- Volume 70, Issue 7, 2021
Volume 70, Issue 7, 2021
- Antimicrobial Resistance
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A stop–gain mutation in sigma factor SigH (MAB_3543c) may be associated with tigecycline resistance in Mycobacteroides abscessus
More LessIntroduction. Tigecycline is currently acknowledged to be one of the most effective antibiotics against infections caused by Mycobacteroides abscessus .
Gap statement. The genetic determinants of tigecycline resistance in M. abscessus are not well understood.
Aim. In this study, we characterized a tigecycline-resistant M. abscessus mutant, designated CL7, to identify the potential resistance mechanism.
Methodology. CL7 was characterized using antimicrobial susceptibility testing, whole-genome sequencing, PCR and RT-qPCR. For biological verification, gene overexpression assays were carried out.
Results. Whole-genome sequencing and the subsequent gene overexpression assays showed that CL7 harboured a stop–gain mutation in MAB_3543 c, which may be responsible for the tigecycline resistance phenotype. This gene encodes an orthologue of SigH, which is involved in the positive regulation of physiological stress response and is negatively regulated by the RshA anti-sigma factor in Mycobacterium tuberculosis . We hypothesized that the MAB_3543 c mutation may disrupt the interaction between SigH and RshA (MAB_3542 c). RT-qPCR analyses revealed the upregulation of MAB_3543 c and other key stress response genes, which has previously been shown to be a hallmark of SigH–RshA bond disruption and tigecycline resistance.
Conclusion. The MAB_3543c mutation may represent a novel determinant of tigecycline resistance in M. abscessus . The findings of this study will hopefully contribute to our knowledge of potential tigecycline resistance mechanisms in M. abscessus , which may lead to better diagnostics and treatment modalities in the future.
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mCIM test as a reliable assay for the detection of CRE in the Gulf region
Introduction. Carbapenem resistant Enterobacterales (CRE) are one of the leading causes of systemic and nosocomial infections and are multidrug-resistant organisms producing different carbapenemases. There are many genotypic and phenotypic methods for detecting the carbapenemases; however, there is a limitation for each. Modified carbapenem inactivation method (mCIM) assay is a recent phenotypic method which has been published by the Clinical and Laboratory Standards Institute.
Hypothesis / Gap Statement. mCIM assay could provide a reliable method for the detection of carbapenemases in CRE.
Aim. Evaluation of the mCIM assay performance for the detection of carbapenemases in Enterobacterales and the identification of the common carbapenemase genes at Eastern Province of Saudi Arabia and Kingdom of Bahrain.
Methodology. A collection of 197 non-duplicate carbapenem resistant Enterobacterales clinical isolates, were evaluated with the mCIM test comparing its performance to multiplex PCR. The minimum inhibitory concentration susceptibility testing was done by the Etest method for imipenem, meropenem, and ertapenem.
Results. The sensitivity of the mCIM assay was 94 % (95 % CI, (89.3–97.1)). In Saudi Arabia and Bahrain, OXA-48 was the most prevalent carbapenemase gene followed by NDM. Coexistence of multiple carbapenemase genes is reported in eleven cases.
Conclusion. These findings indicate that the mCIM test is a reliable and simple assay for detecting the activity of carbapenemase in Enterobacterales , especially in resource-limited laboratories.
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Fluoroquinolone resistance in non-typhoidal Salmonella enterica isolated from slaughtered pigs in Thailand
Introduction. The emergence and spread of non-typhoidal Salmonella enterica (NTS) serovars resistant to fluoroquinolones and third- and higher-generation cephalosporins is a matter of great concern. Antimicrobial-resistant NTS is increasingly being discovered in humans, animals, food animals, food products, and agricultural environments. Pigs are considered a major reservoir of antimicrobial-resistant Salmonella spp.
Hypothesis/Gap Statement. Fluoroquinolone-resistant Salmonella spp. warrant further surveillance and characterization for a better understanding of the bacteria isolated from animals.
Aim. NTS isolated from pork from slaughterhouses across Thailand were characterized in terms of their serovars; resistance to fluoroquinolones, third-generation cephalosporins, and carbapenems; and antimicrobial resistance genes.
Methodology. A total of 387 NTS isolates, collected from slaughtered pigs in ten provinces across Thailand between 2014 and 2015, were characterized based on their serovars, antimicrobial resistance genes, and susceptibility to fluoroquinolones, third-generation cephalosporins, and carbapenems.
Results. Among all NTS isolates, S. enterica serovar Rissen was predominant. Antimicrobial resistance was exhibited in 93/387 isolates (24 %). Although 24 (6.2 %) isolates were susceptible to all the tested antimicrobials, they were found to possess β-lactamase genes, such as bla TEM, bla SHV, or bla CTX-M. Mobilized colistin-resistant genes (mcr) and resistance to colistin were not observed in any tested isolate. Carbapenem resistance was detected in ten isolates (10.7 %); however, bla KPC, bla NDM, bla OXA-48-like, and bla IMP were not present. Among the 93 antimicrobial-resistant isolates, 87.1 % showed fluoroquinolone resistance with the quinolone resistance gene (qnrS) combined with topoisomerase genes parC (T57S) or gyrA (S83E/Y and D124E/G) substitutions, or topoisomerase gene substitutions alone.
Conclusion. We found high fluoroquinolone resistance rates among the NTS isolates from pigs from slaughterhouses. The fluoroquinolone resistance mechanism in NTS was associated with the combination of qnrS and substitutions in gyrA, parC, or both. To prevent the transmission of antimicrobial-resistant NTS between animals and humans, continuous monitoring, surveillance, and regulation of Salmonella in the pork supply chain are pivotal.
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- Clinical Microbiology
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Acceptable performance of the Abbott ID NOW among symptomatic individuals with confirmed COVID-19
Introduction. The ID NOW is FDA approved for the detection of SARS-CoV-2 in symptomatic individuals within the first 7 days of symptom onset for COVID-19 if tested within 1 h of specimen collection.
Gap statement. Clinical data on the performance of the ID NOW are limited, with many studies varying in their study design and/or having small sample size.
Aim. In this study we aimed to determine the clinical performance of the ID NOW compared to conventional RT-PCR testing.
Methodology. Adults with COVID-19 in the community or hospital were recruited into the study. Paired throat swabs were collected, with one throat swab transported immediately in an empty sterile tube to the laboratory for ID NOW testing, and the other transported in universal transport media and tested by an in-house SARS-CoV-2 RT-PCR assay targeting the E gene.
Results. In total, 133 individuals were included in the study; 129 samples were positive on either the ID NOW and/or RT-PCR. Assuming any positive result on either assay represents a true positive, positive per cent agreement (PPA) of the ID NOW compared to RT-PCR with 95 % confidence intervals was 89.1 % (82.0–94.1%) and 91.6 % (85.1–95.9%), respectively. When analysing individuals with symptom duration ≤7 days and who had the ID NOW performed within 1 h (n=62), ID NOW PPA increased to 98.2 %.
Conclusion. Results from the ID NOW were reliable, especially when adhering to the manufacturer’s recommendations for testing.
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The emerging importance of Shiga toxin-producing Escherichia coli other than serogroup O157 in England
Introduction. Shiga toxin-producing Escherichia coli (STEC) can cause severe disease and large outbreaks. In England, the incidence and clinical significance of STEC serogroups other than O157 (non-O157) is unknown due to a testing bias for detection of STEC O157. Since 2013, the implementation of PCR to detect all STEC serogroups by an increasing number of diagnostic laboratories has led to an increase in the detection of non-O157 STEC.
Hypothesis/Gap statement. Due to a bias in testing methodologies to select for STEC serogroup O157 in frontline diagnostic laboratories in most countries, very little surveillance data have been previously generated on non-O157 STEC.
Aim. Five years (2014–2018) of STEC national surveillance data were extracted and descriptive analysis undertaken to assess disease severity of non-O157 STEC strains.
Methods. Data from 1 January 2014 to 31 December 2018 were extracted from the National Enhanced Surveillance System for STEC and analysed.
Results. The implementation of Gastrointestinal Polymerase Chain Reaction (GI-PCR) has resulted in a four-fold increase in the detection of non-O157 STEC cases between 2014 and 2018. There were 2579 cases infected with 97 different non-O157 serogroups. The gender distribution was similar amongst STEC O157 and non-O157 STEC cases with 57 and 56 % of cases being female respectively, but a significantly higher proportion of cases (P <0.001) under 5 years of age was observed among STEC O157 (22 %) cases compared to non-O157 STEC (14 %). The most common non-O157 serogroups were O26 (16 %), O146 (11 %), O91 (10 %), O128 (7 %), O103 (5 %) and O117 (3 %). Overall, rates of bloody diarrhoea were highest in O26 (44 %) and O103 (48 %) cases and lowest in STEC O117 cases (17 %). Strains harbouring Shiga toxin stx1a caused the highest proportion of diarrhoea (93 %) and caused the same level of bloody diarrhoea as stx2a (39 %). However, stx2a caused the highest proportion of vomiting (46 %), hospitalisation (49 %) and considerably more HUS (29 %) than other stx profiles.
Conclusion. The implementation of PCR targeting stx at diagnostic laboratories has shown that non-O157 STEC, most notably STEC O26, are an emerging risk to public health.
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Performance of a loop-mediated isothermal amplification assay (Isoplex CRE-ART) to detect common carbapenemase-encoding genes in Gram-negative bacteria
Carbapenem-resistant Gram-negative bacteria (CR-GNB) are a major source of nosocomial infections worldwide. In this study, the ability of a loop-mediated isothermal amplification (LAMP)-based method (Isoplex CRE-ART) to rapidly detect carbapenemase-encoding genes bla OXA-48-like, bla OXA-23-like, bla OXA-24-like, bla KPC, bla VIM, bla NDM and bla IMP in 231 carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii isolates was investigated. The accuracy of the LAMP test was compared to results of molecular isolate characterization using a Laboratory Developed Test multiplex carbapenemase PCR assay. The LAMP test correctly identified the presence of on-panel carbapenemases with a sensitivity of 99.16 % [95 % confidence interval (CI): 95.39–99.96 %] and a specificity of 98.21 % (95 % CI: 93.72–99.68 %) in 60 min. Our findings suggest that the Isoplex CRE-ART assay is able to rapidly identify carbapenemase genes in CR-GNB and improves options for pathogen characterization in the context of clinical microbiological and infection control diagnostics.
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Hospital transmission of borderline oxacillin-resistant Staphylococcus aureus evaluated by whole-genome sequencing
Introduction. Staphylococcus aureus is a major cause of hospital infections worldwide. Awareness towards methicillin-resistant S. aureus (MRSA) infections is high but attention towards borderline oxacillin-resistant S. aureus (BORSA) is limited, possibly due to an underestimated clinical relevance, presumption of low incidence and diagnostic limitations.
Gap statement. BORSA surveillance has not been routinely implemented, and thus consensus with regard to a definition and infection control measures is lacking.
Aim. Our goals were to investigate the occurrence, molecular characteristics and clinical manifestations of BORSA infections in the hospital setting.
Methodology. Following an increased incidence in 2016, BORSA cases in 2014/2016 (in our institution) were more specifically evaluated. Medical records were reviewed to investigate epidemiological links, clinical characteristics and outcomes. Resistance and virulence markers were assessed by whole genome sequencing (WGS). Conventional methods: amplified fragment length polymorphism (AFLP) ; multilocus sequence typing (MLST) and multiple locus variable-number tandem repeat analysis (MLVA) were compared with core genome MLST (cgMLST) and whole-genome single nucleotide polymorphism (wgSNP) analysis to confirm genetic clusters.
Results. From 2009 to 2013, BORSA comprised 0.1 % of all clinical S. aureus strains. In 2016, the incidence was six-fold higher in comparison to the baseline. Whole-genome SNP and cgMLST confirmed two BORSA clusters among patients with dermatological conditions. Patients with BORSA presented with skin infections, and one case developed a severe invasive infection with a fatal outcome. Infection control measures successfully prevented further transmission in both clusters. WGS findings showed that BORSA strains carried multiple resistance and virulence genes with increased pathogenic potential.
Conclusion. WGS and cgMLST effectively characterized and confirmed BORSA clusters among at-risk patients with clinical manifestations ranging from mild skin infections to life-threatening bacteraemia. Clinical awareness and active monitoring are therefore warranted for the timely implementation of infection control measures to prevent BORSA transmission in high-risk patients.
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Rapid typing of carbapenem-resistant Acinetobacter baumannii and Acinetobacter nosocomialis by multiplex Pan- and OXA-PCR assays
Introduction. Outbreaks of carbapenem-resistant A. baumannii and A. nosocomialis have occurred worldwide in healthcare settings. Rapid and reliable molecular typing of bacterial isolates is vital for the effective surveillance of institutional outbreaks. The Pan-PCR and OXA-PCR assays are two multiplex PCR-based assays for the molecular typing of Acinetobacter species.
Gap statement. However, few studies have investigated the discriminatory power of two multiplex PCR assays in in the genotyping of Acinetobacter species.
Aim. We aimed to evaluate the efficacies of the Pan-PCR and OXA-PCR assays for molecular typing of A. baumannii and A. nosocomialis .
Methodology. A total of 105 carbapenem-resistant A. baumannii isolates (CRABs) and 93 carbapenem-resistant A. nosocomialis isolates (CRANs) obtained from blood cultures were used for molecular typing by the Pan-PCR and OXA-PCR assays and two multilocus sequence typing (MLST) schemes.
Results. The isolates were individually divided into 12 and 21 different sequence types via the Pasteur and Oxford MLST schemes, respectively. Additionally, these isolates were distinguished into 18 different types by the Pan-PCR and OXA-PCR assays. The results of the Pan-PCR and OXA-PCR assays distinguished CRABs and CRANs with a sensitivity of 98.13 % and a specificity of 100 %.
Conclusion. The Pan-PCR and OXA-PCR assays are promising alternative methods for rapid molecular typing of CRABs and CRANs in a routine laboratory setting.
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A review of in vitro attempts to develop the axenic culture of Treponema pallidum and genomics-based suggestions to achieve this elusive goal
More LessTo date, the axenic culture of Treponema pallidum remains a challenge in the field of microbiology despite countless attempts. Here, we conducted a comprehensive bibliographic analysis using several databases and search engines, namely Pubmed, Google scholar, Google, Web of Science and Scopus. Numerous unsuccessful empiric studies have been conducted and evaluated using as criteria dark-field microscopic observation of motile spiral shaped cells in the culture and virulence of the culture through rabbit infectivity. All of these studies failed to induce rabbit infectivity, even when deemed positive after microscopic observation leading to the misnomer of avirulent T. pallidum . In fact, this criterion was improperly chosen because not all spiral shaped cells are T. pallidum . However, these studies led to the formulation of culture media particularly favourable to the growth of several species of Treponema, including Oral Microbiology and Immunology, Zürich medium (OMIZ), Oral Treponeme Enrichment Broth (OTEB) and T-Raoult, thus allowing the increase in the number of cultivable strains of Treponema . The predicted metabolic capacities of T. pallidum show limited metabolism, also exhibited by other non-cultured and pathogenic Treponema species, in contrast to cultured Treponema species. The advent of next generation sequencing represents a turning point in this field, as the knowledge inferred from the genome can finally lead to the axenic culture of T. pallidum .
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- Disease, Diagnosis and Diagnostics
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Serum biomarkers to differentiate Gram-negative, Gram-positive and fungal infection in febrile patients
Introduction. Contamination of specimens and overuse of broad spectrum antibiotics contribute to false positives and false negatives, respectively. Therefore, useful and applicable biomarkers of bacteremia are still required.
Hypothesis/Gap Statement. IL-6 can be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection.
Aim. We aimed to evaluate the diagnostic efficiency of neutrophil/lymphocyte ratio (NLR), procalcitonin (PCT) and interleukin-6 (IL-6) in discriminating Gram-negative (G−) bacteria from Gram-positive (G+) bacteria and fungi in febrile patients.
Methodology. A total of 567 patients with fever were evaluated. Serum levels of IL-6, PCT, NLR and CRP were compared among a G− group (n=188), a G+ group (n=168), a fungal group (n=38) and a culture negative group (n=173). Sensitivity, specificity, Yuden’s index and area under the Receiver operating characteristic (ROC) curve (AUC) were obtained to analyse the diagnostic abilities of these biomarkers in discriminating bloodstream infection caused by different pathogens.
Results. Serum IL-6 and PCT in the G− group increased significantly when compared with both the G+ group and fungal group (P <0.05). AUC of IL-6 (0.767, 95 % CI:0.725–0.805) is higher than AUC of PCT (0.751, 95 % CI:0.708–0.796) in discriminating the G− group from G+ group. When discriminating the G− group from fungal group, the AUC of IL-6 (0.695, 95 % CI:0.651–0.747) with a cut-off value of 464.3 pg ml−1 was also higher than the AUC of PCT (0.630, 95 % CI:0.585–0.688) with a cut-off value of 0.68 ng ml−1. Additionally, AUC of NLR (0.685, 95 % CI:0.646–0.727) in discriminating the fungal group from G+ group at the cut-off value of 9.03, was higher than AUC of IL-6, PCT and CRP.
Conclusion. This study suggests that IL-6 could be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection. In addition, NLR is valuable to discriminate fungal infections from Gram-positive infections in febrile patients with a bloodstream infection.
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Adaptation of gltA and ssrA assays for diversity profiling by Illumina sequencing to identify Bartonella henselae, B. clarridgeiae and B. koehlerae
Introduction. Bartonellosis is an emerging zoonotic disease caused by bacteria of the genus Bartonella . Mixed Bartonella infections are a well-documented phenomenon in mammals and their ectoparasites. The accurate identification of Bartonella species in single and mixed infections is valuable, as different Bartonella species have varying impacts on infected hosts.
Gap Statement. Current diagnostic methods are inadequate at identifying the Bartonella species present in mixed infections.
Aim. The aim of this study was to adopt a Next Generation Sequencing (NGS) approach using Illumina sequencing technology to identify Bartonella species and demonstrate that this approach can resolve mixed Bartonella infections.
Methodology. We used Illumina PCR amplicon NGS to target the ssrA and gltA genes of Bartonella in fleas collected from cats, dogs and a hedgehog in Israel. We included artificially mixed Bartonella samples to demonstrate the ability for NGS to resolve mixed infections and we compared NGS to traditional Sanger sequencing.
Results. In total, we identified 74 Ctenocephalides felis, two Ctenocephalides canis, two Pulex irritans and three Archaeopsylla e. erinacei fleas. Real-time PCR of a subset of 48 fleas revealed that twelve were positive for Bartonella , all of which were cat fleas. Sanger sequencing of the ssrA and gltA genes confirmed the presence of Bartonella henselae , Bartonella clarridgeiae and Bartonella koehlerae . Illumina NGS of ssrA and gltA amplicons further confirmed the Bartonella species identity in all 12 flea samples and unambiguously resolved the artificially mixed Bartonella samples.
Conclusion. The adaptation and multiplexing of existing PCR assays for diversity profiling via NGS is a feasible approach that is superior to traditional Sanger sequencing for Bartonella speciation and resolving mixed Bartonella infections. The adaptation of other PCR primers for Illumina NGS will be useful in future studies where mixed bacterial infections may be present.
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- Medical Mycology
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8-hydroxyquinoline-5-(N-4-chlorophenyl) sulfonamide and fluconazole combination as a preventive strategy for Candida biofilm in haemodialysis devices
Introduction. The presence of Candida biofilms in medical devices is a concerning and important clinical issue for haemodialysis patients who require constant use of prosthetic fistulae and catheters.
Hypothesis/Gap Statement. This prolonged use increases the risk of candidaemia due to biofilm formation. PH151 and clioquinol are 8-hydroxyquinoline derivatives that have been studied by our group and showed interesting anti-Candida activity.
Aim. This study evaluated the biofilm formation capacity of Candida species on polytetrafluoroethylene (PTFE) and polyurethane (PUR) and investigated the synergistic effects between the compounds PH151 and clioquinol and fluconazole, amphotericin B and caspofungin against biofilm cells removed from those materials. Further, the synergistic combination was evaluated in terms of preventing biofilm formation on PTFE and PUR discs.
Methodology. Susceptibility testing was performed for planktonic and biofilm cells using the broth microdilution method. The checkerboard method and the time–kill assay were used to evaluate the interactions between antifungal agents. Antibiofilm activity on PTFE and PUR materials was assessed to quantify the prevention of biofilm formation.
Results. Candida albicans, Candida glabrata and Candida tropicalis showed ability to form biofilms on both materials. By contrast, Candida parapsilosis did not demonstrate this ability. Synergistic interaction was observed when PH151 was combined with fluconazole in 77.8 % of isolates and this treatment was shown to be concentration- and time-dependent. On the other hand, indifferent interactions were predominantly observed with the other combinations. A reduction in biofilm formation on PUR material of more than 50 % was observed when using PH151 combined with fluconazole.
Conclusion. PH151 demonstrated potential as a local treatment for use in a combination therapy approach against Candida biofilm formation on haemodialysis devices.
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- Microbiome and Microbial Ecology in Health
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Dental biofilm and its ecological interrelationships in ovine periodontitis
Introduction. Periodontitis, one of the most common oral disorders in sheep, is caused by a mixed and opportunistic microbiota that severely affects the health and welfare of animals. However, little is known about the ecological processes involved and the composition of the microbiota associated with the development of the disease.
Hypothesis/Gap Statement. Using high-throughput sequencing of the 16S ribosomal RNA gene and network analysis it would be possible to discriminate the microbiomes of clinically healthy sheep and those with periodontitis and possibly identify the key microorganisms associated with the disease.
Aim. The present study aimed to characterise the composition of dental microbiomes and bacterial co-occurrence networks in clinically healthy sheep and animals with periodontitis.
Methodology. Dental biofilm samples were collected from ten sheep with periodontitis and ten clinically healthy animals. Bacteria were identified using high-throughput sequencing of the 16S ribosomal RNA gene.
Results. The most prevalent genera in the dental microbiota of sheep with periodontitis were Petrimonas , Acinetobacter , Porphyromonas and Aerococcus . In clinically healthy animals, the most significant genera were unclassified Pasteurellaceae, Pseudomonas, and Neisseria. Fusobacterium was found at high prevalence in the microbiomes of both groups. The dental microbiota of sheep in the two clinical conditions presented different profiles and the diversity and richness of bacteria was greater in the diseased animals. Network analyses showed the presence of a large number of antagonistic interactions between bacteria in the dental microbiota of animals with periodontitis, indicating the occurrence of a dysbiotic community. Through the interrelationships, members of the Prevotella genus are likely to be key pathogens, both in the dental microbiota of healthy animals and those with periodontitis. Porphyromonas stood out among the top three nodes with more centrality and the largest number of hubs in the networks of animals with periodontitis.
Conclusion. The dental biofilm microbiota associated with ovine periodontitis is dysbiotic and with significant antagonistic interactions, which discriminates healthy animals from diseased animals and highlights the importance of key bacteria, such as Petrimonas , Porphyromonas , Prevotella and Fusobacterium species.
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- Pathogenesis, Virulence and Host Response
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Shigella escapes lysosomal degradation through inactivation of Rab31 by IpaH4.5
Introduction. Shigella flexneri is an intracellular bacterial pathogen that utilizes a type III secretion apparatus to inject effector proteins into host cells.
Hypothesis/Gap Statement. The T3SS effector IpaH4.5 is important for the virulence of Shigella .
Aim. This study aimed to elucidate the molecular mechanism and host target of the IpaH4.5 as well as its roles in S. flexneri infection.
Methodology. The GAP assay was used to identify substrate Rab GTPases of IpaH4.5. A coimmunoprecipitation assay was applied to identify the interaction of Rab GTPases with IpaH4.5. A confocal microscopy analysis was used to assess the effects of IpaH4.5 on mannose 6-phosphate receptor (MPR) trafficking. To identify the effects of IpaH4.5 GAP activity on the activity of lysosomal cathepsin B, the Magic Red-RR assay was used. Finally, the intracellular persistence assay was used to identify IpaH4.5 GAP activity in S. flexneri intracellular growth.
Results. We found that the effector IpaH4.5 disrupts MPR trafficking and lysosomal function, thereby counteracting host lysosomal degradation. IpaH4.5 harbours TBC-like dual-finger motifs and exhibits potent RabGAP activities towards Rab31. IpaH4.5 disrupts the transport of the cation-dependent mannose 6-phosphate receptor (CD-MPR) from the Golgi to the endosome by targeting Rab31, thereby attenuating lysosomal function. As a result, the intracellular persistence of S. flexneri requires IpaH4.5 TBC-like GAP activity to mediate bacterial escape from host lysosome-mediated elimination.
Conclusion. We identified an unknown function of IpaH4.5 and its potential role in S. flexneri infection.
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- Prevention, Therapy and Therapeutics
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Network pharmacology and molecular docking analysis on mechanisms of Tibetan Hongjingtian (Rhodiola crenulata) in the treatment of COVID-19
Introduction. Coronavirus disease 2019 (COVID-19) is a highly contagious disease and ravages the world.
Hypothesis/Gap Statement. We proposed that R. crenulata might have potential value in the treatment of COVID-19 patients by regulating the immune response and inhibiting cytokine storm.
Aim. We aimed to explore the potential molecular mechanism for Rhodiola crenulata (R. crenulata), against the immune regulation of COVID-19, and to provide a referenced candidate Tibetan herb (R. crenulata) to overcome COVID-19.
Methodology. Components and targets of R. crenulata were retrieved from the TCMSP database. GO analysis and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment were built by R bioconductor package to explore the potential biological effects for targets of R. crenulata. The R. crenulata-compound-target network, target pathway network and protein–protein interaction (PPI) network were constructed using Cytoscape 3.3.0. Autodock 4.2 and Discovery Studio software were applied for molecular docking.
Result. Four bioactive components (quercetin, kaempferol, kaempferol-3-O-α-l-rhamnoside and tamarixetin) and 159 potential targets of R. crenulata were identified from the TCMSP database. The result of GO annotation and KEGG-pathway-enrichment analyses showed that target genes of R. crenulata were associated with inflammatory response and immune-related signalling pathways, especially IL-17 signalling pathway, and TNF signalling pathway. Targets-pathway network and PPI network showed that IL-6, IL-1B and TNF-α were considered to be hub genes. Molecular docking showed that core compound (quercetin) had a certain affinity with IL-1β, IL-6 and TNF-α.
Conclusion. R. crenulata might play an anti-inflammatory and immunoregulatory role in the cytokine storm of COVID-19.
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Volumes and issues
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Volume 73 (2024)
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