Prophages encoding human immune evasion cluster genes are enriched in Staphylococcus aureus isolated from chronic rhinosinusitis patients with nasal polyps

Prophages affect bacterial fitness on multiple levels. These include bacterial infectivity, toxin secretion, virulence regulation, surface modification, immune stimulation and evasion and microbiome competition. Lysogenic conversion arms bacteria with novel accessory functions thereby increasing bacterial fitness, host adaptation and persistence, and antibiotic resistance. These properties allow the bacteria to occupy a niche long term and can contribute to chronic infections and inflammation such as chronic rhinosinusitis (CRS). In this study, we aimed to identify and characterize prophages present in Staphylococcus aureus from patients suffering from CRS in relation to CRS disease phenotype and severity. Prophage regions were identified using PHASTER. Various in silico tools like ResFinder and VF Analyzer were used to detect virulence genes and antibiotic resistance genes respectively. Progressive MAUVE and maximum likelihood were used for multiple sequence alignment and phylogenetics of prophages respectively. Disease severity of CRS patients was measured using computed tomography Lund–Mackay scores. Fifty-eight S. aureus clinical isolates (CIs) were obtained from 28 CRS patients without nasal polyp (CRSsNP) and 30 CRS patients with nasal polyp (CRSwNP). All CIs carried at least one prophage (average=3.6) and prophages contributed up to 7.7 % of the bacterial genome. Phage integrase genes were found in 55/58 (~95 %) S. aureus strains and 97/211 (~46 %) prophages. Prophages belonging to Sa3int integrase group (phiNM3, JS01, phiN315) (39/97, 40%) and Sa2int (phi2958PVL) (14/97, 14%) were the most prevalent prophages and harboured multiple virulence genes such as sak, scn, chp, lukE/D, sea. Intact prophages were more frequently identified in CRSwNP than in CRSsNP (P=0.0021). Intact prophages belonging to the Sa3int group were more frequent in CRSwNP than in CRSsNP (P=0.0008) and intact phiNM3 were exclusively found in CRSwNP patients (P=0.007). Our results expand the knowledge of prophages in S. aureus isolated from CRS patients and their possible role in disease development. These findings provide a platform for future investigations into potential tripartite associations between bacteria-prophage-human immune system, S. aureus evolution and CRS disease pathophysiology.

Correlation between Peripheral Blood Eosinophilia and the Histopathological Changes in Nasal Mucosal in Chronic Rhinosinusitis

Background: Chronic rhinosinusitis(CRS) has emerged as one of the major causes of significant morbidity in otorhinolaryngology, as it is often noted to be refractory to medical management and has a tendency to recur post-surgery. Limited research has shown that peripheral eosinophilia is related to the presence of nasal polyps, the extent of the mucosal disease, the severity of tissue eosinophilia, and the risk of recurrence. Aim: This study aimed to establish the significance of peripheral blood eosinophilia, both differential (EC) and absolute eosinophil counts (AEC) - in adult CRS, to correlate the tissue eosinophilia and peripheral blood eosinophilia, and compare the observations in the two types of CRS with nasal polyp and without nasal polyp. Material and Methods: A total of 50 adult patients with CRS who underwent FESS were included in the study and were divided based on the presence (Group 1) or absence (Group 2) of peripheral blood eosinophilia. Results: There were equal number of cases of chronic rhinosinusitis with nasal polyp (CRSwNP) and without polyp (CRSsNP); 25 each. With regard to clinical features, Group 1 had a higher number of cases with nasal obstruction (p-value = 0.023), post-nasal drip (p-value = 0.035), and hyposmia (p-value = 0.021) when compared to Group 2. On histopathology, Group 1 had more areas of edema (p-value = 0.027), and mucous gland hyperplasia (p-value = 0.013) while Group 2 had prominent lymphoplasmacytic infiltrates (p-value = 0.035), neutrophilia (p-value = 0.047), and tissue infiltration of macrophages (p-value = 0.027). Tissue eosinophilia was present in 32 out of the total cases; 20 (71.43%) in Group 1 and 12 (53.33%) in Group 2. The group with tissue eosinophilia had significantly higher eosinophil count (9.24 ± 4.26% vs 5.32 ± 2.9%; p-value < 0.01) as well as AEC (823.335 ± 434.357/µl vs 485.128 ± 285/µl. 907; p-value < 0.01). Conclusion: The study demonstrated that CRS cases with tissue eosinophilia exhibit an elevated peripheral eosinophil count when compared to non-eosinophilic CRS.

Relationship between plasma cyclin-dependent kinase 5 levels and local immunoglobulin levels in patients with nasal polyps

Nasal polyps are the most common benign nasal tumors that can lead to nasal obstruction and other annoying problems for the patient. Several hypotheses have been proposed as the basic mechanism of nasal polyps. In order to investigate one of the possible causes that can be a disorder in the regulation of systemic immune responses, the present study was designed to investigate the relationship between plasma cyclin-dependent kinase 5 (CDK5) levels and local immunoglobulin levels in patients with nasal polyps. A cross-section study was used to evaluate concentrations of local immunoglobulin levels (IgE, IgM, IgA, and IgG) on blood and polyp specimens from 60 patients with nasal polyps, and 60 control groups. Western Blot Analysis was done for CDK5 in plasma cells. IgA, IgG and IgE concentrations were significantly higher in polyp tissue specimens, but not in blood, of nasal polyp patients compared to the control group. Furthermore, plasma CDK5 levels were significantly higher in nasal polyp tissue compared with control. The difference in IgA, IgE and IgG expression between nasal polyp tissue and blood, supported by increased numbers of plasma cells, suggests a local production of these local immunoglobulins in nasal polyps in response to chronic antigens. Among local immunoglobulins, only there was a significant correlation between CDK5 with IgG (positive correlation) and IgE (negative correlation). The exact explanation for the relationship between plasma CDK5 and local immunoglobulins in nasal polyps needs further studies.

Which Is the Best Biologic for Nasal Polyps: Dupilumab, Omalizumab, or Mepolizumab? A Network Meta-Analysis

<b><i>Introduction:</i></b> Compared with the placebo, biologics are beneficial in reducing nasal polyp mass and safe in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, there lacks a head-to-head randomized trial comparing biologics. We aimed to determine the best biologic for CRSwNP. <b><i>Methods:</i></b> We performed a systematic review and network meta-analysis (NMA), which was registered with PROSPERO (No. CRD42021226766). A comprehensive search was performed in PubMed, Embase, Web of Science, and the Cochrane Library on December 29, 2020. Only randomized controlled trials (RCTs) assessing biologics in adult patients for CRSwNP were included. <b><i>Results:</i></b> Nine RCTs with 1,190 patients comparing 3 different biologics (dupilumab, omalizumab, and mepolizumab) and the placebo were included. Dupilumab had the best efficacy in terms of nasal polyp score (NPS), Sino-Nasal Outcome Test-22 (SNOT-22) score, University of Pennsylvania Smell Identification Test (UPSIT) score, and nasal congestion score (NCS) for surface under the cumulative ranking curve (SUCRA) values of 0.900, 0.916, 1.000, and 0.807, respectively. Omalizumab ranked second in efficacy in terms of SNOT-22, UPSIT, and NCS for SUCRA values of 0.606, 0.500, and 0.693, respectively. Mepolizumab ranked second in efficacy in terms of NPS for SUCRA values of 0.563 and had the highest risk of adverse events (AEs) for SUCRA values of 0.746. <b><i>Conclusion:</i></b> This is the first NMA that compared different biologics in patients with CRSwNP. Based on the efficacy (NPS) and safety (AEs), dupilumab is the best choice and omalizumab is the second best option for CRSwNP. Although mepolizumab ranked second in efficacy, it had the highest risk of AEs.