Pathogen-related Factors Research Articles

Antimicrobial resistance: Biofilms, small colony variants, and intracellular bacteria

Soft tissue and bone infections continue to be a serious complication in orthopedic and trauma surgery. Both can lead to a high burden for the patients and the healthcare system. Musculoskeletal infections can be induced by intraoperative contamination, bacterial contamination of open wounds or hematogenous bacterial spread. During the recent decades, advances were achieved in the understanding of pathogenesis and antibiotic resistance. Despite some progress in the diagnosis and advancing of therapeutic concepts, groundbreaking successful improvement of treatment concepts is still missing. Current therapy concepts are based on the two pillars consisting of surgical debridement with joint or bone reconstruction as well as prolonged antibiotic therapy. An improved understanding of both host and pathogen-related factors leading to treatment failure is essential in musculoskeletal infections. Therefore, this review aims to give an overview of pathogen-related pathophysiology in musculoskeletal infections. It describes defense strategies of pathogens such as (1) biofilm, its development, characteristics, and treatment options. In addition, (2) characteristics of small colony variants and (3) intracellular bacteria are highlighted. Lastly (4) an outlook for potential and promising future therapeutic strategies is provided.

Genome sequencing and comparative genomics reveal insights into pathogenicity and evolution of Fusarium zanthoxyli, the causal agent of stem canker in prickly ash

BackgroundFusarium zanthoxyli is a destructive pathogen causing stem canker in prickly ash, an ecologically and economically important forest tree. However, the genome lack of F. zanthoxyli has hindered research on its interaction with prickly ash and the development of precise control strategies for stem canker.ResultsIn this study, we sequenced and annotated a relatively high-quality genome of F. zanthoxyli with a size of 43.39 Mb, encoding 11,316 putative genes. Pathogenicity-related factors are predicted, comprising 495 CAZymes, 217 effectors, 156 CYP450s, and 202 enzymes associated with secondary metabolism. Besides, a comparative genomics analysis revealed Fusarium and Colletotrichum diverged from a shared ancestor approximately 141.1 ~ 88.4 million years ago (MYA). Additionally, a phylogenomic investigation of 12 different phytopathogens within Fusarium indicated that F. zanthoxyli originated approximately 34.6 ~ 26.9 MYA, and events of gene expansion and contraction within them were also unveiled. Finally, utilizing conserved domain prediction, the results revealed that among the 59 unique genes, the most enriched domains were PnbA and ULP1. Among the 783 expanded genes, the most enriched domains were PKc_like kinases and those belonging to the APH_ChoK_Like family.ConclusionThis study sheds light on the genetic basis of F. zanthoxyli’s pathogenicity and evolution which provides valuable information for future research on its molecular interactions with prickly ash and the development of effective strategies to combat stem canker.

Mortality patterns in patients with Staphylococcus aureus bacteremia during the COVID-19 pandemic: Predictors and insights

ObjectivesThis paper aims to determine the Staphylococcus aureus bacteremia (SAB) in-hospital mortality rate and its associated risk factors during the COVID-19 pandemic. MethodsA total of 167 SAB samples were collected between March 2020 and March 2022 at a teaching hospital in Tehran, Iran. The patient's baseline data and antibiograms were collected. The outcome of the study was in-hospital mortality. ResultsThe overall in-hospital mortality rate was 41.9 %, with higher mortality observed in patients over 60 years old (P = 0.032), those with community-acquired Staphylococcus aureus bacteremia (P = 0.010), and those admitted to the ICU (P = 0.016). Antibiotic resistance profiles indicated a higher mortality in resistant S.aureus strains but only significant for ciprofloxacin (P = 0.001), methicillin (P = 0.047), and sulfamethoxazole (P = 0.023). Multivariate analysis identified age, sex, ICU admission, and the source of bacteremia as independent predictors of mortality, while COVID-19 coinfection and resistance to antibiotics were not found to be significant predictors. ConclusionSAB remains a challenging infection that is amplified by the pandemic. Older age and ICU admission are significant mortality predictors. In settings with a high prevalence of MRSA, factors like age, sex, and quality of care outweigh pathogen-related factors such as antibiotic resistance.

The ongoing Streptococcus pyogenes (Group A Streptococcus) outbreak in London, United Kingdom, in December 2022: a molecular epidemiology study

ObjectivesEpidemiological and whole-genome sequencing analysis of an ongoing outbreak of Streptococcus pyogenes (Group A Streptococcus) in London (United Kingdom). MethodsProspective identification of Group A Streptococcus cases from a diagnostic laboratory serving central and south London between 27 November and 10 December 2022. Case notes were reviewed and isolates were retrieved. Case numbers were compared with the previous 5 years. Whole-genome sequencing was performed with long-read, nanopore technology for emm typing and identification of superantigen genes. Associations of pathogen-related factors with an invasive disease were assessed by single-variable and multi-variable logistic regression. ResultsCase numbers began increasing in October 2022 from a baseline of 2.0 cases per day, and in December 2022, the average daily case numbers reached 10.8 cases per day, four-fold the number usually seen in winter. A total of 113 cases were identified during the prospective study period. Three quarters (86/113, 76%) were paediatric cases, including 2 deaths. Of 113 cases, 11 (10%) were invasive. In total, 56 isolates were successfully sequenced, including 10 of 11 (91%) invasive isolates. The emm12 (33/56, 59%) and emm1 (9/56, 16%) types were predominant, with 7 of 9 (78%) emm1 isolates being from the M1uk clone. The majority of invasive isolates had superantigen genes spea (7/10, 70%) and spej (8/10, 80%), whereas, in non-invasive isolates, these superantigen genes were found less frequently (spea: 5/46, 11% and spej: 7/46, 15%). By multivariable analysis of pathogen-related factors, spea (OR 8.9, CI 1.4–57, p 0.020) and spej (OR 12, CI 1.8–78, p 0.011) were associated with invasive disease. Conclusionsemm12 and emm1 types predominate in the ongoing outbreak, which mainly affects children. In this outbreak, the spea and spej superantigen genes are associated with the severity of presentation.

Invasive Fungal Breakthrough Infections under Targeted Echinocandin Prophylaxis in High-Risk Liver Transplant Recipients

Invasive fungal infections (IFIs) are frequent and outcome-relevant complications in the early postoperative period after orthotopic liver transplantation (OLT). Recent guidelines recommend targeted antimycotic prophylaxis (TAP) for high-risk liver transplant recipients (HR-LTRs). However, the choice of antimycotic agent is still a subject of discussion. Echinocandins are increasingly being used due to their advantageous safety profile and the increasing number of non-albicans Candida infections. However, the evidence justifying their use remains rather sparse. Recently published data on breakthrough IFI (b-IFI) raise concerns about echinocandin efficacy, especially in the case of intra-abdominal candidiasis (IAC), which is the most common infection site after OLT. In this retrospective study, we analyzed 100 adult HR-LTRs undergoing first-time OLT and receiving echinocandin prophylaxis between 2017 and 2020 in a tertiary university hospital. We found a breakthrough incidence of 16%, having a significant impact on postoperative complications, graft survival, and mortality. The reasons for this may be multifactorial. Among the pathogen-related factors, we identified the breakthrough of Candida parapsilosis in 11% of patients and one case of persistent IFI due to the development of a secondary echinocandin resistance of an IAC caused by Candida glabrata. Consequently, the efficacy of echinocandin prophylaxis in liver transplantation should be questioned. Further studies are necessary to clarify the matter of breakthrough infections under echinocandin prophylaxis.

Identification of a novel effector gene and its functional tradeoff in Fusarium oxysporum f. sp. cepae that infects Welsh onion

Fusarium oxysporum f. sp. cepae (Foc) is a causal agent of Fusarium wilt in Welsh onion, leading to tremendous production loss. However, pathogenicity-related factors in Welsh onion-infecting Foc have not been elucidated. Here, we screened F. oxysporum f. sp. CepaeEffector candidate Protein (Cep) from next-generation sequencing data of Welsh onion-infecting Foc. Intriguingly, most of the Cep genes (including SIX2 and SIX9) expressed during infection were located on a 3-Mb-sized chromosome in Welsh onion-infecting Foc. Further investigation of the 3-Mb-sized chromosome clarified that the Cep28 is related to virulence, pigmentation, vegetative growth, and stress tolerance and has a functional tradeoff between virulence and vegetative growth.

Why vaccines fail against Piscirickettsiosis in farmed salmon and trout and how to avoid it: A review.

Piscirickettsiosis is the most severe, persistent, and damaging disease that has affected the Chilean salmon industry since its origins in the 1980s. As a preventive strategy for this disease, different vaccines have been developed and used over the last 30 years. However, vaccinated salmon and trout frequently die in the sea cages and the use of antibiotics is still high demonstrating the low efficiency of the available vaccines. The reasons why the vaccines fail so often are still debated, but it could involve different extrinsic and intrinsic factors. Among the extrinsic factors, mainly associated with chronic stress, we can distinguish: 1) biotic including coinfection with sea lice, sealions attacks or harmful algal blooms; 2) abiotic including low oxygen or high temperature; and 3) farm-management factors including overcrowding or chemical delousing treatments. Among the intrinsic factors, we can distinguish: 1) fish-related factors including host's genetic variability (species, population and individual), sex or age; 2) pathogen-related factors including their variability and ability to evade host immune responses; and 3) vaccine-related factors including low immunogenicity and poor matches with the circulating pathogen strain. Based on the available evidence, in order to improve the development and the efficacy of vaccines against P. salmonis we recommend: a) Do not perform efficacy evaluations by intraperitoneal injection of pathogens because they generate an artificial protective immune response, instead cohabitation or immersion challenges must be used; b) Evaluate the diversity of pathogen strains in the field and ensure a good antigenic match with the vaccines; c)Investigate whether host genetic diversity could be improved, e.g. through selection, in favor of better and longer responses to vaccination; d) To reduce the stressful effects at the cage level, controlling the co-infection of pathogens and avoiding fish overcrowding. To date, we do not know the immunological mechanisms by which the vaccines against P. salmonis may or may not generate protection. More studies are required to identify what type of response, cellular or molecular, is required to develop effective vaccines.

Population genomics of the food-borne pathogen Vibrio fluvialis reveals lineage associated pathogenicity-related genetic elements.

Vibrio fluvialis is a food-borne pathogen with epidemic potential that causes cholera-like acute gastroenteritis and sometimes extraintestinal infections in humans. However, research on its genetic diversity and pathogenicity-related genetic elements based on whole genome sequences is lacking. In this study, we collected and sequenced 130 strains of V. fluvialis from 14 provinces of China, and also determined the susceptibility of 35 of the strains to 30 different antibiotics. Combined with 52 publicly available V. fluvialis genomes, we inferred the population structure and investigated the characteristics of pathogenicity-related factors. The V. fluvialis strains exhibited high levels of homologous recombination and were assigned to two major populations, VflPop1 and VflPop2, according to the different compositions of their gene pools. VflPop2 was subdivided into groups 2.1 and 2.2. Except for VflPop2.2, which consisted only of Asian strains, the strains in VflPop1 and VflPop2.1 were distributed in the Americas, Asia and Europe. Analysis of the pathogenicity potential of V. fluvialis showed that most of the identified virulence-related genes or gene clusters showed high prevalence in V. fluvialis , except for three mobile genetic elements: pBD146, ICEVflInd1 and MGIVflInd1, which were scattered in only a few strains. A total of 21 antimicrobial resistance genes were identified in the genomes of the 182 strains analysed in this study, and 19 (90%) of them were exclusively present in VflPop2. Notably, the tetracycline resistance-related gene tet(35) was present in 150 (95%) of the strains in VflPop2, and in only one (4%) strain in VflPop1, indicating it was population-specific. In total, 91% of the 35 selected strains showed resistance to cefazolin, indicating V. fluvialis has a high resistance rate to cefazolin. Among the 15 genomes that carried the previously reported drug resistance-related plasmid pBD146, 11 (73%) showed resistance to trimethoprim-sulfamethoxazole, which we inferred was related to the presence of the dfr6 gene in the plasmid. On the basis of the population genomics analysis, the genetic diversity, population structure and distribution of pathogenicity-related factors of V. fluvialis were delineated in this study. The results will provide further clues regarding the evolution and pathogenic mechanisms of V. fluvialis , and improve our knowledge for the prevention and control of this pathogen.

Silent Hypoxia in COVID-19 Pneumonia: State of Knowledge, Pathophysiology, Mechanisms, and Management.

Patients with COVID-19 often present with life-threatening hypoxemia without dyspnea or signs of respiratory distress. Termed silent or happy hypoxia, it has puzzled clinicians and challenged and defied our understanding of normal respiratory physiology. A range of host- and pathogen-related factors appears to contribute to its development, including SARS-CoV-2's ability to produce different COVID-19 phenotypes; induce endothelial damage and elicit a vascular distress response; invade cells of the central nervous system and disrupt normal interoception and response; and modulate transcription factors involved in hypoxic responses. Because hypoxemia in COVID-19 is associated with increased mortality risk and poorer survival, early detection and prompt treatment is essential to prevent potential complications. Interventions to prevent hypoxemia and improve oxygen delivery to the blood and the tissues include home pulse-oximetry monitoring, optimization of patient positioning, judicious use of supplemental oxygen, breathing control exercises, and timely and appropriate use of ventilatory modalities and adjuncts.

The resurgence of black fungus in the context of Covid -19 second wave epidemic in India

There is a sudden surge of the cases of the black fungus infection ((mucormycosis / Zygomycosis), at a time when India is reeling under a catastrophe created by the second wave of Covid -19. it is like a 'medical tsunami, ' that ravaged the health care system and the administration alike, both being caught unaware. In the beginning, there is an acute shortage of hospital beds earmarked for this infection, and the lifesaving drug, the liposomal Amphotersin B, coupled with the appalling morbidity, mortality, not to speak of the financial burden and the resource crunch, that is inflicted by it.This article briefly reviews the black fungus infection in India, in the pre and post Covid -19 eras. The risk factors for the black fungus, both Covid associated (CAR) as well as non-Covid -19 associated, are discussed. The host as well as pathogen related factors, in the pathogenesis of the black fungus infection, are explored. An alternative explanation to diabetic ketoacidosis, (DKA) in providing the acidic pH required by the fungus, is hypothesized, as the occurrence of the infection, in the absence of DKA, remained inexplicable. It may be noted that the acidic pH is responsible for making available, the free iron from the host ‘s serum, that is needed for the sustenance, grouth and multiplication of the fungus, as well as causing phagocytic dysfunction in the host. The different clinical presentations of mucormycosis, their salient clinical features and the management are outlined in the present article.

Spoligotype-specific risk of finding lesions in tissues from cattle infected by Mycobacterium bovis

BackgroundAlthough the pathogenic effect of members of the Mycobacterium tuberculosis complex in susceptible hosts is well known, differences in clinical signs and pathological findings observed in infected animals have been reported, likely due to a combination of host and pathogen-related factors. Here, we investigated whether Mycobacterium bovis strains belonging to different spoligotypes were associated with a higher risk of occurrence of visible/more severe lesions in target organs (lungs and/or lymph nodes) from infected animals. A large collection of 8889 samples belonging to cattle were classified depending on the presence/absence of tuberculosis-like lesions and its degree of severity. All samples were subjected to culture irrespective of the presence of lesions, and isolates retrieved were identified and subjected to spoligotyping. The association between the presence/severity of the lesions and the isolation of strains from a given spoligotype was assessed using non-parametric tests and Bayesian mixed multivariable logistic regression models that accounted for origin (region and herd) effects.ResultsResults suggested a difference in severity in lesioned samples depending on the strain’s spoligotype. An association between specific spoligotypes and presence of lesions was observed, with a higher risk of finding lesions in animals infected with strains with spoligotypes SB0120, SB0295 and SB1142 compared with SB0121, and in those coming from certain regions in Spain.ConclusionsOur results suggest that strains belonging to certain spoligotypes may be associated with a higher probability in the occurrence of gross/macroscopic lesions in infected cattle, although these observational findings should be confirmed in further studies that allow accounting for the effect of other possible confounders not considered here, and ultimately through experimental studies.

A TRP1-marker-based system for gene complementation, overexpression, reporter gene expression and gene modification in Candida glabrata.

ABSTRACTAlthough less prevalent than its relative Candida albicans, the yeast Candida glabrata is a successful pathogen of humans, which causes life-threatening candidiasis. It is thus vital to understand the pathogenicity mechanisms and contributing genes in C. glabrata. However, gene complementation as a tool for restoring the function of a previously deleted gene is not standardized in C. glabrata, and it is less frequently used than in C. albicans.In this study, we established a gene complementation strategy using genomic integration at the TRP1 locus. We prove that our approach can not only be used for integration of complementation cassettes, but also for overexpression of markers like fluorescent proteins and the antigen ovalbumin, or of potential pathogenicity-related factors like the biotin transporter gene VHT1. With urea amidolyase Dur1,2 as an example, we demonstrate the application of the gene complementation approach for the expression of sequence-modified genes. With this approach, we found that a lysine-to-arginine mutation in the biotinylation motif of Dur1,2 impairs urea-dependent growth of C. glabrata and C. albicans. Taken together, the TRP1-based gene complementation approach is a valuable tool for investigating novel gene functions and for elucidating their role in the pathobiology of C. glabrata.

Respiratory viruses and febrile response in children with febrile seizures: A cohort study and embedded case-control study

ObjectiveThere are limited data on the pathogen-related and host-related factors in the pathogenesis of febrile seizures (FS). We designed a controlled study to compare the role of different respiratory viruses and febrile response in FS. MethodsIn a prospective cohort study of 1899 pediatric emergency room patients aged 6 months-6 years with a positive respiratory virus multiplex PCR, we identified 225 patients with FSs. We first compared the distribution of respiratory viruses in age-stratified patients with FSs with that in other patients. In an embedded case-control study, we compared the febrile response in patients with FSs with that in the controls matched for age, season and the same respiratory virus. ResultsThe relative risk for FS was the highest for coronavirus OC43, 229E, and NL63 infections [RR: 3.2, 95 % confidence interval (CI): 1.4–7.2) and influenza A and B [RR: 2.5, 95 % CI: 1.4–4.7] as compared to those with other respiratory viral infections. The patients with FSs had a stronger febrile response of 39.2 °C (difference: 0.8 °C, 95 % CI: 0.5–1.2) later during hospitalization after acute care than the controls matched for the same respiratory virus. ConclusionsInfluenza and coronaviruses caused relatively more FS-related emergency room visits than other respiratory viruses. Furthermore, the febrile response was stronger in the patients with FSs than in the controls matched for the same respiratory virus. The results suggest that the pathomechanism of FSs includes modifiable pathogen-related and host-related factors with possible potential in the prevention of FSs.

High quality genome sequence of Treponema phagedenis KS1 isolated from bovine digital dermatitis

Treponema phagedenis KS1, a fastidious anaerobe, was isolated from a bovine digital dermatitis (BDD)-infected dairy cattle in Chungnam, Korea. Initial data indicated that T. phagedenis KS1 exhibited putative virulent phenotypic characteristics. This study reports the whole genome assembly and annotation of T. phagedenis KS1 (KCTC14157BP) to assist in the identification of putative pathogenicity related factors. The whole genome of T. phagedenis KS1 was sequenced using PacBio RSII and Illumina HiSeqXTen platforms. The assembled T. phagedenis KS1 genome comprises 16 contigs with a total size of 3,769,422 bp and an overall guanine-cytosine (GC) content of 40.03%. Annotation revealed 3,460 protein-coding genes, as well as 49 transfer RNA- and 6 ribosomal RNA-coding genes. The results of this study provide insight into the pathogenicity of T. phagedenis KS1.

Host- and Pathogen-Related Factors for Acute Cardiac Events in Pneumococcal Pneumonia.

BackgroundAcute cardiac events (ACEs) are increasingly being recognized as a major complication in pneumococcal community-acquired pneumonia (CAP). Information regarding host- and pathogen-related factors for ACEs, including pneumococcal serotypes and clonal complexes, is scarce.MethodsA retrospective study was conducted of a prospective cohort of patients hospitalized for CAP between 1996 and 2019. Logistic regression and funnel plot analyses were performed to determine host- and pathogen-related factors for ACEs.ResultsOf 1739 episodes of pneumococcal CAP, 1 or more ACEs occurred in 304 (17.5%) patients, the most frequent being arrhythmia (n = 207), heart failure (n = 135), and myocardial infarction (n = 23). The majority of ACEs (73.4%) occurred within 48 hours of admission. Factors independently associated with ACEs were older age, preexisting heart conditions, pneumococcal bacteremia, septic shock at admission, and high-risk pneumonia. Among 983 pneumococcal isolates, 872 (88.7%) were serotyped and 742 (75.5%) genotyped. The funnel plot analyses did not find any statistically significant association between serotypes or clonal complexes with ACEs. Nevertheless, there was a trend toward an association between CC230 and these complications. ACEs were independently associated with 30-day mortality (adjusted odds ratio, 1.88; 95% CI, 1.11–3.13).ConclusionsACEs are frequent in pneumococcal pneumonia and are associated with increased mortality. The risk factors defined in this study may help identify patients who must undergo close follow-up, including heart rhythm monitoring, and special care to avoid fluid overload, particularly during the first 48 hours of admission. These high-risk patients should be the target for preventive intervention strategies.

Implementation of a targeted mastitis therapy concept using an on-farm rapid test: antimicrobial consumption, cure rates and compliance

BackgroundAim of the present study was to investigate the implementation of a targeted therapy (tLCT) concept under real-life circumstances, taking both pathogen-related and animal-related factors into account. The reduction of...

Infection Risk-Adjusted Antibiotic Prophylaxis Strategies in Arthroplasty: Short Review of Evidence and Experiences of a Tertiary Center in Spain.

There is growing body of evidence that important patient-, procedure- and pathogen-related factors are linked to higher risks for prosthetic joint infections (PJI) following arthroplasty surgeries. The prior identification and optimization of such risk factors is considered paramount to minimize the incidence of these infections. Without any doubt, antibiotic prophylaxis remains one of the cornerstones among all preventive measures. However, the ideal antibiotic prophylaxis is still in debate and discussions have emerged, whether certain situations deserve adjustments or variations of the standard protocol taking into account antibiotic resistance surveillance data and patient risk factors for infections. This review aims to provide the reader with an overview of possible antibiotic prophylaxis strategies in response to these risks and discusses the clinical experiences so far obtained. We further present preliminary evidence that the use of a reinforced local antibiotic prophylaxis regimen with high-dose dual antibiotic-loaded bone cement may be an effective and easy-to-apply option in patients at high infection risks.

2020 Frank Stinchfield Award: Identifying who will fail following irrigation and debridement for prosthetic joint infection.

Failure of irrigation and debridement (I&D) for prosthetic joint infection (PJI) is influenced by numerous host, surgical, and pathogen-related factors. We aimed to develop and validate a practical, easy-to-use tool based on machine learning that may accurately predict outcome following I&D surgery taking into account the influence of numerous factors. This was an international, multicentre retrospective study of 1,174 revision total hip (THA) and knee arthroplasties (TKA) undergoing I&D for PJI between January 2005 and December 2017. PJI was defined using the Musculoskeletal Infection Society (MSIS) criteria. A total of 52 variables including demographics, comorbidities, and clinical and laboratory findings were evaluated using random forest machine learning analysis. The algorithm was then verified through cross-validation. Of the 1,174 patients that were included in the study, 405 patients (34.5%) failed treatment. Using random forest analysis, an algorithm that provides the probability for failure for each specific patient was created. By order of importance, the ten most important variables associated with failure of I&D were serum CRP levels, positive blood cultures, indication for index arthroplasty other than osteoarthritis, not exchanging the modular components, use of immunosuppressive medication, late acute (haematogenous) infections, methicillin-resistant Staphylococcus aureus infection, overlying skin infection, polymicrobial infection, and older age. The algorithm had good discriminatory capability (area under the curve = 0.74). Cross-validation showed similar probabilities comparing predicted and observed failures indicating high accuracy of the model. This is the first study in the orthopaedic literature to use machine learning as a tool for predicting outcomes following I&D surgery. The developed algorithm provides the medical profession with a tool that can be employed in clinical decision-making and improve patient care. Future studies should aid in further validating this tool on additional cohorts. Cite this article: Bone Joint J 2020;102-B(7 Supple B):11-19.

A bioinformatics approach revealed the transcription factors of Helicobacter pylori pathogenic genes and their regulatory network nodes

Helicobacter pylori is a chronic pathogenic bacteria that causes gastric mucosal damage through various host-related and pathogen-related factors. Thus, a single gene research cannot fully explain its pathogenicity. Purpose of the study: It is necessary to establish a Helicobacter pylori pathogenic gene transcription factor regulatory network (TFRN) and study its central nodes. The expression data of Helicobacter pylori pathogenic genes were obtained through GEO Datasets of NCBI. The genes were screened using linear model-empirical Bayesian statistics in R language Limma package combined with the conventional t -test; the results identified 1231 differentially expressed genes. The functional analysis (gene ontology-analysis) and signal pathway analysis (pathway-analysis) of differentially expressed genes were performed using the DAVID and KEGG databases, respectively. The pathogenic gene regulatory network was constructed by integrating transcriptional regulatory element database (TRED); the disease-related analysis of the pathogenic genes was conducted using the DAVID annotation tool. Five pathogenic genes ( Nos2 , Il5 , Colla1 , Tnf, and Nfkb1) and their transcription factors (Jun, Cebpa, Egrl, Ppara, and Il6) were found to suppress the host immune function and enhance the pathogenicity of Helicobacter pylori by regulating the host immune system. This effect was largely mediated via three signaling pathways: Tnf pathway, PI3K Akt pathway, and Jak–STAT pathway. The pathogenicity of Helicobacter pylori is closely related to the body's immune and inflammatory system. A better understanding of the correlation of the pathogenic factors with the host immune and inflammatory factors may help to determine the precise pathogenic mechanism of H. pylori infection. How to cite: Bai Y, Li W, Xu G, et al. A bioinformatics approach revealed the transcription factors of Helicobacter pylori pathogenic genes and their regulatory network nodes. Electron J Biotechnol 2020;45. https://doi.org/10.1016/j.ejbt.2020.04.002 .

Clinical Manifestations and Outcomes in Immunocompetent and Immunocompromised Patients With Blastomycosis.

Blastomyces is a dimorphic fungus that infects persons with or without underlying immunocompromise. To date, no study has compared the clinical features and outcomes of blastomycosis between immunocompromised and immunocompetent persons. A retrospective study of adult patients with proven blastomycosis from 2004-2016 was conducted at the University of Wisconsin. Epidemiology, clinical features, and outcomes were analyzed among solid-organ transplantation (SOT) recipients, persons with non-SOT immunocompromise (non-SOT IC), and persons with no immunocompromise (NIC). A total of 106 cases met the inclusion criteria including 74 NIC, 19 SOT, and 13 non-SOT IC (malignancy, HIV/AIDS, idiopathic CD4+ lymphopenia). The majority of patients (61.3%) had at least 1 epidemiologic risk factor for acquisition of Blastomyces. Pneumonia was the most common manifestation in all groups; however, immunocompromised patients had higher rates of acute pulmonary disease (P = .03), more severe infection (P = .007), respiratory failure (P = .010), and increased mortality (P = .02). Receipt of SOT primarily accounted for increased severity, respiratory failure, and mortality in immunosuppressed patients. SOT recipients had an 18-fold higher annual incidence of blastomycosis than the general population. The rate of disseminated blastomycosis was similar among NIC, SOT, and non-SOT IC. Relapse rates were low (5.3-7.7%). Immunosuppression had implications regarding the acuity, severity, and respiratory failure. The rate of dissemination was similar across the immunologic spectrum, which is in sharp contrast to other endemic fungi. This suggests that pathogen-related factors have a greater influence on dissemination for blastomycosis than immune defense.