Function and therapeutic prospects of next-generation probiotic Akkermansia muciniphila in infectious diseases.

Akkermansia muciniphila is a gram-negative bacterium that colonizes the human gut, making up 3-5% of the human microbiome. A. muciniphila is a promising next-generation probiotic with clinical application prospects. Emerging studies have reported various beneficial effects of A. muciniphila including anti-cancer, delaying aging, reducing inflammation, improving immune function, regulating nervous system function, whereas knowledge on its roles and mechanism in infectious disease is currently unclear. In this review, we summarized the basic characteristics, genome and phenotype diversity, the influence of A. muciniphila and its derived components on infectious diseases, such as sepsis, virus infection, enteric infection, periodontitis and foodborne pathogen induced infections. We also provided updates on mechanisms how A. muciniphila protects intestinal barrier integrity and modulate host immune response. In summary, we believe that A. muciniphila is a promising therapeutic probiotic that may be applied for the treatment of a variety of infectious diseases.

The effect of leucocytosis on retinopathy of prematurity.

Postnatal leukocytosis reflects the general condition of inflammatory. Infection and inflammatory reaction have been proven to affect the occurrence of ROP and other visual dysfunction. Infants with a gestational age of < 28 weeks who were less than three days of age and admitted to the hospital between September 2015 and March 2021 were included in the study. Infants with a white blood cell (WBC) count ≥ 30 × 109/L were assigned to the leucocytosis group (n = 82). Gestational age- and weight-matched infants without leucocytosis were included as a control group (n = 85). The incidence and prognosis of ROP in preterm infants were compared between the groups. Receiver operating characteristic (ROC) curves were used to analyse the correlation between the WBC count and severe ROP. Compared to the infants in the control group, those in the leucocytosis group had lower 1-min Apgar scores (p < 0.001); higher C-reactive protein (p < 0.001) and procalcitonin (p < 0.001); and higher incidences of intracranial haemorrhage (p = 0.007), leukomalacia (p = 0.045), sepsis (p = 0.006), bronchopulmonary dysplasia (p = 0.017). The maternal age was higher in the leucocytosis group (p < 0.001). After adjusting for gestational age at 45 weeks, the incidence of severe ROP (p = 0.001) and the requirement for ranibizumab injections (p = 0.004) were higher in the leucocytosis group. The cut-off WBC count was determined to be 19.1 × 109/L, with a sensitivity of 88.6%, a specificity of 77.3%, and an area under the curve of 0.941 (95% confidence interval: 0.904-0.978) for the detection of severe ROP. Leucocytosis may be associated with severe ROP in premature infants.

Roles of two-component regulatory systems in Klebsiella pneumoniae: Regulation of virulence, antibiotic resistance, and stress responses.

Klebsiella pneumoniae is an opportunistic pathogen belonging to the Enterobacteriaceae family, which is the leading cause of nosocomial infections. The emergence of hypervirulent and multi-drug resistant K. pneumoniae is a serious health threat. In the process of infection, K. pneumoniae needs to adapt to different environmental conditions, and the two-component regulatory system (TCS) composed of a sensor histidine kinase and response regulator is an important bacterial regulatory system in response to external stimuli. Understanding how K. pneumoniae perceives and responds to complex environmental stimuli provides insights into TCS regulation mechanisms and new targets for drug design. In this review, we analyzed the TCS composition and summarized the regulation mechanisms of TCSs, focusing on the regulation of genes involved in virulence, antibiotic resistance, and stress response. Collectively, these studies demonstrated that several TCSs play important roles in the regulation of virulence, antibiotic resistance and stress responses of K. pneumoniae. A single two-component regulatory system can participate in the regulation of several stress responses, and one stress response process may include several TCSs, forming a complex regulatory network. However, the function and regulation mechanism of some TCSs require further study. Hence, future research endeavors are required to enhance the understanding of TCS regulatory mechanisms and networks in K. pneumoniae, which is essential for the design of novel drugs targeting TCSs.

[Clinical characteristics and risk factors for early-onset necrotizing enterocolitis in preterm infants with very/extremely low birth weight]. / 极/è¶ ä½Žå‡ºç”Ÿä½“é‡æ—©äº§å„¿æ—©å‘åž‹åæ­»æ€§å°è‚ ç»“è‚ ç‚Žä¸´åºŠç‰¹å¾å’Œå±é™©å› ç´ åˆ†æž.

OBJECTIVES: To investigate the clinical characteristics and risk factors for early-onset necrotizing enterocolitis (NEC) in preterm infants with very/extremely low birth weight (VLBW/ELBW). METHODS: A retrospective analysis was performed on the medical data of 194 VLBW/ELBW preterm infants with NEC who were admitted to Children's Hospital Affiliated to Zhengzhou University from January 2014 to December 2021. These infants were divided into early-onset group (onset in the first two weeks of life; n=62) and late-onset group (onset two weeks after birth; n=132) based on their onset time. The two groups were compared in terms of perinatal conditions, clinical characteristics, laboratory examination results, and clinical outcomes. Sixty-two non-NEC infants with similar gestational age and birth weight who were hospitalized at the same period as these NEC preterm infants were selected as the control group. The risk factors for the development of early-onset NEC were identified using multivariate logistic regression analysis. RESULTS: Compared with the late-onset group, the early-onset group had significantly higher proportions of infants with 1-minute Apgar score ≤3, stage III NEC, surgical intervention, grade ≥3 intraventricular hemorrhage, apnea, and fever or hypothermia (P<0.05). The multivariate logistic regression analysis showed that feeding intolerance, blood culture-positive early-onset sepsis, severe anemia, and hemodynamically significant patent ductus arteriosus were independent risk factors for the development of early-onset NEC in VLBW/ELBW preterm infants (P<0.05). CONCLUSIONS: VLBW/ELBW preterm infants with early-onset NEC have more severe conditions compared with those with late-onset NEC. Neonates with feeding intolerance, blood culture-positive early-onset sepsis, severe anemia, or hemodynamically significant patent ductus arteriosus have a higher risk of early-onset NEC.

Epidemiological characteristics and antibiotic resistance mechanisms of Streptococcus pneumoniae: An updated review.

Streptococcus pneumoniae (S. pneumoniae, pneumococcus) is a Gram-positive bacterium, which can cause a variety of diseases including otitis media, nasosinusitis, pneumonia, bacteremia and meningitis. To prevent and control pneumococcus diseases, pneumococcal conjugate vaccines (PCVs) were developed and widely implemented worldwide. The introduction of PCVs reduced the infections caused by PCV serotypes, while serotype replacements affected vaccine effectiveness. S. pneumoniae has developed resistance to multiple antibiotics including penicillin, macrolides, fluoroquinolone, and sulfamethoxazole-trimethoprim. In turn, infections caused by antibiotic resistant strains can affect the treatment of related diseases. Genetic functional studies, molecular detection, and molecular characterization of newly identified mechanisms have been updated in recent years. Hence, this review aims to summarize the serotype distribution, epidemiology and antibiotic resistance mechanism of S. pneumoniae in the vaccine era. A greater understanding of the epidemiological features and antibiotic resistance mechanisms could ultimately assist clinical treatment and prevent the spread of antibiotic resistance strains.

Species-level respiratory microbiome profiling for etiologic diagnosis of children pneumonia using full length 16S rRNA gene sequencing.

PURPOSE: The study was conducted to analyze the role of respiratory microbiome composition in children pneumonia etiology diagnosis. METHODS: The bronchoalveolar lavage fluid bacterial community between the Mycoplasma pneumoniae pneumonia (MP group, n â€‹= â€‹13) and the pathogen negative pneumonia (N group, n â€‹= â€‹20) children were compared using the full-length 16S rRNA gene sequencing. RESULTS: Distinct bacterial communities were identified in two groups and lower α-diversity was revealed in the MP patients indicating the lower abundance microbiota composition. Dominant bacteria were Mycoplasma and Mycoplasma pneumoniae for MP patients at genus and species levels. Possible pathogens were characterized in 17 out of 20 patients in the N group by detection of higher abundance using the 16S rRNA gene sequencing. CONCLUSIONS: The high taxonomic resolution of full-length 16S rRNA gene sequencing assists in improving characterization of potential pathogens, and more studies are necessary to further evaluate the prognostic roles of specific bacteria in the pathogenicity of pneumonia.

Global spread of carbapenem-resistant Enterobacteriaceae: Epidemiological features, resistance mechanisms, detection and therapy.

Bacterial drug resistance has become a global public health threat, among which the infection of carbapenem-resistant Enterobacterales (CRE) is one of the top noticeable issues in the global anti-infection area due to limited therapy options. In recent years, the prevalence of CRE transmission around the world has increased, and the transmission of COVID-19 has intensified the situation to a certain extent. CRE resistance can be induced by carbapenemase, porin, efflux pump, penicillin-binding protein alteration, and biofilm production. Deletion, mutation, insertion, and post-transcriptional modification of corresponding coding genes may affect the sensitivity of Enterobacterales bacteria to carbapenems. Clinical and laboratory methods to detect CRE and explore its resistance mechanisms are being developed. Due to the limited options of antibiotics, the clinical treatment of CRE infection also faces severe challenges. The clinical therapies of CRE include single or combined use of antibiotics, and some new antibiotics and treatment methods are also being developed. Hence, this review summarizes the epidemiology, resistance mechanisms, screening and clinical treatments of CRE infection, to provide references for clinical prevention, control and treatment of CRE infection.

Molecular beacon based real-time PCR p1 gene genotyping, macrolide resistance mutation detection and clinical characteristics analysis of Mycoplasma pneumoniae infections in children.

BACKGROUND: Mycoplasma pneumoniae can be divided into different subtypes on the basis of the sequence differences of adhesive protein P1, but the relationship between different subtypes, macrolide resistance and clinical manifestations are still unclear. In the present study, we established a molecular beacon based real-time polymerase chain reaction (real-time PCR) p1 gene genotyping method, analyzed the macrolide resistance gene mutations and the relationship of clinical characteristics with the genotypes. METHODS: A molecular beacon based real-time PCR p1 gene genotyping method was established, the mutation sites of macrolide resistance genes were analyzed by PCR and sequenced, and the relationship of clinical characteristics with the genotypes was analyzed. RESULTS: The detection limit was 1-100 copies/reaction. No cross-reactivity was observed in the two subtypes. In total, samples from 100 patients with positive M. pneumoniae detection results in 2019 and 2021 were genotyped using the beacon based real-time PCR method and P1-1 M. pneumoniae accounted for 69.0%. All the patients had the A2063G mutation in the macrolide resistance related 23S rRNA gene. Novel mutations were also found, which were C2622T, C2150A, C2202G and C2443A mutations. The relationship between p1 gene genotyping and the clinical characteristics were not statistically related. CONCLUSION: A rapid and easy clinical application molecular beacon based real-time PCR genotyping method targeting the p1 gene was established. A shift from type 1 to type 2 was found and 100.0% macrolide resistance was detected. Our study provided an efficient method for genotyping M. pneumoniae, valuable epidemiological monitoring information and clinical treatment guidance to control high macrolide resistance.

Comparative Genomic Analysis of Streptococcus pneumoniae Strains: Penicillin Non-susceptible Multi-drug-Resistant Serotype 19A Isolates.

Streptococcus pneumoniae can cause several diseases including otitis media, sinusitis, pneumonia, sepsis and meningitis. The introduction of pneumococcal vaccines has changed the molecular epidemiological and antibiotic resistance profiles of related diseases. Analysis of molecular patterns and genome sequences of clinical strains may facilitate the identification of novel drug resistance mechanism. Three multidrug resistance 19A isolates were verified, serotyped and the complete genomes were sequenced combining the Pacific Biosciences and the Illumina Miseq platform. Genomic annotation revealed that similar central networks were found in the clinical isolates, and Mauve alignments indicated high similarity between different strains. The pan-genome analysis showed the shared and unique cluster in the strains. Mobile elements were predicted in the isolates including prophages and CRISPER systems, which may participate in the virulence and antibiotic resistance of the strains. The presence of 31 virulence factor genes was predicted from other pathogens for PRSP 19339 and 19343, while 30 for PRSP 19087. Meanwhile, 33 genes antibiotic resistance genes were predicted including antibiotic resistance genes, antibiotic-target genes and antibiotic biosynthesis genes. Further analysis of the antibiotic resistance genes revealed new mutations in the isolates. By comparative genomic analysis, we contributed to the understanding of resistance mechanism of the clinical isolates with other serotype strains, which could facilitate the concrete drug resistance mechanism study.

Using ROPScore and CHOP ROP for early prediction of retinopathy of prematurity in a Chinese population.

PURPOSE: Retinopathy of prematurity (ROP) is a disease that causes vision loss, vision impairment, and blindness, most frequently manifesting among preterm infants. ROPScore and CHOP ROP (Children's Hospital of Philadelphia ROP) are similar scoring models to predict ROP using risk factors such as postnatal weight gain, birth weight (BW), and gestation age (GA). The purpose of this study was to compare the accuracy and difference between using ROPScore and CHOP ROP for the early prediction of ROP. METHODS: A retrospective study was conducted from January 2009 to December 2019 in China. Patients eligible for enrollment included infants admitted to NICU at ≤32 weeks GA or those with ≤1500 g BW. The sensitivity and specificity of ROPScore and CHOP ROP were analyzed, as well as its suitability as an independent predictor of ROP. RESULTS: Severe ROP was found in 5.0% of preterm infants. The sensitivity and specificity of the ROPScore test at any stage of ROP was 55.8 and 77.8%, respectively. For severe ROP, the sensitivity and specificity was 50 and 87.0%, respectively. The area under the receiver operating characteristic curve for the ROPScore for predicting severe ROP was 0.76. This value was significantly higher than the values for birth weight (0.60), gestational age (0.73), and duration of ventilation (0.63), when each was category measured separately. For the CHOP ROP, it correctly predicted infants who developed type 1 ROP (sensitivity, 100%, specificity, 21.4%). CONCLUSIONS: The CHOP ROP model predicted infants who developed type 1 ROP at a sensitivity of 100% whereas ROPScore had a sensitivity of 55.8%. Therefore, the CHOP ROP model is more suitable for Chinese populations than the ROPScore test. CLINICAL REGISTRATION NUMBER AND STROBE GUIDELINES: This article was a retrospective cohort study and reported the results of the ROPScore and CHOP ROP algorithms. No results pertaining to interventions on human participants were reported. Thus, registration was not required and this study followed STROBE guidelines.

Effect of early prophylactic low-dose recombinant human erythropoietin on retinopathy of prematurity in very preterm infants.

BACKGROUND: Very preterm infants are at risk of developing retinopathy of prematurity (ROP). Recombinant human erythropoietin (rhEPO) is routinely used to prevent anemia in preterm infants; however, the effect of rhEPO on ROP development is still controversial. The purpose of this study was to evaluate the effect of early prophylactic low-dose rhEPO administration on ROP development in very preterm infants. METHODS: A total of 1898 preterm infants born before 32 weeks of gestation were included. Preterm infants received rhEPO (n = 950; 500 U/kg, rhEPO group) or saline (n = 948, control group) intravenously within 72 h of birth and then once every other day for 2 weeks. RESULTS: The total incidence of ROP was not significantly different between the two groups (10.2% vs. 13.2%, p = 0.055). Further analysis showed that rhEPO group had lower rates of type 2 ROP than the control group (2.2% vs. 4.1%, RR 0.98; 95% CI 0.96-1.00; p = 0.021). Subgroup analysis found that rhEPO treatment significantly decreased the incidence of type 2 ROP in infant boys (1.8% vs. 4.3%, p = 0.021) and in those with a gestational age of 28-296/7 weeks (1.1% vs. 4.9%, p = 0.002) and birth weight of 1000-1499 g (1.2% vs. 4.2%, p = 0.002). There was a small increasing tendency for the incidence of ROP in infants with a gestational age of < 28 weeks after rhEPO treatment. CONCLUSIONS: Repeated low-dose rhEPO administration has no significant influence on the development of ROP; however, it may be effective for type 2 ROP in infant boys or in infants with gestational age > 28 weeks and birth weight > 1500 g. Trial registration The data of this study were retrieved from two clinical studies registered ClinicalTrials.gov (NCT02036073) on January 14, 2014, https://clinicaltrials.gov/ct2/show/NCT02036073 ; and (NCT03919500) on April 18, 2019. https://clinicaltrials.gov/ct2/show/NCT03919500 .