Pulmonary abscess caused by Streptococcus pseudopneumoniae in a child: A case report and review of literature.

BACKGROUND: Lung abscess found on chest X-ray and computed tomography examinations is rare in infants and young children. Several pathogens can cause lung abscesses, with the most common pathogens being anaerobes, Streptococci and Staphylococcus aureus. Streptococcus pseudopneumoniae (S. pseudopneumoniae) is a member of the Streptococcaceae family, and is mainly isolated from respiratory tract specimens. There are currently no cases of lung abscess caused by S. pseudopneumoniae in the literature. CASE SUMMARY: A 2-year-old boy was admitted to hospital due to persistent cough and fever. Lung computed tomography examination suggested the formation of a lung abscess. His diagnosis was not confirmed by testing for serum respiratory pathogens (6 items), respiratory pathogen nucleic acid (27 items), and laboratory culture. Finally, metagenomic next-generation sequencing of bronchoalveolar lavage fluid revealed the presence of S. pseudopneumoniae, confirming its role in causing the lung abscess. After receiving antibiotic treatment, reexamination with lung computed tomography showed that the abscess was resorbed and the patient's outcome was good. CONCLUSION: This is the first report of a lung abscess in a child caused by S. pseudopneumoniae infection. Metagenomic next-generation sequencing of bronchoalveolar lavage fluid is helpful in achieving rapid and accurate pathogen identification.

Clonorchis sinensis infection induces pathological changes in feline bile duct epithelium and alters biliary microbiota composition.

BACKGROUND: Clonorchis sinensis is a zoonotic liver fluke that inhabits the bile ducts of the human liver for prolonged periods, leading to cholangiocarcinoma. Recent research indicates associations between altered biliary microbiota and bile duct disorders. However, the impacts of C. sinensis infection on bile duct epithelium and subsequent effects on biliary microbiota remain unknown. METHODS: Feline bile duct samples were collected from both uninfected and C. sinensis-infected cats. Histopathological examination was performed to assess epithelial changes, fibrosis, mucin and cell proliferation using hematoxylin-eosin staining and immunohistochemistry. Additionally, biliary microbiota composition was analyzed through 16S rRNA gene sequencing. Statistical analyses were conducted to compare the microbial diversity and relative abundance between infected and uninfected samples. RESULTS: Histopathological analysis of infected feline bile ducts revealed prominent epithelial hyperplasia characterized by increased cell proliferation. Moreover, periductal fibrosis and collagen fibrosis were observed in infected samples compared to uninfected controls. Biliary microbial richness decreased with disease progression compared to uninfected controls. Streptococcus abundance positively correlated with disease severity, dominating communities in cancer samples. Predictive functional analysis suggested that C. sinensis may promote bile duct lesions by increasing microbial genes for carbohydrate metabolism, replication, and repair. CONCLUSIONS: This study provides comprehensive insights into the pathological effects of C. sinensis infection on feline bile duct epithelium and its influence on biliary microbiota composition. These novel findings provide insight into C. sinensis pathogenesis and could inform therapeutic development against human clonorchiasis. Further research is warranted to elucidate the underlying mechanisms driving these changes and their implications for host-parasite interactions.

Title: L'infection par Clonorchis sinensis induit des changements pathologiques dans l'épithélium des voies biliaires félines et modifie la composition du microbiote biliaire. Abstract: Contexte : Clonorchis sinensis est une douve zoonotique du foie qui habite les voies biliaires du foie humain pendant des périodes prolongées, conduisant au cholangiocarcinome. Des recherches récentes indiquent des associations entre une altération du microbiote biliaire et des pathologies des voies biliaires. Cependant, les impacts de l'infection par C. sinensis sur l'épithélium des voies biliaires et les effets ultérieurs sur le microbiote biliaire restent inconnus. Méthodes : Des échantillons de voies biliaires félines ont été prélevés sur des chats non infectés et infectés par C. sinensis. Un examen histopathologique a été réalisé pour évaluer les modifications épithéliales, la fibrose, la mucine et la prolifération cellulaire à l'aide de la coloration à l'hématoxyline-éosine et de l'immunohistochimie. De plus, la composition du microbiote biliaire a été analysée par séquençage du gène de l'ARNr 16S. Des analyses statistiques ont été menées pour comparer la diversité microbienne et l'abondance relative entre les échantillons infectés et non infectés. Résultats : L'analyse histopathologique des voies biliaires félines infectées a révélé une hyperplasie épithéliale importante caractérisée par une prolifération cellulaire accrue. De plus, une fibrose péricanalaire et une fibrose du collagène ont été observées dans les échantillons infectés par rapport aux témoins non infectés. La richesse microbienne biliaire diminue avec la progression de la maladie par rapport aux témoins non infectés. L'abondance des streptocoques est positivement corrélée à la gravité de la maladie, dominant les communautés dans les échantillons avec cancer. L'analyse fonctionnelle prédictive suggère que C. sinensis pourrait favoriser les lésions des voies biliaires en augmentant les gènes microbiens pour le métabolisme des glucides, la réplication et la réparation. Conclusions : Cette étude fournit des informations complètes sur les effets pathologiques de l'infection à C. sinensis sur l'épithélium des voies biliaires félines et son influence sur la composition du microbiote biliaire. Ces nouvelles découvertes donnent un aperçu sur la pathogenèse de C. sinensis et pourraient éclairer le développement thérapeutique contre la clonorchiase humaine. Des recherches supplémentaires sont nécessaires pour élucider les mécanismes sous-jacents à l'origine de ces changements et leurs implications sur les interactions hôte-parasite.

Antibacterial and Antileishmanial Activity of 1,4-Dihydropyridine Derivatives.

: We have synthesized twenty-three 1,4-dihydropyridine derivatives (1,4-DHPs) by using a microwave-assisted one-pot multicomponent Hantzsch reaction and evaluated their antibacterial activity against a representative panel of cariogenic bacteria and their in vitro antileishmanial activity against Leishmania (L.) amazonensis promastigotes and amastigotes. Thirteen compounds were moderately active against Streptococcus sanguinis, Streptococcus mitis, and Lactobacillus paracasei. Compound 22 (diethyl 4-(3-methoxy-4-hydroxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate) displayed moderate antibacterial activity against S. mitis and S. sanguinis, with a Minimum Inhibitory Concentration (MIC) of 500 µg/mL); compounds 8 (ethyl 2,7,7-trimethyl-4-(3-chlorophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) and 10 (ethyl 2,7,7-trimethyl-4-(3-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) were moderately active against S. sanguinis (MIC = 500 µg/mL) and very active against L. amazonensis promastigotes (IC50 = 43.08 and 34.28 µM, respectively). Among the eight 1,4-DHPs that were active (IC50 < 50 µM) against L. amazonensis promastigotes, compound 13 (ethyl 2,7,7-trimethyl-4-(3,4,5-trimethoxyphenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) was the most active (IC50 = 24.62 µM) and had a Selectivity Index (SI) higher than 4 compared to GM07492A cells. On the other hand, compound 9 (ethyl 2,7,7-trimethyl-4-(2-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) was the most active against L. amazonensis amastigotes (IC50 = 16.27 µM and SI = 6.1) after 24 h of treatment. Based on our results, asymmetric 1,4-DHPs derived from dimedone exhibit antileishmanial potential.

Etiologic Profile of the Pneumococcus in Ghana: A Systematic Review.

Objective: To describe the profile of Streptococcus pneumoniae, identify research gaps, and provide in-depth insights into various aspects related to the pathogen. Methods: Google Scholar, PubMed, and ScienceDirect were searched for all studies on the pneumococcus in Ghana that reported on specimen collected, population and sample size, carriage prevalence, incidence of pneumococcal diseases, age of the study population, types of test performed, serotypes identified, antimicrobial susceptibilities, or molecular analysis on the pneumococci for data extraction. Results: Overall, a total of 7954 results were obtained from the three-database search, and of this, 24 articles were selected after screening. A total of 924 isolates were accounted for by serotyping/serogrouping. The prevalence of pneumococcal carriage in Ghana ranges from 11.0% to 51.4% in the population depending on the age (≤ 24-80 years), sickle cell disease (SCD), human immunodeficiency virus (HIV) status, or health of the study population, and penicillin (Pen)-nonsusceptible isolates ranged from 17% to 63%. The prevalence of pneumococci found as the etiologic agent of diseases among Ghanaians ranges from 3.4% for otitis media to 77.7% for meningitis. Overall, the 13-valent pneumococcal conjugate vaccine (PCV) (PCV-13) carriage serotypes accounted for 28.4% of the reported pneumococcal isolates. PCV-13 invasive serotypes accounted for 22.4% of the reported isolates. The non-PCV-13 carriage serotypes accounted for most (43.9%) of the reported isolates. In the pre-PCV-13 era, the nontypeable (NT) (5.5%) and other nonvaccine types (NVTs) (6.4%) were reported as being predominant. The non-PCV-13 serotypes accounted for 4.4% of the reported isolates in invasive pneumococcal disease (IPD) cases. Multidrug resistance (MDR) ranged from 7.8% to 100%. Conclusion: Predicting the invasiveness of pneumococci using molecular typing is the way to go in the future as this will provide answers to the extent to which capsular switching is contributing to the pneumococcal disease burden in Ghana almost a decade after introducing PCV-13. Continuous monitoring of antibiotic resistance patterns at both phenotypic and genotypic levels, along with serotyping and molecular typing, should be a standard practice in the surveillance of pneumococcal disease burden in Ghana.

Dental plaque caries related microorganism in relation to demographic factors among a group of Iraqi children.

INTRODUCTION: Streptococcusmutans and lactobacilli are most important bacteria in the pathogenesis of dental caries. Cariogenic microflora has been associated to the primary caregiver transmission and sugary diets.

A severe case of reactive infectious mucocutaneous eruption associated with two possible triggers: Coronavirus and group A streptococcus.

Reactive infectious mucocutaneous eruption (RIME) is a newly defined condition characterized by mucocutaneous blistering secondary to upper respiratory infections and encompasses Mycoplasma pneumoniae-induced rash and mucositis, broadening the disease spectrum to include various infectious etiologies. We present a severe RIME case involving a 5-year-old female with concurrent coronavirus NL63 and group A streptococcus infections. Diagnosis complexity stemmed from overlapping clinical features with other severe mucocutaneous eruptions such as Stevens-Johnson syndrome/toxic epidermal necrolysis/drug-induced necrolysis. This case underscores the need for comprehensive infectious workup and emphasizes the clinical diagnostic spectrum of drug-induced and infection-induced desquamative skin and mucosal disease.

Antimicrobial and synergistic effects of lemongrass and geranium essential oils against Streptococcus mutans, Staphylococcus aureus, and Candida spp.

BACKGROUND: The oral cavity harbors more than 700 species of bacteria, which play crucial roles in the development of various oral diseases including caries, endodontic infection, periodontal infection, and diverse oral diseases. AIM: To investigate the antimicrobial action of Cymbopogon Schoenanthus and Pelargonium graveolens essential oils against Streptococcus mutans, Staphylococcus aureus, Candida albicans, Ca. dubliniensis, and Ca. krusei. METHODS: Minimum microbicidal concentration was determined following Clinical and Laboratory Standards Institute documents. The synergistic antimicrobial activity was evaluated using the Broth microdilution checkerboard method, and the antibiofilm activity was evaluated with the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay. Data were analyzed by one-way analysis of variance followed by the Tukey post-hoc test (P ≤ 0.05). RESULTS: C. schoenanthus and P. graveolens essential oils were as effective as 0.12% chlorhexidine against S. mutans and St. aureus monotypic biofilms after 24 h. After 24 h P. graveolens essential oil at 0.25% was more effective than the nystatin group, and C. schoenanthus essential oil at 0.25% was as effective as the nystatin group. CONCLUSION: C. schoenanthus and P. graveolens essential oils are effective against S. mutans, St. aureus, Ca. albicans, Ca. dubliniensis, and Ca. krusei at different concentrations after 5 min and 24 h.

A specific and ultrasensitive Cas12a/crRNA assay with recombinase polymerase amplification and lateral flow biosensor technology for the rapid detection of Streptococcus pyogenes.

The potential of CRISPR/Cas systems for nucleic acid detection in novel biosensing applications is remarkable. The current clinical diagnostic detection of Streptococcus pyogenes (S. pyogenes) is based on serological identification, culture, and PCR. We report a rapid, simple, and sensitive method for detecting and screening for S. pyogenes. This novel method is a promising supplemental test. After 10 min of the sample processing and 10 min of recombinase polymerase amplification, followed by 10 min of Cas12 reaction and 3 min of lateral flow biosensor (LFB) readout, a visible outcome can be observed without the need for magnification within 33 min. This platform is robust, inexpensive, and appropriate for on-site testing. A new technique for detection was created using CRISPR-Cas12a technology, which includes two measurements: a fluorescent-CRISPR-S. pyogenes test and a LFB-CRISPR-S. pyogenes test. An approach utilizing CRISPR Cas12a was developed, and the accuracy and precision of this technique were assessed. The LoD for the fluorescence-CRISPR- S. pyogenes assay was 1 copy/µL, and the technique effectively differentiated S. pyogenes from other microorganisms. Moreover, the detection outcomes were presented in a user-friendly manner using lateral flow biosensor strips. Conclusion: A rapid and sensitive Cas12a/crRNA assay using recombinase RPA and LFB was developed to detect S. pyogenes. The Cas12a/crRNA-based assay exhibited high specificity among different bacteria strains and extremely high sensitivity. The accuracy and rapidity of this method make it a promising tool for S. pyogenes detection and screening. IMPORTANCE: Patients may experience a range of symptoms due to Streptococcus pyogenes infections, including superficial skin infections, pharyngitis, and invasive diseases in subcutaneous tissues like streptococcal toxic shock syndrome. At present, the clinical diagnostic detection of S. pyogenes is based on serological identification, culture, and PCR. These detection methods are time-consuming and require sophisticated equipment, making these methods challenging for routine laboratories. Thus, there is a need for a detection platform that is capable of quickly and accurately identifying S. pyogenes. In this study, a rapid and sensitive Cas12a/crRNA assay using recombinase RPA and LFB was developed to detect S. pyogenes. The Cas12a/crRNA-based assay exhibited high specificity among different bacteria strains and extremely high sensitivity. This method probably plays an important role for S. pyogenes detection and screening.

Transmission potential of Streptococcus pyogenes during a controlled human infection trial of pharyngitis.

Controlled human infection (CHI) models can provide insights into transmission of pathogens such as Streptococcus pyogenes (Strep A). As part of the Controlled Human Infection with Penicillin for Streptococcus pyogenes (CHIPS) trial, we explored the potential for transmission among participants deliberately infected with the Strep A emm75 strain. Three approaches to understanding transmission were employed: the use of agar settle plates to capture possible droplet or airborne spread of Strep A; measurement of distance droplets could spread during conversation; and environmental swabbing of high-touch items to detect Strep A on surfaces. Of the 60 (27%) CHIPS trial participants across five cohorts, 16 were enrolled in this sub-study; availability of study staff was the primary reason for selection. In total, 189 plates and 260 swabs were collected. Strep A was grown on one settle plate from a participant on the second day, using plates placed 30 cm away. This participant received the placebo dose of penicillin and had met the primary endpoint of pharyngitis. Whole-genome sequencing identified this to be the challenge strain. Strep A was not detected on any swabs. In this small sample of CHI participants, we did not find evidence of Strep A transmission by the airborne route or fomites, and just one instance of droplet spread while acutely symptomatic with streptococcal pharyngitis. Although these experiments provide evidence of minimal transmission within controlled clinical settings, greater efforts are required to explore Strep A transmission in naturalistic settings.IMPORTANCEStreptococcus pyogenes remains a significant driver of morbidity and mortality, particularly in under-resourced settings. Understanding the transmission modalities of this pathogen is essential to ensuring the success of prevention methods. This proposed paper presents a nascent attempt to determine the transmission potential of Streptococcus pyogenes nested within a larger controlled human infection model.

Development and validation of carbodiimide-activated ELISA plate for quantifying IgG levels against Streptococcus pneumoniae capsular polysaccharides.

Background: Conventional microtiter plates lack the surface strength needed for effective binding of pneumococcal polysaccharide antigens. This study tackles the limitation by altering the surface of polystyrene plates through carbodiimide activation under acidic pH conditions.Method: The microtiter plates were activated with carbodiimide coupling agents, N,N'-Dicyclohexylcarbodiimide (DCC) and N-Hydroxysuccinimide (NHS). They were subsequently coated with 13 pneumococcal antigens at a concentration of 5 µg/ml with a pH of 3.5. The IgG antibody titer was assessed utilizing the World Health Organization (WHO) ELISA protocol for 30 human serum samples. In addition, validation experiments were conducted to evaluate specificity and precision.Results: The modified plates exhibited two-times higher antibody titers compared to conventional plates across all 13 serotypes. Observations revealed elevated antibody levels, with geometric concentrations ranging between 0.96 µg/ml and 4.24 µg/ml.Conclusion: Carbodiimide activation and acidic pH modification of microtiter plates enhance sensitivity and specificity in detecting pneumococcal antibodies, critical for vaccination planning and immunity assessment.

[Box: see text].

Cytokine secretion by in vitro cultures of lung epithelial cells, differentiated macrophages and differentiated dendritic cells incubated with pneumococci and pneumococcal extracellular vesicles.

Streptococcus pneumoniae is an important human pathogen that can colonize the respiratory tract of healthy individuals. The respiratory tract mucosa is thus the first barrier for this pathogen. In this study, we have tested three models of the respiratory epithelium with immune cells: (i) monolayer of A549 human lung epithelial cells, (ii) A549 + macrophages differentiated from the human monocytic THP-1 cell line (dMφ) and (iii) A549 + dMφ + dendritic cells differentiated from THP-1 (dDC) using a two-chamber system. Pneumococcal strains Rx1 (non-encapsulated) and BHN418 (serotype 6B) were incubated with the cells and secretion of IL-6, IL-8, IL-1ß, TNF-α and IL-10 was evaluated. Overall, the models using co-cultures of A549 + dMφ and A549 + dMφ + dDC elicited higher levels of pro-inflammatory cytokines and the non-encapsulated strain elicited an earlier cytokine response. BHN418 pspA (pneumococcal surface protein A) and pspC (pneumococcal surface protein C) knockouts elicited similar cytokine secretion in the co-culture models, whereas BHN18 ply (pneumolysin) knockout induced much lower levels. The results are in accordance with the activation of the inflammasome by Ply. Finally, we evaluated pneumococcal extracellular vesicles (pEVs) in the co-culture models and observed secretion of pro-inflammatory cytokines in the absence of cytotoxicity. Since pEVs are being studied as vaccine candidate against pneumococcal infections, the co-cultures of A549 + dMφ and A549 + dMφ + dDC are simple models that could be used to evaluate pEV vaccine batches.

Frequency of Mutacin Gene Types in Streptococcus mutans Isolated From Oral Potentially Malignant Disorder (OPMD) Patients.

Objectives Mutacins are potent virulent factors attributing to the virulence in Streptococcus mutans leading to oro-dental diseases, and oral potentially malignant disorders (OPMDs) are considered a premalignant condition of the oro-mucosal layers in the oral cavity. The purpose of this study was to phenotypically characterize S. mutans from the clinical samples of patients with OPMD and to assess the frequency of mutacin genes in comparison with healthy individuals. Methods Saliva samples (n=60) were collected from three different groups and the samples were incubated at 37°C for 48 hours in Mutans-Sanguis agar. After incubation, the isolates were identified phenotypically for S. mutans and the frequency of mutacin genes and its types were assessed by polymerase chain reaction (PCR). Results S. mutans was found to be more prevalent in the OPMD cases (45%) followed by healthy individuals with caries (15%). Mutacin genes were expressed in all the groups except Group 3 (healthy individuals) without caries. Mutacin I was expressed the highest in Group 1 and Group 2 with 88% and 62.5, respectively, and mutacin III was expressed the least in all groups with 0% expression. Conclusion The findings of the study show the presence of mutacin gene types in the clinical strains of S. mutans in association with OPMD and caries. Further experimental evidence may be required to assess the frequency and to design a novel drug targeting the same.

How can we reduce neonatal sepsis after universal group B streptococcus screening?

BACKGROUND: Group B Streptococcus (GBS) infection remains a leading cause of newborn morbidity and mortality. The study aimed to determine the adherence rate to the universal screening policy a decade after its introduction. Secondly, whether the timing of antibiotics given in GBS carriers reduces the incidence of neonatal sepsis. METHODS: Delivery records at Hong Kong Baptist Hospital in 2022 were examined to retrieve antenatal and intrapartum details regarding maternal GBS carrier status, previous maternal GBS carrier status, antibiotic treatment, timing of treatment, neonatal condition at birth and whether the neonate had sepsis. Univariate statistics was used to assess the relationship between maternal GBS carrier and neonatal sepsis overall. Incidence of neonatal sepsis was stratified according to mode of delivery and timing of antibiotic. RESULTS: The adherence rate to the universal GBS screening policy was 97%. The risk of neonatal sepsis was 5.45 (95% CI 3.05 to 9.75) times higher in women who were GBS screened positive when compared to non-GBS carriers (p < 0.001). Amongst term neonates from GBS carriers delivered by Caesarean section, the risk of neonatal sepsis significantly decreased by 70% after antenatal antibiotic treatment (p = 0.041) whereas in term neonates delivered vaginally, the risk of neonatal sepsis decreased by 71% (p = 0.022) if intrapartum antibiotic prophylaxis was given 4 or more hours. CONCLUSION: Giving antenatal antibiotic treatment before Caesarean section or intrapartum antibiotic prophylaxis for 4 or more hours before vaginal delivery may decrease the risk of neonatal sepsis in term neonates delivered from GBS carriers.

Altered intestinal Streptococcus anginosus and 5α-reductase gene levels in patients with hepatocellular carcinoma and elevated Bacteroides stercoris in atezolizumab/bevacizumab non-responders.

Introduction. Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide.Gap statement. Monitoring of HCC and predicting its immunotherapy responses are challenging.Aim. This study explored the potential of the gut microbiome for HCC monitoring and predicting HCC immunotherapy responses.Methods. DNA samples were collected from the faeces of 22 patients with HCC treated with atezolizumab/bevacizumab (Atz/Bev) and 85 healthy controls. The gut microbiome was analysed using 16S rRNA next-generation sequencing and quantitative PCR (qPCR).Results. The microbiomes of patients with HCC demonstrated significant enrichment of Lactobacillus, particularly Lactobacillus fermentum, and Streptococcus, notably Streptococcus anginosus. Comparative analysis between Atz/Bev responders (R) and non-responders (NR) revealed a higher abundance of Bacteroides stercoris in the NR group and Bacteroides coprocola in the R group. Using qPCR analysis, we observed elevated levels of S. anginosus and reduced levels of 5α-reductase genes, essential for the synthesis of isoallolithocholic acid, in HCC patients compared to controls. Additionally, the analysis confirmed a significantly lower abundance of B. stercoris in the Atz/Bev R group relative to the NR group.Conclusions. The gut microbiome analysis and specific gene quantification via qPCR could provide a rapid, less invasive, and cost-effective approach for assessing the increased risk of HCC, monitoring patient status, and predicting immunotherapy responses.

Effects of dietary Hericium erinaceus extract on growth, nutrient utilization, hematology, expression of genes related immunity response, and disease resistance of Nile tilapia (Oreochromis niloticus).

In recent years, there has been a growing focus on using herbal extracts as immune enhancers for aquatic species, replacing antibiotics. In the present study, the effects of dietary supplementation of Hericium erinaceus extract (HE) on growth, feed utilization, hematology, expression of immunity-related genes, and immune responses in Nile tilapia infected by Streptococcus agalactiae were examined. A total of 240 Nile tilapia with an average body weight of 17.28 ± 0.01 g were fed diets enriched with different levels of HE: 0 (HE0), 0.1 (HE0.1), 1.0 (HE1.0), and 5.0 (HE5.0) g/kg. The results showed that growth parameters, feed conversion ratio, and organosomatic indexes were not linearly or quadratically affected by HE supplementation. Fish fed HE0.1 and HE1.0 increased protein efficiency ratio and protein productive values with significant linear and quadratic effects of HE enrichment. In addition, dietary supplementation of HE quadratically increased whole-body protein content. Red blood cell, white blood cell, and hematocrit were linearly and quadratically increased by HE supplementation. HE also linearly and quadratically decreased LDL cholesterol and linearly decreased the total cholesterol levels. Stress markers, serum glucose, and cortisol levels were linearly and/or quadratically decreased in HE-fed fish. The relative mRNA expression of tnf-α, il-1ß, il-6, and il-10 were upregulated in the HE0.1 and HE1.0 groups, while dietary supplementation of HE significantly decreased hsp70cb1 mRNA expression in all groups. After feeding dietary HE supplementation for 10 weeks, fish were intraperitoneally injected with pathogenic S. agalactiae. A high survival after challenge was found in all HE supplementation groups with the highest percent survival observed in the HE1.0 and HE5.0 groups. Our findings represent that supplementation of 1 g/kg of HE (HE1.0) could obtain the greatest effects on immunity and survival of Nile tilapia. In addition, the present study also showed that dietary supplementation of HE can improve protein utilization, hematology, expression of genes related to immunity, stress markers, and resistance of Nile tilapia against pathogenic bacterial infection.

ActA-mediated PykF acetylation negatively regulates oxidative stress adaptability of Streptococcus mutans.

Dental caries is associated with microbial dysbiosis caused by the excessive proliferation of Streptococcus mutans in dental biofilms, where oxidative stress serves as the major stressor to microbial communities. The adaptability of S. mutans to oxidative stress is a prerequisite for its proliferation and even for exerting its virulence. Protein acetylation is a reversible and conserved regulatory mechanism enabling bacteria to rapidly respond to external environmental stressors. However, the functions of protein acetylation in regulating oxidative stress adaptability of S. mutans are still unknown. Here, we unveil the impact of acetyltransferase ActA-mediated acetylation on regulating the oxidative stress response of S. mutans. actA overexpression increased the sensitivity of S. mutans to hydrogen peroxide and diminished its competitive ability against Streptococcus sanguinis. In contrast, actA deletion enhanced oxidative stress tolerance and competitiveness of S. mutans. The mass spectrometric analysis identified pyruvate kinase (PykF) as a substrate of ActA, with its acetylation impairing its enzymatic activity and reducing pyruvate production. Supplementation with exogenous pyruvate mitigated oxidative stress sensitivity and restored competitiveness in multi-species biofilms. In vitro acetylation analysis further confirmed that ActA directly acetylates PykF, negatively affecting its enzymatic activity. Moreover, 18 potential lysine-acetylated sites on PykF were identified in vitro, which account for 75% of lysine-acetylated sites detected in vivo. Taken together, our study elucidates a novel regulatory mechanism of ActA-mediated acetylation of PykF in modulating oxidative stress adaptability of S. mutans by influencing pyruvate production, providing insights into the importance of protein acetylation in microbial environmental adaptability and interspecies interactions within dental biofilms. IMPORTANCE: Dental caries poses a significant challenge to global oral health, driven by microbial dysbiosis within dental biofilms. The pathogenicity of Streptococcus mutans, a major cariogenic bacterium, is closely linked to its ability to adapt to changing environments and cellular stresses. Our investigation into the protein acetylation mechanisms, particularly through the acetyltransferase ActA, reveals a critical pathway by which S. mutans modulates its adaptability to oxidative stress, the dominant stressor within dental biofilms. By elucidating how ActA affects the oxidative stress adaptability and competitiveness of S. mutans through the regulatory axis of ActA-PykF-pyruvate, our findings provide insights into the dynamic interplay between cariogenic and commensal bacteria within dental biofilms. This work emphasizes the significance of protein acetylation in bacterial stress response and competitiveness, opening avenues for the development of novel strategies to maintain oral microbial balance within dental biofilms.

Toxin inhibition: Examining tetracyclines, clindamycin, and linezolid.

PURPOSE: The purpose of this review is to discuss the role of toxin inhibition in select infections and to provide recommendations for appropriate antimicrobial selection when toxin inhibition is indicated. SUMMARY: For select organisms, specifically Clostridioides difficile, Staphylococcus aureus, and Streptococcus pyogenes, toxin production plays an integral role in overall disease pathogenesis and progression. Some expert recommendations include utilization of an antimicrobial with toxin inhibition properties as primary or adjunctive therapy for certain infections due to these organisms, but evolving data have made the choice of antitoxin agent less clear. Clindamycin has been the long-standing standard of care agent for toxin inhibition in necrotizing S. aureus and S. pyogenes infections, but linezolid shows promise as an alternative either in the setting of drug shortages or simply when clindamycin is not optimal, while tetracyclines require further study for this indication. The role for adjunctive toxin inhibition in C. difficile infection (CDI) is less defined, as current first-line therapies already have antitoxin properties. CONCLUSION: Toxin inhibition plays a key role in successful management of patients with infections due to toxin-producing organisms. Adjunctive therapy with a tetracycline could be considered in severe, fulminant CDI, but the associated benefit is variable. The benefit of antitoxin treatment for necrotizing S. aureus and S. pyogenes has been more consistently documented. Recent studies support linezolid as an alternative to clindamycin as an adjunctive S. aureus treatment or as monotherapy when appropriate.

Maternal Streptococcus agalactiae colonization in Europe: data from the multi-center DEVANI study.

INTRODUCTION: Despite national guidelines and use of intrapartum antibiotic prophylaxis (IAP), Streptococcus agalactiae (group B streptococci (GBS)) is still a leading cause of morbidity and mortality in newborns in Europe and the United States. The European DEVANI (Design of a Vaccine Against Neonatal Infections) program assessed the neonatal GBS infection burden in Europe, the clinical characteristics of colonized women and microbiological data of GBS strains in colonized women and their infants with early-onset disease (EOD). METHODS: Overall, 1083 pregnant women with a GBS-positive culture result from eight European countries were included in the study. Clinical obstetrical information was collected by a standardized questionnaire. GBS strains were characterized by serological and molecular methods. RESULTS: Among GBS carriers included in this study after testing positive for GBS by vaginal or recto-vaginal sampling, 13.4% had at least one additional obstetrical risk factor for EOD. The five most common capsular types (i.e., Ia, Ib, II, III and V) comprised ~ 93% of GBS carried. Of the colonized women, 77.8% received any IAP, and in 49.5% the IAP was considered appropriate. In our cohort, nine neonates presented with GBS early-onset disease (EOD) with significant regional heterogeneity. CONCLUSIONS: Screening methods and IAP rates need to be harmonized across Europe in order to reduce the rates of EOD. The epidemiological data from eight different European countries provides important information for the development of a successful GBS vaccine.

S100A12 inhibits Streptococcus pneumoniae and aids in wound healing of corneal epithelial cells both in vitro and in vivo.

Streptococcus pneumoniae, a leading cause of corneal infections worldwide, are extremely aggressive despite antibiotic sensitivity and exhibit increased resistance towards antibiotics. Antimicrobial peptides are often considered as potent alternatives against antibiotic resistance and here we have investigated the possible roles of S100A12, a host defense peptide, in wound healing and S. pneumoniae infection. S100A12 significantly inhibited growth of S. pneumoniae by disruption of membrane integrity along with increased generation of reactive oxygen species. Additionally, S100A12 accelerated cell migration and wound closure in human corneal epithelial cells and in a murine corneal wound model by activation of EGFR and MAPK signaling pathways.

Mechanism of KLF2 in young mice with pneumonia induced by Streptococcus pneumoniae.

BACKGROUND: Streptococcus pneumoniae (Spn) is a major causative agent of pneumonia, which can disseminate to the bloodstream and brain. Pneumonia remains a leading cause of death among children aged 1-59 months worldwide. This study aims to investigate the role of Kruppel-like factor 2 (KLF2) in lung injury caused by Spn in young mice. METHODS: Young mice were infected with Spn to induce pneumonia, and the bacterial load in the bronchoalveolar lavage fluid was quantified. KLF2 expression in lung tissues was analyzed using real-time quantitative polymerase chain reaction and Western blotting assays. Following KLF2 overexpression, lung tissues were assessed for lung wet-to-dry weight ratio and Myeloperoxidase activity. The effects of KLF2 on lung injury and inflammation were evaluated through hematoxylin and eosin staining and enzyme-linked immunosorbent assay. Chromatin immunoprecipitation and dual-luciferase assay were conducted to examine the binding of KLF2 to the promoter of microRNA (miR)-222-3p and cyclin-dependent kinase inhibitor 1B (CDKN1B), as well as the binding of miR-222-3p to CDKN1B. Levels of miR-222-3p and CDKN1B in lung tissues were also determined. RESULTS: In young mice with pneumonia, KLF2 and CDKN1B were downregulated, while miR-222-3p was upregulated in lung tissues. Overexpression of KLF2 reduced lung injury and inflammation, evidenced by decreased bacterial load, reduced lung injury, and lower levels of proinflammatory factors. Co-transfection of miR-222-3p-WT and oe-KLF2 significantly reduced luciferase activity, suggesting that KLF2 binds to the promoter of miR-222-3p and suppresses its expression. Transfection of CDKN1B-WT with miR-222-3p mimics significantly reduced luciferase activity, indicating that miR-222-3p binds to CDKN1B and downregulates its expression. Overexpression of miR-222-3p or downregulation of CDKN1B increased bacterial load in BALF, lung wet/dry weight ratio, MPO activity, and inflammation, thereby reversing the protective effect of KLF2 overexpression on lung injury in young mice with pneumonia. CONCLUSIONS: KLF2 alleviates lung injury in young mice with Spn-induced pneumonia by transcriptional regulation of the miR-222-3p/CDKN1B axis.