Its efficacy is superior to that of the positive control group. This innovative non-releasing hydrogel presents as a promising alternative to conventional antibiotics, offering significant potential for the treatment and healing of diabetic chronic wounds.

Biochemical characterization of paralyzed flagellum proteins A (PflA) and B (PflB) from Helicobacter pylori flagellar motor.

Motility by means of flagella plays an important role in the persistent colonization of Helicobacter pylori in the human stomach. The H. pylori flagellar motor has a complex structure that includes a periplasmic scaffold, the components of which are still being identified. Here, we report the isolation and characterization of the soluble forms of two putative essential H. pylori motor scaffold components, proteins PflA and PflB. We developed an on-column refolding procedure, overcoming the challenge of inclusion body formation in Escherichia coli. We employed mild detergent sarkosyl to enhance protein recovery and n-dodecyl-N,N-dimethylamine-N-oxide (LDAO)-containing buffers to achieve optimal solubility and monodispersity. In addition, we showed that PflA lacking the β-rich N-terminal domain is expressed in a soluble form, and behaves as a monodisperse monomer in solution. The methods for producing the soluble, folded forms of H. pylori PflA and PflB established in this work will facilitate future biophysical and structural studies aimed at deciphering their location and their function within the flagellar motor.

Bladder catheterization improves bacterial interference with asymptomatic Escherichia coli 83972 in an experimental porcine model of urinary tract infection.

Urinary tract infection (UTI) is a common disease with a significant risk of relapse. Deliberate bladder colonization with asymptomatic Escherichia coli is being explored as a potential strategy to fend off invading uropathogens thereby mitigating the risk symptomatic UTI. Currently, one major obstacle is the low success rates for achieving persistent bladder colonization with asymptomatic bacteria and experimental challenge studies are lacking. Here, we assessed the influence of an indwelling bladder catheter on the ability of asymptomatic E. coli to colonize the bladder and to assess the protective efficacy of such colonization against experimental urinary tract infection with uropathogenic E. coli. Pigs with or without indwelling bladder catheters were experimentally inoculated with the asymptomatic E. coli strain 83972 and subsequently challenged by inoculation with the uropathogenic E. coli isolate, UTI89. The animals were monitored with regular urine and blood samples and bladders and kidneys were harvested at termination. All pigs with indwelling catheters were colonized by 83972 in response to inoculation, compared to pigs without catheters in which only one of eight animals were colonized. When removing the catheter, 83972 were spontaneously cleared. Colonization with 83972 prevented experimental infection in 50% of animals compared to controls that all became infected. The presence of indwelling bladder catheters strongly facilitates the colonization of 83972, indicating that individuals using catheters may be particularly suited for receiving this treatment. The research supports prophylactic colonization with 83972 as a potential strategy to reduce the risk of urinary tract infections.

Otitis by Vibrio Alginolyticus: An Emerging Entity without a Defined Seasonal Pattern: Contaminated Water Exposure or Persistent Colonization?

Otitis by Vibrio Alginolyticus: An Emerging Entity without a Defined Seasonal Pattern: Contaminated Water Exposure or Persistent Colonization?

Progranulin inhibits autophagy to facilitate intracellular colonization of Helicobacter pylori through the PGRN/mTOR/DCN axis in gastric epithelial cells.

Helicobacter pylori (H. pylori) infection is the primary risk factor for the progress of gastric diseases. The persistent stomach colonization of H. pylori is closely associated with the development of gastritis and malignancies. Although the involvement of progranulin (PGRN) in various cancer types has been well-documented, its functional role and underlying mechanisms in gastric cancer (GC) associated with H. pylori infection remain largely unknown. This report demonstrated that PGRN was up-regulated in GC and associated with poor prognosis, as determined through local and public database analysis. Additionally, H. pylori induced the up-regulation of PGRN in gastric epithelial cells both in vitro and in vivo. Functional studies have shown that PGRN promoted the intracellular colonization of H. pylori. Mechanistically, H. pylori infection induced autophagy, while PGRN inhibited autophagy to promote the intracellular colonization of H. pylori. Furthermore, PGRN suppressed H. pylori-induced autophagy by down-regulating decorin (DCN) through the mTOR pathway. In general, PGRN inhibited autophagy to facilitate intracellular colonization of H. pylori via the PGRN/mTOR/DCN axis. This study provides new insights into the molecular mechanisms underlying the progression of gastric diseases, suggesting PGRN as a potential therapeutic target and prognostic predictor for these disorders.

Research Progress on Immune Evasion of Mycoplasma hyopneumoniae.

As the main pathogen associated with enzootic pneumonia (EP), Mycoplasma hyopneumoniae (Mhp) is globally prevalent and inflicts huge financial losses on the worldwide swine industry each year. However, the pathogenicity of Mhp has not been fully explained to date. Mhp invasion usually leads to long-term chronic infection and persistent lung colonization, suggesting that Mhp has developed effective immune evasion strategies. In this review, we offer more detailed information than was previously available about its immune evasion mechanisms through a systematic summary of the extant findings. Genetic mutation and post-translational protein processing confer Mhp the ability to alter its surface antigens. With the help of adhesins, Mhp can achieve cell invasion. And Mhp can modulate the host immune system through the induction of inflammation, incomplete autophagy, apoptosis, and the suppression of immune cell or immune effector activity. Furthermore, we offer the latest views on how we may treat Mhp infections and develop novel vaccines.

Selective depletion of Campylobacter jejuni via T6SS dependent functionality: an approach for improving chickens gut health

The targeted depletion of potential gut pathogens is often challenging because of their intrinsic ability to thrive in harsh gut environments. Earlier, we showed that Campylobacter jejuni (C. jejuni) exclusively uses the Type-VI Secretion System (T6SS) to target its prey such as Escherichia coli (E. coli), and phenotypic differences between T6SS-negative and T6SS-positive C. jejuni isolates toward bile salt sensitivity. However, it remains unclear how the target-driven T6SS functionality prevails in a polymicrobial gut environment. Here, we investigated the fate of microbial competition in an altered gut environment via bacterial T6SS using a T6SS-negative and -positive C. jejuni or its isogenic mutant of the hemolysin-coregulated protein (hcp). We showed that in the presence of bile salt and prey bacteria (E. coli), T6SS-positive C. jejuni experiences enhanced intracellular stress leading to cell death. Intracellular tracking of fluorophore-conjugated bile salts confirmed that T6SS-mediated bile salt influx into C. jejuni can enhance intracellular oxidative stress, affecting C. jejuni viability. We further investigated whether the T6SS activity in the presence of prey (E. coli) perturbs the in vivo colonization of C. jejuni. Using chickens as primary hosts of C. jejuni and non-pathogenic E. coli as prey, we showed a marked reduction of C. jejuni load in chickens cecum when bile salt solution was administered orally. Analysis of local antibody responses and pro-inflammatory gene expression showed a reduced risk of tissue damage, indicating that T6SS activity in the complex gut environment can be exploited as a possible measure to clear the persistent colonization of C. jejuni in chickens.

Unveiling the immune dynamics of Neisseria persistent oral colonization.

Commensal bacteria are crucial in maintaining host physiological homeostasis, immune system development, and protection against pathogens. Despite their significance, the factors influencing persistent bacterial colonization and their impact on the host still need to be fully understood. Animal models have served as valuable tools to investigate these interactions, but most have limitations. The bacterial genus Neisseria, which includes both commensal and pathogenic species, has been studied from a pathogenicity to humans perspective but lacks models that study immune responses in the context of long-term persistence. Neisseria musculi, a recently described natural commensal of mice, offers a unique opportunity to study long-term host-commensal interactions. In this study, for the first time, we have used this model to study the transcriptional, phenotypic, and functional dynamics of immune cell signatures in the mucosal and systemic tissue of mice in response to N. musculi colonization. We found key genes and pathways vital for immune homeostasis in palate tissue, validated by flow cytometry of immune cells from the lung, blood, and spleen. This study offers a novel avenue for advancing our understanding of host-bacteria dynamics and may provide a platform for developing efficacious interventions against mucosal persistence by pathogenic Neisseria.

Tropheryma whipplei Colonization in Adults and Children: A Prospective Study.

We conducted a prospective cohort study at the IRCCS Sacro Cuore Don Calabria Hospital in Negrar di Valpolicella from 2019 to 2021 to investigate the duration of T. whipplei colonization. In addition, the correlation between persistent colonization and the continent of origin, current treatment regimen, clinical manifestations, and parasite coinfection was evaluated. The cohort included subjects who were tested in a previous study (years 2014-2016) and found to be positive for T. whipplei DNA in fecal samples. Thirty-three subjects were enrolled in a prospective study between 2019 and 2021. Feces, saliva, urine, and blood were collected at baseline and after 12 months. Medical history, current treatment, and symptoms were recorded. Among them, 25% showed persistent intestinal or oral colonization, 50% had no colonization at both visits, and 25% had intermittent colonization. No association was found between persistent T. whipplei colonization and subjects' continent of origin, current treatment regimen, initial clinical manifestations, and parasite coinfection. The longest duration of persistent T. whipplei intestinal colonization exceeded six years, with 11 subjects presenting persistent positivity for more than three years, including 1 minor. Our research was limited by the lack of a strain-specific identification of T. whipplei that made it impossible to distinguish between persistence of the same T. whipplei strain, reinfection from household exposure, or infection by a new strain. Larger prospective studies are needed to further explore the implications of this persistence and determine the key factors influencing the duration of colonization and its potential health impacts.

Risk Factors and Outcomes of Candida auris in Southeast Michigan

Background: Candida auris is an emerging multidrug resistant fungus that presents a serious global health threat and causes severe infections with a high mortality rate in hospitalized patients with significant underlying comorbidities. We describe the risk factors and clinical outcomes associated with C. auris in Southeast Michigan. Methods: This is a retrospective case series of culture-positive C. auris patients who had contact with our healthcare facility in Detroit from 2021 to 2023. We evaluated demographics, comorbidities, risk factors, and outcomes. A comparative analysis of colonized and infected patients was performed. Results: Forty-eight (81%) colonized and 11 (19%) infected patients were included (Table); 70% were male with median age of 66 years. All variables were comparable between the two groups except chronic kidney disease, which was significantly more prevalent among colonized patients (40% vs 0, p=0.011). All patients had prior exposure to acute care hospital (ACH), 37% to long-term acute care hospital, and 42% to skilled nursing facility within 1 year of diagnosis. Chronic wounds, prior broad-spectrum antibiotic use, and indwelling devices were prevalent in both groups; more than half required mechanical ventilation in the last month, and one third had tracheostomy at the time of C. auris detection. Almost 60% had a prior history of drug-resistant organisms, including multi-drug resistant gram negative (37%) and carbapenem-resistant (20%) organisms. Blood (82%) and wound (18%) were sources of invasive candidiasis. More than half (61%) of the testing was performed at ACH. Nine patients (82%) with invasive disease were treated with echinocandins (88%); among the colonized, two (4%) were treated with echinocandins but had persistent colonization. Thirty-day mortality was not significantly different among the two groups and was nearly 20%. Conclusions: In this large cohort study, a history of healthcare exposure, drug-resistant organisms, use of broad-spectrum antibiotics, indwelling devices, and chronic wounds were common risk factors among C. auris patients. Limiting the use of broad-spectrum antimicrobials and invasive devices, adherence to infection prevention and control practices, and interfacility transfer communication are important mitigating strategies to reduce the incidence and spread of C. auris.

Retrospective genome-oriented analysis reveals low transmission rate of multidrug-resistant Pseudomonas aeruginosa from contaminated toilets at a bone marrow transplant unit

BackgroundPrevention of toilet-to-patient transmission of multidrug-resistant Pseudomonas aeruginosa (MDR PA) poses management-related challenges at many bone marrow transplant units (BMTU). Using whole-genome sequencing (WGS), we conducted a longitudinal retrospective analysis of the toilet-to-patient transmission rate for MDR PA under existing infection control (IC) measures at a BMTU with persistent MDR PA toilet colonization. MethodsThe local IC bundle comprised 1.) patient education regarding IC, 2.) routine patient screening, 3.) toilet flushing volume of 9L, 4.) bromination of toilet water tanks, and 5.) toilet decontamination using hydrogen peroxide. Toilet water was sampled periodically between 2016-2021 (minimum every three months - 26 intervals). Upon MDR PA detection, disinfection and re-sampling were repeated until ≤ 3 cfu/100ml was reached. WGS was performed retrospectively on all available MDR PA isolates (90 of 117 positive environmental samples, 10 of 14 patients – including nine nosocomial). ResultsWGS of patient isolates identified six sequence types (STs), with ST235/CT1352/FIM-1 and ST309/CT3049/no-carbapenemase being predominant (three isolates each). Environmental sampling consistently identified MDR PA ST235 (65.5% ST235/CT1352/FIM-1), showing low genetic diversity (difference of ≤29 alleles by cgMLST). This indicates that direct toilet-to-patient transmission was infrequent although MDR PA was widespread (detection on 79 occasions, detection in every toilet). Only three MDR PA patient isolates can be attributed to the ST235/CT1352/FIM-1 toilet MRD PA population over six years. ConclusionsGenome-oriented environmental and patient surveillance suggests that the persistent presence of MDR PA poses a potential risk for acquisition, but with stringent targeted toilet disinfection, only three highly vulnerable patients experienced nosocomial transmission.

A REVIEW ON CURRENT TRENDS IN Helicobacter pylori MANAGEMENT WITH MEDICINAL PLANTS AND ITS CONSTITUENTS

Helicobacter pylori is a bacterium associated with gastric diseases and disorders of the upper gastrointestinal tract. The gram-negative bacterium Helicobacter pylori is known as a persistent colonizer of the human stomach, and this bacteria is also involved in extra-intestinal diseases. In 1994, the International Agency for Research on Cancer, World Health Organization classified H. pylori as a class 1 carcinogen, the only bacterium given this classification. Besides, the emergence of H. pylori resistance to antibiotics has been a major clinical challenge in the field of gastroenterology, and this concern has been shown an increasing tendency in many regions of the world. To overcome the current circulating difficulties, new potential therapeutic targets were uncovered to find active substances for the treatment of H. pylori infection. Several medicinal plants and their isolated compounds have been reported for their antimicrobial activity against H. pylori. It is demonstrated that they are efficacious against H. pylori strains that are resistant to drugs. The mechanism of action of many of these plant extracts and plant-derived compounds is different from that of conventional antibiotics. Therefore, natural compounds are emerging as a potential source of raw materials with diverse mechanisms of action. Some commonly known mechanisms can be listed as anti-urease activity, anti-adhesive activity, anti-inflammatory and gastroprotective activity, and effects on the oxidative stress process. Recently, new classes of drugs with reasonable antibacterial mechanisms against H. pylori have also been mentioned, including (1) anti-biofilm agents, (2) anti-virulence molecules (anti-VacA, anti-CagA agents, toxin BabA and LPS inhibitors, anti-motility agents, Helicobacter pylori quorum sensing inhibitors), (3) mucolytic agents, and (4) compounds that impact on essential proteins in the physiology of H. pylori such as inosin-5‘monophosphate dehydrogenase and HsrA inhibitors. This review article aims to summarize current prospects, identify possible novel targets, and be considered as a complementary therapy in the eradication treatment against Helicobacter pylori.

Staphylococcus aureus–specific skin resident memory T cells protect against bacteria colonization but exacerbate atopic dermatitis–like flares in mice

BackgroundThe contribution of Staphylococcus aureus (S. aureus) to the exacerbation of atopic dermatitis (AD) is widely documented, but its role as a primary trigger of AD skin symptoms remains poorly explored. ObjectiveTo reappraise the main bacterial factors and underlying immune mechanisms by which S. aureus triggers AD-like inflammation. MethodsWe capitalized on a pre-clinical model, in which different clinical isolates were applied in the absence of any prior experimental skin injury. ResultsWe report that the development of S. aureus-induced dermatitis depended on the nature of the S. aureus strain, its viability, the concentration of the applied bacterial suspension, the production of secreted and non-secreted factors, as well as the activation of accessory gene regulatory quorum sensing system. In addition, the rising dermatitis, which exhibited the well-documented AD cytokine signature, was significantly inhibited in inflammasome adaptor protein ASC- and monocyte/macrophage-deficient animals, but not in T- and B-cell-deficient mice, suggesting a major role for the innate response in the induction of skin inflammation. However, bacterial exposure generated a robust adaptive immune response against S. aureus, and an accumulation of S. aureus-specific γδ and CD4+ tissue resident memory T (Trm) cells at the site of previous dermatitis. The latter both contributed to worsen the flares of AD-like dermatitis upon new bacteria exposures, but also, protected the mice from persistent bacterial colonization. ConclusionThese data highlight the induction of unique AD-like inflammation, with the generation of pro-inflammatory but protective Trm cells in a context of natural exposure to pathogenic S. aureus strains.

Unveiling the immune dynamics of Neisseria persistent oral colonization: a roadmap for innovative vaccine strategies

Abstract Commensals shape host physiology and immunity. Neisseria gonorrhoeae (NG), a human pathogen, causes asymptomatic colonization and animal studies on NG for vaccine-design have been unsuccessful. N. musculi (NM), a mouse commensal, shares host-interaction genes with NG and is a surrogate to study NG colonization. Eight A/J mice were orally inoculated with NM; uninoculated mice served as controls (n=8). Four from each group were euthanized at day 5 and the rest at day 33. Immune signatures and palate transcriptome were compared between inoculated and control mice using Wilcoxon rank-sum test. Transcriptomics revealed enriched mucosal immunity and inflammation in colonized tissue. Day 5 data suggested reduced colonization resistance (reduced monocytes), while data at day 33 showed enriched adaptive (memory B cells) and immunoregulatory cells (Tregs) in colonized tissue. At day 5 of colonization, systemic immune response was pro-inflammatory. Splenic NK cells showed higher IL22, suggesting reinforcement of mucosal immunity during colonization. Systemic immune response displayed reduced enrichment of immune signatures at day 33 of colonization suggesting homeostasis. Positive correlations between NM palate colony counts and enriched immune subsets suggest impact of mucosal colonization on immunophenotypes (p&amp;lt;0.05 for all). This data is crucial for defining transcriptional and immunological endpoints of NM mucosal colonization, aiding in developing vaccine candidates against NG.